Academia.eduAcademia.edu
Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 Contents lists available at SciVerse ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep A review of the medicinal potentials of plants of the genus Vernonia (Asteraceae) Q1 Ngeh J. Toyang a,b,n, Rob Verpoorte c a Virgin Botanicals & Biotech Inc. Columbia, MD, USA Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA c Natural Products Laboratory, Institute of Biology, Universiteit Leiden, Leiden, The Netherlands b a r t i c l e i n f o abstract Article history: Received 30 July 2012 Received in revised form 22 January 2013 Accepted 22 January 2013 Ethnopharmacological relevance: The Vernonia genus has about one thousand species and members of the genus are widely used as food and medicine. The aim of this review is to analyze published data on the ethnomedicinal, ethnoveterinary and zoopharmacognostic uses of plants of the Vernonia genus. This will help to identify the state of ethnopharmacological knowledge in regard to this genus and to propose future research priorities. Materials and methods: The major scientific databases including SciFinder, Sciencedirect, Medline and Google Scholar were queried for information on Vernonia genus using various keyword combinations. The International Plant Name Index was also used to verify the names of species and authors. Results: A total of 109 Vernonia species were reported in the literature to have medicinal properties. One hundred and five (105) plants were linked to the treatment or management of 44 human diseases or health conditions. Plants of the genus also feature in ethnoveterinary and zoopharmacognostic practices. A total of 12 vernonia species were identified to be used in ethnoveterinary medicine while 2 species are used in self medication practices by chimpanzees and gorillas. In vitro and in vivo research studies reporting the validation of the medicinal properties of some species were also reviewed. One hundred and three bioactive compounds isolated from various Vernonia species were also identified. Vernonia amygdalina was identified as the most frequently used member of the Vernonia genus. The Vernolides, a class of sesquiterpene lactone were identified as the most studied compounds from the genus and show interesting bioactivity in antiplasmodial, antileishmanial, antischistosomial, cytotoxicity, antimicrobial and anti-inflammatory assays. Conclusion: This review reveals that the genus Vernonia is endowed with many medicinal plants some of which have potential for the discovery of new drugs. On the basis of results from a combination of in vitro and in vivo efficacy and toxicity studies reported, Vernonia amygdalina holds the most promise for development into a nutraceutical against diabetes and malaria while Vernonia cinerea has potential against cancer and inflammatory conditions. Vernolide A is so far the most promising single agent from a Vernonia species that has potential for development into an anticancer agent. The other Vernonia species and isolated compounds require further studies to ascertain their medicinal potentials. & 2013 Elsevier Ireland Ltd. All rights reserved. Keywords: Vernonia Asteraceae Medicinal plant Ethnomedicine Ethnoveterinary medicine Zoopharmacognosy Phytochemistry Contents 1. Introduction to the genus Vernonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. 3. Review methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3.1. Ethnopharmacological uses of Vernonia species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.1.1. Vernonia adoensis Sch. Bip. ex Walp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.1.2. Vernonia aemulans Vatke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 n Corresponding author at: Institute of Human Virology, University of Maryland School of Medicine, Room S421, 725 West Lombard Street, Baltimore, MD 21201, USA. Tel.: þ1 410 706 1062; fax: þ 1 410 706 5664. E-mail address: ntoyang@som.umaryland.edu (N.J. Toyang). 0378-8741/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2013.01.040 Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 3.1.3. 3.1.4. 3.1.5. 3.1.6. 3.1.7. 3.1.8. 3.1.9. 3.1.10. 3.1.11. 3.1.12. 3.1.13. 3.1.14. 3.1.15. 3.1.16. 3.1.17. 3.1.18. 3.1.19. 3.1.20. 3.1.21. 3.1.22. 3.1.23. 3.1.24. 3.1.25. 3.1.26. 3.1.27. 3.1.28. 3.1.29. 3.1.30. 3.1.31. 3.1.32. 3.1.33. 3.1.34. 3.1.35. 3.1.36. 3.1.37. 3.1.38. 3.1.39. 3.1.40. 3.1.41. 3.1.42. 3.1.43. 3.1.44. 3.1.45. 3.1.46. 3.1.47. 3.1.48. 3.1.49. 3.1.50. 3.1.51. 3.1.52. 3.1.53. 3.1.54. 3.1.55. 3.1.56. 3.1.57. 3.1.58. 3.1.59. 3.1.60. 3.1.61. 3.1.62. 3.1.63. 3.1.64. 3.1.65. 3.1.66. 3.1.67. 3.1.68. 3.1.69. 3.1.70. 3.1.71. 3.1.72. 3.1.73. 3.1.74. Vernonia albicans DC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia ambigua Kotschy & Peyr . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia ampandrandavensis Humbert . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia amygdalina Del. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia anthelmintica Willd. Synonym Centhraterum anthelminticum Vernonia appendiculata Less . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia arborea Buch.- Ham. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia aristifera S.F. Blake. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia auriculifera Hiern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia bahamensis Griseb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia betonicaefolia Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia biafrae Oliv. & Hiern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia blumeoides Hook. F. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia brachycalyx O. Hoffm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia brasiliana (L.) Druce. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia brazzavillensis Aubrév. Ex Compe re . . . . . . . . . . . . . . . . . . . . . Vernonia calvoana Hook. F. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia campeana S. Moore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia canescens HBK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia chalybaea Mart. ex DC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia chapelieri Drake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia chinensis Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia cinerascens Sch. Bip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia cinerea (L.) Less . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia cistifolia O. Hoffm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia cognata Less . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia colorata Drake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia condensata Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia conferta Benth.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia cruda Klatt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia cumingiana Benth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia deppeana Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia extensa DC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia fasciculata Michx.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia fastigiata Oliv. & Hiern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia ferruginea Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia filigera Oliv. & Hiern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia fontinalis S. Moore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia galamensis Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia gerberiformis Oliv. & Hiern . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia glaberrima Welw. ex O. Hoffm. . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia glabra (Steetz) Oliv. & Hiern . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia grantii Oliv. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia guineensis Benth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia herbacea Rusby . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia hildebrandtii Vatke. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia hirsuta (DC.) Sch. Bip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia hochstetteri Sch. Bip. ex Hochst. . . . . . . . . . . . . . . . . . . . . . . . . Vernonia hymenolepis Vatke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia incana Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia jugalis Oliv. & Hiern. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia karaguensis Oliv. & Hiern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia kenteocephala Baker. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia kotschyana Sch. Bip. ex Walp. Synonym Baccharoides adoensis Vernonia lasiopus O. Hoffm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia leiocarpa DC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia leopoldii Vatke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia macrocyanus O. Hoffm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia mapirensis Gleason . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia mespilifolia Less . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia miombicola Wild . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia mollissima D. Don ex Hook. & Arn. . . . . . . . . . . . . . . . . . . . . . . Vernonia myriantha Hook. F.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia natalensis Sch. Bip. ex Walp. . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia neocorymbosa Hilliard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia nestor S. Moore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia nigritiana Oliv. & Hiern.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia noveboracensis (L.) Willd. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia nudicaulis Less.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia oligocephala Edgew . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia oocephala Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vernonia pachyclada Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .............................. .............................. .............................. .............................. Kuntze . . . . . . . . . . . . . . . . . . . . . . . . .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. var. kotschyana (Sch. Bip. ex Walp.) . .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. .............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 . 10 . 10 . 10 . 14 . 14 . 14 . 16 . 16 . 16 . 16 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 17 . 18 . 18 . 18 . 18 . 18 . 18 . 18 . 18 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 19 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 20 . 21 . 21 . 21 . 21 . 21 Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 3 3.1.75. Vernonia patens Kunth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.76. Vernonia patula Mart. ex DC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.77. Vernonia pectoralis Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.78. Vernonia perrottetii Sch. Bip. ex Walp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.79. Vernonia pogosperma Klatt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.80. Vernonia polyanthes Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.81. Vernonia polytricholepis Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.82. Vernonia poskeana Vatke & Hildeb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.83. Vernonia potamophila Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.84. Vernonia prolytricholepsis Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.85. Vernonia pumila Kotschy & Peyr. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.86. Vernonia rhodolepsis Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.87. Vernonia roxburghii Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.88. Vernonia saligna DC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.89. Vernonia scorpioides Pers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.90. Vernonia senegalensis Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.91. Vernonia serratuloides Kunth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.92. Vernonia smithiana Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.93. Vernonia spiciforma Klatt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.94. Vernonia staehelinoides Mart. ex Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.95. Vernonia stellullifera (Benth.) C. Jeffrey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.96. Vernonia stenocephala Oliv. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.97. Vernonia stipulacea Klatt. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.98. Vernonia subuligera O. Hoffm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.99. Vernonia tenoreana Oliv. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.100. Vernonia teres Wall ex DC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.101. Vernonia thomsoniana Oliv. & Hiern ex Oliv. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.102. Vernonia tigna Klatt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.103. Vernonia trichoclada Gleason . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.104. Vernonia trichodesma Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.105. Vernonia tweedieana Baker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.106. Vernonia undulata Oliv. & Hiern. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.107. Vernonia usambarensis O. Hoffm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.108. Vernonia venosa S. Moore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.109. Vernonia zeylanica Less. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.2. In vitro activity analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.3. In vivo activity analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 3.4. Clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 3.5. Toxicity aspects of the Vernonia genus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.6. Phytochemistry of the Vernonia genus: Bioactive compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.6.1. Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.6.2. Flavonoids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.6.3. Terpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.6.4. Miscellaneous compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 4. Conclusion and recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 4.1. Planning future ethnopharmacological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4.2. Selection of species for further studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.3. Selection of compounds for further studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.4. Assay selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.5. Sample collection and preparation for screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.6. Toxicity and safety studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 4.7. Phytochemical, metabolomic analysis and quality issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Uncited references. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 1. Introduction to the genus Vernonia Vernonia (Asteraceae) is the largest genus in the tribe Vernoniae with close to 1000 species (Keeley and Jones, 1979). The genus Vernonia is named after William Vernon, an English botanist who collected and identified this genus in Maryland in the late 1600s before his death in 1711 (Quattrocchi, 1999). The genus is distributed both in the New and Old Worlds although it is to be found mostly in the tropical regions. Vernonia species grow in a wide range of habitats of broad ecological diversity and climatic conditions including tropical forest, marshes and wet areas, dry plains, tropical savannahs, desert xeric or dry sites and even frosty regions of eastern North America (Gleason, 1923; Keeley and Jones, 1979). The genus is morphologically made up of annuals, herbaceous perennials, lianas, shrubs, and trees. The genus Vernonia is known for having several species with food, medicinal and industrial uses. For example, Vernonia. amygdalina, and Vernonia colorata, are eaten as leafy vegetables (Burkill, 1985; Iwu, 1993). Vernonia species frequently used in ethnomedicine include, Vernonia amygdalina, Vernonia condensata, Vernonia cineria, Vernonia guineensis and Vernonia conferta. Vernonia galamensis is used industrially for its seed oil contents. Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 4 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 Vernonia amygdalina is the most studied member of the 2 Vernonia genus as well as one of the most studied plants in Africa 3 Q3 (Ijeh and Ejike 2011). Vernonia amygdalina (Fig. 1) is a shrub of the 4 savannah as well as forest areas throughout tropical Africa 5 (Burkill, 1985). This species and Vernonia colorata are very similar 6 in appearance and are not easily distinguished. Vernonia amygda7 lina leaves have a characteristic odour and a bitter taste, which 8 can be reduced by boiling and discarding the water or soaking and 9 washing in several changes of water before consumption. Analysis 10 showed that the plant is rich in nutrients including amino acids, 11 minerals and vitamins (Alabi et al., 2005; Ejoh et al., 2007; 12 Eleyinmi et al., 2008). The nutritional composition of Vernonia 13 amygdalina is presented in Table 1. 14 Despite the widespread use of plants of the Vernonia genus in 15 food and medicine, to the best of our knowledge, no comprehen16 sive review has before been carried out to document and analyse 17 the contributions of this genus to the nutrition and health of 18 humans and animals in domestic or wild settings. Johri and Singh 19 (1997) reported a review of the medicinal uses of Vernonia species 20 in which 6 species were identified and reviewed in detail while 21 about 20 other species were indicated to be featured in various 22 traditional materia medica with little additional details. To fill this 23 gap, this paper reviews the state of knowledge on the ethnome24 dicinal, ethnoveterinary, zoopharmacognostical, pharmacological 25 evaluation and chemical diversity within the Vernonia genus and 26 proposes strategies for further research to confirm claimed tradi27 tional uses as well as identify species and isolated compounds 28 worthy of further research and development into medicines. 29 30 31 2. Review methodology 32 33 34 a. Literature search: Relevant literature was collected by search35 ing the major scientific databases including SciFinder, Scien36 cedirect, Medline and Google Scholar. Table 2 presents the 37 results of the keyword search from the above databases. We 38 are also aware of the fact that these databases are updated 39 routinely and the data presented in Table 2 is just indicative of 40 the information that was available at the time this paper was 41 being prepared. 42 b. Selection of relevant publications: Two major criteria were used 43 for the selection of relevant references for use in this review. 44 45 i. Folk use: For folk uses, all publications that could be 46 accessed with any information on the ethnomedicinal, 47 ethnoveterinary and zoopharmacognostical uses of Vernonia 48 were considered useful. Restrictions as to the popularity of 49 impact factor of the journal or source were not made because 50 most of such publications are based on the documentation 51 of oral traditions and even a letter detailing the folk use of a 52 remedy could prove valuable. 