Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1

Phloroglucinol is a class of polyphenolic compounds containing aromatic phenyl rings and is known to have various pharmacological activities. Recently, we reported that this compound isolated from <i>Ecklonia cava</i>, a brown alga belonging to the family <i>Laminariaceae</i>...

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Main Authors: Cheol Park, Hee-Jae Cha, Hyun Hwangbo, Seon Yeong Ji, Da Hye Kim, Min Yeong Kim, EunJin Bang, Su Hyun Hong, Sung Ok Kim, Soon-Jeong Jeong, Hyesook Lee, Sung-Kwon Moon, Jung-Hyun Shim, Gi-Young Kim, Suengmok Cho, Yung Hyun Choi
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/5/4637
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author Cheol Park
Hee-Jae Cha
Hyun Hwangbo
Seon Yeong Ji
Da Hye Kim
Min Yeong Kim
EunJin Bang
Su Hyun Hong
Sung Ok Kim
Soon-Jeong Jeong
Hyesook Lee
Sung-Kwon Moon
Jung-Hyun Shim
Gi-Young Kim
Suengmok Cho
Yung Hyun Choi
author_facet Cheol Park
Hee-Jae Cha
Hyun Hwangbo
Seon Yeong Ji
Da Hye Kim
Min Yeong Kim
EunJin Bang
Su Hyun Hong
Sung Ok Kim
Soon-Jeong Jeong
Hyesook Lee
Sung-Kwon Moon
Jung-Hyun Shim
Gi-Young Kim
Suengmok Cho
Yung Hyun Choi
author_sort Cheol Park
collection DOAJ
description Phloroglucinol is a class of polyphenolic compounds containing aromatic phenyl rings and is known to have various pharmacological activities. Recently, we reported that this compound isolated from <i>Ecklonia cava</i>, a brown alga belonging to the family <i>Laminariaceae</i>, has potent antioxidant activity in human dermal keratinocytes. In this study, we evaluated whether phloroglucinol could protect against hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced oxidative damage in murine-derived C2C12 myoblasts. Our results revealed that phloroglucinol suppressed H<sub>2</sub>O<sub>2</sub>-induced cytotoxicity and DNA damage while blocking the production of reactive oxygen species. We also found that phloroglucinol protected cells from the induction of apoptosis associated with mitochondrial impairment caused by H<sub>2</sub>O<sub>2</sub> treatment. Furthermore, phloroglucinol enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) as well as the expression and activity of heme oxygenase-1 (HO-1). However, such anti-apoptotic and cytoprotective effects of phloroglucinol were greatly abolished by the HO-1 inhibitor, suggesting that phloroglucinol could increase the Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress. Taken together, our results indicate that phloroglucinol has a strong antioxidant activity as an Nrf2 activator and may have therapeutic benefits for oxidative-stress-mediated muscle disease.
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spelling doaj.art-f8268a34f7464644a73bc54477374be92023-11-17T07:51:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245463710.3390/ijms24054637Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1Cheol Park0Hee-Jae Cha1Hyun Hwangbo2Seon Yeong Ji3Da Hye Kim4Min Yeong Kim5EunJin Bang6Su Hyun Hong7Sung Ok Kim8Soon-Jeong Jeong9Hyesook Lee10Sung-Kwon Moon11Jung-Hyun Shim12Gi-Young Kim13Suengmok Cho14Yung Hyun Choi15Division of Basic Sciences, College of Liberal Studies, Dong-eui University, Busan 47340, Republic of KoreaDepartment of Parasitology and Genetics, College of Medicine, Kosin University, Busan 49267, Republic of KoreaAnti-Aging Research Center, Dong-eui University, Busan 47340, Republic of KoreaAnti-Aging Research Center, Dong-eui University, Busan 47340, Republic of KoreaAnti-Aging Research Center, Dong-eui University, Busan 47340, Republic of KoreaAnti-Aging Research Center, Dong-eui University, Busan 47340, Republic of KoreaAnti-Aging Research Center, Dong-eui University, Busan 47340, Republic of KoreaAnti-Aging Research Center, Dong-eui University, Busan 47340, Republic of KoreaDepartment of Food and Nutrition, College of Life and Health, Kyungsung University, Busan 48434, Republic of KoreaDepartment of Dental Hygiene & Institute of Basic Science for Well-Aging, Youngsan University, Yangsan 50510, Republic of KoreaDepartment of Convergence Medicine, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Food and Nutrition, College of Biotechnology & Natural Resource, Chung-Ang University, Ansung 17546, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Mokpo National University, Muan 58554, Republic of KoreaDepartment of Marine Life Science, College of Ocean Sciences, Jeju National University, Jeju 63243, Republic of KoreaDepartment of Food Science and Technology, Institute of Food Science, Pukyong National University, Busan 48513, Republic of KoreaAnti-Aging Research Center, Dong-eui University, Busan 47340, Republic of KoreaPhloroglucinol is a class of polyphenolic compounds containing aromatic phenyl rings and is known to have various pharmacological activities. Recently, we reported that this compound isolated from <i>Ecklonia cava</i>, a brown alga belonging to the family <i>Laminariaceae</i>, has potent antioxidant activity in human dermal keratinocytes. In this study, we evaluated whether phloroglucinol could protect against hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced oxidative damage in murine-derived C2C12 myoblasts. Our results revealed that phloroglucinol suppressed H<sub>2</sub>O<sub>2</sub>-induced cytotoxicity and DNA damage while blocking the production of reactive oxygen species. We also found that phloroglucinol protected cells from the induction of apoptosis associated with mitochondrial impairment caused by H<sub>2</sub>O<sub>2</sub> treatment. Furthermore, phloroglucinol enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) as well as the expression and activity of heme oxygenase-1 (HO-1). However, such anti-apoptotic and cytoprotective effects of phloroglucinol were greatly abolished by the HO-1 inhibitor, suggesting that phloroglucinol could increase the Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress. Taken together, our results indicate that phloroglucinol has a strong antioxidant activity as an Nrf2 activator and may have therapeutic benefits for oxidative-stress-mediated muscle disease.https://www.mdpi.com/1422-0067/24/5/4637phloroglucinolROSDNA damageapoptosisNrf2/HO-1
spellingShingle Cheol Park
Hee-Jae Cha
Hyun Hwangbo
Seon Yeong Ji
Da Hye Kim
Min Yeong Kim
EunJin Bang
Su Hyun Hong
Sung Ok Kim
Soon-Jeong Jeong
Hyesook Lee
Sung-Kwon Moon
Jung-Hyun Shim
Gi-Young Kim
Suengmok Cho
Yung Hyun Choi
Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1
International Journal of Molecular Sciences
phloroglucinol
ROS
DNA damage
apoptosis
Nrf2/HO-1
title Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1
title_full Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1
title_fullStr Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1
title_full_unstemmed Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1
title_short Phloroglucinol Inhibits Oxidative-Stress-Induced Cytotoxicity in C2C12 Murine Myoblasts through Nrf-2-Mediated Activation of HO-1
title_sort phloroglucinol inhibits oxidative stress induced cytotoxicity in c2c12 murine myoblasts through nrf 2 mediated activation of ho 1
topic phloroglucinol
ROS
DNA damage
apoptosis
Nrf2/HO-1
url https://www.mdpi.com/1422-0067/24/5/4637
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