Ginsenoside Rg1 regulates autophagy and endoplasmic reticulum stress via the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate alcohol‑induced myocardial injury

Tian,Ge; Li,Jing; Zhou,Lina

doi:10.3892/ijmm.2023.5259

Ginsenoside Rg1 regulates autophagy and endoplasmic reticulum stress via the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate alcohol‑induced myocardial injury

Authors:
- Ge Tian
- Jing Li
- Lina Zhou
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China, Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Geriatrics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
Published online on: May 23, 2023 https://doi.org/10.3892/ijmm.2023.5259
Article Number: 56
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been reported that ginsenoside Rg1 (G‑Rg1) can alleviate alcoholic liver injury, cardiac hypertrophy and myocardial ischemia, as well as reperfusion injury. Therefore, the present study aimed to investigate the role of G‑Rg1 in alcohol‑induced myocardial injury, as well as to elucidate its underlying mechanisms of action. For this purpose, H9c2 cells were stimulated with ethanol. Subsequently, H9c2 cell viability and apoptosis were determined using a Cell Counting Kit‑8 assay and flow cytometric analysis, respectively. The levels of lactate dehydrogenase and caspase‑3 in the H9c2 cell culture supernatant were detected using corresponding assay kits. In addition, the expression of green fluorescent protein (GFP)‑light chain 3 (LC3) and that of C/EBP homologous protein (CHOP) were evaluated using GFP‑LC3 assay and immunofluorescence staining, respectively. The expression levels of apoptosis‑, autophagy‑, endoplasmic reticulum stress (ERS)‑ and adenosine 5'‑monophosphate‑activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway‑related proteins were detected using western blot analysis. The results revealed that treatment with G‑Rg1 enhanced the viability and suppressed the apoptosis of ethanol‑stimulated H9c2 cells. G‑Rg1 also attenuated autophagy and ERS in ethanol‑stimulated H9c2 cells. In addition, the levels of phosphorylated (p)‑protein kinase R (PKR)‑like ER kinase (PERK), p‑eukaryotic translation initiation factor 2a, activating transcription factor 4 (ATF4), CHOP, caspase‑12 and p‑AMPK were downregulated, while the p‑mTOR level was upregulated in ethanol‑stimulated H9c2 cells treated with G‑Rg1. Furthermore, the co‑treatment of G‑Rg1‑treated ethanol‑stimulated H9c2 cells with AICAR, an AMPK agonist, or CCT020312, a PERK agonist, inhibited cell viability and promoted cell apoptosis, autophagy and ERS. Overall, the results of the present study suggest that G‑Rg1 suppresses autophagy and ERS via inhibiting the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate ethanol‑induced H9c2 cell injury.

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