Integrated analyses to explore the mechanism of Gancao Renshen Zhixue Decoction in treating liver cirrhosis

The study aims to explore the key mechanism of Gancao Renshen Zhixue Decoction (GCRSZXD) in treating liver cirrhosis (LC). Common targets of GCRSZXD and LC were obtained, and the hub genes were identified by network construction and differential expression analysis. Key active ingredients were determined by intersecting the top 10 common target-related and hub gene-related active ingredients. Then, enrichment analysis was performed to identify the essential pathways. Besides, the GCRSZXD-Chinese herb-active ingredient-hub gene-signaling pathway-LC network was constructed to explore potential regulatory mechanisms. Molecular docking and molecular dynamic simulation were used to verify the binding ability of key active ingredients with hub genes. Finally, hub gene expression was validated in vitro. Totally 180 common targets and 120 associated active ingredients were identified. Three hub genes, AKT1, EGFR, and SRC were differentially expressed in LC and healthy groups (P < 0.05). Five key active ingredients and three signaling pathways were obtained. Excellent binding effects of receptors and ligands were observed. Additionally, GCRSZXD significantly reduced the expression of AKT1, EGFR, and SRC in the TGF-β1-induced cells. In conclusion, this study reveals the mechanism of GCRSZXD in LC treatment, which provides the theoretical basis for the mechanism research of GCRSZXD.