title: Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes.
abstract: Muscle atrophy is a complex process that occurs as a consequence of various stress events. Muscle atrophy-associated genes (atrogenes) such as atrogin-1/MAFbx and MuRF-1 are induced early in the atrophy process, and the increase in their expression precedes the loss of muscle weight. Although antioxidative nutrients suppress atrogene expression in skeletal muscle cells, the inhibitory effects of flavonoids on inflammation-induced atrogin-1/MAFbx expression have not been clarified. Here, we investigated the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced atrogin-1/MAFbx expression. We examined whether nine flavonoids belonging to six flavonoid categories inhibited atrogin-1/MAFbx expression in mouse C2C12 myotubes. Two major flavones, apigenin and luteolin, displayed potent inhibitory effects on atrogin-1/MAFbx expression. The pretreatment with apigenin and luteolin significantly prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Importantly, the pretreatment of LPS-stimulated myoblasts with these flavones significantly inhibited LPS-induced JNK phosphorylation in C2C12 myotubes, resulting in the significant suppression of atrogin-1/MAFbx promoter activity. These results suggest that apigenin and luteolin, prevent LPS-mediated atrogin-1/MAFbx expression through the inhibition of the JNK signaling pathway in C2C12 myotubes. Thus, these flavones, apigenin and luteolin, may be promising agents to prevent LPS-induced muscle atrophy.
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School.
authors.forename: Chieko
authors.initials: C
authors.lastname: Shiota
authors.forename: Tomoki
authors.initials: T
authors.lastname: Abe
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kawai
authors.forename: Ayako
authors.initials: A
authors.lastname: Ohno
authors.forename: Shigetada
authors.initials: S
authors.lastname: Teshima-Kondo
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Mori
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D047309:Flavones / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009133:Muscular Atrophy / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D047309:Flavones; D009124:Muscle Proteins; D010936:Plant Extracts; D047310:Apigenin; C486691:Fbxo32 protein, mouse; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; D047311:Luteolin