Affiliated Qingyuan Hospital, Guangzhou Medical University (Qingyuan People’s Hospital), Qingyuan 511518, Guangdong, China.
The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510120, Guangdong, China.
Aging (Albany NY). 2024 Mar 27;16(8):6745-6756. doi: 10.18632/aging.205680.
Ginsenoside Rb1 is the major active constituent of ginseng, which is widely used in traditional Chinese medicine for the atherosclerosis treatment by anti-inflammatory, anti-oxidant and reducing lipid accumulation. We explored cellular target and molecular mechanisms of ginsenoside Rb1 based on network pharmacology and experimental validation. In this study, we predicted 17 potential therapeutic targets for ginsenoside Rb1 with atherosclerosis from public databases. We then used protein-protein interaction network to screen the hub targets. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that the effects of ginsenoside Rb1 were meditated through multiple targets and pathways. Next, molecular docking results revealed that in the 10 core targets, CCND1 has the highest binding energy with ginsenoside Rb1. Vascular cell proliferation plays a critical role in atherosclerosis development. However, the effect and direct target of ginsenoside Rb1 in regulating vascular cell proliferation in atherosclerosis remains unclear. Edu straining results indicated that ginsenoside Rb1 inhibited the cell proliferation of endothelial cells, macrophages, and vascular smooth muscle cells. The protein immunoprecipitation (IP) analysis showed that ginsenoside Rb1 inhibited the vascular cell proliferation by suppressing the interaction of CCDN1 and CDK4. These findings systematically reveal that the anti-atherosclerosis mechanism of ginsenoside Rb1 by integrating network pharmacology and experimental validation, which provide evidence to treat atherosclerosis by using ginsenoside Rb1 and targeting CCND1.
人参皂苷 Rb1 是人参的主要活性成分，广泛应用于传统中药治疗动脉粥样硬化，具有抗炎、抗氧化和减少脂质积累的作用。我们基于网络药理学和实验验证探索了人参皂苷 Rb1 的细胞靶标和分子机制。在这项研究中，我们从公共数据库中预测了 17 个人参皂苷 Rb1 治疗动脉粥样硬化的潜在治疗靶点。然后，我们使用蛋白质-蛋白质相互作用网络筛选关键靶点。基因本体论富集和京都基因与基因组百科全书通路富集表明，人参皂苷 Rb1 的作用是通过多个靶点和通路介导的。接下来，分子对接结果表明，在 10 个核心靶标中，CCND1 与人参皂苷 Rb1 的结合能最高。血管细胞增殖在动脉粥样硬化发展中起着关键作用。然而，人参皂苷 Rb1 调节动脉粥样硬化中血管细胞增殖的作用及其直接靶标尚不清楚。Edu 实验结果表明，人参皂苷 Rb1 抑制内皮细胞、巨噬细胞和血管平滑肌细胞的细胞增殖。蛋白质免疫沉淀（IP）分析表明，人参皂苷 Rb1 通过抑制 CCND1 和 CDK4 的相互作用抑制血管细胞增殖。这些发现系统地揭示了人参皂苷 Rb1 通过整合网络药理学和实验验证的抗动脉粥样硬化机制，为通过使用人参皂苷 Rb1 靶向 CCND1 治疗动脉粥样硬化提供了证据。
