白花蛇舌草改善肝纤维化伴骨骼肌损伤机制研究OA

OBJECTIVE To reveal the mechanism by which Hedyotis diffusa achieves synergistic therapeutic effects by regulating liver-muscle metabolic homeostasis through multiple targets.METHODS A mouse model of liver fibrosis with skeletal muscle injury was induced by CCl4;active components entering the blood were identified by HPLC-Q-TOF;111 key targets were screened by net-work pharmacology;their pathways of action were analyzed by KEGG enrichment;high affinity of rutin for tumor protein 53(TP53)and quercetin for tumor necrosis factor(TNF)was verified by molecular docking;and the effects of HDI on skeletal muscle mitochondrial function and respiratory chain gene expression were assessed by metabolomics.RESULTS HDI could simultaneously improve colla-gen deposition in liver tissue and skeletal muscle injury;KEGG enrichment analysis showed that it regulated metabolic disorders through the HIF-1 and Hippo signaling pathways;molecular docking verified the high affinity of rutin for TP53 and quercetin for TNF;metabolomics confirmed that HDI reversed mitochondrial dysfunction in skeletal muscle and repaired respiratory chain gene expres-sion.CONCLUSION This study breaks through the limitations of traditional single-target hepatic stellate cells therapy and provides a new strategy for liver-muscle comorbidity from the perspective of organ interaction.