Objective To investigate the therapeutic effect and potential mechanism of Penthorum chinense (PCP) on primary sclerosing cholangitis (PSC). Methods The chemical constituents of PCP extract were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 50 mice were randomly divided into control group, model group, obeticholic acid (6.5 mg/kg) group and PCP low-, high-dose (2, 4 g/kg) groups, with 10 mice in each group. Mice were fed with 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feed to induce PSC model. After 14 d of intervention, the efficacy of PCP was evaluated by measuring serum biochemical indicators, liver histopathological changes and liver fibrosis markers. To further explore the mechanisms, transcriptomic sequencing, qRT-PCR experiment and quantitative analysis of bile acid profile were performed. Results A total of 331 chemical constituents were identified in PCP extract. Pharmacodynamic results showed that compared with model group, high-dose PCP significantly reduced liver index and levels of liver injury markers in serum (P < 0.05, 0.01, 0.001), and effectively alleviated cholestasis and fibrosis in liver tissue, with effects superior to those of positive drug obeticholic acid. Transcriptomic analysis identified 51 differentially expressed genes. Enrichment analysis suggested that the effect of PCP was associated with pathways such as bile secretion. Mechanistic validation revealed that compared with model group, high-dose PCP significantly down-regulated mRNA expressions of key enzymes for primary bile acid synthesis in liver tissue (P < 0.05), while up-regulated expression of bile acid‑conjugating enzyme (P < 0.001). Serum and liver bile acid profiling revealed that high-dose PCP intervention significantly increased the ratio of conjugated to unconjugated bile acids (P < 0.001). Conclusion PCP ameliorates DDC‑induced cholestatic liver injury and exerts a therapeutic effect on PSC by inhibiting primary bile acid synthesis, promoting bile acid conjugation and excretion.

Penthorum chinense Pursh  /  primary sclerosing cholangitis  /  bile secretion  /  transcriptomics  /  bile acid  /  gallic acid  /  3-indolepropionic acid  /  6-hydroxykaempferol-7-O-glucoside