[Anti-fibrotic effects of Prismatomeris tetrandra ethyl acetate fraction: chemical characterization, bioinformatics analysis, and in vivo validation].

Liver fibrosis is a common pathological stage in the progression of various chronic liver diseases. Current interventions primarily focus on anti-inflammatory and antioxidant effects, lacking safe and universally applicable strategies for reversal. This work aimed to clarify the chemical basis and the potential mechanism of the ethyl acetate fraction of Prismatomeris tetrandra(HG). The constituents of HG were characterized by liquid chromatography-mass spectrometry(LC-MS). Transcriptomic dataset was analyzed for differential expression, which was followed by weighted gene co-expression network analysis(WGCNA). Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses were performed to build a "constituent-target-pathway" network for key pathway screening. A mouse liver fibrosis model was induced by carbon tetrachloride(CCl_4). After mice were administered continuously for 4 weeks, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(COL4) were detected. Hematoxylin and eosin(HE) and Masson staining were performed to assess histological changes, and Western blot was employed to detect the expression of alpha-smooth muscle actin(α-SMA) and the proteins related to death receptor pathway(Fas, Fas ligand [FasL], and Fas-associated death domain protein [FADD]). The results showed that the fraction was rich in coumarins and flavonoids. Bioinformatics analysis indicated that the signaling primarily acted on apoptosis-related pathways. In vivo, HG ameliorated liver injury and oxidative stress, reduced serum fibrosis markers, alleviated collagen deposition, and suppressed hepatic stellate cell(HSC) activation, with an overall dose-dependent trend. Network pharmacology results indicated that HG may reduce extracellular matrix(ECM) deposition by rebalancing inflammatory receptor-kinase signaling and promoting death receptor-mediated programmed cell death. Collectively, HG exhibits a clear anti-fibrotic effect in hepatic fibrosis models, potentially through mobilization of the extrinsic apoptotic pathway, which provides a basis for further validation of key monomers and causal mechanisms.