基于网络药理学牛磺石胆酸抗炎作用及机制  

Study on anti-inflammatory effect of taurolithocholic acid based on network pharmacology and its mechanism

作　　者：王妙然 李月[1,2] 张芸绮[2] 蔺晓菁 钟莹 陈春秀 周永 肖晓秋 李继斌[1] WANG Miao-ran;LI Yue;ZHANG Yun-qi;LIN Xiao-jing;ZHONG Ying;CHEN Chun-xiu;ZHOU Yong;XIAO Xiao-qiu;LI Ji-bin(Dept of Nutrition and Food Hygiene,Chongqing Medical University,Chongqing 400016,China;The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China;Dept of Clinical Nutrition,People’s Hospital of Chongqing Banan District,Chongqing 401320,China)

机构地区：[1]重庆医科大学营养与食品卫生学教研室,重庆400016 [2]重庆医科大学附属第一医院重大代谢性疾病转化医学重庆市重点实验室,重庆400016 [3]重庆市巴南区人民医院临床营养科,重庆401320

出　　处：《中国药理学通报》2021年第11期1614-1619,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81871222);陆军军医大学电磁辐射医学防护教育部重点实验室开放课题(No2017DCKF002)。

摘　　要：目的通过网络药理学分析牛磺石胆酸(taurolithocholic acid,TLCA)抗炎作用机制。方法从数据库中获取TLCA的靶标,构建TLCA抗炎作用的PPI网络并进行可视化。通过GO和KEGG分析作用靶点的基因功能及信号通路。选择靶标TGR5与TLCA进行分子对接评价结合性。用LPS和IFN-γ诱导的RAW264.7细胞验证TLCA抗炎作用。结果筛选出87个潜在抗炎靶点。GO分析表明这些基因主要富集于炎症反应调控、膜筏和蛋白酪氨酸激酶等方面。KEGG通路分析结果提示,PI3K-Akt信号通路、人巨细胞病毒感染可能是TLCA抗炎症的关键通路。细胞实验结果表明,TLCA可降低LPS和IFN-γ诱导的RAW264.7细胞的炎症反应,该作用与TLCA经TGR5下调NF-κB信号通路有关。结论网络药理学揭示了TLCA抗炎的潜在靶点;细胞实验结果表明TLCA可能通过膜受体TGR5调节关键的炎症信号通路。Aim To explore the anti-inflammatory effect of taurolithocholic acid(TLCA)through network pharmacology-based analyses,to verify with in vitro macrophage study and to reveal the possible mechanisms.Methods The potential targets of TLCA were acquired from public database,and then the protein-protein interaction(PPI)networks against inflammation were constructed and visualized by using Cytoscape.Gene ontology(GO)analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were performed.The binding activity of TLCA and its target(TGR5)was evaluated through molecular docking analysis.Lastly,the results of the network analysis were confirmed by lipopolysaccharide and interferon-γinduced RAW264.7 cells.Results There were 87 anti-inflammatory potential targets were screened.GO analysis revealed gene functions were mainly involved in regulation of inflammatory response,membrane raft and protein tyrosine kinase.The results of KEGG pathway analysis suggested that PI3K-Akt signaling pathway,human cytomegalovirus infection might be the critical pathways of TLCA against inflammation.The results of in vitro experiments showed that TLCA decreased the LPS and IFN-γinduced inflammatory response in RAW 264.7 macrophages.Furthermore,the expression of TGR5 protein increased after TLCA treatment.Conclusions The potential therapeutic targets of TLCA against inflammation are revealed through network pharmacology analysis.Our results indicate that TLCA might regulate key inflammatory markers through the membrane receptor TGR5.

关 键 词：网络药理学 多靶点 牛磺石胆酸 RAW264.7细胞 炎症反应 TGR5 

分 类 号：R-332[医药卫生] R285.5