AVALIAÇÃO DA TOXICIDADE AGUDA, DA GENOTOXICIDADE E DA ATIVIDADE ANTIPROLIFERATIVA DO EXTRATO METANÓLICO DAS FOLHAS DE ARISTOLOCHIA NEVESARMONDIANA E DO EXTRATO METANÓLICO OBTIDO POR BIOTRANSFORMAÇÃO

Abstract

The Aristolochiaceae family, to which Aristolochia nevesarmondiana belongs, has a wide global distribution and a historical use in traditional medicine for treating various pathologies, such as asthma, immune disorders, colic, intoxications, lung diseases, diabetes, stomach pain, and cancer. Melanoma is one of the most aggressive types of skin cancer, with alarming projections of increasing global incidence. In this context, investigations into bioactive substances have been conducted to identify new therapeutic approaches. This study evaluated the in vitro antiproliferative activity and in vivo effects of methanolic extracts from Aristolochia nevesarmondiana (EMFAn) and the material biotransformed by the caterpillar Battus polydamas (EMBAn). The in vitro assays showed that EMBAn exhibited better biological activity against tumor cells, although with low selectivity (IS ≤ 1), ranging from 0,5 in murine melanoma (B16-F10) to 1,39 in triple-negative breast adenocarcinoma (MDA-MB-231). Cytotoxicity in normal cells (NCI/3T3) indicated GI50 values of 275,01 µg/mL for EMFAn and 275,47 µg/mL for EMBAn, highlighting similar cytotoxic profiles in non-tumor cells. In the in vivo assays, the acute toxicity of EMBAn in BALB/C mice showed no statistical differences in weight gain between treated groups (2.000 to 50 mg/kg) and controls, both in males (p = 0,5653) and females (p = 0,112). An analysis of antitumor activity demonstrated that although EMFAn showed a tendency to reduce tumors, the effects were not statistically significant, and high mortality rates were observed in treated animals. EMBAn, on the other hand, exhibited a safer toxicity profile. The genotoxic evaluation indicated that EMFAn significantly increased micronucleus formation (p < 0,01), highlighting a greater genotoxic potential compared to EMBAn. Given the results, EMBAn emerges as a promising alternative for future investigations due to its therapeutic potential and lower toxicity. However, additional studies are necessary to improve its selectivity, understand its mechanisms of action, and assess its clinical feasibility in melanoma treatment.