20(S)-protopanaxatriol ameliorates cardiac hypertrophy by activating the AMPK/PGC-1α/PPARγ signaling pathway

IF 7.5 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2026-05-01 Epub Date: 2025-11-19 DOI:10.1016/j.jgr.2025.11.008

Xue Yan , Huajie Zheng , Ju Ye, Donglin Zhang, Rong Lv, Li Yang, Qiong Lai, Lili Ding, Zhengtao Wang

{"title":"20(S)-protopanaxatriol ameliorates cardiac hypertrophy by activating the AMPK/PGC-1α/PPARγ signaling pathway","authors":"Xue Yan , Huajie Zheng , Ju Ye, Donglin Zhang, Rong Lv, Li Yang, Qiong Lai, Lili Ding, Zhengtao Wang","doi":"10.1016/j.jgr.2025.11.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Pathological cardiac hypertrophy, a critical precursor to heart failure, presents a significant therapeutic challenge. The triterpenoid 20(S)-protopanaxatriol (PPT), derived from Panax ginseng Meyer, exhibits antioxidant, anti-inflammatory, and neuroprotective properties. However, its efficacy against cardiac hypertrophy and the underlying molecular mechanisms remain unclear, limiting clinical translation.</div></div><div><h3>Methods</h3><div>We evaluated PPT’s anti-hypertrophic effects in murine models of transverse aortic constriction (TAC), phenylephrine (PE)-infusion, and myocardial infarction (MI). In vitro analyses assessed oxidative stress and mitochondrial function in neonatal rat cardiomyocytes (NRCMs). Network pharmacology identified targets, with AMPK inhibitors validating pathway involvement.</div></div><div><h3>Results</h3><div>Among 18 tested ginsenosides, PPT demonstrated the strongest anti-hypertrophic activity in vitro. In murine models, PPT attenuated myocardial remodeling, improved echocardiographic parameters, and delayed heart failure progression. Mechanistically, PPT suppressed ROS, enhanced mitochondrial biogenesis, and promoted fatty acid oxidation through AMPK/PGC-1α/PPARγ activation.</div></div><div><h3>Conclusion</h3><div>PPT mitigates cardiac hypertrophy by modulating oxidative stress, mitochondrial function, and energy metabolism through AMPK/PGC-1α/PPARγ signaling, highlighting its therapeutic promise for cardiac pathologies.</div></div>","PeriodicalId":16035,"journal":{"name":"Journal of Ginseng Research","volume":"50 3","pages":"Article 100920"},"PeriodicalIF":7.5000,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ginseng Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1226845325001721","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/11/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Pathological cardiac hypertrophy, a critical precursor to heart failure, presents a significant therapeutic challenge. The triterpenoid 20(S)-protopanaxatriol (PPT), derived from Panax ginseng Meyer, exhibits antioxidant, anti-inflammatory, and neuroprotective properties. However, its efficacy against cardiac hypertrophy and the underlying molecular mechanisms remain unclear, limiting clinical translation.

Methods

We evaluated PPT’s anti-hypertrophic effects in murine models of transverse aortic constriction (TAC), phenylephrine (PE)-infusion, and myocardial infarction (MI). In vitro analyses assessed oxidative stress and mitochondrial function in neonatal rat cardiomyocytes (NRCMs). Network pharmacology identified targets, with AMPK inhibitors validating pathway involvement.

Results

Among 18 tested ginsenosides, PPT demonstrated the strongest anti-hypertrophic activity in vitro. In murine models, PPT attenuated myocardial remodeling, improved echocardiographic parameters, and delayed heart failure progression. Mechanistically, PPT suppressed ROS, enhanced mitochondrial biogenesis, and promoted fatty acid oxidation through AMPK/PGC-1α/PPARγ activation.

Conclusion

PPT mitigates cardiac hypertrophy by modulating oxidative stress, mitochondrial function, and energy metabolism through AMPK/PGC-1α/PPARγ signaling, highlighting its therapeutic promise for cardiac pathologies.

Abstract Image

查看原文本刊更多论文

20(S)-protopanaxatriol通过激活AMPK/PGC-1α/PPARγ信号通路改善心脏肥厚

病理性心脏肥厚是心衰的重要前兆，是一项重大的治疗挑战。从人参中提取的三萜20(S)-protopanaxatriol （PPT）具有抗氧化、抗炎和神经保护作用。然而，其抗心肌肥厚的功效和潜在的分子机制尚不清楚，限制了临床转化。方法在大鼠横断主动脉缩窄（TAC）、苯肾上腺素（PE）灌注和心肌梗死（MI）模型中观察PPT的抗肥厚作用。体外分析评估了新生大鼠心肌细胞（NRCMs）的氧化应激和线粒体功能。网络药理学鉴定了靶点，AMPK抑制剂证实了通路参与。结果在18种人参皂苷中，PPT的体外抗肥厚活性最强。在小鼠模型中，PPT减轻心肌重构，改善超声心动图参数，延缓心力衰竭进展。从机制上讲，PPT通过AMPK/PGC-1α/PPARγ激活抑制ROS，促进线粒体生物发生，促进脂肪酸氧化。结论ppt通过AMPK/PGC-1α/PPARγ信号通路调节氧化应激、线粒体功能和能量代谢，减轻心肌肥厚，具有治疗心脏病变的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.