European Journal of Medicinal Plants 33(8): 10-15, 2022; Article no.EJMP.90265 ISSN: 2231-0894, NLM ID: 101583475 New Therapeutic Perspective Based on Anacardium humile in the Treatment of Skin Wound Infected by Staphylococcus aureus Tauanne Fernanda dos Santos a*, Emillene de Holanda Colli a, Diego Francisco Degiovanni Benitez b, Maria Eugênia de Lima Pinheiro a, Barbara dos Reis Dal Lago Rodrigues a, Silvio Rodrigo Arevalos Davalos c, Maria Borges Tavares a, Celso Dal Lago Rodrigues Neto a, Camila Borges Siqueira Campos a, Fernando Araújo de Oliveira b, Gleyson Murillo Aguilera Moraes a, Mellânia Rodrigues Goveia a and Marco Antônio de Souza Borges Tavares c a Santa Casa de Campo Grande, Anhanguera University UNIDERP, Campo Grande, Brazil. b Federal University of Mato Grosso, UFMT, Campo Grande, Brazil. c Federal University of Mato Grosso do Sul, UFMS, Campo Grande, Brazil. Authors’ contributions This work was carried out in collaboration among all authors. All authors read and approved the final manuscript. Article Information DOI: 10.9734/EJMP/2022/v33i830482 Open Peer Review History: This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers, peer review comments, different versions of the manuscript, comments of the editors, etc are available here: https://www.sdiarticle5.com/review-history/90265 Systematic Review Article Received 01 June 2022 Accepted 01 August 2022 Published 03 August 2022 ABSTRACT This is a literature review with the objective of presenting scientific evidence about the therapeutic importance of the use of Anacardium humile for the treatment of infected skin wounds. Retrospective and analytical study carried out from 1999 to 2021, in the Bireme, UpToDate, Pubmed and Scielo databases. The association of the descriptors “Phytotherapy” was used; “Cerrado and Pantanal Plants”; “Wounds contaminated by bacteria”; “elastic fibers”. Of the 248 articles analyzed, 36 were included in the review because they met the inclusion criteria. Among the results, it was evidenced that the conventional treatments, although effective (the gold standard being Sulfadiazine 1% silver), present toxicity to human keratinocytes and fibroblasts, with this, it is concluded that further research will be necessary to prove the effectiveness of new treatment options or association of herbal medicines with treatment. _____________________________________________________________________________________________________ *Corresponding author: E-mail: tauannef@icloud.com; Santos et al.; EJMP, 33(8): 10-15, 2022; Article no.EJMP.90265 Keywords: Phytotherapy; cerrado and pantanal plants; wounds contaminated by bacteria; elastic fibers. 1. INTRODUCTION 3. RESULTS AND DISCUSSION The main cause of delays and aggravations in wound healing is contamination by microorganisms, burdening care in the public health system with longer hospital stays, increasing treatment costs by around 40% [1]. The bacterium S. aureus is the infectious agent most commonly isolated in tissue infections and there is a certain epidemic of infections with strains resistant to beta-lactams [2]. Medicinal plants present relevant alternatives in therapeutic treatments in healing and inflammatory processes for the rehabilitation of skin disorders [3]. The genus Anacardium belongs to the family Anacardiaceae. Its current taxonomy consists of about 10 species. Among the various existing species, those designated as cashews deserve special attention. Cajuí is a terminology used to describe species of the genus Anacardium that have chestnut and small peduncle. It is a native plant that is widely dispersed in the Cerrados, Northeast, Midwest and Southeast regions [4]. Agostini-Costa et al. [5], when describing Anacardium species, classified as cashew (chestnut + stalk) the following species: A. amilcarinum, A. giganteum, A. humile, A. microcarpum, A. nanum and A. pumilum. The species Anacardium humile has peduncles with phenolic compounds, vitamin C, minerals such as calcium, iron, phosphorus, considerable levels of sugars and low pH values, also demonstrating a great nutritional potential, which increases the use of this small cashew from the Cerrado by the processing industry of fruits [6]. The skin is composed of distinct layers: dermis (rich in extracellular matrix proteins and elastic fibers) and epidermis (rich in continuous regenerative cells) [7]. In the skin, elastic fibers are present in the reticular portion, also known as dense unpatterned connective tissue, and fibroblasts are the main cells in this portion of the tissue, producing collagen and elastin proteins [8,9,10]. Elastic fibers are essential as they provide elasticity to the tissue, but as it matures, the tendency is for some of them to join collagen, thus making the tissue more resistant [11]. Wounds are considered a public health problem due to the increasing occurrences of people affected, causing disorders in the economic, social and psychological areas. In addition to interfering with quality of life, it also contributes to increases in public spending on health [12]. A wound is a disruption of the normal structure and function of the skin and soft tissue architecture. When classified as an acute wound, it demonstrates normal physiology, and healing is expected to progress through the expected stages of healing, while a chronic wound is defined as one that is physiologically impaired. All wounds are colonized by microbes; however, not all wounds are infected [13]. To identify an infected wound, clinical signs include local symptoms (cellulitis, lymphangitic streaks, purulence, malodour, wet gangrene, osteomyelitis) and systemic symptoms (fever, chills, nausea, hypotension, hyperglycemia, leukocytosis, mental status change) [14]. 