Pu Chen, Jun Zhou, An-Min Ruan, Yu-Feng Ma, Qing-Fu Wang
{"title":"芍药苷是芍药的主要单体成分,对骨关节炎滑膜炎症具有抗炎作用。","authors":"Pu Chen, Jun Zhou, An-Min Ruan, Yu-Feng Ma, Qing-Fu Wang","doi":"10.1007/s11655-023-3653-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To explore the mechanism of paeoniflorin (PF) on osteoarthritis (OA) synovial inflammation from network pharmacology to experimental pharmacology.</p><p><strong>Methods: </strong>Targets of OA were constructed by detecting the database of network database platforms (Therapeutic Target database, DrugBank and GeneCards), and the targets of PF were constructed by PubChem 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 (qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot were used to verify the potential mechanism of PF in synovial inflammation.</p><p><strong>Results: </strong>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 'tumor-necrosis 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 50 µmol/L PF on human OA FLS. And PF significantly decreased the expression levels of interleukin-1 β, interleukin-6, TNF-α matrix metalloproteinase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and TNF-α in LPS-induced OA FLS.</p><p><strong>Conclusion: </strong>PF exhibited potent anti-inflammatory effect in OA synovial inflammation.</p>","PeriodicalId":10005,"journal":{"name":"Chinese Journal of Integrative Medicine","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Paeoniflorin, the Main Monomer Component of Paeonia lactiflora, Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation.\",\"authors\":\"Pu Chen, Jun Zhou, An-Min Ruan, Yu-Feng Ma, Qing-Fu Wang\",\"doi\":\"10.1007/s11655-023-3653-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To explore the mechanism of paeoniflorin (PF) on osteoarthritis (OA) synovial inflammation from network pharmacology to experimental pharmacology.</p><p><strong>Methods: </strong>Targets of OA were constructed by detecting the database of network database platforms (Therapeutic Target database, DrugBank and GeneCards), and the targets of PF were constructed by PubChem 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 (qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot were used to verify the potential mechanism of PF in synovial inflammation.</p><p><strong>Results: </strong>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 'tumor-necrosis 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 50 µmol/L PF on human OA FLS. 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引用次数: 0
摘要
目的:从网络药理学和实验药理学两方面探讨芍药苷(PF)对骨关节炎(OA)滑膜炎症的作用机制。方法:通过检测网络数据库平台(Therapeutic Target database、DrugBank和GeneCards)的数据库构建OA的靶点,通过PubChem和Herbal Ingredients’Targets数据库构建PF的靶点。基因本体(GO)和京都基因与基因组百科全书(KEGG)通过Database for Annotation, Visualization, and Integrated Discovery (DAVID)数据库对这些共靶向基因进行分析,蛋白质-蛋白质相互作用(PPI)网络通过检索相互作用基因的搜索工具(STRING)数据库进行。采用细胞计数试剂盒-8 (CCK-8)法评估PF对人OA成纤维细胞样滑膜细胞(FLS)的潜在毒性,采用实时定量聚合酶链反应(qPCR)、酶联免疫吸附法(ELISA)和Western blot法验证PF在滑膜炎症中的潜在机制。结果:共鉴定出26个共靶基因。氧化石墨烯富集结果表明,这些共靶基因极有可能定位于细胞质中,其生物学过程主要涉及“细胞对缺氧的反应”、“脂多糖(LPS)介导的信号通路”和“基因表达的正向调节”。KEGG通路分析表明,这些共同靶向基因可能通过与“缺氧诱导因子-1 (HIF-1)信号通路”和“肿瘤坏死因子(TNF)信号通路”相关的途径发挥作用。PPI网络显示,前3位枢纽基因分别为TP53、TNF和CASP3。分子对接结果表明,PF与TNF对接良好。CCK-8在10、20和50µmol/L PF浓度下对人OA FLS无潜在毒性。PF显著降低了lps诱导的OA FLS中白细胞介素-1 β、白细胞介素-6、TNF-α基质金属蛋白酶13 (MMP13)以及具有血栓反应蛋白基元的崩解素和金属蛋白酶5 (ADAMTS5)和TNF-α的表达水平。结论:茯苓多糖对OA滑膜炎症有较强的抗炎作用。
Paeoniflorin, the Main Monomer Component of Paeonia lactiflora, Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation.
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, DrugBank and GeneCards), and the targets of PF were constructed by PubChem 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 (qPCR), 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 'tumor-necrosis 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 50 µmol/L PF on human OA FLS. And PF significantly decreased the expression levels of interleukin-1 β, interleukin-6, TNF-α matrix metalloproteinase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and TNF-α in LPS-induced OA FLS.
Conclusion: PF exhibited potent anti-inflammatory effect in OA synovial inflammation.
期刊介绍:
Chinese Journal of Integrative Medicine seeks to promote international communication and exchange on integrative medicine as well as complementary and alternative medicine (CAM) and provide a rapid forum for the dissemination of scientific articles focusing on the latest developments and trends as well as experiences and achievements on integrative medicine or CAM in clinical practice, scientific research, education and healthcare.