基于特征图谱及分子对接预测黄连异喹啉类生物碱成分治疗T2DM的潜在作用机制  

Prediction of Underlying Action Mechanism of Isoquinoline Alkaloids of Coptis Rhizoma on T2DM through Characteristic Spectrum and Molecular Docking

作　　者：罗沙 李贝 杨俐 李洁 牛文意 覃静 谭睿[1] 魏屹[1] Luo Sha;Li Bei;Yang Li;Li Jie;Niu Wenyi;Qin Jing;Tan Rui;Wei Yi(Collge of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031)

机构地区：[1]西南交通大学生命科学与工程学院,成都610031

出　　处：《中药药理与临床》2021年第4期115-124,共10页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(编号:82074003);国家重点研发计划(编号:2018YFC1706200);四川省重点研发项目(编号:2020ZDYF3291)。

摘　　要：目的:基于特征图谱、网络药理学及分子对接技术,对黄连异喹啉类生物碱成分治疗2型糖尿病(T2DM)的潜在作用机制进行预测分析。方法:利用高效液相色谱法对黄连全株药材不同部位的异喹啉类生物碱成分进行定量测定,建立HPLC特征图谱。借助TCMSP数据库、Swiss Target Prediction数据库及Uniprot数据库筛选和分析黄连目标化合物及作用靶点,通过Genecards、OMIM、TTD和Drugbank数据库筛选出T2DM疾病靶点基因,使用STRING数据库绘制靶点蛋白-靶点蛋白相互作用网络,对交集靶点蛋白利用Metascape数据库进行GO基因生物学功能和KEGG通路分析,采用Cytoscape 3.7.2软件构建"化合物-靶点-通路"关系网络,最后运用AutoDock Vina软件对核心靶点与作用化合物进行分子对接验证。结果:测定了黄连全株药材不同部位的6种异喹啉类生物碱成分含量,建立了黄连不同部位的HPLC特征图谱,并指认6个特征色谱峰。结合网络药理学分析发现,黄连治疗T2DM的核心靶点有32个,分别是PIK3CA、PIK3R1、SRC、STAT3和MCHR1等,核心作用化合物有10个,分别为氢化小檗碱、小檗红碱、小檗浸碱、小檗碱和药根碱等。GO功能富集在155条细胞组分、2 366条生物过程和266条分子功能,主要涉及以醇基为受体的磷酸转移酶活性、蛋白质酪氨酸激酶活性、受体复合体、转移酶活性的正调控、细胞对氮化合物的响应、肽基-丝氨酸修饰、顺行突触信号转导、跨膜受体蛋白酪氨酸激酶信号通路、肽基-酪氨酸磷酸化等方面。KEGG富集主要涉及癌症途径、神经活性配体-受体相互作用、乙型肝炎、血清素能突触、Th17细胞分化、胰岛素抵抗等348条作用通路。分子对接验证结果显示,分子结合能<-5 kcal/mol的占86.67%,氢化小檗碱与MCHR1亲和力最好,结合能达到-8.7 kcal/mol。结论:本研究初步确定了黄连全株药材不同部位生物碱成分组成分布。同时揭示Objective:To predict and analyze the underlying action mechanism of isoquinoline alkaloids of Coptis Rhizoma in treating Type 2 Diabetes Mellitus(T2 DM)based on characteristic spectrum, network pharmacology, and molecular docking. Methods: High-performance liquid chromatography(HPLC) was used to establish the HPLC characteristic chromatograms of isoquinoline alkaloids in different parts of Coptis Rhizoma,and their content was determined. The target compounds and targets of Coptis Rhizoma were screened out by TCMSP, Swiss Target Prediction, and Uniprot. The target disease genes of T2 DM were screened out by GeneCards, OMIM, TTD, and Drugbank. STRING was used to plot the protein-protein interaction(PPI) network. The common target proteins were analyzed by GO and KEGG analyses by Metascape, and Cytoscape 3.7.2 was used to construct a compound-target-pathway network. Finally, AutoDock Vina was used to verify the molecular docking between the core targets and the compounds. Results: The content of six isoquinoline alkaloids in different parts of the whole plant was determined. The HPLC characteristic chromatograms of Coptis Rhizoma were established, and six characteristic chromatographic peaks were identified. The analysis of network pharmacology revealed 32 core targets for the treatment of T2 DM, including PIK3 CA, PIK3 R1, SRC, STAT3, and MCHR1, and 10 core compounds, including(R)-canadine, berberrubine, berlambine, berberine, and jatrorrizine. GO functional enrichment analysis demonstrated 155 cellular components, 2 366 biological processes, and 266 molecular functions, mainly involving phosphotransferase activity with alcohol group as acceptor, protein tyrosine kinase activity, receptor complex, positive regulation of transferase activity, cellular response to nitrogen compound, peptidyl-serine modification, anterograde trans-synaptic signaling, transmembrane receptor protein tyrosine kinase signaling pathway, peptidyl-tyrosine phosphorylation, etc. KEGG analysis mainly involved 348 pathways such as pathways in c

关 键 词：黄连 特征图谱 HPLC 网络药理学 分子对接 异喹啉类生物碱成分 T2DM 

分 类 号：R285[医药卫生—中药学]