Xie Rongfang, Li Chenlu, Zhong Chenhui, Lin Zuan, Li Shaoguang, Chen Bing, Wu Youjia, Hu Fen, Shi Peiying, Yao Hong
Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China.
Department of Hyperbaric Oxygen, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
J Ginseng Res. 2024 Jul;48(4):395-404. doi: 10.1016/j.jgr.2024.02.001. Epub 2024 Feb 22.
Ginsenoside Rg (Rg) is one of the main active components in Chinese medicines, and . Research has shown that Rg has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood.
Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg against myocardial ischemia (MI) were screened and explored.
An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg intervention on H9c2 cells injured by HO showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg was also evaluated.
Rg can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.
人参皂苷Rg（Rg）是中药中的主要活性成分之一。研究表明，Rg对心血管系统具有保护作用，包括抗心肌缺血再灌注损伤、抗凋亡以及促进心肌血管生成，提示其为一种潜在的心血管药物。然而，其涉及的保护机制仍未完全明确。
基于网络药理学、基于配体的蛋白质对接、蛋白质组学、蛋白质免疫印迹法、蛋白质重组及光谱分析（紫外可见光谱和荧光光谱）技术，筛选并探究Rg抗心肌缺血（MI）的潜在靶点和通路。
构建了一个包含19种蛋白质的重要靶点集。通过分子对接进一步鉴定出两种对Rg抗MI具有更有利结合活性的靶点蛋白，包括丝裂原活化蛋白激酶1（MAPK1）和腺苷激酶（ADK）。同时，Rg对HO损伤的H9c2细胞的干预显示出抑制氧化磷酸化（OXPHOS）通路。蛋白质免疫印迹法证实了Rg对MAPK1和OXPHOS通路的抑制作用。通过蛋白质重组和光谱分析，还评估了ADK与Rg之间的结合反应。
Rg可通过靶向MAPK1和ADK并抑制氧化磷酸化（OXPHOS）通路有效减轻心肌细胞氧化应激损伤。本研究为天然活性成分Rg的临床应用提供了科学依据，也为其他天然活性成分作用靶点和通路的研究提供了方法学参考。
