Intracellular anti-leishmanial effect of Spergulin-A, a triterpenoid saponin of Glinus oppositifolius

ABSTRACT

Many of present chemotherapeutics are inadequate and also resistant against visceral leishmaniasis (VL) an immunosuppressive ailment caused by Leishmania donovani. Despite the interest in plant-based drug development, very few number of antileishmanial drugs from plant source is available. Glinus oppositifolius had been reported in favor of being immunomodulators along with other traditional uses. Novel anti-VL therapies can rely on host immune-modulation with associated leishmanicidal action. With this rationale, an n-BuOH fraction of the methanolic extract of the plant and obtained triterpenoid saponin Spergulin-A were evaluated against acellular and intracellular L. donovani. Immunostimulatory activity of them was confirmed by elevated TNF-α and extracellular NO production from treated MФs and was found nontoxic to the host cells. Identification and structure confirmation for isolated Spergulin-A was performed by ESI-MS, ¹³C, and ¹H NMR. Spergulin-A was found ineffective against the acellular forms while, against the intracellular parasites at 30μg/ml, the reduction was 92.6% after 72h. Spergulin-A enhanced ROS and nitric oxide (NO) release and changes in Gp91-phox, i-NOS, and pro and anti-inflammatory cytokines elaborated its intracellular anti-leishmanial activity. The results supported that G. oppositifolius and Spergulin-A can potentiate new lead molecules for the development of alternative drugs against VL.