基于网络药理学和分子对接技术预测西洋参抗衰老的作用机制

doi:10.3976/j.issn.1002-4026.20240005

摘要/Abstract

摘要：

基于网络药理学联合分子对接技术探讨西洋参抗衰老的潜在有效成分及其作用机制。利用斑马鱼衰老模型评价西洋参的抗衰老活性;使用数据库筛选出西洋参活性成分及其与抗衰老相关的潜在靶点,并绘制蛋白互作网络(PPI),筛选核心靶点;对核心靶点进行富集分析和分子对接验证。SA-β-Gal染色结果表明西洋参具有显著的抗衰老活性。数据库筛选出西洋参活性成分11个,抗衰老的潜在核心靶点AKT1、STAT3、JUN等53个。GO和KEGG分析的结果显示西洋参的抗衰老作用可能涉及对外源刺激的反应、凋亡过程负向调控、PI3K-AKT信号通路、ErbB信号通路等。分子对接结果显示有效成分polyacetylene PQ-2和PQ-2与关键靶点结合紧密,AKT1和HRAS与多种成分结合紧密。西洋参可能通过polyacetylene PQ-2和PQ-2等多种成分作用于AKT1、HRAS、MAPK1等多个靶点,进而通过调节内分泌抵抗、ErbB信号通路等多条通路发挥抗衰老作用,为西洋参在抗衰老应用方面提供了理论基础。

关键词: 西洋参, 抗衰老, 网络药理学, 分子对接, 作用机制, 斑马鱼模型

Abstract:

The aim of this study was to explore the potential effective ingredients and mechanism of action of Panax quinquefolius L. in anti-aging based on network pharmacology and molecular docking. The anti-aging activity of P. quinquefolius L. was evaluated in a zebrafish aging model. The active ingredients of P. quinquefolius L. and their potential targets related to anti-aging were screened using databases, and protein-protein interaction networks (PPI) were mapped to screen core targets. Enrichment analysis and molecular docking verification of the core targets were performed. SA-β-Gal staining results showed that P. quinquefolius L. exerted significant anti-aging activity.Database screening identified 11 active ingredients and 53 potential core targets of P. quinquefolius L. in anti-aging, such as AKT1, STAT3, and JUN. The results of GO and KEGG analysis showed that the anti-aging effects of P. quinquefolius L. may involve factors including xenobiotic stimulus response, negative regulation of apoptotic processes, PI3K-AKT signaling pathway, ErbB signaling pathway. Molecular docking results showed that polyacetylene PQ-2 and PQ-2 were tightly bound with their core targets, and tight binding was also seen with AKT1 and HRAS with various active ingredients. P. quinquefolius L. may act on multiple targets such as AKT1, HRAS, and MAPK1 through polyacetylene PQ-2, PQ-2, and other ingredients, and then regulate multiple pathways such as endocrine resistance, ErbB signaling pathway, and other mechanisms to exert an anti-aging effect.Collectively, these dataprovide a theoretical basis for the application of P. quinquefolius L. in anti-aging.

Key words: Panax quinquefolius L., anti-aging, network pharmacology, molecular docking, mechanism of action, zebrafish model

中图分类号:

R285

范伟, 沈川琳, 张轩铭, 杜兴硕, 展文, 孙晨, 靳梦, 李晓彬, 张思晨, 孙博通, 何秋霞. 基于网络药理学和分子对接技术预测西洋参抗衰老的作用机制[J]. 山东科学, 2024, 37(6): 42-50.

FAN Wei, SHEN Chuanlin, ZHANG Xuanming, DU Xingshuo, ZHAN Wen, SUN Chen, JIN Meng, LI Xiaobin, ZHANG Sichen, SUN Botong, HE Qiuxia. Prediction of anti-aging mechanism of Panax quinquefolius L. by network pharmacology and molecular docking[J]. Shandong Science, 2024, 37(6): 42-50.

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编号	Mol ID	英文名	OB/%	DL
XYS1	MOL000358	Beta-sitosterol	36.91	0.75
XYS2	MOL005344	Ginsenoside rh2	36.32	0.56
XYS3	MOL006774	Stigmast-7-enol	37.42	0.75
XYS4	MOL006980	Papaverine	64.04	0.38
XYS5	MOL008173	Daucosterol_qt	36.91	0.75
XYS6	MOL008397	Daturilin	50.37	0.77
XYS7	MOL011394	Ginsenoside F2	36.43	0.25
XYS8	MOL011434	Polyacetylene PQ-2	36.74	0.20
XYS9	MOL011435	PQ-2	36.74	0.19
XYS10	MOL011442	Stigmasta-3,5-dien-7-one	43.87	0.75
XYS11	MOL011455	20-Hexadecanoylingenol	32.70	0.65

编号	活性成分	与靶点对接的结合能/(kcal·mol^-1)
编号	活性成分	AKT1	HRAS	MAPK1	MAPK3	PIK3CA	SRC
XYS4	Papaverine	-8.02	-8.69	-5.86	-6.32	-4.51	-7.90
XYS9	PQ-2	-9.96	-11.08	-6.17	-6.52	-5.16	-7.86
XYS8	Polyacetylene PQ-2	-11.05	-9.87	-8.67	-8.04	-9.04	-9.40
XYS6	Daturilin	-5.29	-5.72	-3.67	-4.34	-3.11	-3.12
XYS11	20-Hexadecanoylingenol	-6.57	-6.85	-3.95	-3.68	-4.06	-4.05
XYS5	Daucosterol_qt	-7.43	-7.07	-5.54	-3.68	-4.30	-4.95