Evaluation of in vitro and in vivo antileishmanial potential of bergenin rich Bergenia ligulata (Wall.) Engl. root extract against visceral leishmaniasis in inbred BALB/c mice through immunomodulation

Abstract

BackgroundMedicinal plants with immunomodulatory properties can provide good alternative therapeutics for curing visceral leishmaniasis. Bergenia ligulata (Wall.) Engl. is an interesting plant with strong antioxidant, antimicrobial, immunomodulatory and hepatoprotective properties.AimThe present study was planned to determine the antileishmanial activity of plant extract by modulating the immune responses of inbred BALB/c mice.MethodologyBergenin, the principle active component of B. ligulata, was quantitated in crude extract by performing RP-HPLC. The therapeutic potential was assessed through in vitro antileishmanial activity and in mice model through parasite load, cytokine assays, IgG antibody levels, DTH responses, histopathology and biochemical enzyme assays.ResultsB. ligulata showed the presence of glycosides, saponins, carbohydrates, tannins, flavonoids and bergenin which contributed to the antileishmanial activity of extract with IC50 of 22.70 μg/mL. Furthermore, the higher dose significantly reduced the parasite load by 95.56 %. The reduction was further associated with significant enhancement of IL-12 and IFN-γ levels in comparison to IL-10 and IL-4 cytokines. The switching towards Th1 type of immune response was also confirmed by elevated antibody levels of IgG2a isotype as compared to IgG1 as well as increased DTH responses. The histology of liver and kidney further complimented the non toxic nature of plant extract in addition to its negligible toxicity on HeLa cells.ConclusionsThe current study revealed the significant antileishmanial and immunomodulatory properties of this plant extract against murine visceral leishmaniasis. Further, the bioactive components will be explored to assess their efficacy for the development of safe and cost effective drug.

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

“…The Bergenin dose was chosen based on previous research. [32][33][34] Sham groups underwent no action apart from opening and stitching of the abdominal cavity. Bergenin (dissolved in physiological saline) groups were given a corresponding dose (10, 20 or 40 mg/kg) of Bergenin by gavage at 3 days (once before the operation, once per day).…”

Evaluation of in vitro antileishmanial efficacy of cyclosporin A and its non-immunosuppressive derivative, dihydrocyclosporin A

“…Meanwhile, TNF-α and IFN-γ, implicated to be involved in the activation of macrophages, were also observed to play a role in preventing parasite replication [32]. Previous studies also verified that drugs which have inhibitory effects on L. donovani, could decrease IL-10 and IL-4 in VL mice [4,33,34]. In this study, the reduction of parasite burden was supported by the increase of IL-12, IFN-γ and TNF-α and decrease of IL-4 and IL-10 after DHCsAd or SSG treatments.…”

Leishmanicidal Activity of Betulin Derivatives in Leishmania amazonensis; Effect on Plasma and Mitochondrial Membrane Potential, and Macrophage Nitric Oxide and Superoxide Production

“…Besides that, medicinal plants and their secondary metabolites may have immunomodulatory properties [ 74 ] [superoxide (O 2 − ) and nitric oxide (NO) production], potentially useful against leishmaniasis [ 75 ]. L. major amastigote elimination depends preferentially on NO production [ 75 ] and L. (V.) braziliensis abolition seems to strictly depend on both O 2 − and ROS generation [ 76 ].…”