Title : Plant species with potential inhibitory activity against snake venom toxins
Abstract:
Snakebite envenoming is a major yet neglected public health problem that disproportionately affects rural and agricultural communities. The World Health Organization classifies it as a neglected tropical disease due to its high incidence, associated morbidity, mortality, and significant socioeconomic burden in vulnerable populations. In the Americas, Mexico stands out for harboring the highest diversity of venomous snake species, which increases the epidemiological relevance of snakebite envenomation in the country. Despite this, access to effective treatment-primarily antivenom-remains limited in many rural regions because of high costs, insufficient supply, and long distances to healthcare facilities. Under these circumstances, traditional medicine often constitutes the first line of response. The use of medicinal plants, prepared as ethanolic extracts, infusions, or poultices, is deeply rooted in local knowledge systems. However, although these remedies are widely employed, most lack rigorous scientific validation regarding their safety and efficacy against snake venom toxins. In Mexico, ethnobotanical records identify several plant species traditionally used to counteract snakebite effects. Among them, fruits of species within the genus Randia, commonly known as “crucetillo,” are frequently cited as antivenom remedies. Similarly, pentalinon andrieuxii has been traditionally used to treat that, suggesting the presence of bioactive compounds with potential inhibitory activity against venom components. From a pharmacological perspective, snake venoms are complex mixtures of biologically active molecules, including phospholipases A₂ (PLA₂), snake venom metalloproteinases (SVMPs), and serine proteinases (SVSPs). These toxins are responsible for local tissue damage, hemorrhage, coagulopathy, necrosis, and systemic toxicity. Identifying plant-derived compounds capable of inhibiting these enzymatic and toxic activities represents a promising complementary strategy to improve snakebite management, particularly in settings where access to antivenom is delayed or limited. The present study aimed to evaluate the inhibitory potential of ethanolic extracts from Randia spp. and Pentalinon andrieuxii against key toxic components of Bothrops asper venom, while also characterizing their phytochemical profiles. Plant material was collected in Hidalgo, San Luis Potosí, and Veracruz. Ethanolic extracts were prepared by maceration from roots, stems, and leaves of P. andrieuxii, and from fruits of Randia spp. The median lethal dose (LD₅₀) of pool of B. asper venom, obtained from 39 adult specimens, was determined. Neutralizing activity was evaluated in CD-1 mice injected intraperitoneally with mixtures containing three LD₅₀ of venom and varying extract doses. Control groups received extracts alone or venom alone. Phytochemical screening was conducted using thin-layer chromatography to detect phenols, flavonoids, tannins, saponins, and terpenes. Results showed that the ethanolic fruit extract of Randia spp. achieved survival rates of 66% at certain doses, whereas extracts from P. andrieuxii did not neutralize venom lethality. Variations in inhibitory capacity may be linked to differences in secondary metabolite composition, particularly terpenes and saponins. Although traditional use suggests therapeutic value, efficacy and safety remain unconfirmed. Further studies are needed to isolate bioactive compounds and conduct rigorous evaluations, supporting the potential development of plant-derived complementary therapies for snakebite envenomation.
