基于网络药理学和分子对接探讨黄连温胆汤治疗幽门螺杆菌相关性胃炎的作用机制

doi:10.3976/j.issn.1002-4026.2023.02.004

摘要/Abstract

摘要：

运用网络药理学和分子对接方法探索黄连温胆汤治疗幽门螺杆菌相关性胃炎的分子机制。应用中药系统药理学数据库与分析平台对黄连温胆汤药物活性成分及药物作用靶点基因进行筛选。通过Genecards 数据库、DisGENET数据库查找幽门螺杆菌相关性胃炎疾病相关靶点,利用维恩在线绘图工具获得疾病与药物的共同靶点基因。利用Cytoscape 3.8.2软件以及STRING数据库分别构建药物-化合物-靶点相互作用网络及蛋白质-蛋白质相互作用网络图。运用DAVID数据库进行基因本体功能和京都基因与基因组百科全书通路富集分析。选取度值排名前3的靶点蛋白和活性成分使用AutoDockTools 1.5.6软件进行分子对接。共筛选得到槲皮素、川皮苷、柚皮素等127种黄连温胆汤药物活性成分,并获得Akt1、JUN、TNF-α、STAT3等101个潜在靶点蛋白,涉及P53信号通路、NOD样受体信号通路、TNF信号通路等90条信号通路。分子对接结果显示关键靶点STAT3、TP53、Akt1与活性成分槲皮素、川皮苷、柚皮素的亲和力较好,其中以Akt1与柚皮素的结合能力最强。通过分析黄连温胆汤治疗幽门螺杆菌相关性胃炎的作用靶点和相关信号通路,能够为临床应用和后续实验研究提供理论基础。

关键词: 黄连温胆汤, 幽门螺杆菌相关性胃炎, 网络药理学, 分子对接

Abstract:

This study aimed to explore the mechanism of Huanglian Wendan Decoction in the treatment of Helicobacter pylori associated gastritis by network pharmacology and molecular docking methods. The active ingredients and drug target genes of Huanglian Wendan Decoction were screened using the traditional Chinese medicine system pharmacology database and analysis platform. The H. pylori associated gastritis disease-related targets were found by the GeneCards and DisGENET databases, and the common target genes of diseases and drugs were obtained via the Venny online mapping tool. Cytoscape 3.8.2 software and the STRING database were used to construct a drug-compound-target interaction network and a protein-protein interaction network diagram, respectively. Gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the DAVID database. The target proteins and active ingredients with the top three selection scores were selected for molecular docking using Autodocktools 1.5.6 software. A total of 127 active ingredients of Huanglian Wendan Decoction were screened, such as quercetin, nobiletin, and naringenin. A total of 101 potential target proteins were obtained, such as Akt1, JUN, TNF-α, and STAT3, which involved 90 signal pathways, including the p53 signal pathway, NOD-like receptor signal pathway, and TNF signal pathway. Molecular docking results revealed that the key targets, STAT3, TP53, and Akt1, had high affinity for the active ingredients quercetin, nobiletin, and naringenin. In addition, Akt1 had the highest binding affinity for naringenin. Network pharmacology and molecular docking analysis predicted the action target and related signal pathway of Huanglian Wendan Decoction in the treatment of H. pylori associated gastritis, which will provide a theoretical basis for clinical application and subsequent experimental research.

Key words: Huanglian Wendan Decoction, Helicobacter pylori associated gastritis, network pharmacology, molecular docking

中图分类号:

R285

刘文文, 高云云, 尹志鹏, 吕刚, 王玉, 赵英会. 基于网络药理学和分子对接探讨黄连温胆汤治疗幽门螺杆菌相关性胃炎的作用机制[J]. 山东科学, 2023, 36(2): 23-32.

LIU Wenwen, GAO Yunyun, YIN Zhipeng, LÜ Gang, WANG Yu, ZHAO Yinghui. Network pharmacology and molecular docking analysis of the mechanism of Huanglian Wendan Decoction in the treatment of Helicobacter pylori associated gastritis[J]. Shandong Science, 2023, 36(2): 23-32.

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药物	MOL ID	共同活性成分	OB/%	DL
黄连-甘草	MOL000098	槲皮苷(quercetin)	46.43	0.28
半夏-生姜	MOL000449	豆甾醇(stigmasterol)	43.83	0.76
半夏-生姜	MOL000358	β-谷甾醇 (beta-sitosterol)	36.91	0.75
陈皮-枳实	MOL005828	川皮苷(nobiletin)	61.67	0.52
陈皮-枳实	MOL005100	5,7-二羟基-2-(3-羟基-4-甲氧基苯基)-色满-4-酮	47.74	0.27
陈皮-枳实-甘草	MOL004328	柚皮素(naringenin)	59.29	0.21
陈皮-甘草	MOL000359	谷甾醇(sitosterol)	36.91	0.75

药物	活性成分	MOL ID	度值
黄连-甘草	槲皮素(quercetin)	MOL000098	133
陈皮-枳实	川皮苷(nobiletin)	MOL005828	39
陈皮-枳实-甘草	柚皮素(naringenin)	MOL004328	37
甘草	毛蕊异黄酮(calycosin)	MOL000417	31
半夏-生姜	β-谷甾醇(beta-sitosterol)	MOL000358	27
半夏	黄芩素(baicalein)	MOL002714	18
甘草	槲皮素衍生物(quercetin der)	MOL004961	16
枳实	四甲氧基乌托林(tetramethoxyluteolin)	MOL007879	38

蛋白名称	基因名称	度值
前列腺素G/H合酶2	PTGS2	121
热休克蛋白90α	HSP90AA1	86
雄激素受体	AR	84
诱导型一氧化氮合酶	NOS2	78
过氧化物酶体增殖物激活受体	PPARG	75
前列腺素G/H合酶1	PTGS1	71
糖原合成酶激酶3β	GSK3B	58
丝氨酸-苏氨酸蛋白激酶Chk1	CHEK1	51
丝裂原活化蛋白激酶14	MAPK14	47
凝血酶原	F2	43
内皮型一氧化氮合酶	NOS3	23
毒蕈碱乙酰胆碱受体M3	CHRM3	16
孕酮受体	PGR	13
凋亡调节因子Bcl-2	BCL2	12
溶质载体家族6	SLC6A4	11

编号	化合物名称	结合自由能/(kJ·mol^-1)			DS(LibDock Score)
编号	化合物名称	STAT3	TP53	Akt1	STAT3	TP53	Akt1
MOL000098	槲皮素	-6	-6.4	-9.2	99.71	93.06	110.1
MOL005828	川皮苷	-5.4	-5.8	-6.3	57.39	74.86	84.86
MOL004328	柚皮素	-6.1	-6.6	-8.9	102.8	105.5	111.9