Ginsenoside Rg3 Protects Heart Tissue from Damage Through Key Cellular Pathways

Jenn Hoskins
27th June, 2024

Ginsenoside Rg3 Protects Heart Tissue from Damage Through Key Cellular Pathways

Image Source: Natural Science News, 2024

Key Findings

  • This study by Guangzhou University of Chinese Medicine found that ginsenoside Rg3 from ginseng helps protect the heart from damage caused by restoring blood flow after a blockage
  • Ginsenoside Rg3 improved heart function and reduced heart tissue damage in mice with induced heart injuries
  • The compound increased levels of GPX4, a protein that prevents a specific type of cell death called ferroptosis, and reduced iron buildup in heart tissue
  • Ginsenoside Rg3 activated the Nrf2 signaling pathway, which boosts the production of antioxidant proteins, including GPX4, to protect heart cells
Ginsenoside Rg3, a component of ginseng, has shown promise in protecting against myocardial ischemia/reperfusion (MI/R) injury, a condition where the heart muscle is damaged due to the restoration of blood supply after a period of ischemia or lack of oxygen. This study conducted by Guangzhou University of Chinese Medicine[1] investigates the role and mechanism of ginsenoside Rg3 in mitigating MI/R injury, focusing on a specific form of cell death known as ferroptosis. Ferroptosis is a regulated cell death characterized by iron-dependent lipid peroxidation, leading to oxidative damage to cell membranes[2]. This process is distinct from other forms of cell death like apoptosis or necrosis. Previous studies have shown that the glutathione-dependent enzyme glutathione peroxidase 4 (GPX4) plays a crucial role in preventing ferroptosis by converting harmful lipid peroxides into non-toxic lipid alcohols[2]. Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is known to regulate oxidative stress responses and has been implicated in the protection against ferroptosis[3]. In this study, the researchers used a mouse model of left anterior descending (LAD) ligation-induced MI/R injury and oxygen-glucose deprivation/reperfusion (OGD/R) as in vitro and in vivo models to assess the cardioprotective effects of ginsenoside Rg3. They employed various techniques, including echocardiographic analysis, TTC staining, and H&E staining, to evaluate cardiac function and infarct size. Western blotting, biochemical analysis, small interfering RNA (siRNA) analysis, and molecular docking were used to explore the underlying mechanisms. The results demonstrated that ginsenoside Rg3 significantly improved cardiac function and reduced infarct size in mice subjected to MI/R injury. Importantly, ginsenoside Rg3 increased the expression of GPX4, a key ferroptosis-related protein, and inhibited iron deposition in the heart tissue of these mice. This suggests that ginsenoside Rg3 effectively prevents ferroptosis in the context of MI/R injury. Further analysis revealed that ginsenoside Rg3 activated the Nrf2 signaling pathway. Nrf2 is a transcription factor that, when activated, moves into the cell nucleus and promotes the expression of antioxidant proteins, including GPX4. The study found that ginsenoside Rg3 regulated the keap1/Nrf2 signaling pathway to mitigate OGD/R-induced ferroptosis in H9C2 cells, a type of cardiomyocyte cell line used for in vitro studies. These findings are consistent with previous research indicating the importance of the Nrf2/System xc-/GPX4 axis in regulating ferroptosis and protecting against MI/R injury[3]. The study also aligns with earlier work that identified ferroptosis suppressor protein 1 (FSP1) as another important factor in ferroptosis resistance, suggesting that multiple pathways can contribute to ferroptosis regulation[2]. In summary, this study by Guangzhou University of Chinese Medicine demonstrates that ginsenoside Rg3 can ameliorate MI/R-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway. By increasing GPX4 expression and activating Nrf2, ginsenoside Rg3 offers a potential therapeutic strategy for protecting the heart against ischemia-reperfusion injury, highlighting its role in regulating ferroptosis and oxidative stress. This research builds on existing knowledge and offers new insights into the mechanisms of ferroptosis regulation in cardiac health.

MedicineHealthBiochem

References

Main Study

1) Ginsenoside Rg3 attenuates myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.

Published 26th June, 2024

https://doi.org/10.1186/s12906-024-04492-4

Related Studies

2) The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

https://doi.org/10.1038/s41586-019-1705-2

3) Naringenin alleviates myocardial ischemia/reperfusion injury by regulating the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) /System xc-/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis.

https://doi.org/10.1080/21655979.2021.1995994


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