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

Mori Ramulus, the dried twigs of <i>Morus alba</i> 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) a...

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Autores principales:	Cheol Park, Seon Yeong Ji, Hyesook Lee, Sung Hyun Choi, Chan-Young Kwon, So Young Kim, Eun Tag Lee, Sung Tae Choo, Gi-Young Kim, Yung Hyun Choi, Mi Ryeo Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Mori Ramulus myoblast ROS apoptosis AMPK muscle atrophy Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c9351b8942c548e999dc207481d07e56
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spelling	oai:doaj.org-article:c9351b8942c548e999dc207481d07e562021-11-11T17:11:09ZMori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK10.3390/ijms2221117291422-00671661-6596https://doaj.org/article/c9351b8942c548e999dc207481d07e562021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11729https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mori Ramulus, the dried twigs of <i>Morus alba</i> 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<sub>2</sub>O<sub>2</sub>) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H<sub>2</sub>O<sub>2</sub>-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<sub>2</sub>O<sub>2</sub>-treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H<sub>2</sub>O<sub>2</sub>-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 <i>c</i> release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H<sub>2</sub>O<sub>2</sub>. Furthermore, AEMR diminished H<sub>2</sub>O<sub>2</sub>-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<sub>2</sub>O<sub>2</sub>-induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H<sub>2</sub>O<sub>2</sub>-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.Cheol ParkSeon Yeong JiHyesook LeeSung Hyun ChoiChan-Young KwonSo Young KimEun Tag LeeSung Tae ChooGi-Young KimYung Hyun ChoiMi Ryeo KimMDPI AGarticleMori RamulusmyoblastROSapoptosisAMPKmuscle atrophyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11729, p 11729 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mori Ramulus myoblast ROS apoptosis AMPK muscle atrophy Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Mori Ramulus myoblast ROS apoptosis AMPK muscle atrophy Biology (General) QH301-705.5 Chemistry QD1-999 Cheol Park Seon Yeong Ji Hyesook Lee Sung Hyun Choi Chan-Young Kwon So Young Kim Eun Tag Lee Sung Tae Choo Gi-Young Kim Yung Hyun Choi Mi Ryeo Kim Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK
description	Mori Ramulus, the dried twigs of <i>Morus alba</i> 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<sub>2</sub>O<sub>2</sub>) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H<sub>2</sub>O<sub>2</sub>-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<sub>2</sub>O<sub>2</sub>-treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H<sub>2</sub>O<sub>2</sub>-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 <i>c</i> release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H<sub>2</sub>O<sub>2</sub>. Furthermore, AEMR diminished H<sub>2</sub>O<sub>2</sub>-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<sub>2</sub>O<sub>2</sub>-induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H<sub>2</sub>O<sub>2</sub>-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.
format	article
author	Cheol Park Seon Yeong Ji Hyesook Lee Sung Hyun Choi Chan-Young Kwon So Young Kim Eun Tag Lee Sung Tae Choo Gi-Young Kim Yung Hyun Choi Mi Ryeo Kim
author_facet	Cheol Park Seon Yeong Ji Hyesook Lee Sung Hyun Choi Chan-Young Kwon So Young Kim Eun Tag Lee Sung Tae Choo Gi-Young Kim Yung Hyun Choi Mi Ryeo Kim
author_sort	Cheol Park
title	Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK
title_short	Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK
title_full	Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK
title_fullStr	Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK
title_full_unstemmed	Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK
title_sort	mori ramulus suppresses hydrogen peroxide-induced oxidative damage in murine myoblast c2c12 cells through activation of ampk
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c9351b8942c548e999dc207481d07e56
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Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK

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