53 ii. In vitro and in vivo confirmation studies: In regard to the 54 confirmation of claimed folk medicinal uses of Vernonia and 55 the bioactive compounds isolated from this genus, only 56 papers that provided complete plant identity including 57 information on the collection and deposition of a voucher 58 specimen, and disease description for correlation with 59 western diagnosis were selected for use in this review. 60 In addition, any other species that were not reported to be 61 used in folk medicine but were reported to be having 62 bioactivity based on in vitro or in vivo studies have been 63 included in this review just to expand the knowledge base 64 on the bioactivity of this genus. 65 Sciencedirect provided the most related articles while Medline 66 gave the fewest related articles. Google Scholar suggested the highest number of articles per search phrase but at least 70– 90% of the suggested articles were out of topic and as such made the sorting of the related from the unrelated articles a tedious task. The keyword search phrases; Vernonia medicinal uses, Vernonia medicinal plants and bioactive compounds from Vernonia suggested most of the articles referenced in this review. Even within these keyword search phrases, only about 40–60% of the articles suggested were useful in this review which has over 400 references out of over 900 papers, books or abstracts reviewed. In terms of journal contribution to this review, the Journal of Ethnopharmacology provided the highest number (100 articles) of journal articles carrying information on the ethnopharmacology of the Vernonia genus. c. Validation of plant names: The International Plant Name Index (www.ipni.org) and the Kew Botanic Garden Plant name database were used to validate plant scientific names. This helped to identify misspellings and the use of synonyms for different species. Author names were also confirmed through this process. 3. Results and discussion Plants of the genus Vernonia are widely used in ethnomedicine, ethnoveterinary medicine and in zoopharmacognosy especially by chimpanzees and gorillas. A total of 109 species of Vernonia have been identified to be used in folk medicine or bioactive. One hundred and three of the species are used in ethnomedicine while twelve of the species are used in ethnoveterinary medicine. Only 2 of the species are used in zoopharmacognosy. Also, 2 of the species listed out of the 109 did not have any application in folk use or zoopharmacognosy. Two of the plants were reported to be used in ethnoveterinary medicine alone. Folk uses of Vernonia species have been reported in all the continents with the exception of Antartica, Australia and Europe (Table 3). Amongst the different Vernonia species, Vernonia amygdalina, Vernonia cinerea, Vernonia colorata, Vernonia guineensis and Vernonia kotschyana are the top five most frequently used species. Detailed description on the ethnomedicinal uses of plants of the genus Vernonia are listed in Table 3 while those used in ethnoveterinary medicine and zoopharmacognosy are listed in Tables 4 and 5. Table 6a (in vitro studies) and Table 6b (in vivo studies) presents a summary of the studies carried out to ascertain the medicinal properties of plants of this genus. Ninety bioactive compounds isolated from species of the genus are presented in Tables 7 and 8 while Fig. 2 illustrates the chemical structures of these compounds. Despite the fact that these compounds were reported to be active, only a small number of the compounds will be considered active going by industry standard where EC50 r10 mM is the reference for activity of pure compounds (Gertsch, 2009). As for crude extracts, activity standard can be very variable since the concentration of the active compound in the crude is what will determine whether there is activity or no activity even when the activity is as a result of synergism. Recent research into ethnoveterinary medicine practices has resulted in the documentation of many plant species used by farmers to control or treat diseases affecting their livestock. Interestingly, some of the ethnoveterinary and zoopharmacognosy uses of plants do correspond with the uses of the same plants in humans. A good example is the use of Vernonia amygdalina to control gastrointestinal parasites in both animals and man as stated by different informants (Huffman, 1997; Mølgaard et al., 2001; Toyang et al., 2007; Yeap et al., 2010). Similarly, researchers have recorded the use of Vernonia amygdalina in self-medication practices amongst chimpanzees to relief Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 5 Table 2 Results of keyword/phrase search for Vernonia. Keyword/phrase Number of hits SciFinder Sciencedirect Medline Google Scholar Vernonia 1230 Vernonia genus 76 Vernonia species 92 Vernonia medicinal uses 34 Ethnomedicinal uses of 3 Vernonia Vernonia medicinal plants 61 Vernonia and 1 ethnoveterinary medicine Vernonia and 2 zoopharmacognosy Bioactive compounds from 43 Vernonia Fig. 1. Vernonia amygdalina Del. picture. Table 1 Nutritional composition of Vernonia amygdalina Del. Leaves. Per 100 g dry weight Value a Proximate values Moisture (%) Dry matter (%) Crude protein (g) Digestible protein (g) Total carbohydrate (g) Ash (g) Reducing sugar (g) Dietary fibre (g) Total lipids Energy (Kcal) 79.92 20.08 19.23 16.58 68.35 7.72 14.31 25.47 4.70 392.67 Vitamins and mineralsa Vitamin C (mg/100 g) Carotenoids (mg/100 g) Ca (mg/100 g) Fe (mg/100 g) Bioavailable Fe (mg) Average nutritive value Oxalic acid (mg/100 g) Polyphenols (mg/100 g) Saponins (mg/100 g) 166.5 30.0 97.0 7.52 2.84 1.10 5.36 9.75 1.425 Sugar contentsb Raffinose Lactose Sucrose Glucose Galactose Fructose Maltose Arabinose a b 5.1 2.61 13.20 7.20 6.56 6.00 7.24 9.25 Ejoh et al. (2007). Alabi et al. (2005). stomach ache including controlling worm infestation (Huffman and Seifu, 1989; Huffman et al., 1993). In regard to chemical diversity, plants of the Vernonia genus are the source of many terpene type compounds particularly 1241 460 980 425 45 222 6 41 0 0 17,500 6,050 11,600 3,690 3,300 459 34 62 1 3,370 158 11 0 80 230 8 813 sesquiterpenes (Chaturvedi, 2011). Flavonoids have also been isolated from some members of the Vernonia genus (Igile et al., 1994; Ku et al., 2002). Even though alkaloids have been reported to be present in some species (Eyong et al., 2011) of the Vernonia genus, no specific alkaloid has so far been isolated from any Vernonia species. A number of difficulties were encountered putting together this review. The first difficulty had to do with deciding which papers carried validated ethnomedicinal data and which ones did not. However, we decided to include all published ethnomedicinal data in regard to the Vernonia genus so long as the source was properly identified. This is because information on the ethnomedicinal uses of plants mostly comes from oral history and as such often require validation based on independent use verifications or clinical trials. In the absence of clinical trials, in vitro/in vivo studies may be used as a preliminary step to lend support to folk medicinal uses of plants. In regard to various biological activity studies carried out, it was also difficult determining the cut off dose for activity as different authors tested formulations at different concentrations even when testing the same plant species for the same biological activity. It is noteworthy to state that validation implies testing for activity in an in vivo model comparable to the one used in folk medicine. Another difficulty encountered is that in some cases only abstracts were found. It was not possible to include such studies without additional details. Publications made in other languages without English abstracts might have also been missed since the keyword search in the databases listed above was performed in English. Ethnopharmacological uses of Vernonia species included in this review are presented below: 3.1. Ethnopharmacological uses of Vernonia species The following section presents a review of ethnopharmacological uses of Vernonia species. More details on the uses of these species and the associated references are indicated in Tables 4–6a. 3.1.1. Vernonia adoensis Sch. Bip. ex Walp. Vernonia adoensis is used in folk medicine to treat chronic cough and fever (Hutchings et al., 1996), tuberculosis and gonorrhea (Burkill, 1985; Kisangau et al., 2007a), malaria (Stangeland et al., 2010), HIV/AIDS (Lamorde et al., 2010), wounds and snake bites (Ragunathan and Solomon, 2009). In ethnoveterinary medicine, this species is used to treat sores (Burkill, 1985). A number of in vitro studies have so far been carried to confirm the activity of this species. The most interesting results obtained concern the antiplasmodial activity where an IC50 value of 2.14 mg/ml was recorded (Stangeland et al., 2010) and antimycobacterium activity Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 3 Ethnomedicinal uses of Vernonia species. Vernonia species Part used Country or region Use in ethnomedicine Reference adoensis Sch. Bip. exWalp L R South Africa Nigeria, Tanzania Hutchings et al. (1996) Burkill (1985) (S) N/I L L L, R L L L L AP L L Sudan Uganda Uganda Ethiopia Tanzania Rwanda Rwanda Rwanda Madagascar India Cameroon R W AP N/I L N/I L L L, R Tanzania Nigeria Madagascar Nigeria Ghana Cameroon Cameroon Sao Tome & Principe Nigeria Uganda Chronic coughs, fever Digestive/appetizer, stomach pain, TB, gonorrhoea, blotches Bacteria Malaria HIV/AIDS infection Wounds, snake bite TB Bacterial and virus infection Gonorhoea Bacteria Febrifuge Earache Male/female sterility (pelvic inflammatory disease, low sperm count) Gonorrhoea, impotence, postpartum pains, dysmenorrhoea Coughs and colds Malaria Malaria Fever malaria Malaria Piles, poor digestion, poisoning, diabetes Malaria Measles Induce labour in childbirth N/I L, R Tanzania DR Congo R, L L St, R R L L L L L L L L L, R L L L L L, R, B Kenya Nigeria Uganda Zimbabwe Nigeria Nigeria Nigeria Ethiopia Rwanda Nigeria Nigeria Ghana Ethiopia Ethiopia Cameroon Cameroon Ethiopia D.R Congo L L R R L L, R Uganda Uganda Cameroon South Africa Uganda West Africa L Tanzania L L L S S WP WP Rwanda Nigeria Nigeria India India India India N/I India appendiculata Less arborea Buch. Ham L L Madagascar India aristifera S.F. Blake auriculifera Hiern R L Mexico Ethiopia aemulans Vatke Oesterr. albicans DC. ambigua Kotschy & Pery. ampandrandavensis Bak. amygdalina Del. anthelmintica Willd. Malaria, back ache, chickenpox, Diarrhoea, dysentery, gastroenteritis, malaria, hepatitis, worms Diarrhoea, stomach ache Haemorrhoid, hypertension Fever/malaria Sexually transmitted diseases Diabetes Pile, stomachic, diarrhoea, hypertension Diabetes mellitus Headache Diarrhea, hepatitis, malaria Diabetes, itching Antisickling Dermatitis Worms Tonsilitis Diarrhoea, enteritis, colic Menstrual cramps Tapeworm, ascaris, stomach-ache Diarrhoea, dysentery, gastroenteritis, malaria, hepatitis, worms Malaria, worms, skin problems Tuberculosis Impotence Infertility, amenorrhoea Malaria Fevers, laxative, cough, ringworm, appetizer, worms, diarrhoea, rheumatism, schistosomiasis, aphrodisiac Skin rashes, Chronic diarhhoea, Herpes zoster, Herpes simplex, Cryptococcal meningitis. Malaria Wounds Circumcision ounds Diabetes mellitus Anthelmintic, stomachic, diuretic intestinal disorders, fever, skin ailments fever, athsma, cough, ulcer, skin, leucoderma, leprosy, dyspepsea, inflammation, astrigent, worms, expectorant, demulcent, diuretic, stomachic, febrifuge, galatogue, tonic, purgative Worms, asthma, kidney conditions, piles, conjunctivitis Febrifuge Wound healing, worms, fever, sprue, jaundice, rheumatic pain Dysentary, hypermenorrhage Toothache Al Magboul et al. (1988) Stangeland et al. (2010) Lamorde et al. (2010) Ragunathan and Solomon (2009) Kisangau et al. (2007b) Vlietinck et al. (1995) Van Puyvelde et al. (1983) Vermani and Garg 2002 Rasoanaivo et al. (1992) Rai and Lalramnghinglova (2011) Focho et al. (2009b) Burkill (1985) (S) Builders et al. (2011) Rasoanaivo et al. (1992) Tor-Anyiin et al. (2003) Asase et al. (2010) Betti (2004) Jiofack et al. (2010) Madureira et al. (2002) Sonibare et al. (2009) Kamatenesi-Mugisha and OryemOriga (2007) Moshi et al. (2010) Longanga et al. (2000) Geissler et al. (2002) Lawal et al. (2010) Ssegawa and Kasenene (2007) Kambizi and Afolayan (2001) Gbolade (2009) Mensah et al. (2008) Ogbera et al. (2010) Giday et al. (2010) Cos et al. (2002) Ajibesin et al. (2008) Egunyomi et al. (2009) Pesewu et al. (2008) Wondimu et al. (2007) Teklehaymanot (2009) Noumi and Yomi (2001) Fonge et al. (2012) Teklehaymanot et al. (2007) Otshudi et al. (2000) Namukobe et al. (2011) Tabuti et al. (2010) Focho et al. (2009a) Van Wyk and Gericke (2000) Tabuti (2008) Burkill (1985) (S) Kisangau etal. (2007b) Ramathal and Ngassapa (2001) Adetutu et al. (2011) Mboto et al. (2009) Rao et al. (2010) Joy et al. (1998) Kumar et al. (2011) Parekh and Chanda (2007, 2008) Johri et al. (1995) Rasoanaivo et al. (1992) Manjunatha et al. (2005) Heinrich (1996) (S) Giday et al. (2009) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 7 Table 3 (continued ) Vernonia species Part used Country or region Use in ethnomedicine Reference bahamensis Griseb. betonicaefolia Bak. biafrae Oliv. & Hiern blumeoides Hook. F. brachycalyx O. Hoffm. L R B L AP L N/I L L L, R L, R Cameroon Uganda Uganda Bahamas Madagascar W. Africa Nigeria Tanzania Kenya Kenya Brazil Focho et al. (2009a) Freiburghaus et al. (1996) Namukobe et al. (2011) Gupta et al. (1993) Rasoanaivo et al. (1992) Burkill (1985) Aliyu et al. (2011a) Moshi et al. (2010) Oketch-Rabah et al. (1997) Oketch-Rabah et al. (1998) Rodrigues (2007) L Congo Cataract Sleeping sickness Placenta removal Jaundice Febrifuge Headache, fever, filarial, iritis, abscess Malaria Back ache, chicken pox Malaria Malaria, stomachache, purgative Exact use not indicated except mention that it is prescribed in low doses because it is poisonous Malaria L L F, L L, Fl L, R AP WP L, Rhizomes Cameroon Uganda Uganda Bahamas Brazil Madagascar China Pakistan Focho et al. (2009b) Ssegawa and kasenene (2007) Hamill et al. (2003) Gupta et al. (1993) Albuquerque et al. (2007) Rasoanaivo et al. (1992) Xie 1975 Hussain et al. (2010) leaves WP N/I Tanzania India India L India Nigeria Equatoria Guinea Tanzania Navel aches, constipation Stomach ache and fever Fever/malaria Bleeding, inflammation, enema Edema, liver Malaria Colds, headache, bacteria, wound Gastritis, Urinary infections, Male sterility, navelaches constipation and internal ulcers Skin infections, mental disorders, depression Astringent, diaphoretic, antirheumatic Worms, asthma, kidney conditions, piles, conjunctivitis Malaria Fever Febrifuge, vermifuge Cholera, dysentery, constipation, fever, impotency, lactation, malaria, night blindness, piles, skin diseases, threadworm, spleen complaints and wounds Malaria, fever brasiliana (L.) Druce brazzavillensis Aubrév. ex Compe re calvoana Hook. F. campanea S. Moore canescens HBK chalybaea Mart. ex DC chapalieri Drak. chinensis Less. cinerascens Sch.Bip cinerea (L.) Less L, B cistifolia O. Hoffm. cognata Less. colorata Drake Mbatchi et al. (2006) Maregesi et al. (2007) Joy et al. (1998) Johri et al. (1995) Padal et al. (2010) Igoli et al. (2005) Akendengué (1992) Moshi et al. (2009) L India N/I N/I India Sri Lanka St Uganda Arthritis, conjunctivitis Inflammation, wounds, liver function, GIT, cough, asthma, bronchitis Good luck charm L India Leprosy and scabies Anitha et al. (2008) N/I N/I WP R, L China India India India, Indonesia, Philippines, Tanzania, W. Africa Lin (2005) Alagesaboopathi (2009) Ayyanar and Ignacimuthu (2005) Burkill (1985) (S) L L N/I Uganda West Indies India W. Africa Brazil South Africa South Africa Ghana South Africa Mali Burkina Faso Comoros South Africa Asthma Worm and skin disease Breast tumor Febrifuge, vermifuge, malaria, incontinence, pile, cough, pneumonia, asthma, bronchitis, tuberculosis, snake-bite. Tonsilitis Measles Cure eruptive boils, leprosy Nasopharyngeal illness Immune enhancing Malaria Tonic, boils Febrifuge/malaria fevers, coughs, diarrhoea, boils, and as a general tonic Wound healing Skin diseases, malaria, liver disorders, stomach ache Diarhea Abdominal pain, colic, rheumatism, dysentery, diabetes, ulcerative colitis Stomach illness Tonic and to treat boils Infectious disease, Anthelmintic, cough, pneumonia, stomachache Fevers, anaemia, stomachic, cough, tonsillitis, stomatitis, worms, jaundice, pneumonia, sores, heartfailure, epilepsy, schistosomiasis, impotence, female sterility, scabies, gonorrhoea, poison-antidote Boils, gonorrhoea, scabies, antidote, emetic, antifebrile, cough, tonsillitis, gastritis, bilharzia, sterility, frigidity, Stomachache, constipation, venereal disease, vertigo, postpartum pain, general weakness L L R B L L L WP L, R L R L R L, R Nigeria South Africa Guinea Kenya Tanzania, D.R Congo, W. Africa L, R, B Tanzania L, R Mozambique Jain and Puri (1984) ; Padal et al. (2010); Allabi et al. (2011) Gupta et al. (2003a) Abeysekera et al. (1999) Ssegawa and Kasenene (2007) Hamill et al. (2003) Brussell (2004) Mini et al. (2010) Burkill (1985) (S) Petri et al. (2008) Clarkson et al. (2004) Kelmanson et al. (2000) Addae-Kyereme et al. (2001) Rabe et al. (2002) Diallo et al. (2002) Nadembega et al. (2011) Kaou et al. (2008) Elgorashi et al. (2003) Allabi et al. (2011) Kelmanson et al. (2000) Magassouba et al. (2007) Gakuya et al. (2012) Burkill (1985) (S) Hedberg et al. (1982) Bruschi et al. (2011) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 8 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 3 (continued ) Vernonia species Part used Country or region Use in ethnomedicine Reference condensata Baker L L Mozambique Brazil Cough, pneumonia Stomach ache, digestive problems, muscular pain, hepatic problems Bandeira et al. (2001) Albuquerque et al. (2007) L Brazil, Nigeria Protection against snake bite L L L L L, B, R Brazil Brazil Brazil Nigeria W. Africa N/I L L N/I N/I L R, L Cameroon Cameroon D R Congo West Africa—Angola Rwanda Rwanda China N/I China Diarrhea Intestinal disorder and cholagogue Headache Laxative Galactogue, aphrodisiac, stomachache, laxative, whooping-cough, convulsive-cough, bronchitis, asthma, wounds, sores, jaundice, poison-antidote, diuretic, gonococcal orchitis, diarrhoea, constipation, worms, ophthalmias, abscess. Wound, galactogogue, jaundice, Stomach ache/cramps Antivenom Pain, galactogogue, abscess, asthma Bacteria Gonorhoea Hepatitis, gastrointestinal diseases, toxicosis, eye disease. Rheumatic arthritis, lumbocrural pain, fracture and malaria Fungus Stomachache Dermatitis Stimulant Alterative, tonic Menstruation, tonic, ague Malaria Inflammation Hepatitis Chest-pain External injury/infection, wounds Diabetes (mellitus), GIT disease Piscicide Dysmenorrhoea Migraine, psoric Malaria diabetes Burns, fresh wound, gonorrhoea, diuretic, amoebic dysentery Snake antidote Schistomiasis pain, toothache, sores, incipient hernia, purgative, dysentery, poison, urethral discharge, vomiting, malaria, jaundice, snake-bite, aphrodisiac, spermatogenesis, Prostatitis and prostate cancer Male infertility Epilepsy, menoxenia, aphrodasiac parasites infection, malaria, bacteria Gastritis, urinary infections, male sterility Syphillis, gonorrhea, male/female infertility (female inflammatory disease, orchitis, epididymytis) dysmenorrhoea Prescribed in low doses, poison Mental