Dencichine ameliorates hepatic fibrosis by modulating the PI3K-AKT

Background: Hepatic fibrosis is a major consequence of various chronic liver injuries and can progress to cirrhosis and hepatocellular carcinoma. As a medicinal and edible traditional Chinese herb, Panax notoginseng contains an active ingredient, Dencichine, which shows promising potential in the treatment of hepatic fibrosis. This study aimed to investigate the mechanism of Dencichine in ameliorating hepatic fibrosis using both in vivo and in vitro models. Methods: C57BL/6J mice were randomly grouped and injected with 10% CCl₄ for 15 weeks to induce hepatic fibrosis. Dencichine treatment was administered from the 7th week onward. LX-2 hepatic stellate cells were induced with 20 ng/mL PDGF-BB for 1–48 hours to establish a fibrotic model, and treatment groups received low-, medium-, and high-dose Dencichine. Liver function was assessed by measuring serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), and laminin (LN). Liver morphology and fibrosis were evaluated using hematoxylin-eosin (H&E) staining, Masson staining, and Sirius red staining. Gene and protein expression levels were analyzed using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. Cell migration was assessed via scratch and Transwell assays, while cell proliferation and cell cycle were examined using EdU assay and flow cytometry. Results: Dencichine significantly reduced serum levels of AST, ALT, HA, and LN in CCl₄-treated mice, alleviated liver injury, and decreased collagen deposition. Furthermore, Dencichine suppressed the expression of cyclin D1 and cyclin E1. It also inhibited the phosphorylation of PI3K and AKT in hepatic fibrotic cells. Conclusion: The findings suggest that Dencichine may effectively attenuate the progression of hepatic fibrosis by inhibiting the PI3K-AKT signaling pathway, thereby exerting anti-fibrotic effects.