Marmara Pharmaceutical Journal 20: 390-400, 2016
DOI: 10.12991/mpj.20162024853
REVIEW
Review on Phytochemistry and Pharmacology of the Genus Licaria
(Lauraceae)
Wan Mohd Nuzul Hakimi Wan SALLEH, Farediah AHMAD
ABSTRACT
he genus Licaria (Lauraceae) is a lowering plant genus,
comprises 40 species and endemic to Central and South
America. Most of the species have been used as traditional
medicine. Phytochemicals isolated from Licaria species are
lignans, neolignans, alkaloids, lactones, triterpenes, and
arylpropanoids. he purpose of this review is to examine in
detail from a phytochemical and pharmacological point of view
what is reported in the past and current literature obtained from
plants belonging to the Licaria genus.
Keywords: Licaria, Lauraceae, Phytochemistry, Pharmacology,
Neolignans
INTRODUCTION
Wan Mohd Nuzul Hakimi Wan Salleh, Farediah Ahmad
Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia
(UTM), 81310 Johor Bahru, Johor, Malaysia
Corresponding author
Farediah Ahmad
E-mail: farediah@kimia.fs.utm.my
Tel: +6075534137; Fax: +6075566162
Submitted / Gönderilme: 17.06.2016
Accepted / Kabul: 02.08.2016
390
Revised / Düzeltme: 28.07.2016
he genus Licaria (Lauraceae) is a Neotropical genus
consisting of 40 species distributed from southern Florida,
Mexico to the south of Brazil and Bolivia. In Brazil, the
occurrence of 20 species and two subspecies, mostly in the
Amazon region. hese trees have a resilient wood, useful
as timber for construction and as firewood (1). he genus
evergreen monoecious, hermaphrodite, trees or rarely
bushes. It is characterized by the combination of lowers with
three 2-locellate stamens, a well-developed cupule, oten
with a double margin and alternate and opposite leaves. he
fruit is a bay with tepals deciduous and an underlying dome
double border (2). Most of Licaria species have ben used
in the ethnomedical folk traditions of indigenous Central
and South America for various ailments such as indigestion
(3), diarrhea (4), stomachache (5), and as stimulant (3). To
date, comparative phytochemical data are available for only
eleven Licaria species. Several bioactive substances including
lignans, neolignans, alkaloids, lactones, triterpenes,
essential oils, arylpropanoids, and other components, have
been isolated from diferent species of Licaria. Literature
reviews show that several of them have been reported with
Marmara Pharm J 20: 390-400, 2016
interesting pharmacological activities such as cytotoxicity
(6), antibacterial (7), antimalarial (8), anti-leishmanial (4),
antioxidant, and antiplatelet inhibitory activities (9). he
aim of this review is to examine from phytochemical and
pharmacological perspectives the diferent Licaria species for
which the extraction, isolation, structural characterization
and description of the biological activity of individual
compounds are reported in the literature. In addition, the
chemical compositions of the essential oils of Licaria species
are also reported. A substructure search performed using
the SciFinder Scholar database and searches by keywords
in PubMed, Medline, and Scopus, indicated that to date 14
species have been cited in this perspective. he discussion
on phytochemistry, pharmacology and essential oils
compositions of each plant is provided.
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
PHYTOCHEMISTRY AND PHARMACOLOGY
A review on the literatures revealed that few phytochemial
studies have been carried out on Licaria species prior to
the current study. Phytochemical investigations have been
conducted on eleven species species of Licaria which are L.
aritu Ducke, L. armeniaca (Nees) Kosterm., L. aurea (Huber)
Kosterm. L. brasiliensis (Nees) Kosterm., L. canella (Meisn.)
Kosterm., L. chrysophylla (Meisn.) Kosterm., L. macrophylla
(A.C. Smith) Kosterm., L. mahuba (A. Samp.) Kosterm., L.
puchury-major (Mart.) Kosterm., L. rigida Kosterm., and
L. triandra (Sw.) Kosterm. he studies have reported the
presence of several classes of natural products including
lignans, neolignans, alkaloids, lactones, triterpenes, and
arylpropanoids. he phytochemical studies of Licaria species
are listed in Table 1 and the chemical structures are shown
in Figure 1.
