Abstract:Objective To investigate the mechanism of action of “YiCeng” in the treatment of knee osteoarthritis（KOA）based on Ultra-high performance liquid chromatography combined with time-of-flight mass spectrometry（UHPLC-TOF-MS） and network pharmacology. Methods UHPLC-TOF-MS was used to qualitatively analyse the chemical constituents of“YiCeng”plaster. Bioinformatic databases such as SwissTargetPrediction and GeneCards were used to collect molecular targets related to KOA，and the intersection of the two was screened to obtain the key targets and construct the protein-protein interaction network，and the intersection targets were analysed for the enrichment of theGO function and KEGG pathway. Cytoscape 3.9.1 software was used to construct a “compound-target-pathway” network and predict the targets of “YiCeng” plaster for the treatment of KOA. Results A total of 216 chemical components were identified in the “YiCeng” plaster，mainly including flavonoids，terpenes，and coumarins. Target protein interaction analysis screened 81 key targets，and KEGG enrichment analysis revealed the possible mechanism of action of the “YiCeng” plaster，which was to treat KOA by regulating signaling pathways such as AMPK，PI3K-Akt，and Toll-like receptors. Conclusion The treatment of KOA with “YiCeng” plaster may depend on the synergistic effects of multiple components，targets and pathways.