Abstract:
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 network 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 collagen 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 expression.
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.
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