Immunotherapeutic potential of Codonopsis clematidea and naringenin against visceral leishmaniasis

In an attempt to explore reasonable and impervious remedies against visceral leishmaniasis, antileishmanial potential of hydroethanolic extract of Codonopsis clematidea (HECC) and its active component, naringenin (NRG) was investigated on the basis of innocuous and immunostimulatory properties. In vitro analysis showed the ability of HECC and NRG to arrest the promastigotes in sub G₀/G₁ phase. Further to evaluate the protective efficacy, inbred BALB/c mice infected with L. donovani were treated with HECC and NRG for 14 days. The treated animals were sacrificed on 7th and 14th post treatment days and scrutinized for clearance of parasite, DTH response, different Th1/Th2 cytokines (IFN-γ, IL-12, TNF-α, IL-17, IL-10, IL-4), T cells and B cell responses. The expression of iNOS, NFκB and the levels of nitric oxide (NO) and reactive oxygen species was also evaluated. The toxic effect of HECC and NRG was checked in terms of biochemical parameters and histological studies. Maximum reduction in parasite load and increase in the DTH response was observed in NRG treated animals in comparison to HECC and infected control. HECC and NRG switched the host Th2 immune response to the Th1-type along with the induction of CD4⁺ and CD8⁺ T cells. CD19 B cells were found to be decreased in NRG and HECC treated animals as compared to infected control. Moreover, treatment of HECC and NRG showed no alterations in hepatic and renal enzymes which was well supported by normal architecture of liver and kidney. The mechanistic details of NRG proved that it increased the NO and ROS production by activating the NFκB and iNOS expression and thus reduced the parasite load. These findings depicted that activity of HECC might be due to the presence of NRG and that the NRG provides an encouraging alternative for the treatment of visceral leishmaniasis with the rejuvenation of immune status of the host.