Swertia purpurascens Wall ethanolic extract mitigates hepatic fibrosis and restores hepatic hepcidin levels via inhibition of TGFß/SMAD/NFκB signaling in rats.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Swertia purpurascens Wall belongs to a well-known genus in traditional systems of medicine worldwide. In folklore, it is used to treat various ailments, including hepatic disorders, as an alternative to the endangered species Swertia chirayita. However, the therapeutic potential of Swertia purpurascens Wall against hepatic fibrosis has not been validated yet. AIM OF THE STUDY The present study was planned to evaluate the efficacy of the Swertia purpurascens Wall extract (SPE) against hepatic fibrosis and elucidate the underlying mechanism of action. MATERIALS AND METHODS: The metabolite profiling of the SPE was done using UHPLC-QTOF-MS/MS. The acute oral toxicity study of SPE at 2 g/kg BW dose was done in rats. Further, the liver fibrosis was induced by the CCl4 intoxication, and the efficacy of SPE at three doses (100, 200 and 400 mg/kg BW) was evaluated by studying biochemical parameters, histopathology, immunohistochemistry, qRT-PCR, western blotting and in silico analysis. RESULTS: UHPLC-QTOF-MS/MS analysis revealed the presence of a total of 23 compounds in SPE. Acute oral toxicity study of SPE at 2 g/kg BW showed no harmful effects in rats. Further, the liver fibrosis was induced by the CCl4 administration, and the efficacy of SPE was evaluated at three doses (100, 200 and 400 mg/kg BW). SPE treatment significantly improved the body weight gain, the relative liver weight, serum liver injury markers and endogenous antioxidant enzyme levels in the CCl4-treated rats. SPE also recovered the altered liver histology and effectively reduced the fibrotic tissue deposition in the hepatic parenchyma. Further, SPE significantly inhibited the fibrotic (TGFß, αSMA, SMADs and Col1A), proinflammatory markers (NFκB, TNFα and IL1ß) and apoptosis in the liver tissue. Interestingly, SPE treatment also restored the altered hepcidin levels in the liver tissue. In silico study revealed the potential of various metabolites as drug candidates and their interaction with target proteins. CONCLUSION: Altogether, SPE showed its therapeutic potential against CCl4-induced hepatic fibrosis by restoring the hepatic hepcidin levels and inhibiting TGFß/SMAD/NFκB signaling in rats.