title: Liquiritigenin restores osteoblast damage through regulating oxidative stress and mitochondrial dysfunction.
abstract: We investigated the protective effect of liquiritigenin, one of the flavonoids present in Glycyrrhizae radix, against antimycin A-induced mitochondrial dysfunction in MC3T3-E1 osteoblast cells. Osteoblastic MC3T3-E1 cells were pre-incubated with liquiritigenin before treatment with antimycin A, and markers of mitochondrial function and oxidative damage were examined. In addition, the effects of liquiritigenin on the activation of phosphoinositide 3-kinase (PI3K) were examined in MC3T3-E1 cells. Liquiritigenin protected MC3T3-E1 cells from antimycin A-induced cell death. However, the PI3K inhibitor, LY294002, significantly attenuated liquiritigenin-mediated cell survival, indicating the involvement of PI3K in the cytoprotective effect of liquiritigenin. Pretreatment with liquiritigenin prior to antimycin A exposure significantly reduced antimycin A-induced PI3K inactivation, mitochondrial membrane potential dissipation, complex IV inactivation, and ATP loss. Liquiritigenin also reduced mitochondrial superoxide generation, nitrotyrosine production, and cardiolipin peroxidation during mitochondrial complex inhibition with antimycin A. Taken together, the results of this study show that modulation of PI3K, antioxidant effects, and the attenuation of mitochondrial dysfunction by liquiritigenin represent an important mechanism for its protection of osteoblasts against cytotoxicity resulting from mitochondrial oxidative stress.
authors.affiliation: Department of Food and Nutrition, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Suh
authors.forename: Young Soon
authors.initials: YS
authors.lastname: Lee
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000968:Antimycin A / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D044950:Flavanones; D000968:Antimycin A; D003576:Electron Transport Complex IV; D019869:Phosphatidylinositol 3-Kinases; C083152:liquiritigenin
keywords: MC3T3-E1 cells; PI3K; antimycin A; liquiritigenin; mitochondrial dysfunction; oxidative stress