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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MDPI AG
2023-02-01
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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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last_indexed | 2024-03-11T07:23:09Z |
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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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