Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK

• Published in: International journal of molecular sciences 2021-10, Vol.22 (21), p.11729
• Main Authors: Park, Cheol, Ji, Seon Yeong, Lee, Hyesook, Choi, Sung Hyun, Kwon, Chan-Young, Kim, So Young, Lee, Eun Tag, Choo, Sung Tae, Kim, Gi-Young, Choi, Yung Hyun, Kim, Mi Ryeo
• Format: Article
• Language: English
• Subjects: AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacology; Apoptosis; Atrophy; BAX protein; Bcl-2 protein; Caspase-3; Cell activation; Cell Line; Cell viability; Cytochrome; Cytochrome c; Cytoplasm; Cytotoxicity; Dexamethasone; DNA damage; Enzyme Activators - chemistry; Enzyme Activators - pharmacology; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Kinases; Membrane potential; Mice; Mitochondria; Mori Ramulus; Morphology; Morus - chemistry; muscle atrophy; Muscles; Musculoskeletal system; myoblast; Myoblasts; Myoblasts - drug effects; Myoblasts - metabolism; Oral administration; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation; Proteins; Reactive oxygen species; Ribose; ROS; Signal transduction; Soleus muscle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111729

Mori Ramulus, the dried twigs of L., has been attracting attention for its potent antioxidant activity, but its role in muscle cells has not yet been elucidated. The purpose of this study was to evaluate the protective effect of aqueous extracts of Mori Ramulus (AEMR) against oxidative stress caused by hydrogen peroxide (H O ) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H O -induced cell viability loss and the collapse of the mitochondria membrane potential. AEMR was also able to activate AMP-activated protein kinase (AMPK) in H O -treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H O -triggered DNA damage was markedly attenuated in the presence of AEMR, which was associated with the inhibition of reactive oxygen species (ROS) generation. Further studies showed that AEMR inhibited cytochrome release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H O . Furthermore, AEMR diminished H O -induced activation of caspase-3, which was associated with the ability of AEMR to block the degradation of poly (ADP-ribose) polymerase, thereby attenuating H O -induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H O -induced C2C12 cell apoptosis, including the restoration of mitochondrial dysfunction. Taken together, these results demonstrate that AEMR could protect C2C12 myoblasts from oxidative damage by maintaining mitochondrial function while eliminating ROS, at least with activation of the AMPK signaling pathway. In addition, oral administration of AEMR alleviated gastrocnemius and soleus muscle loss in DEX-induced muscle atrophied rats. Our findings support that AEMR might be a promising therapeutic candidate for treating oxidative stress-mediated myoblast injury and muscle atrophy.