Xuanhusuosan's Pharmacodynamic Material Basis And Preliminary Molecular Mechanism Of Action In The Treatment Of Osteoarthritis

Xuanhusuosan(XHSS)is composed of Yanhusuo,Buguzhi,Danggui,and Niuxi.It is a classic compound for the treatment of osteoarthritis.As Jun,Yanhusuo has played a major role in pharmacodynamics,and as Chen,Buguzhi replenishi liver and kidney,Danggui promote blood circulation,and Niuxi induce the drug to act on the lesion.XHSS has a classic and effective effect,but the pharmacodynamic basis and mechanism of the treatment of osteoarthritis by XHSS are still unclear.Based on the research of XHSS chemical substance omics,this topic combines serum medicinal chemistry and network pharmacology to study the pharmacodynamic basis and mechanism of XHSS in the treatment of osteoarthritis.The content of this study mainly includes the following parts:1.Rapid identification of the chemical constituents of XHS,Buguzhi and YanhusuoUltra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MSE technology)is one of the important techniques for studying traditional Chinese medicine and compound chemical composition,and its sensitivity,resolution and accuracy are very high.In this study,UPLC-Q-TOF-MSE technology was combined with data processing software MassLynx and UNIFI to characterize the chemical constituents of XHSS and its representative single-flavored Buguzhi and Yanhusuo.The experiment identified 44 compounds in Buguzhi,32 compounds in Yanhusuo,and 115 compounds in XHSS.It laid the foundation for further research on the composition of the body.2.Study on the body composition of XHSS after intragastric ratsAfter fully studying the chemical substance omics of XHSS,this study studied the prototype components and metabolic components in blood,urine and feces after the rats were administered with the medicinal chemistry of serum.Firstly,UPLC-Q-TOF-MSE technique was used to study the in vivo drug-derived components of four representative monomers of psoralen,tetrahydropalmatine,ferulic acid and ecdysterone in XHSS.The metabolic reaction that exists.Then,UPLC-Q-TOF-MSE technique was used to detect the blood samples,urine samples and feces of normal rats after the administration of XHSS,and the drug-derived components of XHSS in rats were identified.A total of 50 drug-derived components were identified from rat blood samples,including 9 prototype components and 41 metabolic components.A total of 92 drug-derived components were identified from rat urine samples,including 23 prototype components.There were 69 metabolic components;77 drug-derived components were identified from rat feces,of which 33 were prototype components and metabolized into 44.The experiment initially determined the pharmacodynamic basis of XHSS for the subsequent study of the mechanism of the treatment of osteoarthritis by XHSS.3.The molecular mechanism of XHSS in the treatment of osteoarthritisBased on the previous study of serum medicinal chemistry,this study further explored the molecular mechanism of XHSS in the treatment of osteoarthritis by using network pharmacology strategy.Taking the nine blood components of XHSS as the entry point,through the prediction of the chemical composition target of Chinese medicine and the analysis of the target of osteoarthritis disease,69 potential targets for the treatment of osteoarthritis were deter mined.point.On this basis,the String platform was used to analyze the protein-protein interaction between the compound and the disease target,and Cytoscape software was used for topology analysis to screen out 10 key targets and visualize the data.Then,using molecular docking technology to verify the activity of 9 compounds and 10 key targets,it was found that all Docking Score values were greater than 4.25,indicating that the nine blood-injected prototype components are active ingredients for the treatment of osteoarthritis.Using the String online database for GO bioanalysis and KEGG pathway analysis,GO bioanalysis found that there were 1344 biology process related to osteoarthritis,128 molecular functions,and 65 cellular components.The KEGG pathway analysis revealed there are 35 related pathways and related metabolism.At the end of the experiment,Cytoscape software was used to construct a network of "XHSS-Chinese medicine-Compounds-Targets-Signaling pathway-Osteoarthritis",It embodies the characteristics of the multi-component,multi-target and multi-channel synergy treatment of osteoarthritis.In summary,based on the three theories of chemical composition,serum medicinal chemistry and network pharmacology,this study explored the chemical composition,pharmacodynamic basis and molecular mechanism of XHSS.Chemical composition(+)-Corydaline,Tetrahydropalmatine,Leonticine,Psoralen,Angelicin,Bakuchiol,Senkyunolide K,Angeloylsenkyunolide F and Ecdysterone as the pharmacodynamic basis of XHSS for the treatment of osteoarthritis,and found the five most important signaling pathways include TNF signaling pathway,IL-17 signaling pathway,MAPK signaling pathway,RLX signaling pathway,TLR signaling pathway,and one important metabolism which is Arachidonic acid metabolism.