title: Magnolol protects osteoblastic MC3T3-E1 cells against antimycin A-induced cytotoxicity through activation of mitochondrial function.
abstract: Antimycin A treatment of cells blocks the mitochondrial electron transport chain and leads to elevated ROS generation. In the present study, we investigated the protective effects of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells. Osteoblastic MC3T3-E1 cells were pre-incubated with magnolol before treatment with antimycin A. Cell viability and mineralization of osteoblasts were assessed by MTT assay and Alizarin Red staining, respectively. Mitochondrial dysfunction in cells was measured by mitochondrial membrane potential (MMP), complex IV activity, and ATP level. The cellular antioxidant effect of magnolol in osteoblastic MC3T3-E1 cells was assessed by measuring cardiolipin oxidation, mitochondrial superoxide levels, and nitrotyrosine content. Phosphorylated cAMP-response element-binding protein (CREB ) was evaluated using ELISA assay. Pretreatment with magnolol prior to antimycin A exposure significantly reduced antimycin A-induced osteoblast dysfunction by preventing MMP dissipation, ATP loss, and CREB inactivation. Magnolol also reduced cardiolipin peroxidation, mitochondrial superoxide, and nitrotyrosine production induced by antimycin A. These results suggest that magnolol has a protective effect against antimycin A-induced cell damage by its antioxidant effects and the attenuation of mitochondrial dysfunction. All these data indicate that magnolol may reduce or prevent osteoblast degeneration in osteoporosis or other degenerative disorders.
authors.affiliation: Department of Food and Nutrition, Education Graduate School, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, South Korea. cheunmi@hanmail.net
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D050882:CREB-Binding Protein / Q000032:analysis; D002308:Cardiolipins / Q000378:metabolism; D002460:Cell Line; D004579:Electron Transport / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D031566:Magnolia / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D002308:Cardiolipins; D017705:Lignans; D010936:Plant Extracts; D020011:Protective Agents; D017382:Reactive Oxygen Species; C005498:magnolol; C002744:3-nitrotyrosine; D014443:Tyrosine; D000968:Antimycin A; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse