# 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.

## Key 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.