Work

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

Year: 2025

Type: article

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.

Source: Journal of Ginseng Research

DOI: 10.1016/j.jgr.2025.11.008