Evaluation of immunotherapeutic potential and antileishmanial efficacy of cicer microphyllum and putranjiva roxburghii against murine visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) is a dreaded protozoan parasitic infection caused by L. donovani or L. infantum. This affliction is considered a neglected disease that affects the most impoverished population around the world. At present lack of effective vaccine, few chemotherapeutics, related toxicities, high cost, and the emergence of resistant strains to the conventional therapeutics are major issues that need to be resolved for VL control and eradication. Pharmacotherapy holds a promising future in drug development owing to extensive secondary metabolite diversity. The current study was therefore designed to evaluate the in vitro and in vivo antileishmanial activity and immunomodulatory potential of Cicer microphyllum and Putranjiva roxburghii against L. donovani. The in vitro activity of plant extracts was tested against SSG-sensitive and -resistant strains of L. donovani promastigotes. The cell membrane integrity, ROS generation, and cell cycle arrest were also evaluated and it was observed that both extracts lead to a loss in the integrity, production of reactive oxygen species and arrest of the cell cycle at the sub-G0/G1 phase in the promastigotes. The in vivo study was carried on the BALB/c mice infected with L. donovani. The infected mice were administered orally with plant extracts viz. CMH and PRH (250 and 500 mg/kg b. wt.) and exhibited a marked decline in hepatic and splenic parasite load compared to the infected controls. The treatment of infected animals with either dose of CMH and PRH resulted in augmentation of delayed-type hypersensitivity response, IgG2a antibody levels, Th1 type-specific cytokines and elevation of CD4+ and CD8+ T lymphocytes. Besides this, the plant extracts showed no toxicity. Thus, the plant extracts demonstrated good antileishmanial and immune modulatory action. newline