机构地区:[1]Department of Orthopaedic Surgery,Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China [2]Department of Orthopaedic Surgery,Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510120,China [3]Department of Orthopaedic Surgery,Beijing Longfu Hospital,Beijing 100010,China
出 处:《Chinese Journal of Integrative Medicine》2024年第5期433-442,共10页中国结合医学杂志(英文版)
基 金:Supported by the National Natural Science Foundation of China (No.81373662 and No.81874475);Capacity Building Project of Chinese and Western Medicine Clinical Collaboration on Major Difficult Disease (No.201803190106)。
摘 要:Objective:To explore the mechanism of paeoniflorin(PF)on osteoarthritis(OA)synovial inflammation from network pharmacology to experimental pharmacology.Methods:Targets of OA were constructed by detecting the database of network database platforms(Therapeutic Target database,Drug Bank and Gene Cards),and the targets of PF were constructed by Pub Chem and Herbal Ingredients'Targets database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of these co-targeted genes were conducted via Database for Annotation,Visualization,and Integrated Discovery(DAVID)database,and protein-protein interaction(PPI)networks were conducted via the search tool for the retrieval of interacting genes(STRING)database.Cell counting kit-8(CCK-8)assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes(FLS),quantitative real-time polymerase chain reaction(q PCR),enzyme-linked immunosorbent assay(ELISA)and Western blot were used to verify the potential mechanism of PF in synovial inflammation.Results:Twenty-six co-targeted genes were identified.GO enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm,and the biological processes mainly involved'cellular response to hypoxia''lipopolysaccharide(LPS)-mediated signaling pathway'and'positive regulation of gene expression'.KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with'hypoxia-inducible factor-1(HIF-1)signaling pathway'and'tumornecrosis factor(TNF)signaling pathway'.The PPI network showed that the top 3 hub genes were TP53,TNF,and CASP3.Molecular docking results showed that PF was well docking with TNF.CCK-8 showed no potential toxicity of 10,20 and 50μmol/L PF on human OA FLS.And PF significantly decreased the expression levels of interleukin-1β,interleukin-6,TNF-αmatrix metalloproteinase 13(MMP13),and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5)and TNF-αin LPS-induced OA FLS.Conclusion:PF exhibi
关 键 词:PAEONIFLORIN OSTEOARTHRITIS synovial inflammation tumor necrosis factor-α network pharmacology Paeonia lactiflora
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