Table 1. Chemical constituents isolated from the genus Licaria
Compounds
Species
Part
L. aritu
L. puchury-major
L. aritu
L. armeniaca
Wood
Seeds
Wood
Trunk wood
L. armeniaca
Trunk wood
L. armeniaca
L. armeniaca
L. puchury-major
L. armeniaca
Trunk wood
Trunk wood
Seeds
Trunk wood
L. armeniaca
L. armeniaca
Trunk wood
Trunk wood
L. armeniaca
Fruits
L. armeniaca
Fruits
L. armeniaca
Fruits
L. aurea
L. aurea
L. aurea
L. aurea
L. aurea
L. chrysophylla
Fruits
Fruits
Fruits
Fruits
Fruits
Bark/fruits
calyx
Bark/fruits
calyx
Neolignans
Licarin A 1
Licarin B 2
(2S,3S,3aR,5R)-3α-Allyl-5-methoxy-2-(3ʹ,4ʹ-methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxo-benzofuran 3
(2S,3S,3aR,5R)-3α-Allyl-5,7-dimethoxy-2-(3ʹ,4ʹ-methylenedioxy-phenyl)-3-methyl2,3,3a,4,5,6-hexahydro-6-oxo-benzofuran 4
Armenin A 7
Armenin B 8
(7S,8R, l’S,2’S, 3ʹS)-2’-Acetoxy-l’-allyl-3’,5’-dimethoxy-8-methyl-7-piperonyl-bicyclo [3.2.1]oct-5’- en-4’-one 9
3a-allyl-5-methoxy-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxobenzofuran 12
Dimethoxy-2-(3,4-methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxobenzofuran
13
(1S,5R,6S,7R,8R)-8-acetoxy-1-allyl-3,5-dimethoxy-7-methyl-6-(3ʹ-methoxy-4ʹ,5ʹ-methylenedioxyphenyl)-4-oxobicyclo[3.2.1]oct-2-ene 17
(1S,5R,6S,7R)-1-Allyl-3-methoxy-7-methyl-6-(3ʹ-methoxy-4ʹ,5ʹ-methylenedioxyphenyl)-4,8-dioxobicyclo[3.2.1]oct-2-ene 18
(1S,5R,6S,7R)-1-Allyl-3-methoxy-7-methyl-6-(3ʹ,4ʹ,5ʹ-trimethoxyphenyl)-4,8-dioxobicyclo[3.2.1]oct-2-ene 19
Grandisin 20
de-O-Methylgrandisin 21
dide-O-Methylgrandisin 22
Virolongin A 23
Virolongin B 24
Eusiderin A 27
391
L. chrysophylla
392
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
Marmara Pharm J 20: 390-400, 2016
L. brasiliensis
Trunk wood
L. brasiliensis
Trunk wood
L. brasiliensis
Trunk wood
L. brasiliensis
Trunk wood
L. brasiliensis
Trunk wood
L. brasiliensis
Trunk wood
Chrysophyllin A 40
L. canella
L. rigida
L. canella
L. canella
L. rigida
L. chrysophylla
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Chrysophyllin B 41
L. chrysophylla
Trunk wood
Chrysophyllon I-A 42
L. chrysophylla
Trunk wood
Chrysophyllon I-B 43
L. chrysophylla
Trunk wood
L. chrysophylla
Bark
Eusiderin I 51
L. chrysophylla
L. chrysophylla
L. chrysophylla
L. chrysophylla
L. chrysophylla
L. chrysophylla
L. chrysophylla
L. chrysophylla
Eusiderin J 52
L. chrysophylla
Eusiderin K 53
L. chrysophylla
Eusiderin L 54
L. chrysophylla
Eusiderin M 55
L. chrysophylla
Virolongin E 56
L. chrysophylla
Virolongin F 57
L. chrysophylla
Virolongin G 58
L. chrysophylla
Trunk wood
Bark
Trunk wood
Bark
Trunk wood
Trunk wood
Bark
Bark/fruits
calyx
Bark/fruits
calyx
Bark/fruits
calyx
Bark/fruits
calyx
Bark/fruits
calyx
Bark/fruits
calyx
Bark/fruits
calyx
Bark/fruits
calyx
Chrysophyllon IV-B 59
Chrysophyllon V1-B 60
Macrophyllin 61
Aurein 67
L. chrysophylla
L. chrysophylla
L. macrophylla
Licaria sp.
Bark
Bark
Trunk wood
Wood
Eusiderin 68
Licaria sp.