2. MATERIALS AND METHODS Characteristics of chronic wounds that prevent an adequate cellular response to healing stimuli include accumulation of devitalized tissue, decreased angiogenesis, hyperkeratotic tissue, exudate, and biofilm formation (ie, bacterial overgrowth on the wound surface) 2021. A search of scientific literature was carried out in the Bireme, UpToDate, Pubmed and Scielo databases, between 1999 and 2020, using the descriptors: “Phytotherapy”; “Cerrado and Pantanal Plants”; “Wounds contaminated by bacteria”; “elastic fibers”. A total of 248 articles were selected and these pre-selected articles were evaluated regarding the inclusion criteria: complete, current articles, in English, Portuguese or Spanish and from reliable platforms, those that did not meet the inclusion criteria were excluded. They were analyzed by titles and abstracts and articles that were repeated in the databases, that is, duplicates, totaling 36 selected articles. Most chronic wounds are colonized by more than one bacterial species causing damage to the host [15] and have their healing phases disordered. The wound gains another regression condition, the cells suffer interruption in their proliferation, the keratinocytes cannot evolve with the normal migratory activity, because they do not respond to stimuli, as well as fibroblasts, which do not meet the growth factor TGF-β1 [16]. 11 Santos et al.; EJMP, 33(8): 10-15, 2022; Article no.EJMP.90265 traumatized and has little tensile strength (ATINGER; STEINBERG; MEYR, 2010). Continuing with the fibroplasia stage, in which fibroblast proliferation, ground substance accumulation and collagen production occur [17]. To finally arrive at the maturation phase, in which key elements of the maturation stage include collagen crosslinking, collagen remodeling, wound contraction and repigmentation [18]. It is at this stage that we will have the presence of collagen fibers, so to be sure about the healing of a wound, it is necessary to quantify the elastic fibers present in it. Wound healing occurs as a cellular response to tissue injury and involves the activation of keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The process involves organized cell migration and recruitment of endothelial cells for angiogenesis. The many growth factors and cytokines released by these cell types coordinate and maintain wound healing. Chronic wounds are trapped in one of the healing stages, usually the inflammatory stage, and fail to progress further, in these situations, the normal physiology of the linear pathway is transformed into the pathophysiology of a chronic cycle, without a clear wound closure outcome. The presence of necrotic tissue, foreign material, and bacteria results in the abnormal production of matrix metalloproteases, which alter the balance of inflammation and impair cytokine function. Topical antibiotics and antimicrobials are used as a way to prevent infection, reduce or eliminate the number of microorganisms present in open wounds [19]. Topical antibiotics must have broad-spectrum bactericidal action and low risk of tissue toxicity, without intervening in the healing process. In some cases, the use of these products within 1-3 hours after contamination is sufficient to prevent tissue infection. Alternatively antibiotics such as penicillin, ampicillin, tetracycline and cephalosporins, for example, can be added to the wash solution [20]. Immediately after skin injury, small vessels within the wound constrict to provide a measure of hemostasis for 5 to 10 minutes (first phase of healing – hemostasis). Platelets aggregate in the cut vessels, trigger the clotting cascade, and release essential growth factors and cytokines that are important for the initiation and progression of healing (eg, platelet-derived growth factor, transforming growth factor beta). The resulting fibrin matrix stabilizes the wound and provides temporary support for the healing process. 