The preventive effect of Mori Ramulus on oxidative stress-induced cellular damage in skeletal L6 myoblasts through Nrf2-mediated activation of HO-1

Cheol Park; Hyesook Lee; Sung Ok Kim; Eun-Woo Lee; Hyun-Tai Lee; Hyun Ju Kwon; Byung Woo Kim; Gi-Young Kim; Mi Ryeo Kim; Yung Hyun Choi

doi:10.1007/s43188-022-00141-5

The preventive effect of Mori Ramulus on oxidative stress-induced cellular damage in skeletal L6 myoblasts through Nrf2-mediated activation of HO-1

Toxicol Res. 2022 Jul 22;39(1):25-36. doi: 10.1007/s43188-022-00141-5. eCollection 2023 Jan.

Authors

Cheol Park¹, Hyesook Lee^{2

3}, Sung Ok Kim⁴, Eun-Woo Lee^{5

6}, Hyun-Tai Lee^{5

6}, Hyun Ju Kwon^{5

6}, Byung Woo Kim^{5

6}, Gi-Young Kim⁷, Mi Ryeo Kim⁸, Yung Hyun Choi^{2

6

9}

Affiliations

¹ Division of Basic Sciences, College of Liberal Studies, Dong-eui University, Busan, 47340 Republic of Korea.
² Anti-Aging Research Center, Dong-eui University, Busan, 47340 Republic of Korea.
³ Department of Convergence Medicine, Pusan National University School of Medicine, Yangsan, 50612 Republic of Korea.
⁴ Department of Food and Nutrition, College of Life and Health, Kyungsung University, Busan, 48434 Republic of Korea.
⁵ Biopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University, Busan, 47340 Republic of Korea.
⁶ Core-Facility Center for Tissue Regeneration, Dong-eui University, Busan, 47340 Republic of Korea.
⁷ Department of Marine Life Science, Jeju National University, Jeju, 63243 Republic of Korea.
⁸ Department of Pharmacology, College of Korean Medicine, Daegu Haany University, Daegu, 42158 Republic of Korea.
⁹ Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan, 47227 Republic of Korea.

Abstract

The aim of the present study is to investigate the preventive effect of water extract of Mori Ramulus (MRWE) on oxidative stress-mediated cellular damages in rat skeletal L6 myoblasts. Our results demonstrated that MRWE pretreatment markedly improved cell survival and suppressed cell cycle arrest at the G2/M phase and apoptosis in hydrogen peroxide (H₂O₂)-treated L6 cells. H₂O₂-triggered DNA damage was also notably reduced by MRWE, which since it was correlated with protection of reactive oxygen species (ROS) production. Additionally, H₂O₂ stimulated cytosolic release of cytochrome c and up-regulation of Bax/Bcl-2 ratio, whereas MRWE suppressed these changes following by H₂O₂. Moreover, MRWE inhibited the cleavage of poly(ADP-ribose) polymerase as well as the activity of caspase-3 by H₂O₂. Furthermore, MRWE enhanced H₂O₂-mediated expression of nuclear factor erythroid 2-associated factor 2 (Nrf2) and its representative downstream enzyme, heme oxygenase-1 (HO-1). However, the protective effects of MRWE on H₂O₂-induced ROS production, cell cycle arrest and apoptosis were significantly attenuated by HO-1 inhibitor. In conclusion, our present results suggests that MRWE could protect L6 myoblasts from H₂O₂-induced cellular injury by inhibiting ROS generation along with Nrf2-mediated activation of HO-1, indicating this finding may expand the scope of application of Mori Ramulus in medicine.

Keywords: Apoptosis; DNA damage; Mori Ramulus; Nrf2/HO-1; ROS.