Wood
L. rigida
Trunk wood
rel-(7S,8R,1ʹS,4ʹS,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 29
rel-(7S,8R,1ʹS,4ʹR,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 30
rel-(7S,8R,1ʹS,5ʹS,6ʹS)-6-Acetoxy-3ʹ-hydroxy-3,5ʹ-dimethoxy-4,5-methylenedioxy-4ʹ-oxo-Δ1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 31
rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6-Acetoxy-3,4,5,3ʹ,5ʹ-pentamethoxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 32
rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6ʹ-Hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 33
rel-(7S,8R,1ʹS,4ʹR,5ʹS,6ʹS)-6ʹ-Acetoxy-4ʹ-hydroxy-3,3ʹ,5ʹ-trimethoxy-4,5-methylenedioxy-Δ1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 34
Canellin A 35
Canellin B 36
Canellin C 37
Chrysophyllon II-A 44
Chrysophyllon II-B 45
Chrysophyllon III-A 46
Chrysophyllon III-B 47
Marmara Pharm J 20: 390-400, 2016
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
(7S,8S)-∆8ʹ-2ʹ,6ʹ-Dimethoxy-3,4,-methylenedioxy-7.O.3ʹ,8.4ʹ,1ʹ.O.7ʹ-neolignan 75
Ferrearin B 76
Ferrearin C 77
rel-(7S,8S,1ʹR,2ʹS)-2ʹ-Hydroxy-3,4-dimethoxy-3ʹ-oxo-∆4ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan 78
Ferrearin G 79
Oxaguianin 80
rel-(7S,8S,1ʹR,5ʹR)-5ʹ-Methoxy-3,4-methylenedioxy-4ʹ-oxo-∆2ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan 81
3ʹ-Methoxyburchellin 82
Eusiderin B 93
Triandrin A 94
Triandrin B 95
Burchellin 96
Lignans
Magnolin 11
Alkaloids
tri-O-Methylmoschatoline 10
Bracteoline 14
O-Methylbracteoline 15
α-Dehydroreticuline 16
Reticuline 83
Orientaline 84
Coclaurine 85
N-methylcoclaurine 86
Norjuziphine 87
Norisoboldine 88
Isoboldine 89
Glaziovine 90
Reticuline N-oxide [91 N-Me (S)]
Reticuline N-oxide [92 N-Me (R)]
Lactones
(-)-Dihydromahubanolide B 65
(-)-iso-Dihydromahubanolide B 66
Miscellaneous compounds
Sitosterol 5
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. rigida
L. triandra
L. triandra
L. triandra
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
Trunk wood
Seeds
Seeds
Seeds
L. armeniaca
Trunk wood
L. armeniaca
L. armeniaca
L. armeniaca
L. armeniaca
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
Seeds
L. mahuba
L. mahuba
Trunk wood
Trunk wood
Dillapiole 38
Elemicin 39
2,3,4,5-Tetramethoxyallylbenzene 48
2,3,4,5-Tetramethoxycinnamyl alcohol 49
2,3,4,5-Tetramethoxycinnamaldehyde 50
Borneol 62
Elemol 63
L. armeniaca
L. armeniaca
L. canella
L. macrophylla
L. puchury-major
L. armeniaca
L. armeniaca
L. canella
L. canella
L. chrysophylla
L. chrysophylla
L. chrysophylla
L. macrophylla
L. macrophylla
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Nerolidol 64
L. macrophylla
Trunk wood
Eugenol 69
Safrole 70
Syringic aldehyde 71
3,4-Methylenedioxycinnamaldehyde 72
3,4-Methylenedioxycinnamyl alcohol 73
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
L. puchury-major
Trunk wood
Trunk wood
Trunk wood
Trunk wood
Trunk wood
6,7-Dimethoxycoumarin 6
393
394
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
L. aritu Ducke
L. aritu is an arboreous Lauraceae species which occurs
along the Manaus-Itacoatiara road, Amazonas State. he
only literature report refers to the isolation from the benzene
extract of the wood have characterize licarin A 1 and B 2 (10).
L. armeniaca (Nees) Kosterm.
L. armeniaca is a tree up to 7 m, widely distributed in the
Amazonian rainforest, Brazil. Four studies have been
reported from this species. he first report was published
in 1978 by Aiba and co-workers (11). hese authors isolated
two novel benzofuranoid neolignans, namely (2S,3S,3aR,5R)3α-allyl-5-methoxy-2-(3ʹ,4ʹ-methylenedioxyphenyl)3-methyl-2,3,3a,4,5,6-hexahydro-6-oxo-benzofuran
3
and
(2S,3S,3aR,5R)-3α-allyl-5,7-dimethoxy-2(3ʹ,4ʹ-methylenedioxy-phenyl)-3-methyl-2,3,3a,4,5,6hexahydro-6-oxo-benzofuran 4, together with sitosterol
5,6,7-dimethoxycoumarin 6, armenin A 7, and armenin
B 8 from the benzene extract of trunk wood. Purification
of the benzene/ethanol extract of the trunk wood by
Alegrio et al. (12) have reported to have a novel neolignan
(7S,8R, l’S,2’S, 3ʹS)-2’-acetoxy-l’-allyl-3’,5’-dimethoxy-8methyl-7-piperonyl-bicyclo [3.2.1]-oct-5’-en-4’-one 9,
including sitosterol 5,6,7-dimethoxycoumarin 6, tri-Omethylmoschatoline 10 and magnolin 11. In addition,
Abdel-Hafiz and co-workers (13) have successfully isolated
two neolignans, 3a-allyl-5-methoxy-3-methyl-2,3,3a,4,5,6hexahydro-6-oxobenzofuran 12 and dimethoxy-2-(3,4methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro6-oxobenzofuran 13, including three alkaloids, bracteoline
14, O-methylbracteoline 15 and α-dehydroreticuline 16.
