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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Mar 11

PMID 36902068

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

Affiliations

Soon will be listed here.

Abstract

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 , a brown alga belonging to the family , has potent antioxidant activity in human dermal keratinocytes. In this study, we evaluated whether phloroglucinol could protect against hydrogen peroxide (HO)-induced oxidative damage in murine-derived C2C12 myoblasts. Our results revealed that phloroglucinol suppressed HO-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 HO 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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References

Choi Y . Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts. Gen Physiol Biophys. 2020; 39(6):519-530. DOI: 10.4149/gpb_2020030. View

Taghizadeh S, Panahi A, Esmaeilzadeh Kashi M, Kretschmer N, Asili J, Emami S . Structural Diversity of Complex Phloroglucinol Derivatives from Eucalyptus Species. Chem Biodivers. 2022; 19(6):e202200025. DOI: 10.1002/cbdv.202200025. View

Tiwari S, Dewry R, Srivastava R, Nath S, Mohanty T . Targeted antioxidant delivery modulates mitochondrial functions, ameliorates oxidative stress and preserve sperm quality during cryopreservation. Theriogenology. 2021; 179:22-31. DOI: 10.1016/j.theriogenology.2021.11.013. View

Shaw P, Chattopadhyay A . Nrf2-ARE signaling in cellular protection: Mechanism of action and the regulatory mechanisms. J Cell Physiol. 2019; 235(4):3119-3130. DOI: 10.1002/jcp.29219. View

Jackson M, McArdle A . Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species. J Physiol. 2011; 589(Pt 9):2139-45. PMC: 3098693. DOI: 10.1113/jphysiol.2011.206623. View

Fulle S, Protasi F, Di Tano G, Pietrangelo T, Beltramin A, Boncompagni S . The contribution of reactive oxygen species to sarcopenia and muscle ageing. Exp Gerontol. 2004; 39(1):17-24. DOI: 10.1016/j.exger.2003.09.012. View

Jenkins T, Gouge J . Nrf2 in Cancer, Detoxifying Enzymes and Cell Death Programs. Antioxidants (Basel). 2021; 10(7). PMC: 8300779. DOI: 10.3390/antiox10071030. View

Lalier L, Vallette F, Manon S . Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death. Biomolecules. 2022; 12(2). PMC: 8961529. DOI: 10.3390/biom12020162. View

Di Filippo E, Mancinelli R, Pietrangelo T, La Rovere R, Quattrocelli M, Sampaolesi M . Myomir dysregulation and reactive oxygen species in aged human satellite cells. Biochem Biophys Res Commun. 2016; 473(2):462-70. DOI: 10.1016/j.bbrc.2016.03.030. View

10.

Kiraz Y, Adan A, Yandim M, Baran Y . Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol. 2016; 37(7):8471-86. DOI: 10.1007/s13277-016-5035-9. View

11.

Vineetha V, Soumya R, Raghu K . Phloretin ameliorates arsenic trioxide induced mitochondrial dysfunction in H9c2 cardiomyoblasts mediated via alterations in membrane permeability and ETC complexes. Eur J Pharmacol. 2015; 754:162-72. DOI: 10.1016/j.ejphar.2015.02.036. View

12.

Yang E, Mahmood U, Kim H, Choi M, Choi Y, Lee J . Phloroglucinol ameliorates cognitive impairments by reducing the amyloid β peptide burden and pro-inflammatory cytokines in the hippocampus of 5XFAD mice. Free Radic Biol Med. 2018; 126:221-234. DOI: 10.1016/j.freeradbiomed.2018.08.016. View

13.

Choi Y . Schisandrin A prevents oxidative stress-induced DNA damage and apoptosis by attenuating ROS generation in C2C12 cells. Biomed Pharmacother. 2018; 106:902-909. DOI: 10.1016/j.biopha.2018.07.035. View

14.

Biessy A, Filion M . Phloroglucinol Derivatives in Plant-Beneficial spp.: Biosynthesis, Regulation, and Functions. Metabolites. 2021; 11(3). PMC: 8003664. DOI: 10.3390/metabo11030182. View

15.

Sukjamnong S, Chen H, Saad S, Santiyanont R . and extracts inhibited AGE-mediated RAGE expression, ROS generation, and inflammation in THP-1 cells. Toxicol Res. 2022; 38(3):331-343. PMC: 9247136. DOI: 10.1007/s43188-021-00114-0. View

16.

Yang Y, Lii C, Lin A, Yeh Y, Yao H, Li C . Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress. Free Radic Biol Med. 2011; 51(11):2073-81. DOI: 10.1016/j.freeradbiomed.2011.09.007. View

17.

Jo H, Park C, Lee H, Kim G, Keum Y, Hyun J . Inhibition of oxidative stress induced-cytotoxicity by coptisine in V79-4 Chinese hamster lung fibroblasts through the induction of Nrf-2 mediated HO-1 expression. Genes Genomics. 2020; 43(1):17-31. DOI: 10.1007/s13258-020-01018-3. View

18.

Lee H, Kim D, Kim J, Park S, Jeong J, Kim M . Urban Aerosol Particulate Matter Promotes Necrosis and Autophagy via Reactive Oxygen Species-Mediated Cellular Disorders that are Accompanied by Cell Cycle Arrest in Retinal Pigment Epithelial Cells. Antioxidants (Basel). 2021; 10(2). PMC: 7909535. DOI: 10.3390/antiox10020149. View

19.

Kang K, Zhang R, Chae S, Lee S, Kim J, Kim J . Phloroglucinol (1,3,5-trihydroxybenzene) protects against ionizing radiation-induced cell damage through inhibition of oxidative stress in vitro and in vivo. Chem Biol Interact. 2010; 185(3):215-26. DOI: 10.1016/j.cbi.2010.02.031. View

20.

Montero L, Sanchez-Camargo A, Ibanez E, Gilbert-Lopez B . Phenolic Compounds from Edible Algae: Bioactivity and Health Benefits. Curr Med Chem. 2017; 25(37):4808-4826. DOI: 10.2174/0929867324666170523120101. View