Panaxydol extracted from Panax ginseng inhibits NLRP3 inflammasome activation to ameliorate NASH-induced liver injury.

ABSTRACT

Activation of NOD-like receptor protein 3 (NLRP3) inflammasome exacerbates liver inflammation and fibrosis in nonalcoholic steatohepatitis (NASH), suggesting that development of inflammasome inhibitor can become leading candidate to ameliorate NASH. Panax ginseng (P. ginseng) contains numerous bioactive natural components to reduce inflammation. This study aims to identify inhibitory components of P. ginseng for NLRP3 inflammasome activation. We separated polar and non-polar fractions of P. ginseng and tested modulation of NLRP3 inflammasome, and then identified pure component for inflammasome inhibitor which ameliorates diet-induced NASH. Non-polar P. ginseng fractions obtained from ethyl acetate solvent attenuated IL-1ß secretion and expression of active caspase-1. We revealed that panaxydol (PND) is pure component to inhibit NLRP3 inflammasome activation. PND blocked inflammasome cytokines release, pyroptotic cell death, caspase-1 activation and specking of inflammasome complex. Inhibitory effect of PND was specific to NLRP3-dependent pathway via potential interaction with ATP binding motif of NLRP3. Moreover, in vivo studies showed that PND plays beneficial roles to reduce tissue inflammations through disruption of NLRP3 inflammasome and to ameliorate the development of NASH. These results provide new insight of natural products, panaxydol, for NLRP3 inflammasome inhibitor and could offer potential therapeutic candidate for reliving NASH.