Barbosa-Filho and co-workers (14) have studied on the
fruits part. he isolation on ethanol/water extract have
found three novel neolignans (1S,5R,6S,7R,8R)-8-acetoxy1-allyl-3,5-dimethoxy-7-methyl-6-(3ʹ-methoxy-4ʹ,5ʹmethylenedioxyphenyl)-4-oxobicyclo[3.2.1]oct-2-ene 17,
(1S,5R,6S,7R)-1-allyl-3-methoxy-7-methyl-6-(3ʹ-methoxy4ʹ,5ʹ-methylenedioxyphenyl)-4,8-dioxobicyclo[3.2.1]oct2-ene 18, and (1S,5R,6S,7R)-1-allyl-3-methoxy-7-methyl6-(3ʹ,4ʹ,5ʹ-trimethoxyphenyl)-4,8-dioxobicyclo[3.2.1]
oct-2-ene 19.
L. aurea (Huber) Kosterm.
L. aurea is a tree widely distributed in the Amazonian
rainforest, Brazil. he ethanolic fruit extract of L. aurea
have found to contain the diaryltetrahydrofuran type
neolignans, grandisin 20, de-O-methylgrandisin 21 and
Marmara Pharm J 20: 390-400, 2016
dide-O-methylgrandisin 22, as well as virolongin A 23 and
virolongin B 24, as reported by Barbosa-Filho and co-workers
(15). Bezerra and co-workers (16) also successfully isolated
grandisin 20 from this species. hree years later, Marques et
al. (17) were studied on wood part and successfully identified
as aurein A-B 25-26, eusiderin A 27, virolongin B 24 and
virolongin C 28.
L. brasiliensis (Nees) Kosterm.
L. brasiliensis is a tree popularly known as ‘louro capitiu’,
grows wild in the Forest Reserve of Jari, Municipality of
Almerim, Brazil (18). Phytochemical studies on the hexane
extract of the trunk wood of this species have led to the
isolation of six new bicycle[3.2.1]octanoid neolignans,
identified as rel-(7S,8R,1ʹS,4ʹS,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹpentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan
29,
rel-(7S,8R,1ʹS,4ʹR,5ʹR)-4ʹ-Hydroxy-3,4,5,3ʹ,5ʹpentamethoxy-6ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan
30,
rel-(7S,8R,1ʹS,5ʹS,6ʹS)-6-acetoxy-3ʹ-hydroxy-3,5ʹdimethoxy-4,5-methylenedioxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ8.1ʹ,7.5ʹ-neolignan31,rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6-acetoxy-3,4,5,3ʹ,5ʹpentamethoxy-4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan 32,
rel-(7R,8S,1ʹS,5ʹS,6ʹS)-6ʹ-hydroxy-3,4,5,3ʹ,5ʹ-pentamethoxy4ʹ-oxo-Δ-1,3,5,2ʹ,8ʹ-8.1ʹ,7.5ʹ-neolignan
33,
and
rel-(7S,8R,1ʹS,4ʹR,5ʹS,6ʹS)-6ʹ-acetoxy-4ʹ-hydroxy3,3ʹ,5ʹ-trimethoxy-4,5-methylenedioxy-Δ-1,3,5,2ʹ,8ʹ8.1ʹ,7.5ʹ-neolignan 34 (18).
L. canella (Meisn.) Kosterm.
L. canella is a botanical species popularly known as ‘louropirarucu’. Within the ethnic group Tacana of the Amazonian
region, this species has the same name and use as Aniba
canelilla, probably due to their aromatic barks. he barks
of both species have ethnopharmacological uses to alleviate
abdominal pain, intestinal cramps or discomfort, without
diarrhea (8). he ethanol extract of the bark of this species
showed activity in vitro against chloroquine sensitive
Plasmodium falciparum (IC50 value of 3.8 μg/mL) and also
resistant strains (IC50 value of 3.2 μg/mL). he extract of the
stem demonstrated low activity against human myeloma cell
line, RPMI 8226 cancer cells (8). Giesbrecht and co-workers
(19) have reported the benzene/ethanol extract of the trunk
wood to have three neolignans, canellin A 35, B 36 and C 37,
as well as dillapiole 38, elemicin 39 and sitosterol 5.
