基于网络药理学研究小柴胡汤治疗乙型肝炎的作用机制

蓝绍航; 唐秋媛; 李娜娜; 陶然; 廖南盛; 蒙荫杰; 何草; 毛德文

doi:10.3969/j.issn.1001-5256.2021.10.010

基于网络药理学研究小柴胡汤治疗乙型肝炎的作用机制

DOI: 10.3969/j.issn.1001-5256.2021.10.010

蓝绍航¹,
唐秋媛^{1, 2, ,},
李娜娜¹,
陶然¹,
廖南盛¹,
蒙荫杰¹,
何草²,
毛德文^{1, 2}

1.
广西中医药大学研究生院，南宁 530001
2.
广西中医药大学第一附属医院肝病科，南宁 530023

基金项目:

国家自然科学基金 (81760851)

详细信息

通信作者:
唐秋媛，tqy9721@163.com

中图分类号: R512.62
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- 文章访问数: 670
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- 被引次数: 0
出版历程
- 收稿日期: 2021-02-10
- 录用日期: 2021-03-15
- 出版日期: 2021-10-20

Mechanism of action of Xiaochaihu decoction in the treatment of hepatitis B based on network pharmacology

1.
Graduate School, Guangxi University of Chinese Medicine, Nanning 530001, China
2.
Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China

Research funding:

National Natural Science Foundation of China (81760851)

摘要

摘要: 目的通过网络药理学研究小柴胡汤治疗乙型肝炎的作用机制。方法利用TCMSP数据库收集小柴胡汤中7味中药的主要化学成分和作用靶点；通过GeneCards和OMIM数据库获取乙型肝炎相关靶点，利用STRING在线平台构建潜在靶点PPI网络并利用R语言获取GO功能富集分析及KEGG通路分析；运用Cytoscape3.7.2构建“活性成分-核心靶点”网络并对网络进行拓扑分析；最后利用AutoDock vina等软件对网络中度值较高的活性成分与核心靶点进行分子对接和可视化分析。结果筛选到小柴胡汤中槲皮素、山奈酚、汉黄芩素、柚皮素等193种主要化学成分和247个相关靶点，其中关键靶点有RELA、MAPK1、TP53、ESR1、EGFR、AKT1等；GO功能富集分析共得到2612条富集结果，主要涉及细胞对化学应激的反应、对药物的反应、氧化应激反应、对脂多糖的反应等生物过程的调节；KEGG通路分析共得到174条通路富集结果，主要涉及乙型肝炎、PI3K-AKT信号通路、MAPK信号通路等；分子对接结果显示主要活性成分与核心靶点的结合力均较强，蛋白结晶复合物构象稳定。结论研究初步表明了小柴胡汤通过多成分、多靶点、多通路发挥治疗乙型肝炎的作用机制。
- 乙型肝炎 /
- 小柴胡汤 /
- 网络药理学 /
- 药理作用分子作用机制
Abstract: Objective To investigate the mechanism of action of Xiaochaihu decoction in the treatment of hepatitis B based on network pharmacology. Methods The TCMSP database was used to obtain the main chemical components and action targets of the seven traditional Chinese medicines in Xiaochaihu decoction; the GeneCards and OMIM databases were used to obtain the targets associated with hepatitis B; the STRING online platform was used to construct a PPI network of potential targets, and R language was used to perform gene ontology (GO) functional enrichment analysis and KEGG pathway analysis; Cytoscape 3.7.2 was used to construct an "active component-core target" network and perform a topology analysis of this network; AutoDock vina and related software were used to perform molecular docking and visualized analysis of the active components with high value and the core targets in the network. Results A total of 193 main chemical components (including quercetin, kaempferol, wogonin, and naringenin) and 247 related targets were screened out, among which the key targets included RELA, MAPK1, TP53, ESR1, EGFR, and AKT1. A total of 2612 enrichment items were obtained by GO functional enrichment analysis, which were mainly involved in regulating the biological processes such as cell response to chemical stress, response to drugs, oxidative stress response, and lipopolysaccharide response. A total of 174 pathways were obtained by the KEGG pathway analysis, mainly involving hepatitis B, PI3K-AKT signaling pathway, and MAPK signaling pathway. Molecular docking results showed that the main active components had strong binding force to core targets, and the protein crystal complex had a stable conformation. Conclusion This study preliminarily shows that Xiaochaihu decoction exerts a therapeutic effect on hepatitis B through multiple components, targets, and pathways.
- Hepatitis B /
- XIAOCHAIHU DECOCTION /
- Network Pharmacology /
- Molecular Mechanisms of Pharmacological Action

