Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress

  • Hyun Hwangbo (Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases, Department of Biochemistry, College of Korean Medicine, Dong-eui University) ;
  • Cheol Park (Department Division of Basic Sciences, College of Liberal Studies, Dong-eui University) ;
  • EunJin Bang (Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases, Department of Biochemistry, College of Korean Medicine, Dong-eui University) ;
  • Hyuk Soon Kim (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University) ;
  • Sung-Jin Bae (Department of Molecular Biology and Immunology, Kosin University College of Medicine) ;
  • Eunjeong Kim (BK21 Plus KNU Creative BioResearch Group, School of Life Sciences, College of National Sciences, Kyungpook National University) ;
  • Youngmi Jung (Department of Biological Sciences, College of Natural Science, Pusan National University) ;
  • Sun-Hee Leem (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University) ;
  • Young Rok Seo (Institute of Environmental Medicine, Department of Life Science, Dongguk University Biomedi Campus) ;
  • Su Hyun Hong (Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases, Department of Biochemistry, College of Korean Medicine, Dong-eui University) ;
  • Gi-Young Kim (Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University) ;
  • Jin Won Hyun (Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Yung Hyun Choi (Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases, Department of Biochemistry, College of Korean Medicine, Dong-eui University)
  • Received : 2024.01.12
  • Accepted : 2024.03.13
  • Published : 2024.05.01
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Abstract

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2023-00217899 and RS2023-00270936).

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