L. chrysophylla (Meisn.) Kosterm.
L. chrysophylla is a tree growing in Amazonian rainforest,
Marmara Pharm J 20: 390-400, 2016
Brazil. he first and up to now, four studies have been
reported from this species. Ferreira and co-workers
(20) have isolated chrysophyllin A 40 and B 41 from
petroleum extract of the trunk wood. Both compounds
were also found from the same species, reported by Lopes
et al. (21). hey also managed to obtain chrysophyllon
I-A 42, chrysophyllon I-B 43, chrysophyllon II-A
44, chrysophyllon II-B 45, chrysophyllon III-A 46,
chrysophyllon III-B 47, 2,3,4,5-tetramethoxyallylbenzene
48, 2,3,4,5-tetramethoxycinnamyl alcohol 49 and
2,3,4,5-tetramethoxycinnamaldehyde 50 form the petroleum
extract of trunk wood. Furthermore, Silva and co-workers
(22) have reported on the other parts of this species which are
from the bark and fruits calyx ethanolic extract. hey found
five new benzodioxane neolignans, eusiderin I-M 51-55,
three new β-aryloxy-arylpropane type neolignan, virolongin
E-G 56-58, together with known compounds, eusiderin A
27 and virolongin B 24. In addition, Bezerra et al. (16) have
studied on the bark extract of this species and successfully
isolated chrysophyllon IV-B 59, chrysophyllon V1-B 60,
chrysophyllon I-B 43, chrysophyllon II-A 44, chrysophyllon
II-B 45, chrysophyllon III-B 47. hey also found that the
isolated compound have strong inhibition of supercoiled
DNA relaxation induced by topo II-α at a concentration of
100 μM. hese results indicate that no obvious correlation
can be derived between the structure of these compounds
and the inhibitory activity of DNA relaxation by DNA
topoisomerase II.
L. macrophylla (A.C. Smith) Kosterm.
L. macrophylla is a tree which grows in the Amazon region,
Brazil (23). Only one study has been reported in the literature
about this plant in 1974, when Franca and coworkers (23)
described the isolation and characterization of a novel
neolignan, macrophyllin 61 from the trunk wood extracts.
Besides, they also managed to get sitosterol 5, borneol 62,
elemol 63, and nerolidol 64.
L. mahuba (A. Samp.) Kosterm.
L. mahuba, an Amazonian Lauraceae has been reported
to have (-)-dihydromahubanolide B 65 and (-)-isodihydromahubanolide B 66. Synthesis of both compounds
was achieved starting from (-)-methyl 5-hydroxymethyl2,2-dimethyl-1,3-dioxolane-4-carboxylate which was readily
available from L-(+)-tartaric acid, as published by Tanaka
and Yamashita (24). Gottlieb and co-workers (25) also
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
395
reported the phytochemical study from the wood of a Licaria
sp. hey were successfully identified two neolignans, namely
aurein 67 and eusiderin 68.
L. puchury-major (Mart.) Kosterm.
L. puchury-major is populary known in Brazil as ‘puchuri’ or
‘pixuri’. heir seeds are used in folk medicine for stomach and
intestinal ailments and also as a calmative in adults and children
to treat insomnia, nervousness and irritability (26). he first
phytochemical study of this species appeared in the literature
in 1973 when Leao da Silva and co-workers (27) isolated and
structurally characterized sitosterol 5, eugenol 69, safrole 70,
syringic aldehyde 71, 3,4-methylenedioxycinnamaldehyde
72 and 3,4-methylenedioxycinnamyl alcohol 73 from
trunk wood extract. In addition, Uchiyama and co-workers
(28) have reported that the EtOH extract of the seeds of L.
puchury-major showed the growth inhibitory activity against
human leukemia Jurkat cells (53.3% inhibition at 30 μg/mL).
