Cytoprotective effects of esculetin against oxidative stress are associated with the upregulation of Nrf2-mediated NQO1 expression via the activation of the ERK pathway

Han,Min  Ho; Park,Cheol; Lee,Dae‑Sung; Hong,Su‑Hyun; Choi,Il‑Whan; Kim,Gi‑Young; Choi,Sung  Hyun; Shim,Jung‑Hyun; Chae,Jung‑Il; Yoo,Young  Hyun; Choi,Yung  Hyun

doi:10.3892/ijmm.2016.2834

Cytoprotective effects of esculetin against oxidative stress are associated with the upregulation of Nrf2-mediated NQO1 expression via the activation of the ERK pathway

Authors:
- Min Ho Han
- Cheol Park
- Dae‑Sung Lee
- Su‑Hyun Hong
- Il‑Whan Choi
- Gi‑Young Kim
- Sung Hyun Choi
- Jung‑Hyun Shim
- Jung‑Il Chae
- Young Hyun Yoo
- Yung Hyun Choi
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Affiliations: Natural Products Research Team, National Marine Biodiversity Institute of Korea, Seocheon 325‑902, Republic of Korea, Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614‑714, Republic of Korea, Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Department of Microbiology, College of Medicine, Inje University, Busan 608‑756, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690‑756, Republic of Korea, Department of Safety and System Management, Korea Lift College, Geochang 670‑802, Republic of Korea, Natural Medicine Research Institute, Department of Pharmacy, College of Pharmacy, Mokpo National University, Jeonnam 534‑729, Republic of Korea, Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Jeonju 561‑756, Republic of Korea, Department of Anatomy and Cell Biology, Dong‑A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602‑714, Republic of Korea
Published online on: December 16, 2016 https://doi.org/10.3892/ijmm.2016.2834
Pages: 380-386

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Abstract

Esculetin, a coumarin derivative isolated from a variety of medicinal herbs, has been reported to possess multiple therapeutic and pharmacological actions. Although several studies have demonstrated the antioxidant activity of esculetin, its mechanisms of action have not been clearly established. The aim of this study was to evaluate the effects of esculetin against hydrogen peroxide (H2O2)‑induced oxidative stress in C2C12 myoblasts and to investigate the mechanisms involved in this process. Our data indicated that esculetin preconditioning significantly attenuated H2O2‑induced growth inhibition and DNA damage and the apoptosis of C2C12 cells by suppressing intracellular reactive oxygen species (ROS) accumulation. Treatment with esculetin effectively increased the phosphorylation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1). Esculetin treatment also activated extracellular signal‑regulated kinase (ERK), and pre‑treatment with PD98059, an ERK‑specific inhibitor, blocked esculetin-mediated phosphorylation of Nrf2 and the induction of NQO1 expression. In addition, the protective effects of esculetin against H2O2‑induced ROS accumulation, apoptosis and growth inhibition were abrogated in the C2C12 cells pre‑treated with PD98059. Thus, the present study demonstrates that esculetin protects C2C12 cells against oxidative stress-induced injury, possibly through the activation of the Nrf2/NQO1 pathway.

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