Exploring the Mechanism of the New Formula Patch of Simplify Xiaoyusan in the Treatment of Osteoarthritis Based on UPLC-Q-TOF-MS and Network Pharmacology
Objective To investigate the pharmacodynamic basis and targets of the new formula patch of simplify Xiaoyusan for treating osteoarthritis by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) coupled with network pharmacology. Methods The active ingredients of the new formula patch of simplify Xiaoyusan were obtained by UPLC-Q-TOF-MS combined with literature search,and the SwissTargetPrediction and Similarity ensemble approach databases were used for target prediction. GeneCards and OMIM databases were used to search for disease targets related to osteoarthritis,which were merged with targets of active ingredients and removed duplicates. The "active ingredients-effective targets" network was constructed by Cytoscape 3.10.2 software. The intersected targets were imported into STRING database to construct the protein interactions network,the intersected targets were further subjected to GO enrichment analysis and KEGG pathway enrichment by using the R(4.2.1)language. The molecular docking of key components and effective targets was carried out by using CB-dock2 online analysis software. Results A total of 54 active ingredients were identified from the new formula patch of simplify Xiaoyusan by applying UPLC-Q-TOF-MS technology,with 332 targets intersecting with osteoarthritis. It was predicted that the main components from the new formula patch of simplify Xiaoyusan,such as chicoric acid,rosmarinic acid,caffeic acid,rhubarb acid,azelaic acid,esculetin,ligustilide,neocryptotanshinone,and ferulic acid might act on key targets,including protein tyrosine phosphatase 11(PTPN11),phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1),phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha (PIK3CA),epidermal growth factor receptor (EGFR) and Janus kinase 2 (JAK2),and display immunomodulatory,anti-inflammatory and analgesic effects through regulating TNF,PI3K-Akt,EGFR tyrosine kinase inhibitor resistance and other signaling pathways. The screened potential active components showed good binding affinity with the core target. The binding energy of PIK3CA and caffeic acid (-9.7 kJ·mol-1) was the highest. Conclusion The study predicted that the main components (chicoric acid,rosmarinic acid,caffeic acid,rhubarb acid,azelaic acid,esculetin,ligustilide,neocryptotanshinone,and ferulic acid) from the new formula patch of simplify Xiaoyusan might act on core targets (PTPN11,PIK3R1,PIK3CA,EGFR,JAK2) via regulating TNF,PI3K-Akt,EGFR signaling pathways to play an immunomodulatory,anti-inflammatory andanalgesic effects.
New formula patch of simplify Xiaoyusanultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometryUPLC-Q-TOF-MSosteoarthritisnetwork pharmacologymolecular dockingmechanism
万方数据
维普
