Hepatoprotective and antifibrotic effects of Eryngium billardieri extract associated with changes in α-SMA and TGF-β mRNA expression in rats with BDL-induced cholestasis

Cholestasis results from defective bile formation and/or obstruction of bile flow, which promotes intrahepatic retention of bile acids and other toxic constituents and can progress to liver fibrosis. In this study, forty-eight male Wistar rats were allocated to eight groups and treated by gavage with Eryngium billardieri extract (100, 200, or 400 mg/kg) for 45 days; biochemical indices, antioxidant status, histopathology, and expression of fibrosis-related markers were evaluated. HPLC–DAD was applied for qualitative fingerprinting of major phenolic constituents, including caffeic, chlorogenic, protocatechuic, and rosmarinic acids. In BDL rats, E. billardieri produced dose-dependent hepatoprotective, antifibrotic, and antioxidant effects, reflected by improved liver function indices and lipid profile, restoration of hepatic antioxidant enzyme activities, attenuation of fibrosis-associated histopathological changes, and reduced expression of the profibrotic markers TGF-β and α-SMA, particularly at 200 and 400 mg/kg. Overall, E. billardieri extract shows preclinical hepatoprotective and antifibrotic activity in a rat model of cholestatic liver injury, potentially by enhancing antioxidant defenses and suppressing fibrogenic responses; these findings are hypothesis-generating and support further mechanistic, translational, and clinical studies before any inference can be made for human disease.