Ethnopharmacological Use, Secondary Metabolites and Biological Activity of Ayapana triplinervis (VAHL) R. M. King and H. Rob.: A Systematic Review

Ayapana triplinervis is a plant species widely used in healing processes and in mystical-religious rituals by traditional communities in South America, Africa and Asia. This study aims to make a systematic review of the ethnopharmacological employment, secondary metabolites and biological activity reported in the scientific literature for A. triplinervis. The systematic literature review included scientific articles and theses published between 1987 and 2021 in Google Scholar, Science Direct, Pubmed, Web of Knowledge and CAPES Periodicals databases in English, Portuguese and Spanish. The results indicated that A. triplinervis is chemodiverse in coumarins and validated the ethnopharmacological action cited by traditional communities as antiviral, antinociceptive


INTRODUCTION
The growing use of natural products as raw materials indispensable to the industry in the search for biologically active compounds: anticancer, antimalarial, biodegradable natural pesticides that contribute to the evolutionary success in plants, has led to the multidisciplinary study of numerous plant species, among the families of medicinal interest is the Asteraceae. [1]he Asteraceae family developed in South America and Brazil emerges as the centre of the most primitive genera. [2]However, phylogenetic, taxonomic and chemosystematic information is incipient and indicates the presence of little known genus. [3]thnobotanical and ethnopharmacological studies indicate the therapeutic interest of species of the Asteraceae family through the medicinal use that traditional communities employ in their social practices, among which Ayapana triplinervis (Vahl) R. M. King e H. Rob.stands out. [4]. triplinervis can be found in two morphotypes (morphotype A and morphotype B) and is widely used in folk medicine and mystical-religious rituals in traditional communities of South America, Asia and Africa.Plants have different forms of defences from phytopathogens and herbivores, including a complex chemical mechanism of secondary metabolites.Species like A. triplinervis produce a broad spectrum of chemicals in various tissues above and below ground used for defence against biotic or abiotic stressors, and used by man as medicines, food and beverage flavourings, fragrances, textile dyes, hygiene products, insect control, among others.[5] Thus, this study aims to make a systematic review of the ethnopharmacological employment, secondary metabolites and biological activity reported in the scientific literature for A. triplinervis.

MATERIALS AND METHODS
The databases used in the search for papers related to Ayapana triplinervis and its synominies were Scholar Google, Science Direct, Pubmed, Web of Knowledge and CAPES Periodicals.The keywords used were Ayapana triplinervis, Eupatorium triplinerves, "Japana-branca", "Japana-roxa", Ayapana, Asteraceae, medicinal plant, ethnopharmacology, ethnomedicine, metabolics, metabolite, botanic aspects, botanical aspects, phytochemistry, and/or essential oil. [6]he search period comprised the years between 1987 and 2021 in English, Portuguese, and Spanish.Articles that did not present any aspect of the proposed theme or that were written in any other languages than those above mentioned, as well as thesis and dissertation results were adopted as exclusion criteria.

Asteraceae Family
The Asteraceae (Compositae) family comprises 1,535 genus, of which 180 are found in Brazil, with approximately 23,000 monophyletic species described and botanically accepted.Known as the family of sunflowers or daisies, the Asteraceae has a head made up of small flowers, called floscules, and anthers fused in a ring with pollen pushed by styles or cypselas, a species of dried fruit with varied aspects, 98% of the genera are small, such as herbs and shrubs and, rarely, trees.9] The secondary metabolites produced by its chemical defense system contributed to the evolutionary success, making it the main responsible for the importance of this family in traditional medicine, with significant use in food, cosmetics and as an ornamental and insecticide plant. [3,8]he family is known to produce polyacetylenes, sesquiterpenoids, terpenoids, tri-terpenoids, flavonoids, coumarins, benzefurans, and benzepyrans. [10]In Amapá, species of the Asteraceae family are used to treat malaria, flu, diarrhea, gastritis and high blood pressure.It is considered an important family of therapeutic interest due to the diversity of species used by traditional medicine, with special emphasis on A. Triplinervis. [11]apana triplinervis (Vahl) R.M. King and H. Rob.
Originally from South America, A. triplinervis (synonym: Eupatorium triplinerves) is found in Brazil, Ecuador, Peru, Puerto Rico and Guyana, in addition to being adapted in other countries such as India and Vietnam [12] and can be found in two morphotypes: [13] Japana-branca (morphotype A) and Japana-roxa (morphotype B), which can measure between 40 and 50 cm in height, erect or semi-prostrate..The species is widely used by traditional communities in South America, Asia and Africa, with special emphasis on mystical-religious rituals in the Amazon.Its leaves are widely used in the form of teas, decoctions or baths for the treatment of viruses, respiratory, gynecological and spiritual diseases, as shown in Table 1.

