Eficácia não-clínica do gel contendo o extrato vegetal de Ipomoea pes-caprae na inibição da toxicidade local produzida pela peçonha da serpente Bothrops erythromelas

Abstract

Snakebite is a relevant public health problem, included by the World Health Organization in the list of Neglected Tropical Diseases. The most clinically relevant genus is Bothrops. Events such as local edema, myotoxicity, hemorrhage and dermonecrosis characterize accidents and can lead to severe damage to patients. The low efficacy of antivenom serum therapy in the face of these events instigates the search for complementary therapies. Medicinal plants have been used for years in traditional medicine for snakebites. The plant species Ipomoea pes-caprae (Ipc), known as “salsada-praia”, is used in traditional medicine to treat inflammation, pain and snake bites. Thus, this study focused on the development and evaluation of a topical gel containing Ipc extract for its antivenom potential. The hydroethanolic extract of Ipc was obtained by maceration. Through Thin Layer Chromatography and analysis by High Performance Liquid Chromatography, the majority presence of phenolic compounds in the extract was identified. Through fractionation of the extract by XAD-4, the enriched fraction (FrEtOH) was obtained, concentrating the phenolic compounds present in the Ipc extract. The Ipc extract and FrEtOH did not show significant in vitro cytotoxicity against murine macrophage cells (RAW 267.3) and mouse embryonic fibroblasts (NIH/3T3). The in vitro enzymatic activities against Bothrops erythromelas (Ber) venom toxins (phospholipase, proteolytic and hyaluronidase) were similarly inhibited by the crude extract and the Ipc fraction. The extract and FrEtOH at concentrations of 5% and 1%, respectively, were incorporated into a Poloxamer and HPMC gel previously developed by the research group. After 180 days of the thermal stability study, the formulations with the extract were stable in terms of organoleptic and physical-chemical properties, as well as the phenolic content varying less than 10%, which is within the specifications according to the Brazilian legislation. The in vivo activities against the local effects produced by the Ber venom (edematogenic, hemorrhagic and dermonecrosis) were reduced by the treatment with the Ipc gel, as well as a better effect was visualized when using the Ipc gel associated with the antivenom. Treatment with the FrEtOH gel inhibited the edematogenic activity. The observed inhibitions were promising, showing a direct action of the extract inhibiting venom toxins and indirect action through the inhibition of endogenous mediators involved in envenomation. In addition, it is possible to propose the active participation in the pharmacological action of the compounds present in the extract, with emphasis on the phenolics that act strongly as anti-inflammatories, antioxidants and metal chelator. In conclusion, the results obtained point to the antiophidic potential of the Ipc extract, which may justify its medicinal use in snake bites, as well as contribute to its use as a raw material in the development of new herbal products on the market for the treatment of the effects sites of bothrops envenoming.