Effect of hederagenin-type triterpene saponin mixture of Sapindus saponaria (Sapindaceae) on Leishmania spp. and its therapeutic potential in cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) causes skin lesions, mainly ulcers, on exposed parts of the body which can leave life-long scars and cause serious disability or stigma. Early diagnosis and treatment reduce the prevalence of the disease, reduce transmission and prevents disabilities and death. Nevertheless, there are very few effective anti-leishmanial medicines that are associated with high toxicity and adverse effects; therefore, more effective and safer drugs are urgently needed. Previously it was found saponins of Sapindus saponaria (Sapindaceae) pericarp had an inhibitory activity in Leishmania panamensis. This work aimed to determine the in vitro cytotoxicity and leishmanicidal activity of a mixture of hederagenin-type triterpene saponins of S. saponaria. The effects of SS on the parasite ultrastructure and on several parasite functions including energy metabolism, cellular stress, protease activity, re-infection capacity, production of reactive oxygen and nitrogen species and formation of lipid bodies were also evaluated. The SS was active against L. braziliensis and L. panamensis amastigotes at 20 μg/mL; nonetheless the cytotoxicity varied according to cell type and origin. Additionally, SS increased the parasite size and the number of electro-dense vacuoles. SS also affected the mitochondrial functioning modulating ROS production, ∆Ψm and ATP levels. Lastly, SS inhibited protease activity in Leishmania and induced the production of nitric oxide in infected cells. In conclusion, SS destabilizes the energy metabolism, the redox balance and the infective capacity of the parasite. These results allow us to point out SS as a lead compound in the development of a drug to effectively treat CL ([Fig. 1]).

Fig. 1 Chemical structures in the hederagenin-type triterpene saponin mixture.

 

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Artikel online veröffentlicht:
16. November 2023