Besides, acetone fraction was found to be the most active
(82.7% inhibition at 30 μg/mL) and induced early apoptosis
at 30 μg/mL within 24 h against Jurkat cells. Bioassay-guided
fractionation of the ethanol extracts led to the isolation of one
phenylpropanoid and ten neolignans. hey were identified as
apiole 74, (7S,8S)-∆8ʹ-2ʹ,6ʹ-dimethoxy-3,4,-methylenedioxy7.O.3ʹ,8.4ʹ,1ʹ.O.7ʹ-neolignan 75, ferrearin B 76, ferrearin
C
77, licarin A 1, rel-(7S,8S,1ʹR,2ʹS)-2ʹ-hydroxy-3,4dimethoxy-3ʹ-oxo-∆4ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan 78, ferrearin
G 79, oxaguianin 80, rel-(7S,8S,1ʹR,5ʹR)-5ʹ-methoxy-3,4methylenedioxy-4ʹ-oxo-∆2ʹ,8ʹ-8.1ʹ,7.O.2ʹ-neolignan
81,
armenin B 8, and 3ʹ-methoxyburchellin 82. he cytotoxic
activity of isolated compounds against Jurkat was tested
by MTT assay and found that compounds 76, 77, 78 and
79 having furanocyclohexenone structure with hemiacetal
in the molecule showed cytotoxic activity at 10 µM. hese
four neolignans induced early apoptosis at 10 µM within
24 h, while compound 75 also induced apoptosis at 100 µM
within 48 h. Studies on this species was continued by Ohsaki
and co-workers (6) and successfully isolated ten alkaloids
from the seeds extract. hey were identified as reticuline
83, orientaline 84, coclaurine 85, N-methylcoclaurine 86,
norjuziphine 87, norisoboldine 88, isoboldine 89, glaziovine
90 and reticuline N-oxide [91 N-Me (S); 92 N-Me (R)].
he cytotoxicity of the obtained compounds was evaluated
against vincristine-sensitive and -resistant P388 cells in the
presence of P388/VCR(+) or the absence of P388/VCR(-) of
low levels of vincristine. Norjuziphine 87, norisoboldine 88,
and isoboldine 89 exhibited potent cytotoxic activity in the
presence of vincristine P388/VCR(+).
396
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
1 R1 = R2 = OCH2O
2 R1 = OCH3 ; R2 = OH
3 R=H
4 R = OCH3
9
10
14 R = H
15 R = OCH3
16
23
24
28
56
57
58
38
6
18 R1 = R2 = OCH2O
19 R1 = R2 = OCH3
25 R1 = OCH3 ; R2 = OCH3
26 R1 = R2 = OCH2O
27
51
52
53
54
55
93
13
20 R1 = R2 = CH3
21 R1 = H ; R2 = CH3
22 R1 = R2 = H
trans, R1 = R2 = R4 = CH3 ; R3 = OCH3 ; X = CH2CH=CH2
trans, R1 = R2 = CH2 ; R3 = OCH3 ; R4 = CH3 ; X = CH2CH=CH2
cis, R1 = H ; R2 = H ; R3 = H ; R4 = H ; X = CH2CH=CH2
trans, R1 = R4 = CH3 ; R2 = H ; R3 = OCH3 ; X = CH2CH=CH2
trans, R1 = R2 = R4 = CH3 ; R3 = OCH3 ; X = CHO
trans, R1 = R2 = R4 = CH3 ; R3 = OCH3 ; X = CH=CHCH2OH
trans, R1 = R2 = CH2 ; R3 = H ; R4 = CH3 ; X = CH2CH=CH2
32 R1 = OAc ; R2 = H
33 R1 = OH ; R2 = H
39
7 R=H
8 R = OCH3
12
17
31
29 R1 = OH ; R2 = H
30 R1 = H ; R2 = OH
5
11
R1 = R2 = CH3 ; X = CH=CHCH3
R1 = R2 = CH3 ; X = CH2CH=CH2
R1 - R2 = CH3 ; X = CH2CH=CH2
R1 = R2 = CH3 ; X = CH=CHCH2OH
R1 = R2 = CH3 ; X = CH=CHCHO
R1 = R2 = CH3 ; X = CHO
37
Marmara Pharm J 20: 390-400, 2016
40 R1 = R2 = OCH2O
41 R1 = R2 = OCH3
34
35 R1 = OCH3 ; R2 = OCH3 ; R3 = H
36 R1 = R2 = OCH2O ; R3 = OCH3
42 R1 = R2 = OCH2O
43 R1 = R2 = OCH3
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
Marmara Pharm J 20: 390-400, 2016
44 R1 = R2 = OCH2O
45 R1 = R2 = OCH3
46 R1 = R2 = OCH2O
47 R1 = R2 = OCH3
59
60
63
72
71
77 R = H
79 R = OCH3
76
82 R = OCH3
96 R = H
90
83 R1 = OH ; R2 = OCH3
84 R1 = OCH3 ; R2 = OH
91 N-CH3 = (S)
92 N-CH3 = (R)
49
50
61
62
67
65 R1 = H ; R2 = C15H31
66 R1 = C15H31 ; R2 = H
64
69 R1 = OCH3 ; R2 = OH
70 R1 = R2 = OCH2O
48
68
73
78
74
75
81
80
85 R = H
86 R = CH3
94
Figure 1. Chemical structures of the compounds isolated from the genus Licaria
88 R = H
89 R = CH3
87
95
397
398
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
Marmara Pharm J 20: 390-400, 2016
Table 2. Essential oils compositions from the genus Licaria
