基于网络药理学和分子对接技术研究黄芩对黑色素瘤的作用机制

Molecular mechanism of Scutellaria baicalensis Georgi in the treatment of melanoma based on network pharmacology and molecular docking technology

基于网络药理学和分子对接技术探讨中药黄芩治疗黑色素瘤的作用机制.利用中药系统药理学数据库和分析平台筛选黄芩的有效成分,利用GeneCards、OMIM、PharmGkb等数据库查找与黑色素瘤有关的靶基因.应用Cytoscape3.7.1软件建立中药-成分-靶点-疾病网络结构图,借助STRING数据库平台构建蛋白质相互作用网络.从黄芩中筛选到36个有效成分,其中22个为核心有效成分,包括黄芩素、汉黄芩素、刺槐素等;与黑色素瘤相关的靶基因有37个,其中13个为核心基因,包括CCD1、AR、IL-6等.GO分析结果显示,黄芩主要参与DNA结合转录激活活性、RNA激活酶Ⅱ特异性等;KEGG分析结果显示,黄芩的37个靶基因富集了癌症信号、细胞凋亡信号通路、p53信号通路等.采用分子对接技术将核心成分黄芩素与其作用的7个核心基因进行分子对接,发现黄芩素与这些靶点之间均具有良好的对接活性.利用皮肤黑素瘤A375细胞模型进行体外实验,结果也证实黄芩素可能是黄芩实现抗黑色素瘤作用的主要活性成分.

Based on network pharmacology and molecular docking technology,the mechanism of Scutellaria baicalensis Georgi in the treatment of melanoma was discussed.The effective components of Scutellaria baicalensis Georgi were screened through the Traditional Chinese Medicine System Pharmacology database and analysis platform(TCMSP),and the targets related to melanoma were found through GeneCards,OMIM,PharmGkb,etc.STRING database was used for the protein-protein interaction(PPI)network analysis and Cytoscape 3.7.1 software was used to construct a network diagram of drug-component-target-disease.Among the 36 ac tive ingredients screened from Scutellaria baicalensis Georgi,22 were core active ingredients,including baicalein,wogonin,acacetin,etc.There are 37 target genes related to melanoma,13 of which are core genes,including CCD1,AR,IL-6 and so on.Go analysis showed that Scutellaria baicalensis Georgi was mainly involved in the activation of DNA binding transcription,the specificity of RNA ActivatorⅡand so on;KEGG analysis showed that 37 target genes of Scutellaria baicalensis Georgi were enriched in cancer signal pathway,apoptosis signal pathway,p53 signal pathway and so on.Baicalein is the core component of Scutellaria baicalensis Georgi.It has good docking activity with seven core genes by molecular docking technique.The results of in vitro exper-iments on A375 melanoma cell model also confirmed that baicalein may be the main active component of Scutellaria baicalensis Georgi for its anti-melanoma effect.