摘要
目的采用网络药理学方法,并结合分子对接技术探讨黄连、厚朴配伍治疗溃疡性结肠炎的潜在作用机制。方法采用TCMSP、OMIM及DisGeNET数据库,筛选黄连、厚朴的主要活性成分、作用靶点及溃疡性结肠炎的作用靶点,并采用Cytoscape 3.7.1软件,构建"药物-活性化学物质-疾病-作用靶点"网络图,借助String数据库平台构建靶点蛋白互作网络。通过DAVID数据库对关键靶点进行GO功能富集以及KEGG信号通路富集分析,并通过Discovery Studio软件对药物活性成分与关键作用靶点进行分子对接验证,进一步采用TNBS诱导UC大鼠模型观察血清以及结肠组织中细胞因子的表达,对网络药理学预测结果进行实验验证。结果黄连共筛选潜在活性成分的作用靶点179个,厚朴共筛选潜在活性成分的作用靶点53个,疾病作用靶点有851个,获得共同基因71个,黄连配伍厚朴及疾病共同的作用靶点8个,分别为NOS2、SLC6A4、CHEK1、PPARG、PTGS1、PTGS2、ESR1、HSP90AA1。GO和KEGG富集分析综合结果显示黄连、厚朴配伍调控溃疡性结肠炎可能与肿瘤坏死因子(TNF)、磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)、缺氧诱导因子1(HIF-1)等信号通路有关。分子对接结果表明,小檗碱、厚朴酚和和厚朴酚与溃疡性结肠炎的NOS2、PTGS2、HSP90AA1等靶点对接吻合度较好。实验验证结果显示,与模型组相比,黄连厚朴配伍组血清TNF-α含量显著下降(P<0.01)、TGF-β含量显著升高(P<0.01),同时,其结肠组织中COX2蛋白表达阳性细胞数量明显下降。结论本研究初步揭示了黄连配伍厚朴多成分、多靶点、多途径治疗溃疡性结肠炎的潜在机制,为进一步机制研究指明了方面,为溃疡性结肠炎临床干预提供了新的可能。
Objective To explore the potential mechanism of the combination of Rhizoma Coptidis and Magnolia Officinalis in the treatment of ulcerative colitis by network pharmacology and molecular docking.Methods TCMSP,OMIM and DisGeNET databases were used to screen the main active components,action targets of Rhizoma Coptidis and Magnolia Officinalis and action targets of ulcerative colitis.Cytoscape 3.7.1 software was used to construct the network diagram of drug-active chemical substances-disease-action targets,and the protein interaction network was constructed with String database platform.GO function enrichment and KEGG signaling pathway enrichment analysis of key targets were carried out by DAVID database,and Discovery Studio software was used to verify the molecular docking between active ingredients and key targets.The expression of cytokines in serum and colon tissue was observed by TNBSinduced UC rat model,and the network pharmacology prediction results were verified by experiments.Results A total of 179 targets were screened for the potential active ingredients in Rhizoma Coptidis,53 targets were screened for the potential active ingredients in Magnolia Officinalis,and 851 targets were screened for the disease.71 common genes were obtained,and 8 common drug and disease targets were obtained,which were NOS2,SLC6 A4,CHEK1,PPARG,PTGS1,PTGS2,ESR1 and HSP90 AA1.GO and KEGG enrichment analysis showed that the regulation of ulcerative colitis by Rhizoma Coptidis and Magnolia Officinalis may be related to tumor necrosis factor(TNF),phosphatidylinositol3 kinase-protein kinase B(PI3 K-Akt),hypoxia inducible factor 1(HIF-1)and other signaling pathways.Molecular docking results showed that berberine,magnolol and honokiol were in good agreement with NOS2,PTGS2 and HSP90 AA1 targets of ulcerative colitis.The experimental results showed that compared with the model group,the serum TNF-αcontent in the compatibility group was significantly decreased,and the TGF-βcontent was significantly increased.At the same time,the number of COX2 protein expression positive cells in the colon tissue was significantly decreased.Conclusion This study preliminarily revealed the potential mechanism of Rhizoma Coptidis combined with Magnoliae Officinalis in the treatment of ulcerative colitis with multiple components,multiple targets and multiple pathways,and pointed out the aspects for further mechanism research,which provided a new possibility for clinical intervention of ulcerative colitis.
作者
李红燕
陈海
谢倩
杨显娟
马荣
黄维
王建
Li Hongyan;Chen Hai;Xie Qian;Yang Xianjuan;Ma Rong;Huang Wei;Wang Jian(School of Pharmacy,Chengdu University of TCM,Chengdu 611137,China;Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China,Chengdu University of TCM,Chengdu 611137,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2021年第8期2749-2761,共13页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
成都中医药大学创新团队院校项目(CXTD2018004):中药“性-效-用”理论与实践,负责人:王建
成都中医药大学西南特色中药资源重点实验室开放研究基金资助项目(2020XSGG025):中药临床合理用药评价,负责人:王建
关键词
黄连
厚朴
溃疡性结肠炎
网络药理学
分子对接
Rhizoma Coptidis
Magnolia Officinalis
Ulcerative Colitis
Network pharmacology
Molecular docking
