[Role and mechanism of Renqing Mangjue in attenuating hepatic fibrosis via PRMT1/H4R3me2a/PAI-1/MCP-1 epigenetic regulatory axis based on network pharmacology and experimental validation].

The current study aims to elucidate the underlying pharmacological mechanisms of the Tibetan medicine Renqing Mangjue against hepatic fibrosis using a research strategy integrating network pharmacology and experimental verification. Through the combination of a rat hepatic fibrosis model induced by diethylnitrosamine(DEN) and the analysis of clinical transcriptome data from the GEO database, the characteristics of its pharmacological effects were objectively evaluated, and its mechanism of action was systematically analyzed. The experimental results showed that the intervention of Renqing Mangjue significantly reduced the levels of serum hepatic fibrosis markers, including procollagen type Ⅲ(PCⅢ), collagen type Ⅳ(Ⅳ-C), and laminin(LN). Specifically, the medium-dose group showed a decrease of 37.8%, 47.1%, and 36.6% respectively compared with the model group(all P < 0.05) and a reduced collagen deposition in the liver tissue. The mechanism study found that it down-regulated the expressions of protein arginine methyltransferase 1(PRMT1), histone H4 arginine 3 dimethylation(H4R3me2a), plasminogen activator inhibitor-1(PAI-1), and monocyte chemoattractant protein 1(MCP-1) and inhibited the PRMT1/H4R3me2a/PAI-1/MCP-1 signaling axis, thereby inhibiting the activation of hepatic stellate cells and the excessive deposition of the extracellular matrix. This study is the first to clarify that Renqing Mangjue may exert an anti-hepatic fibrosis effect through the epigenetic regulation pathway, providing an experimental basis for its clinical application and offering a new paradigm for modern research on Tibetan medicine compounds.