disease, emetic, cough, diarrhoea, relief strangulated hernia. Diarrhoea malaria Cough Colic, sore throat, cough & headache Hepatitis Pereira et al. (1994), Houghton and Osibogun (1993) Begossi et al. (1993) Grandi et al. (1988) Rizzo et al. (1985) Ajibesin et al. (2008) Burkill (1985) (S) conferta Benth. cruda Klatt Bull. cumingiana Benth. deppeana Less. N/I N/I N/I extensa DC N/I fasciculata Michx. N/I L, F fastigiata Oliv. & Hiern L ferruginea Less. N/I fontinalis S. Moore N/I galamensis Less. L L L gerberiformis Oliv. & Hiern N/I glaberrima Welw ex O. R L Hoffm. L glabra (Steetz) Oliv. & Hiern N/I L, R grantii oliv guineensis Benth. herbacea Rusby hildebrandtii Vatke. hirsuta (DC.) Sch. Bip. hochstetteri Sch. Bip. ex Hochst. hymenolepis A. Rich. jugalis Oliv. & Hiern karaguensis Oliv. & Hiern kenteocephala Bak. kotschyana Sch.Bip. ex Walp S. America El Salvador Gautemala and Mexico Thailand USA USA South Africa Bolivia Rwanda Tanzania Ethiopia Tanzania Angola South Africa W. Africa Togo Swaziland W. Africa L L, R L, R Kenya Malawi Congo, W. Africa R R R R R R Cameroon Cameroon Cameroon Cameroon Cameroon Cameroon L/R L, R Brazil Tanzania N/I WP R N/I N/I Tanzania S. Africa S. Africa Swaziland Rwanda N/I L L, R West Africa- Angola Uganda Tanzania L, R L L Africa Madagascar Nigeria N/I Mali Hypertension, neonatal respiration problems Fever/malaria Promote birth, stomach ache and whole plant to cure epilepsy. HIV infection Febrifuge stomach ache, gonorrhea, gingivitis, arthritis, and tuberculosis Ulcers and gastritis Betti (2004) Fonge et al. (2012) Chifundera (1987) Mengome et al. (2010) Vermani and Garg 2002 (2002) Van Puyvelde et al. (1983) Zheng and Xing (2009) Lin et al. (1985) Svetaz et al. (2010) Gupta et al. (1993) Folliard (2008) Ponglux et al. (1992) Smyth (1903) Cook (1869) Clarkson et al. (2004) Malafronte et al. (2009) Mukazayire et al. (2011) Burkill (1985) (S) Teklehaymanot and Giday (2010) Chhabra et al. (1989) Bossard (1993) Van Wyk and Gericke (2000) Burkill (1985) (S) Ananil et al. (2000) Long (2005) Burkill (1985) (S) Owour and Kisangau (2006) Hostettman (1984) Burkill (1985) (S) Noumi (2010) Noumi et al. (2011) Jiofack et al. (2009) Jiofack et al. (2010) Focho et al. (2009b) Focho et al. (2009a) Rodrigues (2007) Hedberg et al. (1982) Ramathal and Ngassapa (2001) Clarkson et al. (2004) Hutchings et al. (1996) Long (2005) Mukazayire et al. (2011) Mengome et al. (2010) Hamill et al. (2003) Hedberg et al. (1982) James (2007) Rasoanaivo et al. (1992) Ibrahim et al. (2009) Inngjerdingen et al. (2004) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 9 Table 3 (continued ) Vernonia species lasiopus O. Hoffm. leiocarpa DC leopoldii macrocyanus O. Hoffm. mapirensis Gleason miombicola Wild Kirkia mollissima Don ex Hook. & Arn. myriantha Hook F. Part used Country or region Use in ethnomedicine Reference L, R R Cameroon Mali Focho et al. (2009a,b) Nergard et al. (2004) R R L, St L L L, B, R N/I L, R L WP, R L L, R Mali Mali Kenya Rwanda Uganda Kenya Mexico Kenya Kenya Tanzania Rwanda Tanzania N/I L L, F WP N/I L L El Salvador Mexico Saudi Arabia, Yemen Angola Bolivia Rwanda Argentina Gastritis and internal ulcers gastritis, gastro duodenal ulcers, ameliorate digestion and wound healing Gastric ulcer Wounds Malaria and Worms bacteria, virus Febrile convulsions Malaria GIT parasites Heart burn, crop pests and maggots Skin diseases Epilepsy, indigestion, parturition Hepatitis, wounds and kids constipation Reproductive health, promote lactation, aphrodisiac, purgative, epilepsy Asthma bacteria Cough, colic and skin diseases spasmodic, fish poison Inflammation Virus and bacteria Excessive sweating Malaria contraceptive Mental illness Malaria Diarrhoea Hysteria, epilepsy ringworm Vomiting, vermifuge, kidney, antidysentery, febrifuge, rheumatism, piles, aphrodisiac, yellow fever, jaundice, constipation, colic, blood purification, eye problems, menstruation Diarrhoea Diuretic, GIT, emetic, fever, worms Alterative, tonic Veneral disease Malaria Stomach disorders, rheumatism, dysentery, diabetes and ulcerative colitis Diarrhoea Diabetes, abdominal pain, colic, rheumatism, dysentery Diabetes, rheumatism & malaise Malaria Wounds Fever Nose bleeding, vermifuge Inflammation, fever, colds, bacteria, hepatitis. Tonic, astringent and strong diaphoretic; fever, piles, malaria, incontinence, amoebiasis, anthelmintic, diarrhea, dropsy, cough, stomachache, colic, conjunctivitis, rheumatism, flatulence, dysuria, leucoderma, psoriasis and other chronic skin diseases. Used in combination with other herbs: Respiratory tract disorders (including asthma, bronchitis, pneumonia, cold, cough, mucus, influenza, tonsillitis, sore throat), Sex stimulant, impotency, spermatorrhea, premature ejaculation, aphrodisiac, Oral infections/lesions (mouth, tooth, tongue) Malaria purgative Bacteria and viruses Liver problems Rheumatism, bronchitis, cough Fever, respiratory disease Cough, fever, prevent miscarriage Cancer, dermatitis Febrifuge Stomachic, gonorrhoea Febrifuge Indigestion, vomiting Clarkson et al. (2004) Mabogo (1990) Long (2005) Clarkson et al. (2004) de Wet et al. (2010) Stafford et al. (2008) Burkill (1985) (S) Burkill (1985) (S) L, R R N/I natalensis Sch.Bip. ex Walp. WP R neocorymbosa Hilliard R, L nestor S.Moore Lt nigritiana Oliv. & Hiern R, F noveboracensis (L.) Willd nudicaulis Less. oligocephala Edgew oocephala Baker pachyclada Baker patens HBK. patula Mart. Ex DC S. Africa S. Africa Swaziland S. Africa S. Africa S. Africa Nigeria W. Africa R R N/I N/I L L Ivory Coast Senegal USA Madagascar S. Africa S. Africa NI L S. Africa S. Africa N/I N/I N/I St,L L WP L, R, Fl Swaziland Nigeria Madagascar Panama Costa Rica Tawain Bangladesh N/I Bangladesh pectoralis Bak. AP perrottetii Sch.Bip ex Walp. L pogosperma Klatt L L polyanthes Less. L, R polytricholepis Baker N/I poskeana Vatke & Hildeb. WP potamophila Baker L prolytricholepsis Bak. AP pumila kotschy & Peyr. R rhodolepsis Bak. AP roxburghii Less. (L. Saurai). S saligna DC N/I Madagascar W. Africa Rwanda Rwanda Brazil Madagascar Tanzania D. R Congo Madagascar E. & W. Africa Madagascar India China Maiga et al. (2005) Diallo et al. (2002) Kareru et al. (2008) Vlietinck et al. (1995) Ssegawa and Kasenene (2007) Muregi et al. (2007a, 2007b) Heinrich (1996) (S) Gakuya et al. (2012) Njoroge and Bussmann (2007) Burkill (1985) (S) Mukazayire et al. (2010) Hedberg et al. (1982) Gupta et al. (1993) Meckes et al. (1995) Al-Musayeib et al. (2012) Burkill (1985) (S) Morales-Escobar et al. (2007) Cos et al. (2002) Goleniowski et al. (2006) Diehl et al. (2004) Aliyu et al. (2011a) Smyth (1903) Aliyu et al. (2011a) Clarkson et al. (2004) Thring and Weitz (2006) De Wet et al. (2008) Deutschlander et al. (2009) Long (2005) Aliyu et al. (2011a) Williams et al. (2005) Gupta et al. (1996) Gupta et al. (1993) Chiu and Chang (1987) Saha and Paul (2012) Mollik et al. (2010) Rasoanaivo et al. (1992) Burkill (1985) (S) Vlietinck et al. (1995) Mukazayire et al. (2011) Braga et al. (2007) Aliyu et al. (2011a) Burkill (1985) (S) Babady-Bila et al. (2003) Rasoanaivo et al. (1992) Burkill (1985) (S) Rasoanaivo et al. (1992) Chandra et al. (1985) Huang et al. (2003) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 Q9 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 3 (continued ) Vernonia species Part used Country or region Use in ethnomedicine Reference senegalensis Less. L L L, R, B Brazil Trinidad Tanzania Serratuloides Kunth smithiana Less. N/I WP, R Mexico Congo spiciforma Klatt staehelinoides Mart. Ex Baker stellullifera (Benth.) C. Jeffrey stenocephala Oliv. stipulacea Klatt AP L Madagascar S. Africa Respiratory tract infection, tuberculosis, uterus prolapse skin disorders, including chronic wounds and ulcers Aphrodasiac, witchcraft Boils, gonorrhoea, scabies, antidote, emetic, antifebrile, cough, tonsillitis, gastritis, bilharzia, sterility, frigidity, Toothache Rheumatic pains, heart troubles, venereal discharge, stomach complaints, arbotifacient Febrifuge Malaria WP Cameroon Stops miscarriage, dysentery Jiofack et al. (2010) L R R R R WP, Fl Uganda S. Africa S. Africa Tanzania Uganda India Pre-hepatic jaundice Diarrhoea, fever, flu, contraceptive. HIV virus Galactogogue Sleeping sickness Ulcers, wounds, acaricide N/I S. Africa Bacteria Ssegawa and kasenene (2007) Bessong et al. (2005) Bessong et al. (2006) Burkill (1985) (S) Freiburghaus et al. (1996) Garg and Siddique (1992), Johri and Singh (1997) Mungarulire (1990) tigna Klatt L N/I N/I Gabon S. Africa Swaziland trichoclada Gleason trichodesma Bak. tweedieana Baker undulata Oliv. & Hiern usambarensis O. Hoffm. venosa S.Moore zeylanica Less N/I L L L R N/I St Bolivia Madagascar Brazil Gabon Tanzania Sudan Sri Lanka Fever, fish poison Abortificient Menstrual irregularities, abortifacient, worms, arthritis and aphrodisiac Inflammation Malaria Immune enhancing Enema, piles Excessive menses Bacteria inflammation scorpioides Pers. subuligera O. Hoffm. teres thomsoniana Oliv. & Hiern ex Oliv. Buskuhl et al. (2010) Wong (1976) Hedberg et al. (1982) Heinrich (1996) (S) Burkill (1985) (S) Rasoanaivo et al. (1992) Pillay et al. (2007) Burkill (1985) (S) Mabogo (1990) Long (2005) Morales-Escobar et al. (2007) Rasoanaivo et al. (1992) Petri et al. (2008) Burkill (1985) (S) Hedberg et al. (1982) Al Magboul et al. (1988) Ratnasooriya et al. (2007) B-Bark; L-Leaf; R-Root; S-Seed; St-Stem; WP-Whole plant; S: Secondary reference source. with inhibition of growth by 31 mg/disc in a disc diffusion assay (Chimponda and Mukanganyama, 2010). Further research is required to confirm the folk use of the plant to treat other diseases and conditions including HIV/AIDS, wounds and snake bite. 3.1.2. Vernonia aemulans Vatke Vernonia aemulans is used in Rwanda against some bacterial infections especially gonorrhea (Van Puyvelde et al., 1983; Vlietinck et al., 1995; Vermani and Garg, 2002). Laboratory studies showed weak antimicrobial and antiviral activities (Vlietinck et al., 1995). In three of the reports found, the species was erroneously referred to as Vernonia aemulans whereas the correct name is Vernonia aemulans according to the IPNI database. 3.1.3. Vernonia albicans DC Vernonia albicans is used to treat earache problems in India (Rai and Lalramnghinglova, 2011). This species is not widespread in distribution possibly explaining its limited use. 3.1.4. Vernonia ambigua Kotschy & Peyr Information on the use of this species is from Cameroon, Nigeria and Tanzania where it is used to treat reproductive problems including urinary tract infections (Focho et al., 2009a), cough and colds (Burkill, 1985) as well as malaria (Builders et al., 2011). The claimed antplasmodial activity of Vernonia ambigua has been confirmed in vitro and in vivo (Builders et al., 2011). Phytochemical analyses have also revealed the presence of major classes of compounds in the plant including alkaloids, flavonoids and terpenes (Kunle and Egharevba, 2009; Builders et al., 2011). The plant was safe at 5000 mg/kg in an acute toxicity study (Builders et al., 2011). 3.1.5. Vernonia ampandrandavensis Humbert Vernonia ampandrandavensis is used in Madagascar to treat malaria (Rasoanaivo et al., 1992). 3.1.6. Vernonia amygdalina Del. Vernonia amygdalina is the most studied member of the Vernonia genus. This species is associated with the treatment and control of over twenty diseases and conditions in folk medicine (Tables 3–5). The species has found use in human folk medicine as well as in ethnoveterinary medicine and zoopharmacognosy. The major medicinal benefits of this species have been highlighted in reviews by Yeap et al. (2010) and Ijeh and Ejike (2011). Considering the diseases and conditions that are routinely treated with Vernonia amygdalina, one may see that there is some agreement on the use of leaves against gastrointestinal tract (GIT) conditions such as diarrhoea, constipation, stomachache, intestinal worms and bacterial infections. The plant is also used for the treatment of urinary tract infections, diabetes and malaria. In ethnoveterinary medicine, the plant is mostly used against parasitic infections especially those of the GIT tract (Alawa et al., 2003; Nalule et al., 2011). Vernonia amygdalina is also only one of two species reported to have have zoopharmacognostic importance. An interesting observation for the use of the species against Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 11 Table 4 Ethnoveterinary uses of Vernonia species. Species Part used Country Use in ethnomedicine Reference adoensis Sch. Bip. Ex Walp amygdalina Del. L L L L,R L L L, R L N/I Kenya Nigeria Ethiopia Uganda Kenya Cameroon Uganda Eathipia Pakistan Burkill (1985) (S) Alawa et al. (2003) Yineger et al. (2007) Tabuti et al. (2003) Githiori et al. (2006) Toyang et al. (2007) Nalule et al. (2011) Regassa (2000) Muhammad et al. (2005) N/I S Pakistan India Sores Worms Diarrhea, scabies and hepatitis Cough, diarrhoea and measles Nematocide Worms Worms Ticks Prevention of indigestion and halitosis in camel, digestive disorders, Cold/rhinitis, Pneumonia, systemic disorders Worms Nematocide R L N/I R L, R L St R L Rajasthan Nigeria Ethiopia Cameroon Uganda Ethiopia South Africa South Africa Trinidad Food poison, fever, dysentery Diarrhea, fleas Trypanosomiasis Worms, promote calf growth Worms hepatitis Heartwater in goats, Used to treat calves, worms in donkeys and domestic animals Bathe dogs with leaves so that they are more alert, mange, wounds anthelmintica Willd. cinerea (L.) Less conferta Benth. filigera Oliv. & Hiern guineensis Benth. grantii Oliv hymenolepis A. Rich. mespilifolia Less neocorymbosa Hilliard scorpioides (Lam.) Pers Hussain et al. (2008) Githiori et al. (2006), Hördegen et al. (2003) Galav et al. (2010) Chah et al. (2009) Teklehaymanot (2009) Toyang et al. (2012a) Nalule et al. (2011) Yineger et al. (2007) Dold and Cocks (2001) McGaw and Eloff (2008) Lans et al. (2001) Table 5 Zoopharmacognostic uses of Vernonia species. amygdalina Del. Pith Tanzania GIT parasite load reduction in chimpanzees Huffman and Seifu (1989), Huffman et al. (1993) Cistifolia O. Hoffm. Fr. Pith Central Africa GIT parasites and other stomach problems Cousins and Huffman (2002) B-Bark; L-Leaf; -Root; S-Seed; St-Stem; WP-Whole plant; Fr-Fruit; S: Secondary reference source. GIT parasites is in self medication practices by Chimpanzees and gorillas in the Central African region (Ohigashi et al., 1994; Koshimizu et al., 1994). To confirm the effect of self medication practices by chimpanzees, Huffman et al. (1993) observed a wild female chimpanzee suffering from gastrointestinal upset (flatulence and diarrhea) which self medicated using Vernonia amygdalina. The chimpanzee was followed for approximately 5 h over a two-day period and laboratory examination of two fecal samples, one collected approximately 1 h and another 20.5 h after ingestion of the plant’s bitter pith, revealed a notable drop in the degree of parasitic infection by a Ternidens sp. Vernodalin and vernonioside BI have been suggested to be responsible for the antibacterial effect responsible for the zoopharmacognostic effect of Vernonia amygdalina in chimpanzees following in vitro bioassay studies (Jisaka et al., 1993; Huffman et al., 1993). Challand and Willcox (2009) reported the first clinical trial results using a preparation of Vernonia amygdalina against malaria where a 32% parasitaemia reduction was achieved with 500 mg/ kg/day  7 days. In a mouse model using Plasmodium berghei, an 82.3% parasite reduction was achieved with 1000 mg/kg/day  4 days (Omoregie et al., 2010). When the plant was compared with other medicinal plants, Vernonia amygdalina accounted for 9.1% of the time that medicinal plants were used as an alternative medicine in central Nigeria (Amira and Okubadejo, 2007). Apart from its use in medicine, Vernonia amygdalina has other non medicinal uses including the use to protect metal from corrosion (Avwiri and Igho, 2003). On the phytochemistry of the plant, several compounds including flavonoids and terpenoids have been isolated from the plant. A good number of the compounds (e.g., vernolide and water soluble peptides called edotides) isolated from Vernonia amygdalina have shown cytotoxicity against cancer cell lines (Jisaka et al., 1992; Izevbigie, 2003; Erasto et al., 2006; Opata and Izevbigie, 2006)). Despite the great activity reported for in vitro activity, no clinical trials have been carried out to support the efficacy of this species or its isolated molecules in treating cancers. Fifteen of the compounds isolated from Vernonia amygdalina, most of which have also been isolated from other Vernonia species have been shown to be bioactive in various assays (Table 8). Octahydrovernodalin is the most important bitterprinciple in the plant resulting in the common name of ‘‘bitterleaf’’ for the plant (Yeap et al., 2010). A freeze dried sample of the extract of Vernonia amygdalina is one of the few herbal products that have been formulated into tablets for the control of diabetes mellitus in Nigeria (Emeje et al., 2011). Another tablet formulation of Vernonia amygdalina is in use to boast the immunity of HIV patients (Momoh et al., 2012). Biomass root culture extracts of Vernonia amygdalina killed abnormal cells among primary cells harvested from patients with acute lymphoblastic leukemia and acute myeloid leukemia (Khalafalla et al., 2009). Vernonia amygdalina is also used routinely by HIV patients for malaria, fevers, as a dewormer, and for stomach pains (Lubinga et al., 2012). This species was the second most used (21%) concomitant herbal preparation taken by HIV patients on antiretroviral therapy (ART) surveyed in western Uganda (Lubinga et al., 2012). Aloe vera was the most used herbal preparation. On the safety, this plant is used as a vegetable indicative of the fact that it is generally considered safe for use in medicine. For example, in a chronic toxicity study, rats were fed with up to 75% (w/w) powdered Vernonia amygdalina leaves mixed with grower mash for 65 days and at the end of the study the only gross change observed was the lightening of the skin of the rats in the treatment group versus the control group (Ibrahim et al., 2001). Microscopical examination of major organs showed that organ morphology was normal in both the treatment and control groups. Also, no adverse effects were found in studies on the Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 12 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 6a In-vitro studies carried out on the bioactivity of Vernonia species. Species Study Activity/results Reference adoensis Sch. Bip. exWalp Antioxidant Antiplasmodial Antimycobacterium 193.2 mmol/g 2.14 mg/ml 31 mg/disc Antibacterial Antibacterial Antibacterial Antibacterial Antiplasmodial antioxidant Antidiabetic Antiplasmodial Cytotoxicity (C-1008 Vero cells) Antifungal Antimutagenic Anthelmintic 70 mg/ml NA NA MIC ¼ 2.5 mg/ml IC50 ¼ 31.62 mg/ml 200 mg/ml 50 mg/ml 9.83 mg/ml 60.33 mg/ml Stangeland et al. (2010) Stangeland et al. (2010) Chimponda and Mukanganyama (2010) Kisangau et al. (2007a) Al Magboul et al. (1988) Van Puyvelde et al. (1983) Aliyu et al. (2011a) Builders et al. (2011) Builders et al. (2011) Erasto et al. (2009) Omoregie et al. (2010) Omoregie et al. (2010) ambigua Kotschy and Peyr amygdalina Del. Antimicrobial Antimicrobial Hemolytic activit Anthelmintic Antioxidant Antioxidant Antiviral Antibacterial Antibacterial Hepatoprotective Antioxidant Antibacterial Antiamoebic