Activity of rutin, a potent flavonoid against SSG-sensitive and -resistant Leishmania donovani parasites in experimental leishmaniasis

Abstract

The current treatment approach for leishmaniasis has been questioned in terms of development of the resistance and life threatening side-effects. The utility of the drug can only be confirmed by inspecting its safety window along with its impact against different strains of parasite including the resistant ones. The aim of this study was to evaluate the therapeutic effects of a flavonoid, rutin (RTN) against sodium stibogluconate (SSG) sensitive (S-) and resistant (R-) strain of L. donovani. RTN exhibited its anti-promastigote activity via arresting the cells at sub G0/G1 phase. Further RTN resulted in decline of splenic parasite burden. The parasiticidal activity was associated with the elicitation of cell-mediated immune response in terms of increased DTH response, augmented levels of T cells (CD4+, CD8+), Th1 cytokines, NO and ROS. RTN also up-regulated the expression of NF-ĸB and iNOS gene in S- as well as R- strain infected mice. Where no therapeutic effect of SSG was seen in the R-strain infected mice, the RTN treatment was able to control the disease in even R-strain infected mice. Moreover RTN was found to be devoid of any hepatic or renal toxicity. RTN could control the infection and it even had the capacity to counteract the resistant parasite by restoring the ability of host to produce protective immune response and microbicidal NO via up-regulating NF-ĸB and iNOS gene. This finding elucidates RTN to be a strong candidate in the antileishmanial drug pipeline not only against the sensitive but resistant strains also.