Avaliação da atividade leishmanicida e citotoxicidade de extratos de Berberis e do cloridrato de berberina para o tratamento das leishmanioses

Abstract

Leishmaniasis is a disease caused by an obligate intracellular protozoal which parasite the phagocytic mononuclear system cell. The main clinic manifestations are cutaneous (CL) and visceral leishmaniasis (VL). In most cases the current treatment protocols present toxicity and poor effectiveness. Furthermore, these parasites are becoming more resistant against conventional treatment methods. Therefore, the importance of finding new treatments has become crucial. An alternative is to use, essentially, medicinal plants. It is known that plants of the genus Berberis are used to treat other diseases as hypertension and gastrointestinal disorders. Due to successes of this plant in other treatments, the study of Berberis sp. leishmanicidal activity has become crucial to investigate phytotherapeutic innovative approaches for the leishmaniasis treatment. This research studied the in vitro and in vivo efficacy of berberine chloride and extracts of Berberis laurina and Berberis glazioviana against Leishmania amazonensis and Leishmania infantum along with the cytotoxicity against HepG2 A16 cells to determine the therapeutic index of each substance. Berberine chloride presented a more cytotoxic effect as an active constituent at high concentrations in the HepG2 cells (CC50 = 88.20 ± 19.30 μg/mL), while the hydroethanolic, methanolic and ethanolic berberine extracts presented low cytotoxicity in HepG2 cells (>1000 μg/mL; 834.30 ± 78.71 μg/mL and 557.85 ± 69.75 μg/mL) and high anti-Leishmania activity and selectivity indexes against promastigotes of both Leishmania species. In the in vivo study, we used murine models of visceral and cutaneous leishmaniasis, demonstrating that berberine chloride (10mg/kg) and the extracts were able to reduce the parasite load in the liver and spleen. In conclusion, this study presented outcomes of the leishmanicidal activity using berberine chloride and berberine extracts against L. infantum and L. amazonensis associated with moderate and low cytotoxicity. Furthermore, the results obtained, suggest that this substance is a promising candidate to develop new therapeutic alternatives derived from natural products to treat leishmaniasis with high efficacy, reducing side effects.