Exploring the Difference in Mechanism of Action of Anoectochilus Roxburghii Leaves and Anoectochilus Formosanus Leaves in the Treatment of Liver Fibrosis Based on Integrative Metabolomics and Network Pharmacology

OBJECTIVE To preliminarily analyze the differences in the mechanism of action between the leaves of Anoectochilus roxburghii(Arl) and Anoectochilus formosanus(Afl) in the treatment of liver fibrosis, so as to provide reference information for the difference in clinical efficacy, and to conduct a more precise utilization of the plant resources. METHODS Metabolomics technology was used to analyze differential metabolites between Arl and Afl, and network pharmacology methods were applied to explore the differences in the effects of their differential metabolites in the treatment of liver fibrosis. RESULTS In metabolomics analysis, 46 differential metabolites between Arl and Afl were obtained, which mainly belong to flavonoids, glycosides and glycerophospholipids. Among them, 23 differential metabolites had potential medicinal activities. Based on network pharmacology analysis, the 759 related targets of 23 differential metabolites were predicted and 249 intersection targets were obtained by mapping with related targets of liver fibrosis diseases, 48 key targets including AKT1, STAT3 and VEGFA, etc were predicted as the main differential targets for the treatment of liver fibrosis. The key differential compounds with more targets were the compounds with higher content of Arl than Afl, indicating that Arl was richer in effective compounds that could be used to treat liver fibrosis. GO enrichment function and KEGG enrichment analysis showed that the A. roxburghii and A. formosanus were involved in the treatment of liver fibrosis with differential pathways, the VEGF signaling pathway was the main differential signaling pathway of the differential compounds with higher content of Arl than Afl, and the PI3K-Akt signaling pathway was the main differential signaling pathway of the differential compounds with lower content of Arl than Afl in the treatment of liver fibrosis. Molecular docking results showed that the differential components had good binding activity to their corresponding key targets. CONCLUSION This study indicates that the differential metabolites are present in Arl and Afl, which predicts the difference in the mechanism in the treatment of liver fibrosis disease and preliminarily verifies the action target. It provides guidance for the accurate utilization of A. roxburghii.