Species
Locality
Parts/Major components
L. canella
Brazil
Leaves: Benzyl Benzoate (69.7-73.0%), α-copaene (4.5-4.9%), α-phellandrene (3.3-4.2%),
α-pinene (3.0-3.5%) (4)
L. excelsa
Costa Rica
Leaves: α-Pinene (42.9%), β-pinene (22.0%) (31)
L. macrophylla
Brazil
Wood: Elemol (25.0%), nerolidol (5.0%), borneol (3.0%) (27)
L. martiniana
Brazil
Leaves: β-Caryophyllene (41.7%), β-selinene (7.9%), isovalerate linalool (5.9%), linalool
(5.3%) (9)
Brazil
Stems: β-Caryophyllene (21.4%), spathulenol (11.5%), linalool (6.5%), α-cadinol (5.9%),
γ-cadinene (5.7%) (9)
L. puchury-major
L. salicifolia
L. triandra
Brazil
Twigs: Eugenol (61.0%), safrole (20.1%), eucalyptol (10.8%), α-terpineol (6.8%) (32)
Brazil
Leaves: Eucalyptol (47.6%), safrole (21.7%), α-terpineol (11.7%) (32)
Brazil
Seeds: Safrole (51.3%), eugenol (3.3%), methyl eugenol (2.9%) (33)
Brazil
Seeds: Safrole (36.1%), 1,8-cineole (21.1%), limonene (12.2%), α-terpineol (10.7%) (34)
Brazil
Seeds: Safrole (58.4%), dodecanoic acid (13.7%), α-terpineol (8.4%) (5)
France
Leaves: α-Phellandrene (17.2-22.0%), α-santalene (0.8-20.3%), p-cymene (1.5-17.4%),
β-santalene (0.2-7.0%) (35)
France
Bark: p-Cymene (10.1-13.0%), α-phellandrene (5.3-8.1%), 7-epi-α-santalene (7.3-7.6%),
α-cadinol (4.5-6.5%), caryophyllene oxide (4.3-6.2%) (35)
France
Fruits: α-Cantalene (2.0-19.0%), p-cymene (11.0-13.5%), α-phellandrene (5.8-13.0%),
β-santalene (0.7-9.2%) (36)
Cuba
Leaves: Selin-11-en-4α-ol (15.1%), β-pinene (10.6%), β-caryophyllene (9.5%), spathulenol (5.6%) (29)
Cuba
Leaves: β-Eudesmol (11.4%), caryophyllene oxide (3.0%) (29)
Costa Rica
Leaves: α-Pinene (40.9%), β-pinene (28.5%) (E)-caryophyllene (6.5%) (30)
L. rigida Kosterm.
L. rigida, collected at the Ducke Forest Reserve, near Manaus,
Amzonas State, have been investigated by Fo et al. (7). hey
managed to isolate three neolignans from the trunk wood
extract, namely eusiderin 68, eusiderin B 93, canellin A 35
and canellin C 37.
L. triandra (Sw.) Kosterm.
L. triandra is a tree 7-16 m high. It is frequent in woodlands
on limestone or shale, 100-1000 m, lowering in SeptemberNovember, fructifying in January-September. It grows wild
in Florida and West Indies southward to Martinique (29).
he leaves are used locally as folk medicine such as against
indigestion, stomachache and as stimulant (3). Phytochemical
investigation from the seeds of this species have aforded two
new neolignans, identified as triandrin A-B 94-95 (18) as
well as a known benzofuranoid neolignan, burchellin 96 as
reported by Castro and Ulate (30).
Literatures revealed that few essential oils studies have been
carried out on Licaria species. he chemical compositions
of the essential oils of Licaria species have been conducted
on seven species, which are L. canella (4), L. excelsa (31),
L. macrophylla (27), L. martiniana (9), L. puchury-major
(5,32,33,34), L. salicifolia (35), and L. triandra (29,31,36).
he major components of the essential oil compositions
from Licaria species are tabulated in Table 2. Monoterpenes
hydrocarbon was found as the major group components,
in the essential oil of L. triandra (Cuba: 42.9%; Costa Rica:
77.7%) (29,31) and L. excelsa (85.7%) (31). Meanwhile,
oxygenated monoterpenes and benzenoids were found from
the essential oil of L. puchury-major (seeds: 34.3%) (5) and
L. canella (leaves: 71.3-74.9%) (4), respectively. In addition,
sesquiterpene hydrocarbons were found from the essential
oil of L. martiniana (47.0-65.8%) (9). Benzyl benzoate,
eugenol, and safrole were the major components identified
with more than 50% in the essential oils of Licaria species.
