Ginsenoside compound-Mc1 attenuates oxidative stress and apoptosis in cardiomyocytes through an AMP-activated protein kinase–dependent mechanism

So hyeon Hong, Hwan Jin Hwang, Joo Won Kim, Jung A. Kim, You Bin Lee, Eun Roh, Kyung Mook Choi, Sei-Hyun Baik, Hye-Jin Yoo

Research output: Contribution to journalArticle

Abstract

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H2O2) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)–induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H2O2-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H2O2-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress–related cardiac diseases.

Original languageEnglish
JournalJournal of Ginseng Research
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Ginsenosides
Oxidative stress
Adenosine Monophosphate
Cardiac Myocytes
Oxidative Stress
oxidative stress
apoptosis
Apoptosis
Proteins
proteins
bcl-2-Associated X Protein
AMP-activated protein kinase
AMP-Activated Protein Kinases
High Fat Diet
high fat diet
Nutrition
Cells
Catalase
catalase
superoxide dismutase

Keywords

  • AMP-activated protein kinases
  • Antioxidant
  • Cardiomyocyte

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Complementary and alternative medicine

Cite this

Ginsenoside compound-Mc1 attenuates oxidative stress and apoptosis in cardiomyocytes through an AMP-activated protein kinase–dependent mechanism. / Hong, So hyeon; Hwang, Hwan Jin; Kim, Joo Won; Kim, Jung A.; Lee, You Bin; Roh, Eun; Choi, Kyung Mook; Baik, Sei-Hyun; Yoo, Hye-Jin.

In: Journal of Ginseng Research, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H2O2) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)–induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H2O2-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H2O2-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress–related cardiac diseases.",
keywords = "AMP-activated protein kinases, Antioxidant, Cardiomyocyte",
author = "Hong, {So hyeon} and Hwang, {Hwan Jin} and Kim, {Joo Won} and Kim, {Jung A.} and Lee, {You Bin} and Eun Roh and Choi, {Kyung Mook} and Sei-Hyun Baik and Hye-Jin Yoo",
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T1 - Ginsenoside compound-Mc1 attenuates oxidative stress and apoptosis in cardiomyocytes through an AMP-activated protein kinase–dependent mechanism

AU - Hong, So hyeon

AU - Hwang, Hwan Jin

AU - Kim, Joo Won

AU - Kim, Jung A.

AU - Lee, You Bin

AU - Roh, Eun

AU - Choi, Kyung Mook

AU - Baik, Sei-Hyun

AU - Yoo, Hye-Jin

PY - 2019/1/1

Y1 - 2019/1/1

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AB - Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H2O2) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)–induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H2O2-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H2O2-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress–related cardiac diseases.

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