基于网络药理学和分子对接探究三棱-莪术抗乳腺癌的作用机制

doi:10.3976/j.issn.1002-4026.2022.05.004

Abstract

Abstract:

To explore the active ingredients and mechanisms of Sparganii Rhizoma-Curcumae Rhizoma herbal pair in breast cancer using network pharmacology and molecular docking. The effective active ingredients and corresponding targets of Sparganii Rhizoma and Curcumae Rhizoma were searched and screened using the traditional Chinese medicine systems pharmacology database and analysis platform,and the disease targets of breast cancer were searched using the OMIM and GeneCards databases. Cytoscape 3.7.2 software was used to construct a visual network diagram of drug-ingredient-disease-targets. A protein-protein interaction network (PPI) was constructed using STRING database platform, and the MCODE plug-in in Cytoscape was used for analysis to screen the top 10 core targets. Gene ontology and Kyoto encyclopedia of genes and genomes(KEGG) enrichment pathway analyses of the targets of action were performed using DAVID database, and the network diagram of ingredient-target-pathway was plotted. Finally, molecular docking was performed using autodock Vina and other software to verify the interaction between the core ingredients and the core targets. Seven active components and 73 action targets were obtained through screening. There were 43 common targets of Sparganii Rhizoma and Curcumae Rhizoma and breast cancer. The active components were hederagenin, beta-sitosterol, formononetin, stigmasterol, and trans-gondoic acid. The PPI network showed that the key targets were JUN, CASP3, PTGS2, ESR1, MPK14, PPARG, SIRT1, NOS3, TGFB1 and NOS2. The KEGG pathway enrichment analysis revealed 72 items. According to the P values, the first 20 items related to breast cancer were eliminated via screened, including the PI3K-Akt signaling pathway, VEGF signaling pathway, p53 signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the active ingredients had strong binding ability in docking with the core targets. Therefore, our results suggest that Sparganii Rhizoma-Curcumae Rhizoma herbal pair has characteristics of a multi-ingredient, multi-target, and multi-pathway on breast cancer, which provides a theoretical basis for its clinical application in the future.

Key words: network pharmacology, molecular docking, Sparganii Rhizoma-Curcumae Rhizoma, breast cancer, mechanism

CLC Number:

R285

LIU Xue-ting, SUN Xiao-hui, ZHU Jian-min, LI Lin, LI Wen-yue. Mechanism of the anti-breast cancer effect of Sparganii Rhizoma-Curcumae Rhizoma herbal pair based on network pharmacology and molecular docking[J].Shandong Science, 2022, 35(5): 26-36.

Figures/Tables 10

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References 30

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序号	生物过程	基因数	P值
1	对雌二醇的反应	8	2.51×10^-9
2	缺乏配体的外源性凋亡信号通路	6	2.02×10^-9
3	对药物的反应	10	4.89×10^-8
4	RNA聚合酶Ⅱ启动子转录的正调控	14	4.45×10^-7
5	RNA聚合酶Ⅱ启动子起始转录	7	1.99×10^-6
6	类固醇激素介导的信号通路	5	1.21×10^-5
7	血管生成	7	1.80×10^-5
8	转录DNA模板正调控	9	3.45×10^-5
9	对脂多糖的反应	6	5.31×10^-5
10	缺氧反应	6	6.65×10^-5

序号	分子功能	基因数	P值
1	酶结合	14	8.27×10^-13
2	类固醇激素受体	7	4.84×10^-9
3	类固醇结合	5	5.57×10^-7
4	RNA聚合酶II转录因子活性,配体激活序列特异性DNA结合	5	1.84×10^-6
5	序列特异性DNA结合	9	3.50×10^-5
6	蛋白质同源二聚活性	10	6.21×10^-5
7	转录因子结合	7	6.78×10^-5
8	核心启动子序列特异性DNA结合	4	1.65×10^-4
9	蛋白质结合	34	3.54×10^-4
10	半胱氨酸型内肽酶活性参与细胞凋亡过程	3	4.63×10^-4

序号	细胞组分	基因数	P值
1	膜筏	6	1.06×10^-4
2	细胞质	19	1.83×10^-4
3	核	25	1.93×10^-4
4	传递神经元	6	2.05×10^-4
序号	细胞组分	基因数	P值
5	核质	17	2.63×10^-4
6	线粒体外膜	5	3.77×10^-4
7	胞膜微囊	4	4.50×10^-4
8	核染色质	5	9.96×10^-4
9	线粒体	10	2.84×10^-3
10	内质网	7	1.12×10^-2

PDB编号	核心靶点	有效活性成分	结合自由能/(kJ·mol^-1)
6OSN	JUN	常春藤皂苷元	-5.3
		反式软骨酸	-5.2
		β-谷甾醇	-6.2
PDB编号	核心靶点	有效活性成分	结合自由能/(kJ·mol^-1)
		芒柄花黄素	-5.4
		豆甾醇	-6.3
2DKO	CASP3	常春藤皂苷元	-8.1
		反式软骨酸	-5.1
		β-谷甾醇	-7.7
		芒柄花黄素	-6.5
		豆甾醇	-8.2
3NT1	PTGS2	常春藤皂苷元	-9.2
		反式软骨酸	-5.9
		β-谷甾醇	-9.1
		芒柄花黄素	-9.3
		豆甾醇	-8.7

Mechanism of the anti-breast cancer effect of Sparganii Rhizoma-Curcumae Rhizoma herbal pair based on network pharmacology and molecular docking

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