Antiplasmodial Antiplasmodial Antibacterial Antimicrobial Antiviral Antibacterial Cytotoxicity ERK kinase (cancer) Cytotoxicity Cytotoxicity Cytotoxicity Antibacterial Antimycoplasma Antiplasmodial Antibacterial Antileishmanial Antibacterial Antiplasmodial Antiplasmodial Antiplasmodial Protein oxidation inhibition Immunomodulator Antioxidant activity Liver protection and antioxidant Antioxidant Antioxidant Cytotoxicity Antioxidant Antioxidant Liver protection Uterine contractility Anthelmintic Antileishmanial activity Anti trichomonas Anthelmintic Cytotoxicity P-glycoprotein inhibition Insecticide Antibacterial Anthelmintic Insecticide Cytotoxicity A 200 mg/ml Nematode eggs  76–957 mg/ml Larvae  196.6– 596.3 mg/ml MIC: 10–15 mg/ml Diffusion: A Human erythrocyte (genotype SS) 2% v/v Hymenolepis diminuta cestodes 34–11.6 mg/ml 100–300 mg/ml A A 0.47–1.25 mg/ml A A A Disc diffusion 250 mg/ml IC50 ¼ 8.72–13.8 mg/ml IC50 ¼ 10 mg/ml A Disc diffusion A A (Agar well diffusion) IC50 ¼ 5.68 mg/ml IC50 ¼ 3 mg/ml IC50 ¼ 1000 mg/ml 1 mg/ml A A LC50 ¼ 17 mg/ml NI NA ED50 ¼13.3–18.5 mg/ml MIC ¼ 3.13–12.5 mg/ml IC50 o10 mg/ml A IC50 o50 mg/ml IC50 ¼ 43.31 mg/ml NA A A Erasto et al. (2006) Obaseiki-Ebor et al. (1993) Ademola and Eloff (2011) IC50 ¼ 2.3 mg/ml A IC50 ¼ 1.0 mg/ml IC50 ¼ 1.0 mg/ml A (aqueous) A 100 mg/ml 411.6 mg/ml 100 mg/ml (Aq) A Haemonchus larvae 125 mg/ml ¼ 57% inhibition Taxol resistant prostate cancer cells  100 mg/ml (73% DNA synthesis inhibition) 20 mg/ml A (4% extract) Disc diffusion 2 mg/ml NI (3.3–86 mg/ml) Ayoola et al. (2008) Iwalewa et al. (2005) Salawu et al. (2011a) Salawu et al. (2011a) Achel et al. (2012) Babalola et al. (2001) Attah et al. (2012) Alawa et al. (2003) Alawa et al. (2012) Hakizamungu et al. (1992) Nweze et al. (2012) Cameron et al. (2012) Ogundare et al. (2006) Oboh and Masodje (2009) Oboh (2006) Mølgaard et al. (2001) Anyasor et al. (2010) Owolabi et al. (2008) Vlietinck et al., 1995 Adetutu et al. (2011) Okigbo and Mmeka (2008) Adesanoye et al. (2012) Erasto et al. (2007) Taiwo et al. (1999) Otshudi et al. (2000) Zofou et al. (2011) Madureira et al. (2002) Cos et al. (2002) Yongabi et al. (2009) Cos et al. (2002) Hamill et al. (2003) Izevbigie (2003) Izevbigie et al. (2004) Gresham et al. (2008) Yedjou et al. (2008) Jisaka et al. (1993) Jisaka et al. (1993) Muraina et al. (2010) Jisaka et al. (1992) Cheruiyot et al. (2009) Tadesse et al. (1993) Akinpelu (1999) Tona et al. (2004) Adiukwu et al. (2011) Masaba (2000) Njayou et al. (2008) Koko et al. (2008) Nwanjo (2005) Iwalokun et al. (2006) Oga et al. (2012) Adeniyi et al. (2010) Salawu et al. (2011b) Innocent and Deogracious (2006) Higashi et al. (1991) Farombi and Owoeye (2011) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 13 Table 6a (continued ) Species anthelmintica Willd. auriculifera Hiern blumeoides brachycalyx O.Hoffm. brasiliana Druce brazzavillensis Aubrév. Ex Compe re cinarescens cinerea (L.) Less colorata Drake condensata Baker conferta cruda Klatt Bull. cumingiana Benth. fastigiata Oliv. & Hiern glaberrima Welw ex O. Hoffm. glabra (Steetz) Oliv. & Hiern guineensis Benth. Study Activity/results Reference Antioxidant Antidiabetic and lipid lowering Melanogenesis inhibition Anthelmintic cytotoxicity Cytotoxicity Tyrosine kinase attenuation Antiplasmodial Antibacterial Antitrypanosomal Antibacterial Antioxidant Antiplasmodial and Antileishmania Brine shrimp toxicity Mutagenicity insecticide Antitrypanosomal Antiplasmodial Antiplasmodial 50 mg/ml A Fasakin et al. (2011) Fatima et al. (2010) 100 mg/ml 5 mg/ul NI NI 20 mg/ml IC50 ¼ 37.7 mg/ml A r19 mg/ml MIC ¼ 2.5 mg/ml r60 mg/g (antioxidant capacity) A Ma et al. (2008) Hördegen et al. (2006) Lambertini et al. (2004) Zhao et al. (2012) Zhou et al. (2012) Muregi et al. (2003) Hamill et al. (2003) Freiburghaus et al. (1996) Aliyu et al. (2011a) Aliyu et al. (2011b) Oketch-Rabah et al. (1997) LD50 ¼0.29–2.6 mg/ml NA A NA IC50 ¼ 40 ng/ml IC50 ¼ 22 mg/ml Oryema et al. (2011) Rojas de Arias et al. (1995) Rojas de Arias et al. (1995) Rojas de Arias et al. (1995) Carvalho et al. (1991) Mbatchi et al. (2006) Maregesi et al. (2010) Iwalewa et al. (2003) Rajamurugan et al. (2011) Iwalewa et al. (2003) Iwalewa et al. (2003) Latha et al. (1998) Gupta et al. (2003a) Pratheeshkumar and Kuttan (2009) Cytotoxic activity Antimicrobial IC50 ¼ 62.5 mg/mL A 46–558 mg/ml A A A 50 mg/ml Fenton reaction: IC50 ¼130 mg/ml; Superoxide reaction: IC50 ¼190 mg/ml; Lipid peroxidation: IC50 ¼ 130.5 mg/ml; Nitric Oxide inhibition:IC50 ¼210 mg/ml A MIC: 1.56–50 mg/ml Antifungal Antibacterial Smoking cessation Antileishmanial A A A IC50 ¼ 143–443 mg/ml Zhu et al. (2008) Yoga Latha et al. (2009, 2010b, 2011) Mini et al., 2010 Mini et al. (2010) Leelarungrayub et al. (2010) Camacho et al. (2003) Antibacterial Antioxidant Antioxidant (DPPH inhibition) Antiinflammatory and antioxidant Insecticidal Antibacterial Antiplasmodial Antidiabetic Genotoxicity Antiplasmodial Antiplasmodial Toxoplasma/antiplasmodial Antiplasmodial Antiplasmodial MIC ¼ 0.31 mg/ml IC50 ¼ 0.4 mg/ml EC50–50 mg/ml A: IC50 ¼130.5 mg/ml; 210 mg/ml Rizvi et al. (2011) Rizvi et al. (2011) Leelaprakash et al. (2011) Pratheeshkumar et al. (2009) LC50 ¼ 1.63 mg/ml 1 mg/ml (disc diffusion) IC50 ¼ 14 mg/ml A NA 4100 mg/ml IC50 ¼ 2.35–12.5 mg/ml IC50 ¼ 17 mg/ml/2.35 mg/ml IC50 o5 mg/ml A Arivoli et al. (2011) Kelmanson et al. (2000) Clarkson et al. (2004) Sy et al. (2005) Elgorashi et al. (2003) Addae-Kyereme et al. (2001) Benoit et al. (1996) Benoit-Vical et al. (2000) Kaou et al. (2008) Kraft et al. (2003) 45000 mg/ml A Monteiro et al. (2001) Da Silva et al. (2011) 1 mg/ml (herb mixture) LC50 ¼ 3.78 mg/ml IC50 ¼ 28.33 mg/ml Franc- a et al. (2010) Mengome et al. (2010) Mengome et al. (2010) NI A NA 10 mg/ml NI NI A A IC50 ¼ 3–5 mg/ml IC50 ¼ 67.3 mg/ml LC50 ¼ 2 mg/ml Van Puyvelde et al. (1983) Liu et al. (2009) Liu et al. (2010) Clarkson et al. (2004) Ananil et al. (2000) Ananil et al. (2000) Ananil et al. (2000) Achola et al. (1996) Tchinda et al. (2002) Toyang et al. (2012a) Toyang et al. (2012b) Antiplasmodial Analgesic Antioxidant Antipyretic Antiinflammatory Adjuvant-induced arthritis Antibacterial Free radical protection Mutagenicity Antincociceptive and Antiinflammatory immunostimulatory Loa-loa (filarial worm) Eukaryotic cells growth inhibition Antimicrobial Antiinflammatory Antiinflammatory antiplasmodial Cytotoxicity Antiviral Antibacterial Antihypertensive antitrypanosidal Cytotoxicity Anthelmintic (Adult Trichuris muris worms) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 6a (continued ) Species hirsuta (DC.) Sch. Bip. hymenolepis incana Less karaguensis Oliv. & Hiern kotschyana Sch.Bip. ex Walp lasiopus O. Hoffm. leopoldii Vatke miombicola Wild Kirkia myriantha Hook F. natalensis Sch.Bip. ex Walp oligocephala Edgew oocephala pogosperma Klatt polyanthes Less. scorpioides Pers. staehelinoides Mart. ex Baker subuligera thomsooniana Oliv. & Hiern ex Oliv. tweediana Baker venosa S.Moore Study Activity/results Reference Antimicrobial Antiplasmodial Loa-loa (filarial worm) Eukaryotic cells growth inhibition Antiacterial Antibacterial Antibacterial Immunomodulating Antibacterial Antiviral, Antifungal Antiplasmodial Antimalarial/cytotoxicity Cytotoxicity antiplasmodial Hepatoprotective Antiprotozoal Cytotoxicity Antimicrobial Antibacterial Antiviral Antiplasmodial Antiplasmodial Antiplasmodial Antiinflammatory Antiplasmodial Antibacterial Antibacterial Antifungal Antiviral Antihypertensive Antibacterial Antifungal Antibacterial Antibacterial wound healing Cytotoxicity/ Antiinflammatory Antiplasmodial Antitrypanosomal Antibacterial MIC Z 200 mg/ml IC50 ¼ 14 mg/ml LC50 ¼ 3.78 mg/ml IC50 ¼ 28.33 mg/ml Toyang et al. (2012b) Clarkson et al. (2004) Mengome et al. (2010) Mengome et al. (2010) A A A A NA A IC50 ¼ 1 mg/ml IC50 ¼ 1.4 mg/ml/ A IC50 ¼ 1.0 mg/ml 1 mg/ml 8.0–41.9 mg/ml IC50 o50 mg/ml MIC o500 mg/ml NA NA IC50 ¼ 28 mg/ml A IC50 ¼ 19.5 mg/ml 250 mg/ml IC50 ¼ 3.5 mg/ml MIC r 2.5 mg/ml 500 mg/ml 500 mg/ml 500 mg/ml A A A A MIC 625–2500 mg/ml A A Bardón et al. (2007) Mungarulire (1990, 1993) Deeni and Hussain (1994) Nergard et al. (2004) Vlietinck et al., 1995 Vlietinck et al., 1995 Muregi et al. (2003) Irungu et al. (2007) Koul et al. (2003) Muregi et al. (2003) Mukazayire et al. (2010) Al-Musayeib et al. (2012) Mothana et al. (2009) Mothana et al. (2009) Cos et al. (2002) Cos et al. (2002) Clarkson et al. (2004) Kraft et al. (2003) Clarkson et al. (2004) Fawole et al. (2009) Clarkson et al. (2004) Aliyu et al. (2011a) Vlietinck et al. (1995) Vlietinck et al. (1995) Boily and Van Puyvelde (1986) Romanezi da Silveira et al. (2003) Silva et al. (2012) Freire et al. (1996) Freire et al. (1996) Bardón et al. (2007) Leite et al. (2002) Pagno et al. (2006) A r19 mg/ml NI Pillay et al. (2007) Freiburghaus et al. (1996) Mungarulire (1990) Agar well diffusion NI Diaz et al. (2008) Al Magboul et al. (1988) Antibacterial Antibacterial A¼ Active; NA ¼not active; NI ¼Not indicated. effect of various formulations of metformin and Vernonia amygdalina extract loaded with PEGylated-mucin on haematological and liver indices in alloxan-induced diabetic rats (Momoh et al., 2011). However, depending on the type of infection being treated, very high doses of the preparation might be required and as such it is recommended that every in vivo study be accompanied by at least an acute toxicity study. The routine consumption of this species as a green leafy vegetable throughout West and Central Africa and for several medicinal purposes confirms the importance of this species as a source of nutrition and medicine. 3.1.7. Vernonia anthelmintica Willd. Synonym Centhraterum anthelminticum Kuntze This species is distributed throughout Africa and Asia. The plant is widely used as an anthelmintic (Githiori et al., 2006; Hussain et al., 2008) and to control diabetes (Fatima et al., 2010; Ramautarsing, 2008; Rao et al., 2010). Parekh and Chanda (2007, 2008) listed several uses of this plant in Indian folk medicine (Table 3). The plant is used in ethnoveterinary medicine to control GIT infections, halitosis, indigestion and pneumonia (Muhammad et al., 2005). Alcoholic extracts of the seeds were shown to have potent anthelmintic activity in vitro and in vivo (Singh et al., 1985 and Iqbal et al., 2006). The seeds are known to contain epoxy and vernolic acids that are thought to contribute to the antidiabetic activity of this plant. Given the confirmation of the antidiabetic properties of this plant in vitro and in vivo, a clinical trial to determine the efficacy in humans is recommended. 3.1.8. Vernonia appendiculata Less Vernonia appendiculata is used in Madagascan folk medicine as a febrifuge (Rasoanaivo et al., 1992). Bayer Consumer Care of Germany has filed a utility patent claiming the use of this species to improve the status of the skin (Segond et al., 2008). This patent reveals that Vernonia appendiculata does have useful dermatological properties. 3.1.9. Vernonia arborea Buch.- Ham. This is one of the lesser known species of Vernonia with only one report on the folk uses of the leaves (Manjunatha et al., 2005). The plant extract showed wound healing properties in vivo and demonstrated oral toxicity with LD50 value of 300 mg/kg (Manjunatha Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 15 Table 6b In-vivo studies carried out on the bioactivity of Vernonia species. Species Study Activity/results (ED50/LD50) Reference ambigua Kotschy and Peyr amygdalina Del. Antimalarial Mice: 600 mg/kg; oral (Plasmodium berghei) Builders et al. (2011) Antidiabetic Antidiabetic Antidiabetic Antidiabetic Antidiabetic Antidiabetic Antidiabetic Antidiabetic Antidiabetic Rat: 400 mg/kg; Oral Rat: 160 mg/kg; Oral Rat: 500 mg/kg; Oral Rat: 400 mg/kg; Oral Rat: 500 mg/kg; Oral Rat: 250 mg/kg; Oral Rat: 100 mg/kg; Oral Rat: 800 mg/kg; Oral Rat: 100 mg/kg combined with Azadirachta; Oral Rat: 400 mg/kg; Oral Rabbit: A; 80 mg/kg; LD50 1122 mg/kg IP Rat 200 mg/kg Oral Rat: 250 mg/kg Rabbit: A 50 g/human Rat: 100 mg/kg (oral) Rat: 300 mg/kg 15% extract: Chicken Rat: 1265.22 mg/kg Rat 200 mg/kg Rat: 800 mg/kg Rat: 10 kg/ml Ong et al. (2011) Akah et al. (2009) Osinubi (2006) Akinola et al. (2010) Akinola et al. (2011) Taiwo et al. (2008) Adikwu et al. (2010) Momoh et al. (2011) Atangwho et al. (2009) and Atangwho et al. (2012) Atangwho et al. (2010) Akah and Okafor (1992) Fasola et al. (2010) Oyeyemi et al. (2008) Owolabi et al. (2011) Okolie et al. (2008) Adaramoye et al. (2008a) Spencer et al. (2011) Owen et al. (2011) Nwanjo (2005) Nwanjo (2005) Adaramoye et al. (2008b) Owu et al. (2008) Dogs: 500 mg/dog Mice: 50 mg/kg Rat:400 mg/kg Adedapo et al. (2007) Alawa et al. (2012) Georgewill and Georgewill (2009a, 2009b) Oyagbemi and Adejinmi (2012) Adesanoye and Farombi (2010) Koffuor et al. (2011) Taiwo et al. (2010) Challand and Willcox (2009) Antidiabetic Antidiabetic Antidiabetic Spermiogram effect Antioxidant Hypoglycemic (Antidiabetic) Lipid-lowering Hepatoprotection/hypolipidemic Lipid lowering Acute toxicity Antioxidant (oxidative stress) Antioxidant Gastric acid secretion stimulation Anthelmintic Antileishmanial Antiinflammatory(arthritis) Coccidiosis (Eimeria sp.) Hypertoprotection Antihypertensive Antihypertensive Antimalarial Antimalarial (Plasmodium berghei) Atopic dermatitis Antimalarial Liver protection Testicular health Antimalarial Hepatoprotection Antimalarial anthelmintica Willd. arborea Buch. Ham. brasiliana (L.) Druce. cinerea (L.) Less Chicken: 10% feed Rat: 500 mg/kg Mice: 55 mg/kg Rat: 50 mg/kg Human clinical trial: 500 mg/kg/day  7 days. 32% complete parasite clearance 1000 mg/kg/day  4 days: 82.3% clearance Immunomodulation (CD4) Antimalarial Antipyretic Anti-lipidaemic Antipyretic Antimalarial 14-day toxicity Radiation protection Tissue damage protection Anthelmintic Antiinflammatory/arthritic Acute toxicity Anthelminitc Anthelmintic Antidiabetic Wound healing Wound healing Acute toxicity antimalarial antimalarial Antipyretic Free radical protection Antitumor Mice: 7 mg/ml Mice: 600 mg/kg Rat: 15% W/W Rat: 100 mg/kg combine with Ocimum Mice; 125 mg/kg Mice: 50 mg/kg Mice: Leaf ED50 125 mg/kg  4 days (67% clearance; RT ED50 ¼ 250 mg/kg  4 days (53.5% clearance) Rat: 200 mg/kg Mice: 250 mg/kg Rat: 800 mg/kg Rat: 30% feed Mice: 200 mg/kg Mice: 200 mg/kg Mice 42000 mg/kg Rat: 500 mg/kg Rat: 60 mg/kg Sheep: 3000 mg/kg Mice/rat: 500 mg/kg Mice: 45000 mg/kg NI Lamb: 40.3 mg/kg Rat: 100 mg/kg Rat: 30 mg/kg Rat: 30 mg/kg Rat: 300 mg/kg Mice: 1 g/kg (oral) Plasmodium berghei Mice: 1000 mg/kg (oral) Plasmodium berghei Rat: 500 mg/kg (oral) Mice: 500 mg/dose  5 days Mice: 500 mg/kg Immunomodulation Gamma irradiation protection Cell mediated immune response Acute toxicity Mice: Mice: Mice: Mice: 20 mg/kg 20 mg/kg 20 mg/kg LD50 42000 mg/kg Omoregie et al. (2010) Ngatu et al. (2012) Melariri et al. (2011) Arhoghro et al. (2009) Asuquo et al. (2010) Iwalokun (2008) Iwalokun et al. 2006 Abosi and Raseroka (2003) Momoh et al. (2010) Adiukwu et al. (2011) Adiukwu et al. (2011) Ugwu et al. (2011) Njan et al. (2008) Njan et al. (2008) Njan et al. (2008) Owoeye et al. (2010, 2011) Josiah et al. (2012) Iqbal et al. (2006) Otari et al. (2010) Otari et al. (2010) Chopra et al. (1934) Hördegen et al. (2003) Fatima et al. (2010) Pradhan et al. (2009) Manjunatha et al. (2005) Pradhan et al. (2009) Carvalho et al. (1991) Ameida Alves et al. (1997) Gupta et al. (2003b) Pratheeshkumar and Kuttan (2010a) Sangeetha and Venkatarathinakumar (2011) Pratheeshkumar and Kuttan (2011a) Pratheeshkumar and Kuttan (2010b) Pratheeshkumar and Kuttan (2012a) Yoga Latha et al. (2010a) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 6b (continued ) Species cognata Less. colorata (Willd.) Drake condensata Baker galamensis guineensis Benth. kotschyana Sch.Bip. ex Walp lasiopus O. Hoffm. noveboracensis (L.) Willd polyanthes scorpioides tenoreana Oliv. zeylanica (L.) Less Study Activity/results (ED50/LD50) Reference Antiinflammatory Analgesic, antipyretic, antiinflammatory hepatoprotective Antiinflammatory (neuropathic pain) Nephrotoxicity protection Antiarthritic activity Acute toxicity Antioxidant Antidiabetic Antiinflammatory Analgesic/ulcer Antivenom Rat: 250 mg/kg Rat: 100–400 mg/kg Mazumder et al. (2003) Iwalewa et al. (2003) Rat: 250 mg/kg Rat: 200 mg/kg Leelaprakash et al. (2011) Thiagarajan et al. (2012) Rat: 500 mg/kg Rat: 100 mg/kg Rat: 42000 mg/kg Rat: 2 g/kg Rat: 300 mg/kg Rat: 84.2 mg/kg Mice: 241 mg/kg/200 mg/kg 100 mg/kg 60% survival in 48 h compared to 0% for control Mice: 3400 mg/kg None Rat: 100 mg/kg Mice: 2.7 mg/kg Mice: 1000 mg/kg Rat: 700 mg/kg (Tablet formulation study) Rat: 200 mg/kg Rat: 200 mg/kg Rat:200 mg/kg Rat; oral: 4 5000 mg/kg Mice: LD50 44000 mg/kg Rat: 1000 mg/kg Mice: 100 mg/kg Mice: 50 mg/kg Rat Rat Rat Mice (500 mg/kg) Human Mice: 50 mg/kg Mice: 400 mg/kg Sreedevi et al. (2011) Latha et al. (1998) Rajamurugan et al. (2011) Mota et al. (2011) Sy et al. (2004) Cioffi et al. (2004) Frutuoso et al. (1994). Pereira et al. (1994) Rat: 1 mg/kg (oral) NA (100 mg gel) NA (harmful in fresh excission wounds) Mice: 1 mg/ear Rat: Weak Rat: 1500 mg/kg LD50 ¼ 1429.6 mg/ml Romanezi da Silveira et al., 2003 Leite et al. (2002) Dalazen et al. (2005) Rauh et al. (2011) Taiwo et al. (2008) Ratnasooriya et al. (2007) Ratnasooriya et al. (2007) Acute toxicity Embryotoxicity Antiinflammatory Antinociceptive Acute toxicity Antidiabetic Sedative Analgesic Antiulcer Acute toxicity Acute toxicity Ulcer Ulcer Antiinflammatory Sedative Analgesic Antiulcer Antimalarial Contact dermatitis Antiulcer Antinociceptive/ antiinflammatory Blood pressure Wound healing Wound healing Inflammation (ear oedema) Antidiabetic Analgesic Brine shrimp toxicity Monteiro et al. (2001) Monteiro et al. (2001) Da Silva et al. (2011) Risso et al. (2010) Risso et al. (2010) Autamashih et al. (2011) Johri et al. (1995) Johri et al. (1995) Johri et al. (1995) Autamashih et al. (2011) Toyang et al. (2012b) Germano et al. (1996) Austarheim et al. (2012) Ibrahim et al. (2009) Johri et al., 1995 Johri et al., 1995 Johri et al., 1995 Muregi et al. (2007a, 2007b) Fortina et al. (2002) Barbastefano et al. (2007) Temponi et al. (2012) A¼ Active; NA ¼not active; NI ¼Not indicated. et al., 2005). Kumari et al. (2003) isolated Zaluzanin with antifungal properties from the plant. More bioactivity studies are needed to ascertain the claimed medicinal properties of the species. 3.1.10. Vernonia aristifera S.F. Blake Vernonia aristifera S.F. Blake is indicated to be a synonym of Critoniopsis foliosa (Benth.) H.Rob. in theplantlist.org. Vernonia aristefera is also synonym to Vernonia steetzii Sch.Bip. The only folkloric use reported for this species is in Mexico where the roots are used to control dysentery and hypermenorrhage (Heinrich, 1996). 3.1.11. Vernonia auriculifera Hiern The leaves are used in Cameroon to treat cataract and in Ethiopia to treat toothache (Focho et al., 2009b; Giday et al., 2009). The plant also has application in reproductive health (Namukobe et al., 2011). Vernonia auriculifera was ranked as the second most used medicinal plant amongst the Meinits in Ethiopia (Giday et al., 2009). Reference is made to the use of a leaf decoction in Cameroon as an eye drop (Focho et al., 2009a). Despite the use as eye drop, no information is available on the possible irritant or toxic properties of this plant. This species was shown to have antiplasmodial activity (Muregi et al., 2003) and antimicrobial activity (Hamill et al., 2003) in vitro though no reports were found on traditional use related to these actvities. 