Natural small molecule hinokitone mitigates NASH fibrosis by targeting regulation of FXR-mediated hepatocyte apoptosis.

Introduction: Liver fibrosis is the common fate of NASH and poses a major health threat with very limited pharmacological treatments.

Objectives: This study aims to investigate the preventive effect of hinokitone (HO), an isolated compound from Agathis dammara, on NASH fibrosis and its underlying mechanism.

Methods: To investigate the effect of HO on NASH fibrosis, C57BL/6 mice were either fed a high-fat diet (HFD) in conjunction with intraperitoneal injection of CCl for 8 weeks or single CCl for 14 days to establish mouse liver fibrosis model, and HO was administered by gavage simultaneously.

Naringenin ameliorates MASH fibrosis via regulating TAK1/MAPK/FoxO3a-mediated apoptosis in the activated hepatic stellate cells.

This study aims to explore the regulating effect and mechanism of naringenin (NGN) on the hepatic stellate cells (HSCs) apoptosis and its preventive effects on MASH fibrosis. C57BL/6 mice were subjected to either high-fat diet (HFD) plus carbon tetrachloride (CCl) injection (HFD + CCl) for 8 weeks to induce a MASH fibrosis model or bile duct ligation (BDL) to establish a liver fibrosis model, NGN was administered by gavage. LX2 cells were stimulated by oleic acid (OA) and lipopolysaccharide (LPS) (OA + LPS) to study the effects of NGN on activated hepatic stellate cell (HSC).