Shiota Chieko, Abe Tomoki, Kawai Nobuhiko, Ohno Ayako, Teshima-Kondo Shigetada, Mori Hiroyo, Terao Junji, Tanaka Eiji, Nikawa Takeshi
Department of Nutritional Physiology, Institute of Health Biosciences, Tokushima University Graduate School.
J Nutr Sci Vitaminol (Tokyo). 2015;61(2):188-94. doi: 10.3177/jnsv.61.188.
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.
肌肉萎缩是一个复杂的过程，它是由各种应激事件引起的。肌肉萎缩相关基因（萎缩基因），如萎缩素-1/MAFbx和MuRF-1，在萎缩过程早期被诱导，其表达增加先于肌肉重量的减轻。尽管抗氧化营养物质可抑制骨骼肌细胞中萎缩基因的表达，但黄酮类化合物对炎症诱导的萎缩素-1/MAFbx表达的抑制作用尚未阐明。在此，我们研究了黄酮类化合物对脂多糖（LPS）诱导的萎缩素-1/MAFbx表达的抑制作用。我们检测了六种黄酮类化合物中的九种黄酮是否能抑制小鼠C2C12肌管中萎缩素-1/MAFbx的表达。两种主要的黄酮，芹菜素和木犀草素，对萎缩素-1/MAFbx的表达显示出强大的抑制作用。用芹菜素和木犀草素预处理可显著防止LPS刺激引起的C2C12肌管直径减小。重要的是，用这些黄酮预处理LPS刺激的成肌细胞可显著抑制C2C12肌管中LPS诱导的JNK磷酸化，从而显著抑制萎缩素-1/MAFbx启动子活性。这些结果表明，芹菜素和木犀草素通过抑制C2C12肌管中的JNK信号通路来阻止LPS介导的萎缩素-1/MAFbx表达。因此，这些黄酮，芹菜素和木犀草素，可能是预防LPS诱导的肌肉萎缩的有前途的药物。
