基于分子对接探讨中药丹参抗癌的活性成分及分子机制研究  

Study on the anticancer active components and molecular mechanism of Salvia miltiorrhiza based on molecular docking

作　　者：刘嘉玲 杨欣 文元奇 宋家伟 黄国江 LIU Jialing;YANG Xin;WEN Yuanqi;SONG Jiawei;HUANG Guojiang

机构地区：[1]贵州中医药大学,贵州贵阳550005

出　　处：《中医临床研究》2024年第36期36-42,共7页Clinical Journal Of Chinese Medicine

基　　金：大学生创新创业项目(省级):贵中医大创合字(2023)110号;贵州省高等学校中药(民族药)药性与效应研究重点实验室黔教技[2023]018号。

摘　　要：目的:基于网络药理学及分子对接筛选丹参抗癌活性成分,为开发抗癌药物提供理论依据。方法:通过中药系统药理学数据库与分析平台(TCMSP)构建丹参小分子配体库,借助Swiss Target Prediction软件对化学成分靶标蛋白进行预测,通过DAVID 6.8对靶标蛋白进行通路富集分析。采用Rstudio软件ggplot 2绘制通路图,基于Cytoscape 3.5.1构建丹参活性成分-靶标-通路网络模型,初步筛选丹参抗癌的关键活性成分及核心靶点。通过分子对接(SYBYL 2.1)分析关键化学成分与核心靶点的空间匹配程度,通过Ligplot软件计算原紫草酸与核心靶标形成的氢键、疏水作用和结构比对。结果:丹参小分子活性成分41个,共筛选出615个靶标蛋白,涉及110条代谢途径,采用Rstudio的ggplot 2输出前15条通路。28个靶标蛋白参与癌症通路(P-Value=2.21E-08),涉及胰腺癌、膀胱癌、小细胞肺癌等13条相关癌症通路。通过半柔性和全柔性对6个活性成分进行验证分析,发现丹参醌酚Ⅱ、丹参新酮Ⅱ、原紫草酸、异丹参酮II、紫丹参乙素、紫丹参萜醚b为丹参抗癌的关键活性成分。其中原紫草酸为丹参抗癌的核心活性成分。丹参发挥抗癌的核心靶点为磷脂酰肌醇-3-激酶催化亚基δ(Phosphatidylinositol-3-Kinase Catalytic Subunit Delta,PIK3CD)、酪氨酸激酶受体2(Receptor Tyrosine Kinases 2,ERBB2)、磷脂酰肌醇-3-激酶催化亚基β(Phosphatidylinositol-3-Kinase Catalytic Subunit Beta,PIK3CB)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)和磷脂酰肌醇-3-激酶催化亚基α(Phosphatidylinositol-3-Kinase Catalytic Subunit Alpha,PIK3CA),最重要的靶点为磷脂酰肌醇3激酶(Phosphatidylinositol 3-Kinase,PIK3Cs)。结论:从分子层面筛选出丹参的抗癌活性成分及关键靶点,为今后的实验研究提供理论依据。Objective:Taking the active components of Salvia Miltiorrhiza as the breakthrough point,the anti-cancer active components of Salvia Miltiorrhiza were screened based on network pharmacology and molecular docking to provide theoretical basis for the discovery and development of anti-cancer drugs.Methods:The small molecular ligand library of Salvia Miltiorrhiza was constructed through TCMSP(Traditional Chinese Medicine Systems Pharmacology)database,and the chemical component target protein was predicted by Swiss Target Prediction software.Pathway enrichment analysis of target proteins was performed by DAVID 6.8.Rstudio software ggplot2 was used to draw the pathway diagram,and the active component-target-pathway network model of Salvia Miltiorrhiza was constructed based on Cytoscape 3.5.1,and the key active components and core targets of anti-cancer Salvia Miltiorrhiza were preliminatively screened.The spatial matching degree between the key chemical components and the core target was analyzed by molecular docking(SYBYL2.1),and the hydrogen bond,hydrophobic action and structural comparison between proto-violet oxalic acid and the core target were calculated by Ligplot software.Results:There were 41 small molecule active components of Salvia Miltiorrhiza,a total of 615 target proteins were screened,involving 110 metabolic pathways,and the first 15 pathways were output by ggplot2 of Rstudio.28 target proteins were involved in cancer pathways(P-Value=2.21E-08),involving 13 related cancer pathways such as pancreatic cancer,bladder cancer,and small cell lung cancer.Through semi-flexible and full flexible verification analysis of 6 active ingredients,it was found that that miltionone II,miltirone II,prolithospermic acid,Isotanshinone II,Przewaquinone B,przewalskin b were the key active ingredients of Salvia Miltiorrhizaa gainst cancer.Among them,protoviolet oxalic acid was the core active ingredient of Salvia Miltiorrhiza.The core anti-cancer targets of Salvia Miltiorrhiza were PIK3CD,ERBB2,PIK3CB,EGFR and PIK3CA,and the m

关 键 词：丹参 癌症 活性成分 通路分析 分子对接 

分 类 号：R979.1[医药卫生—药品]