基于网络药理学和分子对接分析续断-桑寄生改善多囊卵巢综合征的作用机制

doi:10.3976/j.issn.1002-4026.2022.03.002

摘要/Abstract

摘要：

运用网络药理学方法分析续断-桑寄生药对改善多囊卵巢综合征的主要活性成分、靶点和通路。通过中药系统药理学数据库与分析平台,获取续断、桑寄生的主要活性成分及潜在靶点,并利用Cytoscape软件构建中药-成分-靶点网络;依托Disgenet、OMIM数据库获得多囊卵巢综合征疾病靶点并进行合并,借助Venn在线工具获得药物和疾病的共同靶点;运用STRING数据库构建蛋白质-蛋白质相互作用网络;利用Metascape数据库对交集靶点进行京都基因和基因组百科全书通路(KEGG)富集分析及基因本体(GO)富集分析;采用Cytoscape软件构建成分-靶点-通路网络;用分子对接技术验证靶点间结合的可靠性。结果表明,从续断-桑寄生药对中筛选得到174个靶点,其中交集于多囊卵巢综合征的80个共有靶点主要涉及癌症通路、丙型肝炎信号通路、糖尿病并发症中的AGE-RAGE信号通路等多条信号通路。续断-桑寄生药对通过槲皮素、β-谷甾醇等活性物质形成多靶点、多通路调控网络,调节激素代谢,降低炎症细胞因子水平,从而达到系统改善多囊卵巢综合征的目的。

关键词: 多囊卵巢综合征, 续断, 桑寄生, 网络药理学, 分子对接

Abstract:

The study's aim was to explore the main active ingredients, targets, and pathways of the combined medicine, Dipsaci Radix-Taxilli Herba, involved in the improvement of polycystic ovary syndrome via network pharmacology. The main active ingredients and potential targets of Dipsaci Radix-Taxilli Herba were obtained through the traditional Chinese medicine(TCM) systems pharmacology database and analysis platform, and the TCM-ingredient-target network was constructed using the Cytoscape software. The disease targets of polycystic ovary syndrome were obtained through Disgenet and OMIM databases, and they were compared to obtain common drugs and disease targets with the help of online venn tools. Protein-protein interaction network was constructed using the STRING database, and Kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses were performed for the intersecting targets using Metascape database. Furthermore, the ingredient-target-pathway network was constructed via the Cytoscape software, and the reliability of inter-target binding was verified using the molecular docking technique. Among the 174 screened targets of the combined medicine, 80 common targets intersected with polycystic ovary syndrome, which mainly included cancer, hepatitis C signaling, AGE-RAGE signaling in diabetic complications, and other signaling pathways. The medicine, Dipsaci Radix-Taxilli Herba, forms multitarget and multichannel regulatory network through quercetin, β-sitosterol, and other active substances; improves hormone metabolism; reduces inflammatory cytokine levels; and achieves the goal of systemic improvement in polycystic ovary syndrome.

Key words: :polycystic ovary syndrome, Dipsaci Radix, Taxilli Herba, network pharmacology, molecular docking

中图分类号:

R285

韩聪,夏铭鸿,胡渊龙,张建伟. 基于网络药理学和分子对接分析续断-桑寄生改善多囊卵巢综合征的作用机制[J]. 山东科学, 2022, 35(3): 7-16.

HAN Cong,XIA Ming-hong,HU Yuan-long,ZHANG Jian-wei. Analysis of the mechanism of Dipsaci Radix-Taxilli Herba underlying the improvement of polycystic ovary syndrome via network pharmacology and molecular docking[J]. Shandong Science, 2022, 35(3): 7-16.

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中药	编码	活性化合物	OB%	DL	编号
续断	MOL003152	Gentisin	64.06	0.21	XD1
续断,桑寄生	MOL000358	beta-sitosterol	36.91	0.75	A
续断	MOL000651	Sweroside aglycone	68.68	0.08	XD2
续断	MOL009312	(E,E)-3,5-Di-O-caffeoylquinic acid	48.14	0.68	XD3
续断	MOL009314	Cantleyine	70.62	0.08	—
续断	MOL009317	Cauloside A	43.32	0.81	—
续断	MOL008188	Japonine	44.11	0.25	—
续断	MOL009322	Sylvestroside III	48.02	0.53	XD4
桑寄生	MOL000119	ZINC02040970	40.43	0.43	SJS1
桑寄生	MOL000125	(-)-alpha-Pinene	46.25	0.06	SJS2
桑寄生	MOL000130	CAM	67.17	0.05	SJS3
桑寄生	MOL000193	(Z)-caryophyllene	30.29	0.05	SJS4
桑寄生	MOL000098	quercetin	46.43	0.75	SJS5

序号	生物学功能	基因数	P值
1	蛋白结构域特异性结合	16	5.25×10^-9
2	脂质结合	15	3.47×10^-14
3	细胞因子受体结合	14	3.98×10^-7
4	蛋白质同源二聚化活性	12	1.35×10^-9
5	蛋白酶结合泛素样	11	1.10×10^-11
6	RNA聚合酶II转录因子结合	10	1.38×10^-10
7	蛋白连接酶结合	9	1.32×10^-8
8	激酶调节活性	9	2.69×10^-5
9	蛋白激酶活性	9	3.80×10^-5
10	内肽酶活性	8	5.25×10^-9

序号	生物学过程	基因数	P值
1	凋亡信号通路	30	5.62×10^-30
2	损伤反应	30	1.17×10^-27
3	血管发育反应过程	30	1.00×10^-26
4	细胞粘附的调节	27	4.57×10^-23
5	对有毒物质的反应	26	7.08×10^-26
6	对无机物的反应	26	4.27×10^-25
7	生长调节	24	1.58×10^-20
8	跨膜受体蛋白酪氨酸激酶信号通路	24	3.47×10^-19
9	对损伤活性氧代谢过程	23	1.74×10^-27
10	对脂多糖的反应	23	5.13×10^-26

序号	细胞组分	基因数	P值
1	膜筏	15	1.70×10^-39
2	细胞外间质	10	2.63×10^-34
3	核被膜	9	9.77×10^-31
4	膜侧	9	1.86×10^-25
5	质膜蛋白复合物	9	2.51×10^-23
6	细胞质核周区	9	3.55×10^-19
7	胞体	7	3.98×10^-19
8	RNA聚合酶II转录调节复合物	6	9.55×10^-19
9	突触后膜	6	1.70×10^-18
10	血小板α颗粒腔	5	3.63×10^-11