The Active Ingredients and Potential Mechanism of Qijia Rougan Decoction in Autophagy and Hepatic Stellate Cell Activation Modulation in Liver Fibrogenesis

TL;DR

This study explores how Qijia Rougan decoction may reduce liver fibrosis by affecting cell activation and autophagy processes.

Contribution

The study identifies active compounds and the PI3K/AKT/mTOR pathway as key mechanisms of Qijia Rougan decoction in liver fibrosis.

Findings

Qijia Rougan decoction reduced liver fibrosis markers and HSC activation in rats.

The decoction suppressed autophagosome formation and α-SMA expression in HSC-T6 cells.

Network analysis revealed 274 compounds and 12,883 targets linked to the PI3K/AKT pathway.

Abstract

Background and Objectives: Liver fibrosis results from chronic inflammation. Qijia Rougan decoction, a traditional Chinese medicinal formulation, shows hepatoprotective potential, yet its mechanisms remain unclear. This study aims to investigate its antifibrotic effects and underlying mechanisms.

Methods: Rat liver fibrosis was induced by carbon tetrachloride (CCl4) and ethanol exposure. Histopathological assessment was performed using hematoxylin–eosin (HE) and Masson's trichrome staining. Hepatic stellate cell (HSC) activation and autophagic processes were examined through western blot analysis, immunofluorescence staining, and other in vitro assays. Components of Qijia Rougan decoction were analyzed by BATMAN-TCM platform. The pharmacological network was constructed using BATMAN-TCM platform, while disease-related targets were identified through DisGeNET database. Pathway enrichment analysis was conducted using KEGG pathway database.

Results: Significant reductions in hepatic index and serum biomarkers (ALT, AST, ALP, TBA, and γ-GT) were observed following Qijia Rougan decoction treatment, with maximal efficacy at 6 weeks. The decoction downregulated of LC3B and α-SMA expression in fibrotic tissues. In vitro, it suppressed LPS-induced α-SMA expression and autophagosome formation in HSC-T6 cells. Network pharmacology analysis of Qijia Rougan decoction identified 274 bioactive compounds and 12,883 potential targets, with pathway analysis indicating PI3K/AKT signaling as the predominant regulatory mechanism.

Conclusion: Qijia Rougan decoction alleviates liver fibrosis, potentially by inhibiting HSC activation and autophagy processes via PI3K/AKT/mTOR pathway.

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