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Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes

  • SHIOTA Chieko
    Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Science
  • ABE Tomoki
    Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School
  • KAWAI Nobuhiko
    Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Science
  • OHNO Ayako
    Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School
  • TESHIMA-KONDO Shigetada
    Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School
  • MORI Hiroyo
    Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Science
  • TERAO Junji
    Department of Food Science, Institute of Health Biosciences, Tokushima University Graduate School
  • TANAKA Eiji
    Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Science
  • NIKAWA Takeshi
    Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School

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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.

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