3.1.12. Vernonia bahamensis Griseb. As implied by the name, Vernonia bahamensis is native to Bahamas and it is used to control jaundice (Gupta et al., 1993). 3.1.13. Vernonia betonicaefolia Baker Vernonia betonicaefolia Synonym Cyanthillium cinereum (L.) H.Rob. is used in Madagascan folk medicine as a febrifuge (Rasoanaivo et al., 1992). A plant by the name Cyanthillium cinereum was found to be routinely used against numerous conditions in India (Guha et al., 2009). Interestingly, Vernonia cinerea was listed as the synonym for Cyanthillium cinereum in the study (Guha et al., 2009). This brings to light a major identification problem as IPNI (ipni.org) list Cyanthillium cinereum and Vernonia cinerea as totally different plants. The Plant List (theplantlist.org) however list Cyanthillium cinereum as the synonym of Vernonia betonicaefolia. Because no plant name database has been found that indicates Vernonia cinerea as a synonym of Cyanthillium cinereum it is very likely that the study carried out by Guha et al. (2009) including all its folk uses may be associated with Vernonia cinerea and not Vernonia betonicaefolia. In addition, Guha et al. (2009) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 reported that sesquiterpene lactones have been isolated from Cyanthillium cinereum and referenced Chea et al. (2006). Chea et al. (2006) isolated sesquiterpenes from Vernonia cinerea and the paper makes no mention of Cyanthillium cinereum. It is thus recommended that future studies on the species pay particular attention to its identification. 3.1.14. Vernonia biafrae Oliv. & Hiern Despite the acclaimed potency of this species in treating or alleviating headache, fever and filarial worms in the eye (Burkill, 1985), no further ethnobotanical survey carried out after 1970 has documented the use of this species even though it is distributed throughout West Africa. 3.1.15. Vernonia blumeoides Hook. F. Vernonia blumeoides is used in Nigeria to treat malaria and unspecified infectious diseases (Aliyu et al., 2011a). 3.1.16. Vernonia brachycalyx O. Hoffm. The use of this plant to treat backache and chicken pox is suggestive of the fact that the plant may possess muscle relaxant and antiinflammatory as well as antiviral properties (Moshi et al., 2010). The preliminary antiplasmodial property of the plant was confirmed following the isolation of antiprotozoal coumarins and sesquiterpenes from the roots and leaves of the plant (OketchRabah et al., 1997, 1998). 3.1.17. Vernonia brasiliana (L.) Druce This species is considered poisonous and its use is restricted in Brazil (Rodrigues, 2007). The plant has been shown to have antiplasmodial activity in vitro and in vivo (Carvalho et al., 1991). Ameida Alves et al. (1997) reported the isolation of antiplasmodial triterpenes from the plant. The crude extract at 1000 mg/kg showed 45% parasitaemia clearance in vivo but none of the pure triterpenes were active against Plasmodium berghei in vivo despite the fact that one of the compounds isolated showed 45% clearance at 25 mg/ml against Plasmodium falciparum in vitro. The lack of in vivo activity could be attributed to several factors including poor metabolism and bioavailability in addition to other factors. 17 was assigned to it but Correa et al. (2011) found no DNA inhibition activity and moderate cytotoxicity in the extracts of this plant. 3.1.22. Vernonia chalybaea Mart. ex DC Vernonia chalybaea is used in Brazil as a treatment for edema and liver disease (Albuquerque et al., 2007). Bohlmann et al. (1982) isolated Glaucolide B from this plant. Studies by other investigators have shown that Glaucolide B has antibacterial, cytotoxic and clastogenic activity (Lopes, 1991; Burim et al, 1999). It is as such to be expected that this plant may have significant medicinal potential. 3.1.23. Vernonia chapelieri Drake Vernonia chapelieri is used in Madagascar to treat malaria (Rasoanaivo et al., 1992). 3.1.24. Vernonia chinensis Less. Vernonia chinensis is used in China to treat colds, headache, bacteria infections and wounds (Xie, 1975). The plant is the source of several cytotoxic sesquiterpenes including Vernchinilide A, B and E (Chen et al., 2005). 3.1.25. Vernonia cinerascens Sch. Bip This species is used to treat gastritis, urinary tract infections, male sterility, navel aches, constipation and internal ulcers (Hussain et al., 2010). Vernonione isolated from the plant showed urease inhibitory activity (Ahmad et al., 2012). A previous study of the species resulted in the isolation of compounds with supposed antioxidant as well as urease inhibitory activity (Ahmad et al., 2011). 3.1.20. Vernonia campeana S. Moore The reports on the use of this species are so far limited to Uganda. Two independent surveys have reported the use of this species in treating fever (Hamill et al., 2003; Ssegawa and Kasenene, 2007). The fever in each case is associated with malaria and stomach ache, the activity might thus be antipyretic but also related to malaria. 3.1.26. Vernonia cinerea (L.) Less Vernonia cinerea is reportedly used in folk medicine in East and West Africa as well as in India and South America. There are cross similarities in some of the uses across the continents especially against ailments such as malaria, infertility, skin conditions and worms (Jain and Puri, 1984; Moshi et al., 2009; Padal et al., 2010). This species is also claimed to have antidepressant action (Muir, 1981). In ethnoveterinary medicine, this plant is used against food poisoning and fever (Galav et al., 2010). Various bioactivity studies have confirmed some of the medicinal properties of this species notably, the analgesic, antipyretic, anti-inflammatory, antibacterial and antifungal effects (Tables 6a and 6b). This species is also the source of cytotoxic and antiplasmodial sesquiterpene lactones especially the vernolides (Table 8). Supplementation with preparations of Vernonia cinerea combined with exercise provided beneficial effect on reduced smoking rate which may be related to oxidative stress and beta-endorphine levels (Leelarungrayub et al., 2010). The callus root cultures are a source of alkaloids (Maheshwari et al., 2007). The most indepth studies on the pharmacology of this plant has been carried out by Pratheeshkumar and Kuttan (2009, 2010a, 2010b, 2011a, 2011b, 2011c, 2011d, 2012a, 2012b) evaluating both the crude extract and the sesquiterpene vernolide A (63) focusing on the possible cytotoxic effect on cancer cells. The ethnobotanical surveys combined with bioactivity and phytochemical studies make this a very promising plant for in depth studies of the activities and the subsequent development of various standardized remedies or pure compounds. 3.1.21. Vernonia canescens HBK Vernonia canescens is used in the Bahamas to control bleeding, inflammation and as an enema (Gupta et al., 1993). It is considered to be a medicinal plant in Colombia even though no use 3.1.27. Vernonia cistifolia O. Hoffm. Very little is known about the use of this species in folk medicine. The only report available on the use of this species in ethnomedicine is for nasopharyngeal illness (Burkill 1985). 3.1.18. Vernonia brazzavillensis Aubrév. Ex Compe re Vernonia brazzavillensis is used to treat malaria in folk medicine in Congo (Mbatchi et al., 2006). The in vitro antiplasmodial activity of this species has been confirmed providing preliminary justification for the use of this species against malaria. 3.1.19. Vernonia calvoana Hook. F. This species is amongst the less known species of the genus. The only report on the ethnomedicinal uses of this species is found in Focho et al. (2009b) to relief navel aches and constipation. Further studies are required to confirm the claimed folk uses of this plant and to identify the bioactive compounds in this plant. Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 18 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] of Vernonia colorata and Vernonia amygdalina seems an important first step, before starting extensive activity studies. A metabolomics approach might be an interesting and fast way to identify in both species the compounds related to activity (Wang et al., 2005a). 3.1.30. Vernonia condensata Baker This species is commonly used in Brazil and Nigeria. The common use of the plant in Brazil and Nigeria is for protection against snake bite (Pereira et al., 1994 and Houghton and Osibogun, 1993). The plant extract (100 mg/kg) produced a survival rate of 60% for mice injected with 5 mg/kg jararaca snake venom after 48 h compared to zero survival for mice in the control group (Pereira et al., 1994). Other indications of the species in Brazil mostly concern use in managing GIT conditions. Analgesic and ulcerogenic properties have been confirmed in the plant (Frutuoso et al., 1994). Monteiro et al. (2001) carried out toxicological evaluation of the tea extract and concluded that the extract showed low acute toxicity and had neither teratogenic nor mutagenic properties. Valverde et al. (2001) isolated vernonioside B2 from Vernonia condensata with analgesic and antiinflammatory properties. 3.1.31. Vernonia conferta Benth. West Africa and Nigeria in particular is where Vernonia conferta is reported to be used in folk medicine. The plant is used as a galactogogue, aphrodisiac, laxative, against stomachache, whooping-cough, convulsive-cough, bronchitis, asthma, wounds, sores, jaundice, poison-antidote, diuretic, gonococcal orchitis, diarrhoea, constipation, worms, ophthalmias and abscesses (Burkill, 1985; Ajibesin et al., 2008). The plant is used in Zairean pharmacopoeia as antivenom (Chifundera, 1987). In a bioactivity confirmation study against the filarial worm (loa–loa), Mengome et al. (2010) found inhibitory activity while the root, showed relatively low cytotoxic activities (Ayim et al., 2007). The plant is used in ethnoveterinary medicine in Nigeria (Chah et al., 2009). Fig. 2. Root samples of Vernonia guineensis (A) compared with root samples of American ginseng (B) and white Chinese ginseng (C). The root morphology of the three plants are very similar and seem to have one common biological effect as a stimulant and that may be why these plants are all called ginseng despite belonging to different plant genus. The plant is also reported to be used in the diet of gorillas in the Central African region (Cousins and Huffman, 2002). 3.1.28. Vernonia cognata Less Vernonia cognata is used as an immune enhancer and this has been confirmed in vitro (Petri et al., 2008). Glaucolide B was isolated from the extract of this plant Bardón et al. (1988). Studies by other investigators have shown that Glaucolide B has antibacterial, cytotoxic and clastogenic activity (Lopes, 1991; Burim et al, 1999). The plant extract showed antioxidant activity in an in vivo rat model (Mota et al., 2011). Glaucolide B has also been shown to have molluscicidal activity (Alarcon et al., 1990). 3.1.29. Vernonia colorata Drake Vernonia colorata is the second most popular species of the Vernonia genus after Vernonia amygdalina. The plant is used throughout sub-Saharan Africa medicinally against a plethora of conditions (Table 4). In vitro antibacterial and antiplasmodial activity has been reported for a pure molecule (Vernodalin) isolated from the plant (Rabe et al., 2002; Chukwujekwu et al., 2009). Other bioactive compounds isolated from Vernonia colorata includes, vernolide, Vernolide D, Dihydrovernolide, dihydrovernodalin (Rabe et al., 2002; Kraft et al., 2003; Chukwujekwu et al., 2009). A chemical comparison 3.1.32. Vernonia cruda Klatt Vernonia cruda is erroneously referred in the two publications found as Vernoniacrudia. This species is reported to be used against sexually transmitted diseases (Van Puyvelde et al., 1983; Vermani and Garg, 2002). However, it did not show acivity against gonorrhea in vitro. 3.1.33. Vernonia cumingiana Benth. Vernonia cumingiana is reported to be used to treat inflammation in China. Liu et al. (2009) isolated seven new Vernocuminosides from the plant of which Vernocuminoside B showed potent anti-inflammatory activity while the other compounds showed only marginal activity. In another study, several stigmatane type glycosides were also isolated from the species and found to have only weak anti-inflammatory activity (Liu et al., 2010). The antiinflammatory compounds isolated support the use of this species in the management of several inflammation related ailments. The claimed traditional use against malaria is yet to be studied. 3.1.34. Vernonia deppeana Less. Vernonia deppeana is used as an antifungal for dermatitis and for stomachache (Gupta et al., 1993; Folliard, 2008; Svetaz et al., 2010). 3.1.35. Vernonia extensa DC Vernonia extensa is used in Thailand as a stimulant (Ponglux et al., 1992). Two bitter principles have been isolated from this species in addition to a number of other steroid glycosides (Ponglux et al., 1992). Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 3.1.36. Vernonia fasciculata Michx. This is one of only two Vernonia species reported to be used as an herbal remedy in USA as an alterative (to restore to normal health) and tonic (Smyth, 1903). One report on the use of this species in the US dates back to Cook (1869)). Cook (1869) indicates the root is bitter, with stimulating and relaxing qualities, and leaving a full tonic impression when taken. The plant is used in painful menstruation, leucorrhea, ague, as a hepatic and was prescribed by physicians (Cook, 1869). The flowers also have medicinal value and Cook (1869) thought they are superior to Chamomile. 3.1.37. Vernonia fastigiata Oliv. & Hiern Vernonia fastigiata is used against malaria. In vitro studies have confirmed the antiplasmodial activity of this species has thus lending support to its use in folk medicine (Clarkson et al., 2004). Roos et al. (1998) isolated five antibacterial compounds from extracts of this plant. 3.1.38. Vernonia ferruginea Less. Vernonia ferruginea is used in Bolivia against inflammatory conditions (Malafronte et al., 2009). In a phytochemical study several flavonoids were isolated from this species (Malafronte et al., 2009). 3.1.39. Vernonia filigera Oliv. & Hiern This species is used mainly in ethnoveterinary medicine for the treatment of trypanosomiasis (Teklehaymanot, 2009). In phytochemical studies, the pharmacologically important sesquiterpene lactones vernolepin and vernodalin have been isolated from the above ground parts of this plant (Abegaz et al., 1994). 3.1.40. Vernonia fontinalis S. Moore Vernonia fontinalis is one of the lesser known species of the Vernonia genus. In Rwanda, it is used in ethnomedicine to treat hepatitis (Mukazayire et al., 2011). 3.1.41. Vernonia galamensis Less. Vernonia galamensis is more known as a plant of commerce for the value of its seed oil than for its medicinal potential (Baye et al., 2001; McClory and Atkinson, 2010). Commercial tablet preparations of this plant are now available for use against diabetes (Autamashih et al., 2011). At an oral dose of 5000 mg/ kg in rats, no toxicity or adverse effects were observed for extracts from this plant. The leaf and root extracts of Vernonia galamensis also demonstrated membrane stabilizing property as determined by the percentage inhibition of RBC lysis in vitro (Johri et al., 1995). Most of the phytochemical studies on the plant have focused on the essential oils found in the seed (Ncube et al., 1998). 3.1.42. Vernonia gerberiformis Oliv. & Hiern Vernonia gerberiformis is used in Angola as a piscicide (Bossard, 1993). 3.1.43. Vernonia glaberrima Welw. ex O. Hoffm. Vernonia glaberrima is reported to be used against malaria, migraine, psoric and dysmenorrhoea (Van Wyk and Gericke, 2000; Burkill, 1985; Ananil et al., 2000). Ananil et al. (2000) carried out bioactivity screening of this plant for antiviral and antimicrobial activities. The plant extract showed antibacterial activity but the information on the antiviral activity was inconclusive. 19 3.1.44. Vernonia glabra (Steetz) Oliv. & Hiern This species is used in ethnomedicine against diabetes, wounds, gonorrhoea and dysentery (Burkill, 1985; Long, 2005). The stated ethnomedicinal uses of this species have not been verified. The species has, however, been shown to have blood pressure ameliorating properties (Achola et al., 1996). 3.1.45. Vernonia grantii Oliv. Vernonia grantii is reported to be used against schistosomiasis infection in Africa (Hostettman, 1984). The leaves and roots are used in ethnoveterinary medicine to control worms in livestock (Nalule et al., 2011). 3.1.46. Vernonia guineensis Benth. Vernonia guineensis is gradually gaining popularity as one of the most used Vernonia species in Central Africa and in Cameroon in particular where it is commonly referred to as the African ginseng. This is not surprising because the root morphology have a striking resemblance to that of Panax ginseng (Fig. 2). Studies point to the use of the plant in the treatment of various ailments in human and ethnoveterinary medicine as presented in Tables 3–5. Recent studies have confirmed the presence of antitrypanosomal compounds in the root extract (Tchinda et al., 2002). Since malaria and trypanosomiasis are both protozoan borne, the use of this plant to treat malaria could be linked to the same compounds with antitrypanosomal acitivity identified by Tchinda et al. (2002). Our research has also confirmed the presence of cytotoxic activity in the crude extract against cancer cell lines providing preliminary support for its folk use against prostate cancer (Toyang et al., 2012a). Given the increasing popularity of this species in ethnomedicine, more studies are necessary to validate the claimed medicinal properties and safety of this species. 3.1.47. Vernonia herbacea Rusby This species is one of the poisonous species of Vernonia in Brazil (Rodrigues, 2007). Despite the restricted use of this species in ethnomedicine, the roots were found to possess inulin which is used to measure the glomerular filtration rate (GFR) in kidney function studies. Dias-Tagliacozzo et al. (1996) was able to demonstrate that inulin from Vernonia herbacea was as good as imported inulin used to determine GFR in experiments of kidney microperfusion as a marker of tubular water reabsorption. This species as such provides a substance useful in research and diagnosis. 3.1.48. Vernonia hildebrandtii Vatke This species is native to Tanzania. Mental disease, cough, diarrhoea, and strangulated hernia are some of the conditions treated with Vernonia hildebrandtii including inducing emesis (Hedberg et al., 1982). 3.1.49. Vernonia hirsuta (DC.) Sch. Bip. Notable amongst the uses of this plant is its antimalarial activity which has been confirmed in vitro (Clarkson et al., 2004). Colic, sore throat, cough & headache are some of the additional treatments used in ethnomedicine (Hutchings et al., 1996; Clarkson et al., 2004). 3.1.50. Vernonia hochstetteri Sch. Bip. ex Hochst. Vernonia hochstetteri is used in ethnomedicine to treat hepatitis (Mukazayire et al., 2011). 3.1.51. Vernonia hymenolepis Vatke Hypertension and neonatal respiration problems are some of the conditions treated with Vernonia hymenolepis (Mengome et al., 2010). The plant extract was active against the loa loa Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Q4 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 Q6 Q5 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] filarial parasite (Mengome et al., 2010). Two antitumor elemanolide sesquiterpene lactones, Vernolepin (55) and vernomenin (58) have been isolated from Vernonia hymenolepis (Kupchan et al., 1968, 1969b). 