Benzyl benzoate was found in 69.7-73.0% from the leaves oil
of L. canella (4). Other studies have demonstrated that benzyl
benzoate is efective at denaturing dust miteallergen (37) and
can eradicates mites and reduce their populations (38). In
addition, eugenol presented 61.0% from the twigs oil of L.
Salleh and Ahmad
Phytochemistry and Pharmacology of the Genus Licaria
Marmara Pharm J 20: 390-400, 2016
puchury-major (32). It has been shown in the pharmacological
studies that eugenol demonstrated anesthetic, hypothermic,
muscle-relaxant, antistress efect and anticonvulsant
activities (39,40). Besides, the seeds oil from the same species
has successfully found safrole in 51.3% (33) and 58.4% (5).
Studies have revealed the genotoxic (41) and carcinogenic
(42) potentials of safrole. he study of Taiwanese oral cancer
patients suggests that safrole may form stable safrole-DNA
adducts in human oral tissues following betel quid chewing,
which may contribute to oral carcinogenesis (43).
he in vitro antibacterial activity of the essential oil of L.
triandra was studied against five bacteria strains (Bacillus
cereus, Staphylococcus aureus, Listeria monocytogenes, Bacillus
subtilis and Escherichia coli) using the disc difusion method.
he essential oil showed weak activity against the bacteria
tested (29). Palazzo and co-workers (31) have evaluated in
vitro cytotoxicity activity of the essential oils of L. excelsa
and L. triandra against human breast adenocarcinoma cells
(MDA-MB-231/MDA-MB-231) and human breast ductal
carcinoma cells (Hs 578T). he essential oil of L. triandra
was found weak activity with 25% kill at 100 µg/mL, while
L. excelsa oil found to be inactive. he evaluation of the antileishmanial activity of the essential oil of L. canella indicated
moderate activity against Leishmania amazonensis with IC50
value of 19 μg/mL. Meanwhile, the essential oil displayed low
cytotoxicity against Artemia salina with LC50 value of 5.25 μg/
mL (4). Besides, the essential oils of L. martiniana showed
Licaria (Lauraceae) Türlerinin Fitokimyasal ve Farmakolojik
Özellikleri Üzerine Bir Derleme
ÖZ
Licaria (Lauraceae) çiçekli bir bitki olup 40 cinsi vardır ve
bu cinslerin bazıları Orta ve Güney Amerika’ya ait endemik
bitkilerdir. Licaria (Lauraceae) türlerinin çoğu geleneksel halk
weak antioxidant (DPPH >1000 μg/mL) and antiplatelet
inhibitory activities (leaves 4.2%; stems 36.9%) at quantitative
spectrometric assays (9).
CONCLUSION
In this review, we summarized the secondary metabolites
isolated from the genus Licaria and their pharmacological
properties. Most of the species produced lignans and
neolignans. Apart from that, further phytochemical studies
need to be carried out in the near future to provide a more
detailed pattern of the natural constituents and of the
biologically active principles in extracts. As a conclusion, it
is evident that the genus Licaria comprises therapeutically
promising and valuable plants, some of which are used in the
traditional medicine of indigenous populations. Meanwhile,
there are only few studies describing their pharmacological
properties, this genus merits more attention in the on-going
search for new bioactive compounds.
ACKNOWLEDGMENTS
he authors thank to Research University Grant (GUPQJ130000.2526.03H93) for financial support and the
Department of Chemistry, Faculty of Science, Universiti
Teknologi Malaysia (UTM) for research facilities.
ilacı olarak kullanılmaktadır. Licaria türlerinden izole edilen
fitokimyasallar; lignanlar, neolignanlar, alkaloidler, laktonlar,
triterpenler ve arilpropanoit’lerdir. Bu derlemenin amacı,
Licaria türlerine ait bitkileri konu alan hem eski hem de güncel
literatürün bitkilerin farmakolojik ve fitokimyasal özellikleri
açısından ayrıntılı olarak incelenmesidir.
Anahtar kelimeler: Licaria, Lauraceace, Fitokimya, Farmakoloji,
Neolignanlar
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