基于网络药理学与细胞实验的三白汤治疗皮肤色素沉着机制探究与初证  

Research and Verification of the Mechanism of Sanbai Decoction in the Treatment of Skin Pigmentation Based on Network Pharmacology and Cell Experiment

作　　者：马梓育 陆洋[1,2] Ma Ziyu;Lu Yang(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Shenzhen Research Institute,Beijing University of Chinese Medicine,Shenzhen 518000,China)

机构地区：[1]北京中医药大学中药学院,北京100029 [2]深圳北京中医药大学研究院,深圳518000

出　　处：《世界科学技术-中医药现代化》2021年第7期2153-2169,共17页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(8217141502):基于中医阴阳理论构建“蟾酥—牛黄”药对有效成分粒径可变纳米递药系统并联合光动力调控肿瘤免疫微环境的探索和实践,负责人:陆洋。

摘　　要：目的探究并验证三白汤治疗皮肤色素沉着的作用机制。方法通过TCMSP、TCMID以及BATMAN-TCM数据库收集三白汤化学成分和作用靶点,通过检索GeneCards、DisGeNET数据库获得皮肤色素沉着的疾病靶点。取两靶点集的交集,进而保留相关化学成分,应用Cytoscape建立化学成分-潜在靶点网络。将交集靶点导入STRING数据库,得到交集靶点的相互作用网络。采用CytoHubba、DAVID和Kobas对交集靶点的相互作用网络进行拓扑分析、GO和KEGG富集分析。利用AutoDock 4.2对关键靶点进行分子对接研究。基于B16-F10黑色素瘤细胞,构建抗黑色素模型,验证分子对接结果。结果筛选获得三白汤活性成分29个、潜在作用靶点23个。拓扑分析得到酪氨酸酶、雌激素受体1、孕激素受体等8个关键靶点,主要参与涉及男性性腺发育、对雌二醇的反应等GO富集分析所示的生命过程。KEGG通路分析得到123条主要信号通路,主要涉及黑色素合成、雌激素信号通路、酪氨酸代谢等。分子对接结果显示,三白汤化学成分与潜在靶点具有较好的结合活性。细胞实验表明,三白汤中代表性成分的抗黑色素活性顺序与分子对接结果一致。结论三白汤通过其中芍药内酯苷、β-谷甾醇、α-香树精等有效成分,作用于连环蛋白β1(catenin beta 1,CTNNB1)、酪氨酸酶(tyrosinase,TYR)等靶点,调节黑色素合成、酪氨酸代谢等信号通路,最终减少黑色素合成以治疗色素沉着。Objective To explore and verify the effective material basis and mechanism of Sanbai Decoction in the treatment of skin pigmentation.Methods The chemical components and targets of Sanbai Decoction were collected through TCMSP,TCMID and BATMAN-TCM databases,and disease targets for skin pigmentation were obtained by searching the GeneCards,DisGeNET database.The intersection of the two target sets was taken,and then the relevant chemical composition was retained.The Cytoscape was used to establish a chemical composition-potential target network.The intersection targets were imported into the STRING database to get the interaction network of the intersection targets.CytoHubba,DAVID and Kobas were used to conduct topological analysis,GO and KEGG enrichment analysis on the interaction network of the intersection target.The AutoDock 4.2 was used to conduct molecular docking research on key targets.Based on B16-F10 melanoma cells,an anti-melanin model was constructed to verify the results of molecular docking.Results 29 active ingredients of Sanbai Decoction and 23 potential targets were screened.Topological analysis obtained 8 key targets including tyrosinase,estrogen receptor 1,and progesterone receptor,which were mainly involved in the life process of GO enrichment analysis,such as male gonadal development and response to estradiol.KEGG pathway analysis revealed 123 main signal pathways,mainly related to melanin synthesis,estrogen signal pathway,and tyrosine metabolism.The molecular docking results showed that the chemical components of Sanbai Decoction had good binding activity with potential targets.Cell experiments showed that the antimelanin activity sequence of the representative components of Sanbai Decoction was consistent with the molecular docking results.Conclusion Sanbai Decoction acts on CTNNB1,TYR and other targets through effective ingredients such as Albiflorin,β-sitosterol,andα-Amyrin,to regulates the synthesis of melanin,Tyrosine metabolism and other signaling pathways,and ultimately reduce melanin

关 键 词：三白汤 皮肤色素沉着 网络药理学 分子对接 细胞实验 

分 类 号：R289.5[医药卫生—方剂学]