What does this research mean for the field?

20(S)-protopanaxatriol mitigates pathological cardiac hypertrophy and delays heart failure progression by activating the AMPK/PGC-1α/PPARγ signaling pathway. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

November 20, 2025Journal of Ginseng ResearchOpen Access

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

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Why the study?

The efficacy of 20(S)-protopanaxatriol against cardiac hypertrophy and its underlying molecular mechanisms remain unclear, limiting clinical translation.

Does 20(S)-protopanaxatriol ameliorate cardiac hypertrophy in preclinical murine models?

Structured PICO

Does 20(S)-protopanaxatriol ameliorate cardiac hypertrophy in preclinical murine models?

Population

Murine models of cardiac hypertrophy, specifically male C57BL/6J mice (8-10 weeks old) subjected to transverse aortic constriction (TAC), phenylephrine (PE) infusion, or myocardial infarction (MI), and primary neonatal rat cardiomyocytes (NRCMs) from 1-2-day-old SD rats.

Intervention

20(S)-protopanaxatriol (PPT) administered at 100 mg/kg/day orally (TAC and MI models) or 100 mg/kg every other day (PE model) for 2 to 8 weeks in vivo; 5-10 μM in vitro.

Comparator

Vehicle control (0.5% carboxymethylcellulose or saline) and an active comparator, Carvedilol (30 mg/kg/day).

Outcome

Cardiac hypertrophy and remodeling, evaluated by echocardiographic parameters (HW/BW, HW/TL, LVPWd, LVIDs, EF, FS), myocyte cross-sectional area, and hypertrophic gene expression (Anp, Bnp, Myh7).surrogate

20(S)-protopanaxatriol mitigates pathological cardiac hypertrophy and restores mitochondrial energy metabolism in preclinical models by activating the AMPK/PGC-1α/PPARγ pathway, highlighting its potential as a novel therapeutic agent.

Limitations

PE and TAC models induce pressure overload but do not fully replicate genetic HCM mechanisms (e.g., MYH7/MYBPC3 mutations).
The pharmacokinetic profile of PPT remains uncharacterized.

Implication

Does not support clinical use; hypothesis-generating for PPT in human HF trials.

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.