1% silver sulfadiazine has a broad spectrum against gram positive (Staphylococcus aureus) and gram negative bacteria (Pseudomonas spp, Proteus spp, Escherichia coli, Enterobacter, Klebsiella sp), and most fungi; are intended to penetrate the necrotic tissues performing debridement and assist in the epithelialization of wounds). It is one of the most effective agents in the treatment of thermal injuries due to the high risk of infection, the ointment remains effective for up to three days and the dressings can be kept for up to seven days [19]. In vitro studies suggest toxicity to human keratinocytes and fibroblasts, however, when it is associated with aloe vera, it can be reversed [21]. The inflammatory phase is sometimes called the lag phase because wound strength does not immediately return. The inflammatory phase is usually completed within three days, except in the presence of infection or other factors associated with impaired wound healing. In chronic wounds, the normal progression of healing is often stalled at this inflammatory stage. The presence of necrotic tissue, foreign material, and bacteria results in the abnormal production of matrix metalloproteases, which alter the balance of inflammation and impair cytokine function. Next, we have the epithelialization phase which refers to the proliferation of basal cells and migration of epithelial cells that occur at the fibrin bridge within a clot. Proliferation continues until individual cells are surrounded by cells of a similar type. Migration ceases when this layer is rejuvenated. The surface layer of the epithelium creates a barrier to bacteria and other foreign bodies. However, it is very thin, easily Another therapeutic measure that has been widely used in medical practice is the use of natural products, due to their numerous beneficial, safe and low-cost properties [22]. Phytotherapics can be strong coadjuvants in treatments, as well as associated with drugs already on the market, a need that meets new discoveries identified in plants, such as the Brazilian Cerrado biome, which has species with healing properties (CHAVES et al., 2016). Among species of this biome is Anacardium humile that belongs to the Anacardiaceae family, of Brazilian origin, native to tropical America and 12 Santos et al.; EJMP, 33(8): 10-15, 2022; Article no.EJMP.90265 adapt to environmental aggressions. These substances can be isoflavonoids, indoles, phytosterols, polysaccharides, sesquiterpenes, alkaloids, glucans, tannins, vitamins and minerals [30]. The knowledge about certain plant species with antimicrobial properties has been revised and expanded, due to the growing problems associated with the use of different antibiotics. In an extensive study on medicinal plants, a concrete evaluation was made on the antimicrobial activity of extracts, essential oils and substances obtained from plant species against Gram-positive, Gram-negative bacteria and fungal species [31]. popular in South America, has a high concentration of flavonoids and phenolic compounds that are metabolites with antiinflammatory, antioxidant and antibiotic power (GODINHO et al., 2015). The antibacterial action of the leaf can be a strong ally in the treatment of infections caused by pathogens capable of developing resistance to antibiotics and has received increasing attention with the increase in infections in skin and soft tissues by methicillinresistant S. aureus (MRSA) [2]. The use in folk medicine of the species A. Humile is demonstrated in the Treaty of Medicinal Plants from Minas Gerais, Natives and Cultivated [23], a book based on interviews with more than 80 healers from Minas Gerais and a bibliographic survey of medicinal plants used in the state. Verde, Paula and Caneiro [24] carried out a survey in the city of Mossâmedes (GO) of the species widely used as medicinal plants by the local population, in which the leaves of the species A. humile were cited in the treatment of ovarian inflammation. In folk medicine, this species also has applications such as: cautery, in skin disorders, against diarrhea, cough and to lower the glucose content in diabetics [25]. 4. CONCLUSION New therapeutic options have emerged, among them Anacardium humile has shown satisfactory effects on healing, without adverse effects. Thus, further studies should be carried out with such techniques, as they present evidence that they can be effective in the treatment of contaminated wounds. CONSENT AND ETHICAL APPROVAL It is not applicable. The literature has few references to studies of biological activities with A. humile, being restricted to germination studies [26], genetic divergence between populations [27], insecticidal activities. Phytochemical investigations carried out by FERREIRA [28] led to the isolation of compounds from the secondary metabolism of A. humile. Among them are derivatives of gallic acid, catechins and flavonoids. In the same study, the author found that the methanolic extract of A. humile leaves was able to significantly inhibit the formation of ethanolinduced ulcerative lesions in Swiss rats, attributing this protective activity to the presence of the components found. COMPETING INTERESTS Authors have interests exist. declared that no competing REFERENCES 1. 2. Antimicrobial or antibiotic substances constitute a special group of therapeutic agents, generally produced and obtained from living organisms. 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Hat; 2001. the Peruvian rainforest with a particular _________________________________________________________________________________ 29. © 2022 Santos et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Peer-review history: The peer review history for this paper can be accessed here: https://www.sdiarticle5.com/review-history/90265 15