3.1.52. Vernonia incana Less This species is not linked to any ethnomedicinal use in this review. Bardón et al. (2007) however showed that the chloroform extract possessed antibacterial activity in vitro especially against gram positive bacteria. The plant extract was not toxic in the brine shrimp lethality assay as well as in the molluscicidal assay. 3.1.53. Vernonia jugalis Oliv. & Hiern The reported use of this species is mainly in East Africa. Separate studies in Tanzania and Uganda recorded different uses for the species. In Tanzania the plant is used to promote birth, treat stomachache and whole plant to cure epilepsy (Hedberg et al., 1982) and in Uganda Vernonia jugalis is used to treat malaria (Hamill et al., 2003). 3.1.54. Vernonia karaguensis Oliv. & Hiern This species is claimed to have anti HIV activity (James 2007). In terms of bioactivity, the species has been found to possess antibacterial activity (Mungarulire, 1990). 3.1.55. Vernonia kenteocephala Baker Vernonia kenteocephala is used as a febrifuge in Madagascar (Rasoanaivo et al., 1992). 3.1.56. Vernonia kotschyana Sch. Bip. ex Walp. Synonym Baccharoides adoensis var. kotschyana (Sch. Bip. ex Walp.) Vernonia kotschyana is used in the treatment of a number of ailments across Central and West Africa. In Mali, Vernonia kotschyana is used in Malian folk medicine for the treatment of gastritis, gastro duodenal ulcers, as an aid to ameliorate digestion and as a wound healing remedy (Nergard et al., 2004). Germano et al. (1996) confirmed the anti-ulcer activity of this species in an in vivo study. In addition, the species has been found to possess antibacterial as well as immunomodulating properties (Nergard et al., 2005a, 2005b). 3.1.57. Vernonia lasiopus O. Hoffm. The use of this species is restricted to East Africa. The plant is used against malaria it has shown antiplasmodial activity in vitro (Irungu et al., 2006; Muregi et al., 2007a,b). Other bioactivity studies carried out have demonstrated possible cytotoxic, antiviral and antifungal activities of Vernonia lasiopus (Koul et al., 2003). The leaf and root extracts of Vernonia lasiopus also demonstrated membrane stabilizing property as determined by the percentage inhibition of RBC lysis in vitro (Johri et al., 1995). 3.1.58. Vernonia leiocarpa DC Vernonia leiocarpa is used in El Salvador to treat asthma and in Mexico to treat bacterial infections (Gupta et al., 1993; Meckes et al., 1995). 3.1.59. Vernonia leopoldii Vatke Vernonia leopoldii is used in Saudi Arabia and Yemen to treat cough, colic and skin diseases (Al-Musayeib et al., 2012). The plant extract has shown in vitro antiprotozoal, cytotoxic and antimicrobial activity (Mothana et al., 2009; Al-Musayeib et al., 2012). 3.1.60. Vernonia macrocyanus O. Hoffm. Only one reference has mentioned the use of this species in ethnomedicine as a fish poison and to relief spasms in Angola (Burkill, 1985). 3.1.61. Vernonia mapirensis Gleason Vernonia mapirensis is used to relief inflammation in Bolivia (Morales-Escobar et al., 2007). 3.1.62. Vernonia mespilifolia Less This species is used only in ethnoveterinary medicine practices (Dold and Cocks, 2001). 3.1.63. Vernonia miombicola Wild Vernonia miombicola is used against viral and bacterial infections (Cos et al., 2002). The species was studied for antibacterial and antiviral infections in vitro and the activity was found to be weak (Cos et al., 2002). 3.1.64. Vernonia mollissima D. Don ex Hook. & Arn. Vernonia mollissima is cited to be used as a diaphoretic to enhance perspiration in Argentina (Goleniowski et al., 2006). On the phytochemistry, sesquiterpenes have been isolated from this plant (Catalán et al., 1986). Krebs et al. (1990) also reported isolation work on the plant. Vernonia mollissima and Vernonia rubricaulis have been reported to be toxic causing bloat and hepatotoxicity in livestock in Brazil (Tokarnia et al., 2002). 3.1.65. Vernonia myriantha Hook. F. This species is used in Southern Africa. The antimalarial activity of the plant has been confirmed in vitro and the dichloromethane leaf extract was found to be most potent (Clarkson et al., 2004). The root extract also showed moderate activity against the plasmodium parasite. The plant is used to treat mental illness as well as a contraceptive (Mabogo, 1990; Long, 2005). 3.1.66. Vernonia natalensis Sch. Bip. ex Walp. As the name implies, this species is indigenous to South Africa where it used to treat malaria and diarrhoea (Clarkson et al., 2004; de Wet et al., 2008). The species has been independently reported to possess antiplasmodial activity by two research studies (Kraft et al., 2003; Clarkson et al., 2004. Fawole et al. (2009) found anti-inflammatory activity in the plant extract in vitro. 3.1.67. Vernonia neocorymbosa Hilliard This is another species that is mostly found in South Africa. It is reported to be used both in ethnomedicine to treat hysteria and epilepsy (Stafford et al., 2008) and in ethnoveterinary medicine to control worms (McGaw and Eloff, 2008). Bohlmann et al. (1983) isolated terpene derivatives from this species even though no studies have linked them to any bioactivity properties of the plant. 3.1.68. Vernonia nestor S. Moore Vernonia nestor is used against ringworm (antifungal condition) in Nigeria (Burkill, 1985). 3.1.69. Vernonia nigritiana Oliv. & Hiern. This species is widely used in West Africa as an emetic, emmenagogue, for blood purification, against rheumatism, as an aphrodisiac amongst other uses listed in Table 3. No bioactivity studies in regard to the claimed ethnomedicinal uses have been reported. However, a bitter glycoside, vernonin has been isolated Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 from the roots. Vernonin has a digitalis (digoxin) like action on the heart but it is weaker than digoxin (Burkill, 1985). 3.1.70. Vernonia noveboracensis (L.) Willd. This is one of the 2 species of Vernonia reported to be used in USA. This report on this species dates back to 1903 and it is used as an alterative and as a tonic (Smyth, 1903). The species has also been found to have contact dermatitis effect (Fortina et al., 2002). 3.1.71. Vernonia nudicaulis Less. Vernonia nudicaulis is used in Madagascar to treat venereal disease (Aliyu et al., 2011a). 3.1.72. Vernonia oligocephala Edgew Vernonia oligocephala is a species found mainly in Southern Africa and it is used in ethnomedicine to treat malaria, stomach disorders, rheumatism, dysentery, diabetes and ulcerative colitis (Clarkson et al., 2004; Long, 2005; Thring and Weitz, 2006; de Wet et al., 2008; Deutschlander et al., 2009). The antiplasmodial activity of this plant has been confirmed in vitro (Clarkson et al., 2004). 3.1.73. Vernonia oocephala Baker Vernonia oocephala is used in Nigeria to treat malaria and a number of unspecified infectious diseases (Aliyu et al., 2011a). 3.1.74. Vernonia pachyclada Baker This species is endemic to Madagascar and it is used for wound healing. Phytochemical studies of the species led to the isolation of cytotoxic sesquiterpenes from the plant (Williams et al., 2005). 3.1.75. Vernonia patens Kunth Vernonia patens is used in Panamanian ethnomedicine as a antipyretic to control fever (Gupta et al., 1993). The methanol extract of the stem and leaf of this plant showed activity in a brine shrimp and crown gall tumor inhibition assay suggesting the plant may have cytotoxic properties (Gupta et al., 1996). 3.1.76. Vernonia patula Mart. ex DC This species is erroneously spelled as paltula in one of Ref. Ku et al. (2002). It is considered to be one of only three Vernonia species in Tawain (Chiu and Chang, 1987). It is used against hepatitis, inflammation, colds, as antipyretic and antiviral. The widest application of this plant in ethnomedicine is in Bangladesh where it has over fifteen folk medicinal uses (Saha and Paul, 2012). The plant material was analyzed and found to have flavonoids which are thought to be responsible for the claimed medicinal properties of the species (Ku et al., 2002). The plant is amongst the few Vernonia species that are claimed to have alkaloids even though no alkaloid has been reported isolated from this species (Saha and Paul, 2012). 3.1.77. Vernonia pectoralis Baker Vernonia pectoralis is used in folk medicine in Madagascar to treat malaria (Rasoanaivo et al., 1992). 3.1.78. Vernonia perrottetii Sch. Bip. ex Walp. This plant is used as a purgative in West Africa (Burkill, 1985). 3.1.79. Vernonia pogosperma Klatt Bioactivity studies to verify the claimed medicinal uses of this species showed the presence of antibacterial and antiviral activity (Vlietinck et al., 1995). This confirmed an earlier antimicrobial activity study of the species (Boily and Van Puyvelde, 1986). 21 3.1.80. Vernonia polyanthes Less. This species has been reported to be used in Brazil to treat rheumatism, bronchitis and cough (Braga et al., 2007). However, the only bioactivity study of the plant is on its use to manage blood pressure (Romanezi da Silveira et al., 2003). The plant has been shown to have antiulcer effect (Barbastefano et al., 2007) as well as antinociceptive and anti-inflammatory activity (Temponi et al., 2012). 3.1.81. Vernonia polytricholepis Baker Vernonia polytricholepis is used in Nigeria to treat fever and respiratory conditions (Aliyu et al., 2011a). 3.1.82. Vernonia poskeana Vatke & Hildeb. Vernonia poskeana is used mainly in Tanzania against cough, fever and to prevent miscarriage (Burkill, 1985). 3.1.83. Vernonia potamophila Baker Vernonia potamophila is used to treat cancers and dermatological problems (Babady-Bila et al., 2003). 3.1.84. Vernonia prolytricholepsis Baker Vernonia prolytricholepsis is used in Madagascar as a febrifuge (Rasoanaivo et al., 1992). 3.1.85. Vernonia pumila Kotschy & Peyr. The claimed uses for this species are as a stomachic by improving stomach function and appetite, and against gonorrhoea (Burkill, 1985). It is however not clear whether or not the species is used for the same purposes in East and West Africa where it is found. 3.1.86. Vernonia rhodolepsis Baker Vernonia rhodolepsis is used in Madagascar as a febrifuge (Rasoanaivo et al., 1992). 3.1.87. Vernonia roxburghii Less. Vernonia roxburghii is used in India to relief indigestion and vomiting (Chandra et al., 1985). 3.1.88. Vernonia saligna DC Vernonia saligna is used in India against respiratory tract infection, tuberculosis and uterine prolapse (Huang et al., 2003). 3.1.89. Vernonia scorpioides Pers. Vernonia scorpioides is used against skin disorders, wounds and ulcers (Buskuhl et al., 2010) and as an aphrodisiac, and interestingly in witchcraft (Wong, 1976). This species of Vernonia has received a reasonable bioactivity and phytochemical scrutiny. Moderate bactericidal, fungicidal, wound healing, cytotoxicity to cancer cells and anti-inflammatory properties have been exhibited by this plant in vitro (Table 7a). In regard to its phytochemistry, the first study report on the species was inDrew et al. (1980). Several bioactive sesquiterpene lactones were isolated from the species (Buskuhl et al., 2010). Lopes (1991) also reported that sesquiterpene lactones isolated from this species demonstrated antifeedant, molluscicide, antimicrobial and analgelsic activities. 3.1.90. Vernonia senegalensis Less. Even though the author that reported the ethnomedicinal uses of this species listed it as a synonym to Vernonia colorata Drake, the International Plant Name Index (www.ipni.org) list Vernonia senegalensis Less. as a separate species. Studies are thus required to confirm the taxonomic classification of this species and to Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 22 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 6c Results of studies requiring validation or missing in some important data. species Study Activity/results Reference adoensis Sch. Bip. exWalp aemulans Vatke Oesterr. amygdalina Del. Antibacterial Antibacterial, antiviral Antibacterial Antidysenterial cytotoxicity Sickle cell effect Anthelmintic Antioxidant 70 mg/ml 500 mg/ml 500 mg/ml MIC 41000 mg/ml IC50 ¼ 1000 mg/ml Concentration used not stated In vivo sheep: 3000 mg/kg In vivo: 2 g/kg Kisangau et al. (2007a) Vlietinck et al. (1995) Vlietinck et al. (1995) Otshudi et al. (2000) Gresham et al. (2008) Afolabi et al. (2012) Iqbal et al. (2006) Mota et al., 2011 anthelmintica Willd. cognata Less. determine the differences in their chemical profiles. The plant is associated with many ethnomedicinal uses against boils, gonorrhea, scabies, gastritis, sterility and frigidity (Hedberg et al., 1982) none of which has been confirmed. 3.1.91. Vernonia serratuloides Kunth Vernonia serratuloides Kunth synonym Vernonanthura serratuloides (Kunth) H.Rob. Vernonia serratuloides Kunth is used in Mexico to relief toothache suggesting the plant may have antiinflammatory or numbing properties (Heinrich, 1996). 3.1.92. Vernonia smithiana Less. In Congo, this species is used against various ailments including rheumatic pain (Table 4). 3.1.93. Vernonia spiciforma Klatt Vernonia spiciforma is used in Madagascar as a febrifuge (Rasoanaivo et al., 1992). 3.1.94. Vernonia staehelinoides Mart. ex Baker Vernonia staehelinoides is used against malaria (Pillay et al., 2007). The antiplasmodial activity of this species has been confirmed in vitro (Pillay et al., 2007). A bioactive compound (Hirsutinolide) was also isolated from the plant and showed good selectivity against the plasmodium parasite. It is a promising compound for development against malaria. 3.1.95. Vernonia stellullifera (Benth.) C. Jeffrey The whole plant is used in ethnomedicine in Cameroon to prevent miscarriage and dysentery (Jiofack et al., 2010). It is also said to be used as a ‘‘tetam.’’ Unfortunately no definition was found for the term ‘‘tetam.’’ 3.1.96. Vernonia stenocephala Oliv. This species is used in Ugandan ethnomedicine to treat prehepatic jaundice (Ssegawa and kasenene, 2007). 3.1.97. Vernonia stipulacea Klatt Vernonia stipulacea is used against viral related conditions in South Africa particularly against the HIV virus. The methanol extract of the plant stimulated reverse transcriptase activity in the HIV-1 virus at 100 mg/ml (Bessong et al., 2005). Percentage inhibition of the virus was however low. The authors of the study indicate that the activity though weak could be linked to sesquiterpene lactones known to be present in Vernonia species but no phytochemical studies have been carried out to the compounds present in the plant. 3.1.98. Vernonia subuligera O. Hoffm. The root of this species is used as a galactogogue. The plant is used in Uganda for the treatment of sleeping sickness and has been confirmed to have antitrypanosomial activity (Freiburghaus et al., 1996). 3.1.99. Vernonia tenoreana Oliv. This species was not recorded to have any folk use. However, the species showed antidiabetic activity in a random screen (Taiwo et al., 2008). 3.1.100. Vernonia teres Wall ex DC The whole plant of Vernonia teres is used in India to treat ulcers, wounds and as an acaricide (Garg and Siddique, 1992; Johri and Singh, 1997). 3.1.101. Vernonia thomsoniana Oliv. & Hiern ex Oliv. Mungarulire (1990) studied this Zulu medicinal plant for its claimed antibacterial activity and found it to be active against a selected number of bacteria species. 3.1.102. Vernonia tigna Klatt Two independent research studies point to the use of this species as an abortifacient (Mabogo, 1990; Long, 2005). 3.1.103. Vernonia trichoclada Gleason Vernonia trichoclada is used in Bolivia to relieve inflammatory conditions (Morales-Escobar et al., 2007). 3.1.104. Vernonia trichodesma Baker Vernonia trichodesma is used in Madagascar as a febrifuge (Rasoanaivo et al., 1992). 3.1.105. Vernonia tweedieana Baker Vernonia tweedieana was studied and found to have immune enhancing effects (Petri et al., 2008). Organic solvent extracts of the plant showed antibacterial activity and yielded flavonoids in a phytochemical study of the species (Diaz et al., 2008). 3.1.106. Vernonia undulata Oliv. & Hiern This species is used in Gabon as an enema and for piles (Burkill, 1985). 3.1.107. Vernonia usambarensis O. Hoffm. Vernonia usambarensis is used in Tanzania to control excessive menses (Hedberg et al., 1982). 3.1.108. Vernonia venosa S. Moore Vernonia venosa is used against bacterial infections in Sudanese ethnomedicine (Al Magboul et al., 1988). The in vitro antibacterial activity of this species has been confirmed (Al Magboul et al, 1988). Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 23 OH OH OH OH HO HO OH O O O O HO OH HO OH OH O O 1. Luteolin OH O Luteolin 7-O-B-glucoside 2. Methyl caffeate OH HO O OH O O HO OH 3. OH O OH HO O O OH O 4. Luteolin 4'-O-glucoside OH 5. Lutein 6. Urticifolene HO CO2H OH O HO O HO O HO O O OH O OH O HO OH 8. Chlorogenic acid OH OH OH 7. 3,5-Dicaffeoylquinic acid OH O HO HO OH OH O O HO HO OH O O OH O O HO OH O HO OH O 10. Gallic acid HO O OH O HO OH 9. 4,5-dicaffeoylquinic acid OH OH 11. 3,4-dicaffeoylquinic acid Fig. 3. Bioactive compounds isolated from Vernonia species. Their biological activity, sources and names are given in Table 8. A total of 103 bioactive compounds are included in this review. 3.1.109. Vernonia zeylanica Less Vernonia zeylanica is a Shrub 1–2.5 m tall and endemic to Sri Lanka. This plant, especially the stem is used in the treatment of boils and bone fractures (Ratnasooriya et al., 2007). 3.2. In vitro activity analysis The crude extracts of 40 plants were identified to have been evaluated for various bioactivity effects involving over 150 in vitro studies (Table 6a). Five of the in vitro studies were considered questionable due to the high dose of extract used raising questions as to whether it was possible to achieve such doses in vitro (Table 6c). The top 5 in vitro studies included antimicrobial, antioxidant, anti-inflammatory, antiplasmodial and cytotoxicity studies. Most of the assays used in the in vitro experiments are standard assays routinely used to screen for bioactivity in the early phase of the drug discovery process. Despite the fact that standard assays were used in the studies covered in this review, there is no guarantee that plants showing potent activity in vitro will also have good efficacy without toxicity in vivo. Toxicity as such is probably the next most important consideration once any activity has been established in vitro. The claimed in vitro active dose for the studies reported ranged from o1 mg/ml to several mg/ml depending on the type of assay. Samples reported to be having activity at very high doses (e.g., Table 6c) will certainly not be able to make it in vivo as a large quantity of the sample will be required to dose the animals possing sample preparation, administration and potential toxicity problems. Generally, it is expected that the compounds or extracts active at lower microgram per ml concentrations will have a better chance of showing activity in vivo as a smaller quantity of the sample will be required to produce the desired effect. Even though establishing activity thresholds for different assays might prove to be useful, a careful selection of candidates for in vivo studies will always require a combination of criteria including in vitro activity, formulation, route of administration, pharmacokinetics and toxicity. Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 24 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] OH O OH O O O O OCH3 13 12. Vernonione HO O R1 OH HO RO R4 HO R2 OH R3 R1 R2 R3 R4 O N O 16. R=CH3 17. R=H HN O 18. Uridine 14. Vanillic acid COOH -OCH3 OH H 15. Methyl gallate COOH OH OH OH R1 OH R2 O O HO OR H H OH OH O O O O 1 2 21. R = CH 3, R = H 22. R1 = H, R 2 = CH 3 19. 3'-methylquercetin R=CH3 20. Quercetin R=H Fig. 3. Continued. 3.3. In vivo activity analysis About 110 in vivo studies utilizing crude extracts from 18 Vernonia species were reviewed (Table 6b). Almost 50% of these studies were carried out on Vernonia amygdalina with a majority of the studies focusing on its antidiabetic activity. The top 3 diseases or conditions studied in vivo included diabetes, inflammation and malaria. Due to the fact that in vivo studies are usually more expensive and complicated, they often come in only after bioactivity has been determined in vitro. Establishment of in vivo activity is very important as it is the best predictor that a plant extract may or may not have clinical utility and as such determines the potential for further development studies. While the data in Table 6b may point to some activity of the Vernonia species studied, it is difficult to state categorically what might work clinically. The fact is that even though the methods used in the studies are mostly based on well known protocols, there are many factors (e.g., animal breed, sex, age, diet, health status and environment) that could lead to variation in experimental outcomes. For example, the antidiabetic effect of the leaves of Vernonia amygdalina was evaluated in about 11 different studies in rats and the ED50 based on effect on fasting glucose levels varied from 100 mg/kg to 800 mg/kg (Table 6b). Similarly, the antimalarial activity of Vernonia amygdalina was evaluated in 6 studies in mice and one human study (Table 6). The values of the active dose varied from 125 mg/kg to 1000 mg/kg with 67% parasitaemia clearance at 125 mg/kg for 4 days compared to 82.3% clearance at 1000 mg/kg for 4 days. By comparison, the antidiabetic and antimalarial ED50s were less than the 14-day chronic toxicity dose of 42000 mg/kg reported in mice for Vernonia amygdalina (Njan et al., 2008). Judging from this example, the reported active dose for the same plant could vary significantly between studies. Due to the fact that it is difficult to overcome this variation, the significance of the ED50 of each experiment should never be considered in isolation without taking into account other factors such as formulation, pharmacokinetics and toxicity. Two in vivo studies were considered questionable due to the high dose of extract used raising questions as to whether it was practical to achieve such doses in a clinical setting (Table 6c). 3.4. Clinical trials Human studies or clinical trials usually come last in the drug discovery process. In ethnomedicine, human trials can however be considered validation studies as ethnomedicines generally are already being used in folk medicines in humans before the arrival of researchers to evaluate the efficacy and safety of selected remedies. In this review, only Vernonia species was found to have been subjected to a human study (Table 6b). Vernonia amygdalina was used in 2 human trials against malaria and diabetes. The antimalarial activity was found to be weak at the dose tested as only 32% of participants had total parasite clearance following 7 days of treatment (Challand and Willcox, 2009). In regard to the antidiabetic effect in humans, Okolie et al (2008) reported that Vernonia amygdalina elicited significant reductions (Po 0.05) in blood glucose levels at a dose of 50 g/participant. More studies are certainly required with larger sample size to validate the results of these preliminary trials as well as other claims that have demonstrated good activity in vivo. Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 25 H H H H H H H R2 H H H HO R1 O H H H H O 24. B -amyrin R1=OH R 2=CH3 25. B -amyrin acetate R1=OAc R2=CH3 26.. Oleanolic acid R1=OH R 2= COOH 23.α-amyrin H H 27. Lupenyl acetate H R 1O OH O H H H O H O H H H H HO R H 28. Lupeol R 2O H 31. Vernoguinosterol R1=R 2=H 32. Vernoguinoside (R1=H, R2=Glc) 29. Friedelanone R= =O 30. Friedelin acetate R= OCOCH3 HO O OH O O OH OH HO HO O O O OH H 3 CO O O O 33. Vernoguinoside A HO R3 OH O OH OH R2 OH HO O H R1 34. Vernonioside A3 35. Vernonioside B1 O H R1 Glco Glco HO OH 36. Vernonioside B2 R2 R3 O H H,H OH Fig. 3. Continued. 3.5. Toxicity aspects of the Vernonia genus Vernonia herbacea and Vernonia colorata are the only two species of Vernonia identified in ethnomedicine as poisonous (Rodrigues, 2007; Maiga et al, 2005). A number of limited studies have been carried out to determine the safety of commonly used Vernonia species. Amole et al., 2006 and Njan et al., 2008 found no toxicity effect in extracts of Vernonia amygdalina in in vivo rat studies. In another Vernonia amygdalina study, the plant extract exhibited hepatoprotective and not hepatoxic effect in rats (Ojiako and Nwanjo, 2006). In acute toxicity studies in a rabbit model, Akah and Okafor (1992) observed an LD50 of 1122 mg/kg through intraperitoneal injection using an extract of Vernonia amygdalina. Yoga Latha et al. (2011) and Rajamurugan et al. (2011) found no toxicity in mice (LD50 42000 mg/kg) and brineshrimp using a methanol extract of Vernonia cineria. A tea from the leaves of Vernonia condensata produced an LD50 of 3400 mg/kg for males and 5000 mg/kg for female mice (Monteiro et al., 2001). In another study, the most lethal extract of Vernonia condensata using a single solvent was found to be the dichloromethane extract with LD50 of 500 mg/kg while the aqueous and ethanol extracts showed LD50 42000 mg/kg (Risso et al., 2010). However, the acetone extract with an LD50 of 1000 mg/kg showed the best margin of safety (370.4) compared with its antinociceptive activity (ED50:2.7 mg/kg). Apart from the in vivo studies, several in vitro studies have been carried out on the cytotoxicity, embryotoxicity, mutagenicity and genotoxicity of some Vernonia species (Ananil et al., 2000; Zhu et al., 2008; Monteiro et al., 2001; Elgorashi et al., 2003). Glaucolide B from Vernonia eremophila showed no clastogenic action on mammalian cells in vivo but was cytotoxic and clastogenic in vitro (Burim et al., 1999). Because most of the reported cytotoxicity studies involved more cancer cell lines than normal cell lines, most of these studies would be associated with anticancer rather than general toxicity. It is worth noting that Vernonia noveboracensis was implicated in a case of contact dermatitis in a human subject (Fortina et al., 2002). 3.6. Phytochemistry of the Vernonia genus: Bioactive compounds 3.6.1. Alkaloids A relatively small number of species of the Vernonia genus have been reported to contain alkaloids. Qualitative phytochemical studies have led to the identification of alkaloids in Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] OH OH O OH O O O O O O O H CH3 OH O O O O H H CH3 OH O 39. Lasiopulide O O O 38. 11β, 13-Dihydrovernodalin 37. Vernodalol O OCOMe O OCOMe OH OCOMe OCOMe O HO R1O O OCOMe OR2 HO O O O O 43. Glaucolide B O 42. Glaucolide O O O O OCOMe O O O O 40. R1 = CH 3 ; R2= 4-OH-methacryloyl 41. R1= H; R2=4-OH-methacryloyl O O OR HO O O O O O O 44. R=Ac = Glaucolide K 45. R=H =Glaucolide L HO HO 46. Glaucolide M OAc O O OCOMe OAc O O O O O O OCOMe 47. Hirsutolide O 48. Hirsutinolide O O HO O HO HO O O 49 OAc O OAc O HO OR OR2 I O O CH2OR1 OAc O O O O Piptocarphins O O 50 O O O 51. R = 4-OH-methacryloyl 52. R= methacryloyl 53. A 54. F R1 II III O R2 I I II CH2CH3 III Fig. 3. Continued. Vernonia ambigua (Aliyu et al., 2011), Vernonia amygdalina (Nwanjo, 2005; Ayoola et al., 2008; Sharma et al., 2010), Vernonia blumeoides (Aliyu et al., 2011), Vernonia cinerea (Maheshwari et al., 2007 (1), Vernonia colorata (Neuwinger, 1996), Vernonia condensata (Risso et al., 2010), Vernonia kotschyana (Deeni and Hussain 1994), Vernonia oocephala (Aliyu et al., 2011) and Vernonia patula (Saha and Paul, 2012). The quantitative identification and spectroscopic characterization of the alkaloids of the above identified species is required for a better understanding of the role that these alkaloids play in the bioactivity of these plants. 3.6.2. Flavonoids Flavonoids are among the two major classes of compounds encountered in the Vernonia genus (Carvalho et al., 1999). Most of the flavones and phenolic compounds have been isolated from Vernonia amygdalina and Vernonia cinerascens and have exhibited potent antioxidant as well as urease inhibitory activity (Igile et al., 1994; Ahmad et al., 2011). Reference has also been made to the effect that the biological activity of several Vernonia species could be attributed to the presence of flavonoids in the plants especially their antioxidant activities (Atangwho et al., 2009; Khalafalla et al., 2009; Kunle and Egharevba 2009). Table 8 presents Vernonia species identified to be having bioactive flavonoids. 3.6.3. Terpenoids Terpenoids or terpenes are the largest known class of secondary metabolites in plants (Connolly and Hill, 1991). They play a role in interaction of plants with their environment and have been shown to have a broad range of biological activities such as antibiotic, cytotoxic, Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 Q7 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 27 O O O H H O O OH H H H O O CH2OH H CH2OH H O OH H H H H O 55. Vernolepin O HO 56. Vernodalin O O O 57. Vernodalinol O H H H O O O O O H H O H O H O H H H O H O O 58. Vernomenin O 60. 4,15 dihydrovernodalin 59. Epivernodalol O HO H O H O H3CO O O O H O H O H O O OH O H OH H H H O H O O O 61. 11, 13 dihydrovernodalin 62. Vernolide 63. Vernolide A O H O O HO H CH2OH H O H3CO H O HO O O O H H H O O O H OAc H OAc O O O O O 64. Vernolide B 65. Vernolide D 66. Vernomygdin O H O O H HO HO OH H O HO O O O H O H H H O OH OEt H H O O O O O O 67. Hydroxyvernolide 68. Zulazanin D 69. Vernobockolide B Fig. 3. Continued. antimalarial, antifeedant, insecticidal, moluscidal and herbicidal properties (Zhang et al., 2005; Roberts, 2007; Gershenzon and Dudareva, 2007; Kaur et al., 2009). For example, the anticancer drug, Taxol and the antimalarial drug Artemisinin are widely known terpene baseddrugs (Wang et al., 2005b). Terpenoids are thus an interesting target for finding novel leads for medicines. Terpenoids are subdivided in to monoterpenes, sesquiterpenes, diterpenes, triterpenes, and carotenoids. The monoterpenes and sesquiterpenes are the main constituents of essential oils obtained from most plants of the Asteraceae family including the Vernonia genus (Ogunbinu et al., 2009). Most of the essential oils are known to be highly medicinal and aromatic, thus their use in various applications including the perfumery industry. Sesquiterpenes form the most interesting group of compounds among the terpenoids in terms of structural diversity and biological activity (Matejić et al., 2010; Fraga, 2011). Merfort (2011) in a review on the pharmacology of sesquiterpene lactones distinguished four major classes of sesquiterpenes: the germacranolides, eudesmanolides, guaianolides, and pseudoguaianolides. The Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] H H OR2 1 R O OR2 R 1O H O H O OR3 OR3 O O O A 70. 72. R1=H R2=B O D B R2=C O Cl OH OH R1=H O O O 74. C R 3=Ac 71. R1=H R 2=A R 3=Ac R 3=Ac 73. R1=H R 2=D R 3=Ac R1=H R2=C R3=Ac O O HO HO HO OR2 R1 R1 HO H O O H O H O OR3 OCH3 OR2 O O O 79 O O 75. R1=H R2=C HO O O R1 R2 76. OH Me 77. H Me 78. OH Ac R 3=Ac H R 3O OR2 O H O OR1 O OR1 OH O OR2 O O O O O A= B= O OAc O 80. 81. 82. 83. 84. 85. 86. R1 H H H Ac Ac Ac Ac R2 A H H B B A H R3 H H CH3 H CH3 CH3 H OAc O O O O 91 O 87. R1 = H; R 2 = methcryloyl 88. R1 = H; R 2 = iso-butyroyl 89. R1 = H; R 2 = angeloyl 90. R1 = Ac; R2 = methacryloyl Fig. 3. Continued. sesquiterpene lactones are characterized by the presence of a lactone group their structure. The lactone functionality has been shown to be responsible for most of the biological activity of members of this class of compounds especially when it comes to cytotoxicity (Schmidt, 1999; Kuo et al., 2003; Buskuhl et al., 2010). Apart from their interesting bioactivity, the understanding of the biosynthesis of sesquiterpenes combined with their structural diversity has made these compounds to be useful in the chemotaxonomy of the Asteraceae (Zdero et al., 1991; Zidorn, 2006). Among plants of the Vernonia genus so far studied for biological activity, a good number of the biological activity claims have been associated with the presence of terpenoids in the plants. Despite the fact that the literature reports the isolation of hundreds of terpenoids from the Vernonia genus, only a limited number have been tested for bioactivity. Fig. 3 presents some of the important biologically active terpenoids that have been isolated from the Vernonia genus. Table 8 lists bioactive compounds isolated from Vernonia species and state their bioactivities. This includes also bioactive compounds isolated from Vernonia species not currently used in ethnomedicine to the best of our knowledge. 3.6.4. Miscellaneous compounds In addition to the flavonoid and several terpenoids identified in the genus Vernonia with bioactivity, two coumarins and one sucrose ester from the genus were also reported to be active. Table 8 carries the bioactivity information of these compounds while Fig. 2b illustrates the structures of the compounds. 4. Conclusion and recommendations This review summarizes information on the ethnomedicinal uses and confirmed in vitro and in vivo bioactivity of plants of the genus Vernonia. The review confirms the importance of the genus as a source of nutrition and medicine for humans, domesticated as well as wild animals. Despite the great potential that this genus Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 29 O O H O O O HO OH O O O O O OH O O O O 93. 16, 17-Dihydrobrachycalyxolide 92. Eremantholide B O OH O O O OH O O O H O O O O H O O O O O O O O 95. Vernodalidimer B O H O OH COOMe O 94. Vernodalidimer A H O O O OH O O O H O MeO2C O O H H O H O 97. Scorpioidine O 98. 11B, 13-Dihydrovernolide RO 2)-B-D-Glc R= B-D-Gal-(1 96. Vernocuminoside B OH O OH O O O O O CHO O R O O OH CHO O H O O 102. Vernomelitensin OH O 101. Vernopicrin O CH2OH O O 99. Tetrahydrovernodalin R= =CH 2 100. Hexahydrovernodalin R= -CH3 RO RO OR O 103. Pentaisovaleryl sucrose OR R= isoveryl (COCH2CH(CH3)2) CH2OH OR Fig. 3. Continued. holds as a source of new drugs, much remains to be done to properly document the folk uses of plants of this genus as the basis of further studies aimed at the validation of claimed bioactivities and finally, isolation and identification of the bioactive molecules, which are needed for quality control of possible phytomedicines and which may serve as leads for developing novel drugs. We have made the best effort to summarize the information available using figures and tables in addition to narratives. Tables 4–6 presents the folk and zoopharmacognostic uses of Vernonia species whereas Tables 7 and 8 summarizes the results of in vitro and in vivo studies of crude extracts and isolated compounds. A combined analysis of this information can assist researchers in the selection of interesting species or isolated compounds for further studies. Validating the bioactivity of traditional uses of these species will help establish evidence-based traditional medicine in regard to the Vernonia species. In order to fully benefit from the potential medicinal and other properties of this genus, the following future directions are recommended: 4.1. Planning future ethnopharmacological studies With approximately 1000 recorded species of the Vernonia genus in existence, this review reveals that only about 10% of the species have been documented in ethno studies for their folk uses. The role of the ethnopharmacological based drug discovery approach has been cited to be having advantage over random plant collection and screening approach due to its higher probability to yield plants with bioactivity properties compared to the Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 7 Q10 Vernonia species identified to be having bioactive flavonoids. Vernonia species Type of study Flavonoids identified Reference ambigua amygdalina cinerea Antimicrobial Antioxidant Antidiabetic Leukaemia Antiinflammatory cognata zeylenica antioxidant Antinociceptive activity Based on crude extract analysis (CEA) Isolated flavonoid (Table 9) CEA CEA Luteolin Luteolin 7-O-glucoside Luteolin 49-O-glucoside Chlorogenic acid 3,5-dicaffeoylquinic acid 3,4-dicaffeoylquinic acid 4,5-dicaffeoylquinic acid Methyl caffeate Gallic acid CEA CEA Kunle and Egharevba. (2009) Igile et al. (1994) Atangwho et al. (2009) Khalafalla et al. (2009) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Mota et al., 2011 Ratnasooriya et al. (2007) random approach (Fabricant and Farnsworth, 2001). Efforts to continue the documentation of the folk uses of species of this as well as other genuses is encouraged both for the purposes of validating already existing information and for identification of yet to be studied species as possible drug leads. 4.4. Assay selection This review has identified 105 Vernonia species with claimed medicinal properties. Out of this number, only 41 have undergone any in vitro or in vivo validation studies (Table 7a and b). Amongst the 41 species that have been studied, less than 50% of the studies have been in vivo involving only 18 species. Of all the in vivo studies carried out, only 3 of the studies were in humans (Fortina et al, 2002; Okolie et al., 2008; Challand and Willcox, 2009). The human clinical trial especially by by Challand and Willcox (2009) showed that it was feasible to run a clinical trial using a remedy prepared according to traditional prescription. On the basis of the results obtained with only 32% complete clearance of the malaria parasite at a dose of 500 mg/ kg/day for 7 days, a follow up study utilizing a higher dose was recommended since there was no apparent toxicity observed at the dose used. Given the burden of malaria as the leading cause of death in sub Sahara Africa and the poor access to recommended combination therapies, priority should be given to the confirmation and possible optimization of the effect of Vernonia amygdalina clinically against malaria and other conditions. Assay selection is very important for sensitive and reproducibility of results in natural products research (Phillipson, 1995). Vernonia amygdalina for example has been shown to have antimicrobial activity in numerous experiments but surprisingly, Kubmarawa et al. (2007) found no antimicrobial in extracts of this plant. Assay sensitivity and sample preparation are amongst critical factors required for reproducibility of activity. Several rapid and cheap assays have been developed for the screening of plant extracts and isolated compounds for bioactivity (Tan et al., 1991; Borris, 1996; Zgoda and Porter, 2001; Cos et al., 2006). Despite the fact that some of these assays have standard protocols and have been in use for decades, their results sometimes require confirmation in more advanced and expensive assays. This may account for reason why few studies have been carried out to verify the activity of plant species identified to be having folk uses. This attests to the fact that some of the so called inexpensive assays may not be all that cheap especially in developing countries. The few validation studies can as such be accounted for by the fact that most of the plants abound in developing countries and researchers in these countries often do not have access to even basic research facilities. Apart from increasing funding for basic research in developing countries, collaboration between researchers in developing countries and their counterparts in developed countries should be encouraged. 