基于网络药理学及体外细胞实验分析生姜泻心汤治疗溃疡性结肠炎的潜在作用  

Analysis of Potential Effect of Shengjiang Xiexin Decoction on Ulcerative Colitis Based on Network Pharmacology and In VitroCell Experiment

作　　者：熊诗琳 林小荷 黄松[1] 侯少贞[1] 刘昌辉[1] 姜小艳 梁健[1] XIONG Shilin;LIN Xiaohe;HUANG Song;HOU Shaozhen;LIU Changhui;JIANG Xiaoyan;LIANG Jian(School of Meteria Medica Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510006,China;Shenzhen Traditional Chinese Medicine hospital,Shenzhen Guangdong 518033,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006 [2]深圳市中医院,广东深圳518033

出　　处：《新中医》2024年第5期36-43,共8页New Chinese Medicine

基　　金：国家自然科学基金青年项目(82004025);广东省南沙区重点领域科技项目(2021ZD006);广州市科技计划项目(202002020032)。

摘　　要：目的:基于网络药理学及体外细胞实验分析生姜泻心汤治疗溃疡性结肠炎(UC)的潜在作用。方法:运用中医系统药理学数据库及分析平台(TCMSP)筛选生姜泻心汤的活性成分及相关靶点,利用GeneGards、在线人类孟德尔遗传(OMIM)、药物遗传学和药物基因组学知识库(PharmGkb)、治疗靶点数据库(TTD)和开放数据药物和药物靶标数据库(DrugBank)筛选UC疾病靶点,将药物靶点与疾病靶点匹配所得交集靶点导入互作基因/蛋白质检索工具(STRING)数据库构建蛋白相互作用(PPI)网络,并构建药物-成分-靶点-疾病网络。采用分子对接分析核心靶点和活性成分结合力,并通过脂多糖(LPS)诱导人结直肠腺癌细胞(Caco2细胞)损伤模型,给予生姜泻心汤干预24 h后,采用qPCR和免疫荧光探索生姜泻心汤对核心靶点的作用。结果:生姜泻心汤治疗UC的有效成分共215个,靶点171个,其中潜在核心有效成分为姜烯酮A、槲皮素、山柰酚、汉黄芩素和柚皮素;核心靶点包括HIF1A、STAT3、CTNNB1、CASP3、AKT1、IL-1β、TP53、EGFR和JUN。分子对接结果显示,AKT1、TP53和IL-1β与姜烯酮A、槲皮素、山柰酚、汉黄芩素和柚皮素均有较强的结合能力。细胞实验发现,生姜泻心汤干预LPS刺激Caco2细胞模型,能显著地抑制AKT1、TP53和IL-1β基因和蛋白的表达。结论:生姜泻心汤能够调控AKT1、TP53和IL-1β等靶点,发挥治疗UC的作用。Objective:To analyze the potential effect of Shengjiang Xiexin Decoction on ulcerative colitis(UC)based on network pharmacology and in vitro cell experiment.Methods:The active components and related targets of Shengjiang Xiexin Decoction were screened out via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).UC disease targets were screened out by GeneGards,Online Mendelian Inheritance in Man(OMIM),Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGkb),Therapeutic Target Database(TTD),and Database for Drug and Drug Target(DrugBank).The intersection targets obtained by matching drug targets with disease targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins(STRING)to construct the protein-protein interaction(PPl)network,and the drug-component-target-disease network was constructed.The binding of core targets and active components was analyzed by molecular docking,and the damage model of human colorectal adenocarcinoma cell(Caco2 cell)was induced by lipopolysaccharide(LPS).After the intervention of Shengjiang Xiexin Decoction for 24 hours,the effect of Shengjiang Xiexin Decoction on the core targets was investigated by qPCR and immunofluorescence.Results:There were 215 active components and 171 targets in Shengjiang Xiexin Decoction for the treatment of UC,among which the potential core active components were gingerenone A,quercetin,kaempferol,baicalin and naringin.Core targets included HIF1A,STAT3,CTNNB1,CASP3,AKT1,IL-1β,TP53,EGFR and JUN.Molecular docking results showed that AKT1,TP53 and IL-1β could strongly bind with gingerenone A,quercetin,kaempferol,baicalein and naringin.The cell experiment results showed that Shengjiang Xiexin Decoction could interfere with the model of LPs in stimulating Caco2 cells,and significantly inhibit the gene and protein expressions of AKT1,TP53 and IL-1β.

关 键 词：溃疡性结肠炎 生姜泻心汤 网络药理学 体外细胞实验 作用机制 

分 类 号：R285.5[医药卫生—中药学]