Ginsenoside Rg1 ameliorates experimental autoimmune myasthenia gravis by regulating T cell subsets, inhibiting PI3K-AKT pathway and modulating gut microbiota and metabolites

IF 7.5 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2026-05-01 Epub Date: 2026-01-30 DOI:10.1016/j.jgr.2026.100988

Yan Li , Yu-nan Shan , Lin Xu , Zhi-lin He , Guan-qing Wang , Qing Wang , Yan-bin Li , Wei Chen

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引用次数: 0

Abstract

Background

Ginsenoside Rg1 (GRg1), a bioactive saponin derived from ginseng, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, and neuroprotective effects. However, its role in myasthenia gravis (MG) remains unexplored. This study investigated the therapeutic potential of GRg1 in experimental autoimmune myasthenia gravis (EAMG).

Methods

The EAMG model was established in Lewis rats using the AChR97-116 peptide. ELISA was employed to determine serum anti-AChR antibody levels in rats, while Flow cytometry or PCR was used to analyze T cell subsets. Gut microbiota composition was assessed via 16S rRNA sequencing, while non-targeted metabolomics identified metabolic changes. Network pharmacology and molecular docking were employed to predict GRg1’s therapeutic targets in EAMG, followed by experimental validation using immunohistochemistry.

Results

GRg1 administration significantly alleviated the clinical symptoms of EAMG rats, reduced serum anti-AChR antibody levels, and modulated T cell responses. KEGG analysis implicating the PI3K-AKT pathway. Molecular docking confirmed strong binding affinities between GRg1 and key PI3K-AKT proteins. Immunohistochemistry revealed GRg1-mediated inhibition of PI3K/AKT phosphorylation in splenic tissues. Additionally, GRg1 restored gut microbiota homeostasis. Metabolomic analysis further revealed significant differences in metabolites between EAMG and CFA rats, which were inhibited after GRg1 treatment.

Conclusions

GRg1 ameliorates EAMG through immunomodulation, PI3K-AKT pathway inhibition, gut microbiota restoration, and metabolic reprogramming, highlighting its potential as a novel therapeutic agent for MG.

Abstract Image

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人参皂苷Rg1通过调节T细胞亚群、抑制PI3K-AKT通路和调节肠道微生物群和代谢物来改善实验性自身免疫性重症肌无力

人参皂苷Rg1 （GRg1）是一种从人参中提取的生物活性皂苷，具有多种药理作用，包括抗炎、抗氧化和神经保护作用。然而，其在重症肌无力（MG）中的作用尚不清楚。本研究探讨了GRg1在实验性自身免疫性重症肌无力（EAMG）中的治疗潜力。方法采用AChR97-116肽建立Lewis大鼠EAMG模型。ELISA法检测大鼠血清抗achr抗体水平，流式细胞术或PCR法检测T细胞亚群。通过16S rRNA测序评估肠道微生物群组成，而非靶向代谢组学鉴定代谢变化。采用网络药理学和分子对接方法预测GRg1在EAMG中的治疗靶点，并进行免疫组化实验验证。结果grg1可显著缓解EAMG大鼠的临床症状，降低血清抗achr抗体水平，调节T细胞反应。KEGG分析提示PI3K-AKT通路。分子对接证实GRg1与关键的PI3K-AKT蛋白之间具有很强的结合亲和力。免疫组化显示grg1介导的脾组织PI3K/AKT磷酸化抑制。此外，GRg1还能恢复肠道微生物群的稳态。代谢组学分析进一步揭示了EAMG和CFA大鼠之间代谢物的显著差异，GRg1处理后这些代谢物被抑制。结论grg1通过免疫调节、PI3K-AKT通路抑制、肠道菌群恢复和代谢重编程等途径改善EAMG，显示其作为MG新型治疗药物的潜力。

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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.