The keywords snakebites, snake envenomation, snake venom, normal inhibitors, antivenom activity, toxins, plants, phospholipase inhibitors and metalloprotease inhibitors were used individually, but mostly in combination. consequences of SBEs. In this review, we systematically synthesize the literature on plant metabolites that can be used as toxin-inhibiting agents, as well as present the potential mechanisms of action of molecules derived from natural sources. These findings aim to further our understanding of the potential of natural products TC-E 5006 and provide new lead compounds as auxiliary therapies for SBEs. Keywords: bioactive compounds, plants, envenomation, snakes, snakebites Snakebite Envenomings Snakebite envenomations (SBEs) represent a serious and neglected public health problem that occurs worldwide, especially in developing countries in tropical and subtropical regions (1, 2). These countries have high incidences of cases because, to some extent, they still conserve their forests and TC-E 5006 biodiversity; however, at the same time, human expansion and urbanization tend to invade places where biodiversity is greater and this leads to an increase in contact between humans and snakes (2, 3), especially in the countries of Asia, Sub-Saharan Africa and Latin America (4). Worldwide, about 1.8 to 2.7 million snakebites are estimated to occur annually, which resulted in about 138,000 deaths and approximately 400,000 cases of people who have permanent physical sequelae (Figure?1) (1, 5, 6). The highest incidence occurs in Asia, which presents 73% of the total world cases (~2 million cases), most of them in India, where more than 46,000 deaths were reported in 2020 (1). Africa and the Middle East are in second place, and present about 580,000 SBEs (21%), of which 7,000 to 32,000 deaths occurred TC-E 5006 in sub-Saharan Africa alone (1, 7, 8). Together Latin America and the Caribbean present about 150,000 SBEs (5%), with 5,000 deaths, most of them in South America with 50,000 cases, particularly in Brazil with 26,000-29,000 cases per year, of which one third occur in the Amazon region (6, 9). These estimates may show lower numbers than what occurs in reality, since a considerable portion of cases go unreported (4). Underreporting occurs due to SBEs occurring in remote rural areas where there is difficulty accessing health services (4, 10). Open in a separate window Figure?1 Global distribution of snakebite cases. Adapted from J.M. Gutirrez et al. (2017) Ref. (6) The final figure was prepared using canva.com. Among the snakes of greater clinical importance that cause high levels of morbidity or mortality, those that belong to the families Elapidae and Viperidae stand out (11). On the Asian continent, the clinically important species of the family Viperidae, include Rabbit polyclonal to TP53BP1 the genera (e.g., (e.g., and and genera (12). In Asia, snakes belonging to the family Elapidae include (e.g., and (6, 13). In regard to the clinically important African species, some of the same Asian genera of the family Elapidae are also reported, such as (e.g., and and genera (6, 14). While, in Central and South America, cases predominate with species belonging to the Viperidae, especially (e.g., and (e.g., and (e.g., and studies that have demonstrated that bioactive molecules isolated and derived from natural products show antivenom activities (10). Therefore, based on the available literature, this updated review highlights some of the natural bioactive compounds that have been isolated from plants, and may be used as potential adjuvant inhibitors of snake venom toxins, as well as presenting new perspectives regarding their potential use in the development of new therapies for snakebites. Figure?2 represents an overview of the roadmap proposed in this review. Open in a separate window Figure?2 Mind map of the topics covered in this review. Snake photo: Asenate A. X. Adri?o. The final figure was prepared using canva.com. An extensive literature review was carried out using different scientific electronic sources, including databases such as Scifinder, Pubmed, Scopus, Web of Science and Google Scholar. The study databases included original papers published in peer-reviewed journals, books, dissertations, theses and patents, and all data of scientific information written or translated into English published until November 2021 was considered. The keywords snakebites, snake envenomation, snake venom, natural inhibitors, antivenom activity, toxins, plants, phospholipase inhibitors and metalloprotease inhibitors were used individually, but mostly in combination. Data showing the bioactivity of compounds isolated from plants used in and.