Studies on the protective and immunomodulatory efficacy of Withania somnifera along with cisplatin against experimental visceral leishmaniasis.

Visceral leishmaniasis (VL) or kala-azar continues to persist as one of the major public health problems in many tropical countries. However, no effective treatment for cure of the disease is yet available. The present study was designed to investigate the nephroprotective and immunomodulatory effect of Withania somnifera in cisplatin-treated Leishmania donovani-infected BALB/c mice. Administration of cisplatin (5 mg/kg body weight (b.wt.) daily for 5 days, i.p.) reduced the parasite load in L. donovani-infected BALB/c mice but produced damage in liver and kidney as manifested biochemically by an increase in SGOT, SGPT, serum creatinine, and blood urea nitrogen, respectively. The biochemical analysis was further substantiated by histopathological changes induced in the liver and kidney by cisplatin. However, W. somnifera (350 mg/kg b.wt. daily for 15 days, orally) when given along with cisplatin, significantly reversed these changes and enhanced the antileishmanial efficacy of the drug, cisplatin. But, when W. somnifera was given alone per se it showed less antileishmanial potential. The results also indicate that W. somnifera in combination with cisplatin resulted in significant selective upregulation of Th1 type of immunity because it guided expression of T helper cell (Th1)1 cytokines, IFN-gamma and IL-2; augmented levels of IgG2a over IgG1; and heightened DTH (delayed type hypersensitivity) responses while Th2 cytokines, IL-4, and IL-10 were downregulated. Flow cytometric analysis of W. somnifera and cisplatin-treated animals showed an increase in the percentage of T cells (CD4+, CD8+) and NK1.1 suggesting its effect on activation of T cells. These results confirm the protective and immunomodulatory activity of W. somnifera suggesting that it along with cisplatin may be a critical remedy for the amelioration of adverse effects of cisplatin. Thus, this combination appears to offer a fruitful strategy for treatment of VL.