Tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis

Abstract

Effect of pure herb, Tinospora cordifolia was studied for its hepatoprotective, nephroprotective and immunomodulatory activity against high dose cisplatin treatment in Leishmania donovani infected BALB/c mice. Administration of cisplatin (5mg/kg b.wt. daily for 5days, 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 serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum urea, serum creatinine and various electrolytes etc. These biochemical analyses were further supported by cisplatin induced morphological changes in kidney, liver and spleen. To combat this pure herb, T. cordifolia (100mg/kg b.wt. for 15days daily) was used in combination with cisplatin in L. donovani infected BALB/c mice and it was found that all the aforementioned changes were effectively attenuated by T. cordifolia when administered in combination with cisplatin. Moreover, flow cytometric analysis of lymphocyte surface markers of T cells (CD3+, CD4+ and CD8+), NK1.1 and B cells (CD19) indicated prominent enhancement in proliferation and differentiation of lymphocytes. T. cordifolia in combination with cisplatin selectively induced Th1 type of immune response as depicted by enhanced levels of IFN-γ and IL-2 whereas Th2 specific cytokines IL-4 and IL-10 observed a moderate decline. Confirmation of Th1 polarization was further obtained from augmented levels of IgG2a over IgG1 and heightened DTH (delayed type hypersensitivity) response. Thus, our results suggest that treatment by T. cordifolia may be a critical remedy for the amelioration of adverse effects of cisplatin. Thus, this might serve as a novel combination against visceral leishmaniasis in future.