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图 1 药物靶点和疾病靶点Venny图

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图 2 交集基因GO条形图

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图 3 交集基因KEGG点图

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图 4 关键化合物与核心靶点分子对接图

注：a，槲皮素-MAPK1；b，山奈酚-RELA；c，黄芩素-TP53；d，柚皮素-ESR1。

下载: 全尺寸图片幻灯片

表 1 小柴胡汤部分活性成分信息

MOL ID	MOL Name	OB	DL	来源药物
MOL000354	Isorhamnetin	49.6	0.31	柴胡，甘草
MOL000359	Sitosterol	36.91	0.75	黄芩，甘草
MOL000422	Kaempferol	41.88	0.24	柴胡，人参，甘草
MOL000098	Quercetin	46.43	0.28	柴胡，大枣，甘草
MOL000449	Stigmasterol	43.83	0.76	柴胡，半夏，人参，黄芩，甘草
MOL000358	Beta-sitosterol	36.91	0.75	黄芩，人参，半夏，生姜，甘草
MOL005360	Malkangunin	57.71	0.63	人参，甘草
MOL000787	Fumarine	59.26	0.83	人参，大枣
MOL002714	Baicalein	33.52	0.21	半夏，黄芩
MOL002776	Baicalin	40.12	0.75	柴胡，半夏
MOL002879	Diop	43.59	0.39	黄芩，人参
MOL003896	7-Methoxy-2-methyl isoflavone	42.56	0.2	甘草
MOL000497	Licochalcone A	40.79	0.29	甘草
MOL000392	Formononetin	69.67	0.21	甘草
MOL004328	Naringenin	59.29	0.21	甘草
MOL012940	Spiradine A	113.52	0.61	甘草
MOL008034	21302-79-4	73.52	0.77	大枣
MOL008647	Moupinamide	86.71	0.26	大枣
MOL002773	Beta-carotene	37.18	0.58	大枣
MOL000096	(-)-catechin	49.68	0.24	大枣
MOL012940	Spiradine A	113.52	0.78	大枣
MOL006936	10, 13-eicosadienoic	39.99	0.2	半夏
MOL006937	12, 13-epoxy-9-hydroxynonadeca-7, 10-dienoic acid	42.15	0.24	半夏
MOL006957	(3S, 6S)-3-(benzyl)-6-(4-hydroxybenzyl) piperazine-2, 5-quinone	46.89	0.27	半夏
MOL003578	Cycloartenol	38.69	0.78	半夏
MOL006967	Beta-D-ribofuranoside, xanthine-9	44.72	0.21	半夏
MOL006129	6-methylgingediacetate2	48.73	0.32	生姜
MOL001771	Poriferast-5-en-3beta-ol	36.91	0.75	生姜
MOL008698	Dihydrocapsaicin	47.07	0.19	生姜
MOL004609	Areapillin	48.96	0.41	柴胡
MOL013187	Cubebin	57.13	0.64	柴胡
MOL004624	Longikaurin A	47.72	0.53	柴胡
MOL004628	Octalupine	47.82	0.28	柴胡
MOL004644	Sainfuran	79.91	0.23	柴胡
MOL003648	Inermin	65.83	0.54	人参
MOL005308	Aposiopolamine	66.65	0.22	人参
MOL005314	Celabenzine	101.88	0.49	人参
MOL005321	Frutinone A	65.9	0.34	人参
MOL005356	Girinimbin	61.22	0.31	人参
MOL000173	Wogonin	30.68	0.23	黄芩
MOL002915	Salvigenin	49.07	0.33	黄芩
MOL002927	Skullcapflavone Ⅱ	69.51	0.44	黄芩
MOL002932	Panicolin	76.26	0.29	黄芩
MOL002934	Neobaicalein	104.34	0.44	黄芩

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表 2 小柴胡汤度值前10位化学成分基本信息

NO.	MOL ID	MOL Name	化学式	Degree	来源药物
1	MOL000098	槲皮素(quercetin)	C₁₅H₁₀O₇	100	柴胡，甘草，大枣
2	MOL000422	山奈酚(kaempferol)	C₁₅H₁₀O₆	32	柴胡，甘草
3	MOL000173	汉黄芩素(wogonin)	C₁₆H₁₂O₅	31	黄芩
4	MOL004328	柚皮素(naringenin)	C₁₅H₁₂O₅	25	甘草
5	MOL000392	芒柄花素(formononetin)	C₁₆H₁₂O₄	20	甘草
6	MOL000497	甘草酮(licochalcone A)	C₂₁H₂₂O₄	20	甘草
7	MOL002714	黄芩素(baicalein)	C₁₅H₁₀O₅	19	黄芩，半夏
8	MOL000354	异鼠李素(isorhamnetin)	C₁₆H₁₂O₇	18	柴胡，甘草
9	MOL003896	7-甲氧基-2-甲基异黄酮 (7-Methoxy-2-methyl isoflavone)	C₁₇H₁₃NO₅	18	甘草
10	MOL002773	β-胡萝卜素(beta-carotene)	C₄₀H₅₆	18	大枣

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表 3 关键化合物与核心靶点分子对接

有效成分	结合能(kcal/mol)
有效成分	MAPK1	RELA	TP53	ESR1
槲皮素(quercetin)	-7.4	-7.8	-7.0	-8.6
山奈酚(kaempferol)	-7.2	-7.1	-8.1	-7.2
汉黄芩素(wogonin)	-9.4	-8.3	-8.9	-7.5
柚皮素(naringenin)	-8.6	-7.7	-7.8	-9.1

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