4.3. Selection of compounds for further studies 4.5. Sample collection and preparation for screening Of the 90 compounds isolated from Vernonia species and showing bioactivity, 26 of the compounds demonstrated IC50 r10 mM. Going by the industry standard, this will be considered to be promising especially for those that were active at 1.0 mM level. These compounds such as Vernolide A that have demonstrated very good activity in several drug discovery related assays are good candidates for further preclinical studies. For compounds showing activity IC50 Z10 mg/ml, these could be considered as useful candidates for activity optimization through structural modifications and also structure activity relationship (SAR) studies. In terms of in vivo studies, by far more studies have been carried out using crude extracts than they have been with pure compounds. It is unclear whether this trend is indicative of the fact that researchers did not find the in vitro activity of pure compounds worthy of further pursuit or it is due to the lack of sufficient quantities of the pure compounds to be able to move to in vivo studies; the later is more likely to be true exposing one of the drawbacks in natural product drug discovery given the low yields usually obtained for pure compounds. Results presented in Table 7a and b on in vitro/in vivo bioactivity of plants reveals that the same plant species from different origin can give different activity in the same assay. These variations can be attributed to various factors including but not limited to environment, season, age of plant, part of plant, time of day collected, post harvest handling, extraction solvent (Eloff, 1998) and sensitivity of assay (Phillipson, 1995). Careful attention should as such be paid during ethnomedicine surveys to ensure all specific details on the collection process are not missed from the informants. 4.2. Selection of species for further studies 4.6. Toxicity and safety studies Despite the fact that the majority of plants used in ethnomedicine are considered to be safe, there is still great need to formally evaluate the safety of medicinal plants. This is especially important if the method of preparation differs from the folk method such as using organic versus aqueous solvents. Since Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 31 Table 8 Bioactive compounds that have so far been isolated from the Vernonia genus. Compounds Vernonia species Bioactivity Reference Infectious disease Lutein (5) Urticifolene (6) Vernonione (12) 2-hydroxy-3-methoxy-5-(2-propenyl)-phenol (13) Vanillic acid (14) Methyl gallate (15) isoferulic acid (16) caffeic acid (17) Uridine (18) 30 -methylquercetin (19) Quercetin (20) 20 -epicycloisobrachycoumarinone epoxide (21) urticifolia urticifolia cinerascens cinerascens cinerascens cinerascens cinerascens cinerascens cinerascens cinerascens cinerascens brachycalyx cycloisobrachycoumarinone epoxide (22) brachycalyx a-amyrin (23) b-amyrin (24) auriculifera auriculifera brassiliana Antibacterial IC50  18–256 mg/ml Antibacterial IC50  18–256 mg/ml Urease inhibitor: IC50–227.6 mM Antioxidant IC50 ¼85.05 mg/ml; Antiurease IC50 Z 236 mg/ml Antioxidant IC50 ¼210.8 mg/ml; Antiurease IC50 4 236 mg/ml Antioxidant IC50 ¼108.4 mg/ml; Antiurease IC50 4 236 mg/ml Antioxidant IC50 ¼298.2 mg/ml; Antiurease IC50 r59 mg/ml Antioxidant IC50 ¼600 mg/ml; Antiurease IC50 r 59 mg/ml Antioxidant IC50 ¼439.2 mg/ml; Antiurease IC50 4118 mg/ml Antioxidant IC50 ¼186.5 mg/ml; Antiurease IC50 4236 mg/ml Antioxidant IC50 ¼51.45 mg/ml; Antiurease IC50 4236 mg/ml Antiplasmodial activity: IC50–0.11 mM Antileishmania activity: IC50–37.1 mM Antiplasmodial activity: IC50–0.11 mM Antileishmania activity: IC50–39.2 mM Antibacterial; MIC: 0.12–1.0 mg/ml Antibacterial; MIC: 0.12–1.0 mg/ml Plasmodium falciparum IC50 425 mg/ml b-amyrin acetate (25) Oleanolic acid (26) Lupenyl acetate (27) Lupeol (28) auriculifera auriculifera auriculifera brasiliana Antibacterial; MIC: 0.5–1 mg/ml Antibacterial; MIC: 0.12–1.0 mg/ml Antibacterial; MIC: 0.12–1.0 mg/ml Antiplasmodial IC45 ¼ 25 mg/ml Friedelanone (29) Friedelin acetate (30) Vernoguinosterol (31) Vernoguinoside (32) Vernoguinoside A (33) Vernonioside A3 (34) Vernodalol (37) brasiliana brasiliana guineensis guineensis guineensis amygdalina amygdalina Antibacterial; MIC: 0.25–1.0 mg/ml Antibacterial; MIC: 0.5–1.0 mg/ml Antitrypanosomiasis; IC50:3–5 mg/ml Antitrypanosomiasis; IC50: 3–5 mg/ml Antifungal: MIC/MFC¼ 7.85 mg/ml Antischistosomal 200 ppm Antibacterial MIC ¼0.25–0.5 mg/ml Antifungal LC50 ¼0.5 mg/ml Kiplimo et al. (2011b) Kiplimo et al. (2011b) Ahmad et al. (2012) Ahmad et al. (2011) Ahmad et al. (2011) Ahmad et al. (2011) Ahmad et al. (2011) Ahmad et al. (2011) Ahmad et al. (2011) Ahmad et al. (2011) Ahmad et al. (2011) Oketch-Rabah et al. (1997) Oketch-Rabah et al. (1997) Kiplimo et al. (2011a) Kiplimo et al. (2011a) Ameida Alves et al. (1997) Kiplimo et al. (2011a) Kiplimo et al. (2011a) Kiplimo et al. (2011a) Ameida Alves et al. (1997) Kiplimo et al. (2011a) Kiplimo et al. (2011a) Tchinda et al. (2002) Tchinda et al. (2002) Donfack et al. (2012) Jisaka et al. (1992) Erasto et al. (2006), Koshimizu et al. (1994) Jisaka et al. (1992) Kraft et al. (2003) Kraft et al. (2003) Lopes (1991) Buskuhl et al. (2010) Pillay et al. (2007) 11b,13-dihydrovernodalin (38) Glaucolide B (43) Hirsutinolide (48) 8a-(2-methylacryloyloxy)-3-oxo-1-desoxy-1,2dehydrohirsutinolide-13-O-acetate (49) 8a-(50-acetoxysenecioyloxy)-3-oxo-1-desoxy-1,2dehydrohirsutinolide-13-O-acetate (50) Vernolepin (55) Vernodalin (56) amygdalina colorata eremophila scorpioides staehelinoides Antischistosomal 200 ppm Antiplasmodial; IC50  4.0–4.8 mg Antiplasmodial; IC50  1.1–2.3 mg Antibacterial Antiplasmodial IC50 ¼0.2 mg/ml Antiplasmodial IC50 ¼0.26 mg/m staehelinoides Antiplasmodial IC50 ¼0.26 mg/ml Pillay et al. (2007) amygdalina amygdalina Jisaka et al. (1993) Jisaka et al. (1993) Koshimizu et al. (1994) Jisaka et al. (1992) Rabe et al. (2002) Chukwujekwu et al. (2009) Jisaka et al. (1993) Koshimizu et al. (1994) Erasto et al. (2006) Antibacterial Antibaceterial MIC ¼ 0.1–8.0 mg/ml Antileishmania colorata Antischistosomal 200 ppm Antibacterial: MIC 0.1–0.25 mg/ml Antiplasmodial IC50 ¼0.52 mg/ml Vernomenin (58) 4,15-dihydrovernodalin (60) amygdalina amygdalina Antibacterial Antibacterial Vernolide (62) amygdalina Antibacterial MIC ¼ 0.25–0.5 mg/ml Antifungal LC50 ¼0.2–0.4 mg/ml Antileishmania Vernolide D (65) Hydroxyvernolide (67) Zaluzanin D (68) 13-acetoxy-14hydroxy-8S*methacryloyloxy 1S*( 1OS*),4R*,5R*-diepoxygermacr-7( 11 )-.ene-6S*, 1 2-olide (87) 13-acetoxy-14-hydroxy-8S*isobutyroyloxy-1 S*( IOS* ), 4R*,5R* diepoxygermacr-7( 11)-ene6S*,12olide (88) colorata Antischistosomal 200 ppm Antiplasmodial IC50 ¼1.87 mg/ml cineria colorata amygdalina Antiplasmodial IC50 ¼3.5 mM Antibacterial: MIC ¼0.1–0.5 mg/ml Antileishmania arborea fastigiata Antischistosomal 200 ppm Antifungal Antibacterial (B. subtilis): MIC ¼5 mg/ml Koshimizu et al. (1994) Jisaka et al. (1992) Chukwujekwu et al. (2009) Chea et al. (2006) Rabe et al. (2002) Koshimizu et al. (1994) Jisaka et al. (1992) Kumari et al. (2003) Roos et al. (1998) fastigiata Antibacterial (B. subtilis): MIC ¼5 mg/ml Roos et al. (1998) fastigiata Antibacterial (B. subtilis): MIC ¼10 mg/ml Roos et al. (1998) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] Table 8 (continued ) Compounds 13-acetoxy-14-hydroxy-8S*-angeloyloxy-1S*( 10S*),4R*,5R*diep oxygermacr-7(11 )-ene-6St,12olid (89) l3,l4diacetoxy8S*methacryloyloxy1 S*( 10S*), 4R*,5R*diepoxygermacr7( 11 )-ene-6S*,1 2-olide (90) 13-acetoxy-14-hydroxy-8S*methacryloy1oxy 1 S*( 10S), 2R*,3S*, 4R*,5R*triepoxyger-macr7(11) ene-6S*, 12olide (91) Eremantholide B (92) 16,17-dihydrobrachycalyxolide (93) Vernonia species Bioactivity Reference fastigiata Antibacterial (B. subtilis): MIC ¼5 mg/ml Roos et al. (1998) fastigiata Antibacterial (B. subtilis): MIC ¼5 mg/ml Roos et al. (1998) Antibacterial Antiplasmodial activity: IC50 ¼ 5.9–32 mM Antileishmania activity: IC50 ¼34 mM Antibacterial: MIC 44 mg/ml Lopes (1991) Oketch-Rabah et al. (1998) Rabe et al. (2002) Igile et al. (1994) Koul et al. (2003) triflosculosa Antioxidant Cytotoxicity IC50: HT-29 ¼6.5 mM; T47-D¼ 43.5 mM; HCT15¼ 109.79 mM; SiHa 497.4 mM NK-kB (IC50-0.5 mg/ml) TNF-a (1C50-4.55 mg/ml) Kos et al. (2006) brachycalyx 11b,13-dihydroxyvernolide (98) colorata Cytotoxic/antitumor and immune modulatory effects Luteolin (1) Lasiopulide (39) amygdalina lasiopus 8a-(4-hydroxymethacryloyloxy)-10a-hydroxy-13methoxy-hirsutinolide (40) 8a-methacryloyloxy-10a-hydroxy-13methoxyhirsutinolide (41) Glaucolide (42) Glaucolide B (43) ‘‘ NK-kB (IC50-0.5 mg/ml) TNF-a (1C50-1.62 mg/ml) scorpioides eremophila Glaucolide K (44) Glaucolide L (45) Glaucolide M (46) Hirsutolide (47) Hirsutinolide (48) piptocarphin A (53) pachyclada pachyclada pachyclada bockiana scorpioides bockiana piptocarphin F (54) bockiana Vernolepin (55) amygdalina Cytotoxic activity Hela cell-IC50 ¼2.1 mM Clastogenic action 4 mg/ml in vitro Cytotoxicity IC50 48 mg/ml Clastogenic action in vivo 4640 mg/kg Cytotoxic activity Human ovarian cancer (A2780) IC50 ¼ 5.8 mM Human ovarian cancer (A2780) IC50 ¼ 24.5 mM Human ovarian cancer (A2780) IC50 ¼ 3.3 mM Anti tumor P388: IC50 0.73 mg/ml Cytotoxic activity Hela Cell line IC50 ¼3.3 mM P-388 tumor: 4.6 mg/kg; IC50: 0.77 mM HL-60: IC50 ¼ 3.87 mM P-388 tumor: IC50 1.32 mM HL-60: IC50 ¼ 5.69 mM Antiplatelet: Active at 10 mg/ml hymenolepis Vernodalin (56) amygdalina Vernomenin (58) Vernodalinol (57) amygdalina amygdalina hymenolepis Epivernodalol (59) amygdalina lasiopus 4, 15-dihydrovernodalin (60) amygdalina Vernolide (62) amygdalina Vernolide A (63) cineria Vernolide B (64) 8a-tigloyloxyhirsutinolide-13-O-acetate (83) Vernomygdin (66) Hydroxyvernolide (67) Vernobockolide B (69) Vernchinilide A (70) Vernchinilide B (71) Vernchinilide E (72) cineria cineria amygdalina amygdalina bockiana chinensis chinensis chinensis Kos et al. (2006) Buskuhl et al. (2010) Burim et al. (1999) Burim et al. (1999) Burim et al. (1999) Williams et al. (2005) Williams et al. (2005) Williams et al. (2005) Huo et al. (2008) Buskuhl et al. (2010) Huo et al. (2008) Liao et al. (2012) Huo et al. (2008) Liao et al. (2012) Laekeman et al. (1985) Cytotoxicity: IC50 ¼ 0.12 mg/ml Jisaka et al. (1993) Antitumor against Walker intramuscular carcinosarcoma 256 in rat Kupchan et al. (1968) ED50 12.5 mg/kg Cytotoxicity: IC50 ¼ 0.11 mg/ml Jisaka et al. (1993), Kupchan et al. (1969a) Cytotoxicity: IC50 ¼ 0.17 mg/ml Jisaka et al., 1993 Cytotoxicity: IC50 ¼ 70–75 mg/ml Luo et al. (2011a, 2011b) Cytotoxicity: IC50 ¼ 20 mg/ml Kupchan et al. (1969b) Antioxidant and chemopreventive: cytotoxicity GI50 ¼ 1.76 mg/ml Farombi and Owoeye (2011) Cytotoxicity IC50: HT-29 ¼21.9 mM; T47-D ¼22.5 mM; Koul et al. (2003) HCT¼ 39.3 mM; SiHa ¼43.4 mM Cytotoxicity: IC50 ¼ 0.07 mg/ml Jisaka et al. (1993); Koshimizu et al. (1994) Cytotoxicity: IC50 ¼ 0.11 mg/ml Jisaka et al. (1993), Sayed et al. (1982) Cytotoxic activity ED50 (lg/mL) KB¼ 0.02 DLD-1 ¼0.05 NCIKuo et al. (2003) 661 ¼0.53 Hela ¼0.04 Apoptosis 0.1 mg/ml Pratheeshkumar and Kuttan (2011b) Immune response 500 mg/kg Pratheeshkumar and Kuttan (2011c ,2012a) Antiangiogenesis In vitro IC50 ¼0.1 mg/ml; in vivo ¼ 500 mg/kg Pratheeshkumar and Kuttan (2011d) Antimetastatic effect ¼500 mg/kg Pratheeshkumar and Kuttan (2012b) Cytotoxic activity Ed50 (mg/mL) KB ¼3.78 NCI-661 ¼ 5.88 Hela ¼6.42 Kuo et al. (2003) Cytotoxicity IC50: HT29-3.50 mM; HepG2-4.27 mM Khay et al. (2012) IC50-1.5 mg/ml Kupchan et al. (1969) Cytotoxicity: IC50 ¼ 0.19 mg/ml Jisaka et al. (1993) Cytotoxicity; P388 (IC50: 1.81 mM) Huo et al. (2008) Cytotoxicity; P388 (IC50: 4 mM) Chen et al. (2005) Cytotoxicity; P388 and A-549 (IC50: 0.51 and 2.7 mM) Chen et al. (2005) Cytotoxicity; P388 and A-549 (IC50: 0.23 and 3.1 mM) Chen et al. (2005) Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 33 Table 8 (continued ) Compounds Vernonia species Bioactivity Reference 8b-(2-methylacryloyloxy)-hirsutinolide-13-O-acetate (73) 8b-(2-hydroxymethyl-acryloyloxy)hirsutinolide 13-Oacetate (74) 8a-tigloyloxyhirsutinolide 13-O-acetate (75) 8a-(4-hydroxymethacryloyloxy)-10a-hydroxy-13methoxyhirsutinolide (76) 8a-methacryloyloxy-10a-hydroxy-13-Omethylhirsutinolide (77) 8a-[4-hydroxymethacryloyloxy]-10ahydroxyhisutinolide-13-O-acetate (78) 8a-acetoxy-10a-hydroxy-13-O-methylhirsutinolide (79) Vernodalidimer A (94) Vernodalidimer B (95) 1,2,20 ,30 -tetrahydrovernodalin (99) 1,2,11,13,20 ,30 -hexahydrovernodalin (100) Vernopicrin (101) chinensis Cytotoxicity P388 and A-549 (IC50: 0.36 and 2.0 mM) Chen et al. (2005) chinensis Cytotoxicity P388 and A-549 (IC50: 4.0 and 6.0 mM) Chen et al. (2005) chinensis chinensis Cytotoxicity; A-549 (IC50: 7.8 mM) HL-60: IC50 ¼ 12.5 mM Chen et al. (2005) Chen et al. (2005) chinensis HL-60: IC50 ¼ 5.69 mM Chen et al. (2005) chinensis HL-60: IC50 ¼ 5.69 mM Chen et al. (2005) chinensis anthelmintica anthelmintica amygdalina amygdalina guineensis Chen et al. (2005) Liu et al. (2010) Liu et al. (2010) Jisaka et al. (1993) Jisaka et al. (1993) Toyang et al. (2013a) Vernomelitensin (102) guineensi 2,3,4,30 ,40 -O-pentaisovalerylsucrose (103) guineensi HL-60: IC50 ¼ 5.96 mM Cytotoxicity: HL-60- IC50 ¼ 0.72 mM Cytotoxicity: HL-60- IC50 ¼ 0.47 mM Cytotoxicity: IC50 ¼ 0.14 mg/ml Cytotoxicity: IC50 ¼ 0.52 mg/ml Cytotoxicity (MDA-MD-231; MCF-7; HCT—116; HL-60; A549; A375; OVCAR3; Mia-Paca; DU-145; PC-3  1.00) IC50 ¼ 0.35 mM  2.04 mM Cytotoxicity (MDA-MD-231; MCF-7; HCT—116; HL-60; A549; A375; OVCAR3; Mia-Paca; DU-145; PC-3  1.00) IC50 ¼ 0.14 mM  1.56 mM Cytotoxicity: PC-3, DU145, AT3B-1 (IC50: 5.7 mg/ml, 4.27 mg/ml, 5.76 mg/ml) Musculoskeletal and joint disease Luteolin (1) cinerea Antiinflammatory 97 2 mM Methyl caffeate (2) cinerea 257 2 mM Luteolin 7-O-glucoside (3) cinerea 107 2 mM Luteolin 40 -O-glucoside (4) cinerea 567 22 mM 3,5-dicaffeoylquinic acid (7) cinerea 137 2 mM Chlorogenic acid (8) cinerea 137 1 mM 4,5-dicaffeoylquinic acid (9) cinerea 177 3 mM Gallic acid (10) cinerea 307 2 mM 3,4-dicaffeoylquinic acid (11) cinerea 177 3 mM Vernonioside B2 (36) 8a-(4-hydroxymethacryloyloxy)-10a-hydroxy-13methoxy-hirsutinolide (51) 8a-methacryloyloxy-10a-hydroxy-13methoxyhirsutinolide (52) vernolide-A (63) Vernolide-B (64) 8a-tigloyloxyhirsutinolide (80) 8a-hydroxyhirsutinolide (81) 8a-hydroxyl-1-O-methylhirsutinolide (82) 8a-tigloyloxyhirsutinolide-13-O-acetate (83) 8a-(2-methylacryloyloxy)-hirsutinolide-13-O-acetate (84) 8a-(2-methylacryloyloxy)-1a-methoxyhirsutinolide-13O-acetate (85) hirsutinolide-13-oacetate (86) Vernocuminoside B (96) condensata triflosculosa analgesic and antiinflammatory:50 mg/kg Antiinflammatory effect (TNF-a and IL-8); NF-B 4.55 mM Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Abeysekera et al. (1999) Valverde et al. (2001) Kos et al. (2006) triflosculosa Antiinflammatory effect (TNF-a and IL-8); NF-B 1.62 mM Kos et al. (2006) triflosculosa triflosculosa cineria cineria cineria cineria cineria IC50:NO(2.4 mM); NF-kB(1.6 mM) IC50:NO(1.2 mM); NF-kB(12.8 mM) IC50:NO(5.7 mM); NF-kB(3.1 mM) IC50:NO(24.7 mM); NF-kB(1.9 mM) IC50:NO(28.1 mM); NF-kB(  mM) IC50:NO(20 mM); NF-kB(0.6 mM) IC50:NO(6.6 mM); NF-kB(5.2 mM) Youn Youn Youn Youn Youn Youn Youn cineria IC50:NO(1.5 mM); NF-kB(13.6 mM) Youn et al. (2012) cineria cumingiana IC50:NO(2.7 mM); NF-kB(10.2 mM) Youn et al. (2012) Antiinflammatory effect (inhibition of the platelet-activating factor) Liu et al. (2009) 50 mM Endo and exo parasites Vernonioside B1 (35) amygdalina Anthelmintic Glaucolide B (43) Vernodalin (56) 11,13-dihydrovernodalin (61) Scorpioidine (97) eremophila amygdalina amygdalina scorpioides Molluscide (adult Biomphalaria glabra): 100 ppm¼ 90% kill Insecticide Insecticide Anthelmintic, larvicidal chronic toxicity studies are more expensive to run, it is recommended that at least acute toxicity studies using appropriate invivo models be carried out once the medicinal properties of plants have been confirmed in vitro. Toyang et al. (2013a) Toyang et al. (2012a) et et et et et et et al. al. al. al. al. al. al. (2012) (2012) (2012) (2012) (2012) (2012) (2012) Huffman et al. (1993), Koshimizu et al. (1994) Alarcon et al. (1990) Ganjian et al. (1983) Ganjian et al. (1983) Drew et al. (1980) 4.7. Phytochemical, metabolomic analysis and quality issues By comparison, more phytochemical studies have been carried out on various species of the Vernonia genus than biological Please cite this article as: Toyang, N.J., Verpoorte, R.. review of the medicinal potentials of plants of the genus Vernonia (Asteraceae). Journal of Ethnopharmacology (2013), http://dx.doi.org/10.1016/j.jep.2013.01.040i 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 34 N.J. Toyang, R. Verpoorte / Journal of Ethnopharmacology ] (]]]]) ]]]–]]] 1 activity studies. Despite this, most of the species of Vernonia 2 that have been identified to be medicinal are yet to be phyto3 chemically analysed. For example, out of the 105 plants identified 4 to be used in folk medicine (Tables 3–5), only 23 plants have been 5 phytochemically studied and some of their bioactive metabolites 6 identified (Table 8). In phytochemical and metabolomic studies, 7 specific active or marker compounds can be identified and can be 8 useful for drug discovery as well as quality control of medicinal 9 plant products and differentiation of closely related species. 10 Phytochemical and metabolomic analysis are as such recom11 mended as one of the priority areas for future research in the 12 Vernonia genus. This effort would however require standardized 13 methods including extraction preparation due to differences in 14 origin of the species and other environmental factors. 15 In conclusion, this review reveals that the genus Vernonia is 16 endowed with many medicinal plants some of which have 17 potential for the discovery of new drugs. On the basis of results 18 from a combination of in vitro and in vivo efficacy and toxicity 19 studies reported, Vernonia amygdalina holds the most promise for 20 development into a nutraceutical against diabetes and malaria 21 while Vernonia cinerea has potential againt cancer and inflamma22 tory conditions. Vernolide A (63) is so far the most promising 23 single agent that could be developed into an anticancer agent out 24 of the 103 identified bioactive compounds from Vernonia species. 25 The other Vernonia species and isolated compounds require 26 further studies to validate or ascertain their medicinal potentials. 27 28 29 Q2 Uncited references 30 31 Adenuga et al. (2010), Anastasia (2011), Anibijuwon et al. 32 (2012), Asaolu et al. (2010), Ayare (2005), Ba et al. (2008), Barbosa 33 et al. (2004), Bardón et al. (1988), Batista et al. (2009), Cartagena 34 et al. (2008), Deng et al. (2002), Fennell et al. (2004), Freire et al. 35 (2002), Gokilaveni et al. (2006), Graham et al. 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