Biological Activity of A. triplinervis
Regarding phytochemical studies and validation of ethnopharmacological use, although most authors do not differentiate the chemical composition of each morphotype as a function of the species' biological activity, some studies have been dedicated to evaluating the medicinal use indicated by traditional communities, and its correlation with the secondary metabolites.
A. triplinervis is compared with Matricaria chamomilla in relation to its medicinais properties, thus, evaluations of the antinociceptive, anxiolytic, antidepressant, antiulcerative, antineoplastic and antimelanogenic potential in vitru and in vivo have received special attention by the scientific community, as demonstrated by the Table 2.
Pretreatment with hydromethanolic extract of A. triplinervis leaves prevented ulcerative lesions and stimulated the production of prostaglandins, as well as scavenging free radicals and inhibiting oxidative peroxidation in albino winstar rats as a mechanism of action of antiulcer activity. [33]Another study demonstrated that the major compound found in the essential oil of A. triplinervis, thymohydroquinone dimethyl ether, is able to block the initial stages of viral infection, preventing the entry of ZIKAV into the cell by default in the endocytosis stages of viral particles. [34]A. triplinervis extracts can also inhibit gene expression of IL-1β, IL-6, COX-2 and iNOS and protect against the deleterious action of hyperglycemic expression in vitro tests. [35]harmacognosy Reviews, Vol 16, Issue 32, Jul-Dec, 2022 Evaluation of the Biocidal Activity of A. triplinervis A. triplinervis has been evaluated for use as chemical control of harmful pathogens in agriculture or in the control of vectors of infectious diseases.Verpoort and Diwal [37] determined moderate biocidal activity of the ethanol extract on Bacillus subtilis.Jelager, Gurib-Fakime Adsersen, [38] evaluating the antimicrobial activity of methanolic plant extracts, observed moderate inhibition against gram positive and gram negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Candida alicans and antifungal activity in Aspergillus Niger.
Gupta and co-works [23] conducted a study evaluating the antimicrobial activity of extracts in petroleum ether and methanol with a positive test for steroids, coumarins, tannins and saponins; and determined high bactericidal activity in gram positive bacteria such as B. subtilis, S. aureus, S. epidermidis, Micrococcus leuteus and in gram negative bacteria such as E. coli, P. aeruginosa, S. typhi, Vibrio cholerae, Vibrio parahaemolyticus; and in the fungi A. niger, A. flavus, Alternaria solani and Fusarium solani.
In another study conducted by Lopes and co-works, [39] the authors described the antimicrobial activity of the non-polar fraction of the methanolic extract of the species against gram-negative bacteria E. coli with the presence of saponins, reducing sugars, coumarins, alkaloids, triterpenoids and steroids.
In other studies, Sugumar, Karthikeyan and Gowdhami [24] indicated that A. triplinervis essential oil has moderate antibacterial activity against S. typhae and Shigella sonnei, and high antifungal activity against Macrophomina phaseoline and Botryodiplodia theobromae.
Unnikrishnan et al. [25] reported antimicrobial activity in P. aeruginosa, Klebsiella pneumoniae, E. coli, S. aureus, Penicillium chrysogenum and C. albicans.Its major compound, thymoquinone dimethyl ether, showed lower antimicrobial activity, suggesting that it depends on its minor constituents.
Facknath and Lalljee [40] evaluated different extractions of A. triplinervis in agricultural pests such as Plutella xylostella, Crocidolomia binotalis and Myzus persicae and concluded that alkaloids and tannins exhibited the greatest food deterrent in P. xylostella and C. binotalis, followed by phenols and flavonoids.In the case of M. persicae, extracts of A. triplinervis stopped the growth and development of nymphs and observed significant pest control properties, indicating them as good candidates for further study of their potential as botanical pesticides as an alternative to synthetic insecticides.Rodrigues and co-works [41]

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
Melo and co-works [29] hydroalcoholic extract Anxiolytic, antidepressant, antinociceptive and antioxidant in an animal model.

Figure 1 :
Figure 1: Secondary metabolites reported in the scientific literature for A. triplinervis.
of the species.In vitro and in vivo biological activity studies demonstrate the validation of the ethnopharmacological action reported by traditional communities, such as antiviral, antinociceptive, antiulcerative, anxiolytic, biocidal and indicate the phytotherapic potential of the species.