Ginsenoside Rs3 (G-Rs3) inhibits agonist- and oxLDL-mediated platelet activation and attenuates in vivo arterial thrombosis

IF 7.5 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2026-05-01 Epub Date: 2026-03-12 DOI:10.1016/j.jgr.2026.101020

Jung-Hae Shin , Abdul Wahab Akram , Evelyn Saba , Myung Chul Kim , Sung Dae Kim , Sang Joon Park , Dongmi Kwak , Hyuk-woo Kwon , Man Hee Rhee

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引用次数: 0

Abstract

Background

Platelet hyperactivation and thrombo-inflammatory processes are critical drivers of cardiovascular diseases. Although conventional antiplatelet therapies reduce thrombotic risk, their use is limited by bleeding complications and drug resistance. Ginsenoside Rs3 (G-Rs3) exhibits anti-inflammatory potential; however, the specific mechanisms underlying the antiplatelet and thrombo-inflammatory activity of ginsenoside Rs3 (G-Rs3) remain unclear.

Methods

Human platelets were treated with G-Rs3 in vitro to evaluate its effects on aggregation, intracellular signaling, granule secretion, and thrombo-inflammatory signaling markers. Network pharmacological analyses were performed to predict pathway-level modulations. The in vivo antithrombotic efficacy of G-Rs3 was assessed using a murine FeCl₃-induced thrombosis model.

Results

G-Rs3 inhibited platelet aggregation in a dose-dependent manner following stimulation with collagen, thrombin, and U46619. It suppressed Ca²⁺ mobilization, dense granule secretion, and phosphorylation of key signaling molecules, including InsP₃R, ERK1/2, MAPKs, PI3K, Akt, GSK3, and Syk. Additionally, G-Rs3 inhibited integrin αIIbβ3 activation, reduced platelet adhesion, and enhanced cyclic nucleotide–mediated negative regulation, as evidenced by elevated VASP phosphorylation and increased cAMP/cGMP levels. Notably, G-Rs3 attenuated oxLDL-enhanced upregulation of the pro-inflammatory platelet markers CD62P and CD162, highlighting its potential to suppress platelet-driven thrombo-inflammatory responses under atherogenic conditions. Further, network pharmacology analysis revealed that G-Rs3 targets multiple interconnected thrombo-inflammatory pathways, including MAPK, PI3K-Akt, Ras, calcium, and cyclic nucleotide signaling. In vivo, G-Rs3 significantly delayed thrombus formation and moderately prolonged occlusion time.

Conclusion

These findings highlight G-Rs3 as a novel natural antithrombotic agent with anti-thrombo-inflammatory properties. Further studies are required to determine its translational potential and establish its therapeutic viability and safety profile.

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人参皂苷Rs3 （G-Rs3）抑制激动剂和氧化低密度脂蛋白介导的血小板活化和减轻体内动脉血栓形成

背景：血小板过度活化和血栓炎症过程是心血管疾病的关键驱动因素。虽然传统的抗血小板疗法可以降低血栓形成的风险，但其使用受到出血并发症和耐药性的限制。人参皂苷Rs3 （G-Rs3）具有抗炎潜能；然而，人参皂苷Rs3 （G-Rs3）抗血小板和血栓炎症活性的具体机制尚不清楚。方法用G-Rs3体外处理人血小板，观察其对血小板聚集、细胞内信号、颗粒分泌和血栓炎性信号标志物的影响。进行网络药理学分析以预测通路水平的调节。采用小鼠fecl3诱导血栓形成模型评估G-Rs3的体内抗血栓作用。结果g - rs3在胶原蛋白、凝血酶和U46619刺激下呈剂量依赖性抑制血小板聚集。它抑制Ca2+的动员、致密颗粒的分泌和关键信号分子的磷酸化，包括InsP3R、ERK1/2、MAPKs、PI3K、Akt、GSK3和Syk。此外，G-Rs3抑制整合素α ib β3活化，降低血小板粘附，增强环核苷酸介导的负调控，VASP磷酸化升高，cAMP/cGMP水平升高。值得注意的是，G-Rs3减弱了氧化低密度脂蛋白增强的促炎血小板标志物CD62P和CD162的上调，突出了其在动脉粥样硬化条件下抑制血小板驱动的血栓炎症反应的潜力。此外，网络药理学分析显示G-Rs3靶向多种相互关联的血栓炎症通路，包括MAPK、PI3K-Akt、Ras、钙和环核苷酸信号。在体内，G-Rs3显著延缓血栓形成，适度延长血栓闭塞时间。结论G-Rs3是一种具有抗血栓炎症特性的新型天然抗血栓药物。需要进一步的研究来确定其转化潜力，并确定其治疗可行性和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE

CiteScore

11.40

自引率

9.50%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.