Protective Effects of Panax ginseng Extract on Endothelin-1- and Isoproterenol-Induced Cardiac Hypertrophy via Maintenance of Mitochondrial Function and Calcium-Reactive Oxygen Species (ROS) Homeostasis

TL;DR

This study shows that Panax ginseng extract protects heart cells from stress-induced damage by maintaining mitochondrial function and reducing harmful reactive oxygen species.

Contribution

The study reveals a novel mechanism by which Panax ginseng extract protects the heart through mitochondrial and ROS regulation under stress.

Findings

PG reduced ET-1-induced cardiac hypertrophy and mitochondrial fragmentation in rat heart cells.

PG preserved ATP levels and reduced intracellular calcium and ROS in stressed cells.

In mice, PG improved heart function and reduced fibrosis during ISO-induced stress.

Abstract

Background: Mitochondrial dysfunction and oxidative stress are central to the development of cardiac hypertrophy and heart failure. Panax ginseng (PG), a principal herb used in Kampo medicine, has been reported to exert cardioprotective effects; however, its intracellular actions under endothelin-1 (ET-1)- and β-adrenergic stress remain incompletely defined.

Purpose: To determine whether a standardized PG extract attenuates cardiac hypertrophy and whether its effects are associated with mitochondrial function and Ca2+-reactive oxygen species (ROS) homeostasis in complementary cellular and in vivo stress models.

Methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to ET-1 to induce hypertrophy and mitochondrial fragmentation. Mitochondrial morphology, intracellular Ca²⁺, ROS, and adenosine triphosphate (ATP) levels were quantified by fluorescence imaging and biochemical assays. In mice, isoproterenol (ISO) was administered for 14 days to induce cardiac stress; PG was given orally. Cardiac structure and function were evaluated by histology and echocardiography. Expression of mitochondrial fusion/fission markers was analyzed. All experiments used predefined exclusion criteria and blinded analyses.

Results: PG was associated with reduced ET-1-induced hypertrophy in a concentration-dependent manner (IC50 = 7.5 µg/mL), was associated with reduced mitochondrial fragmentation and loss of membrane potential, preserved ATP levels, and mitigated increases in intracellular Ca2+ and ROS in NRVMs. In ISO-treated mice, oral PG (50 mg/kg/day for 14 days) improved systolic function, limited hypertrophic remodeling, and reduced interstitial fibrosis.

Conclusion: PG exhibits pharmacological cardioprotection associated with modulation of mitochondrial dynamics and attenuation of cellular stress responses. These findings support further investigation of PG as a mitochondria-engaging natural product with the potential to mitigate pathological cardiac remodeling and heart failure progression.

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