Effectiveness of harmaline along with meglumine antimoniate on Leishmania major

Leishmaniasis is a disease caused by Leishmania species and transmitted via sandflies. Current control strategies against reservoir hosts and vectors are not eco-friendly. Using harmaline (HA) from Peganum harmala, and meglumine antimoniate (MA) could be a promising therapy. The study aimed to explore the potential treatment outcomes and action mechanisms of HA and MA against Leishmania major stages by investigating their effectiveness through molecular docking, anti-leishmanial effects, safety assessment, and apoptotic profile evaluations. According to the molecular docking results, the protein-ligand interaction profiler identified that Bcl-2 interacts with HA mainly through hydrogen bonds, while Bax uses both hydrogen and hydrophobic interactions, indicating a stronger binding of HA to Bax compared to Bcl-2. The HA combined with MA (HA/MA) showed potent anti-leishmanial activity without toxicity. In vitro studies significantly demonstrated that HA inhibited the growth of promastigotes and amastigotes. The HA/MA was more effective in inhibiting parasite growth. Based on the study findings, HA and HA/MA mixture can be considered a viable treatment option for cutaneous Leishmaniasis.