Glabridin inhibits dexamethasone-induced muscle atrophy.
Glabridin inhibits dexamethasone-induced muscle atrophy.
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光甘草定抑制地塞米松引起的肌肉萎缩。
DOI：
10.1016/j.abb.2019.02.006
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hitoshi Ashida
中科院分区：
文献类型：
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作者：
Yasukiyo Yoshioka;Yusuke Kubota;Yumi Samukawa;Yoko Yamashita;Hitoshi Ashida
众所周知，防止肌肉萎缩有助于提高生活质量和延长健康寿命。最近，我们报道了含有光滑素的甘草黄酮油，它是一种戊烯基异黄酮，可以增加小鼠的肌肉质量。在本研究中，我们在培养的小鼠肌管和肌肉中观察了光滑蛋白对地塞米松诱导的肌肉萎缩的预防作用，并阐明了其作用机制。C2C12肌管经光滑霉素处理后，可通过诱导泛素连接酶MuRF1和Cbl-b的表达而抑制地塞米松诱导的蛋白质降解，但不能抑制阿托金-1。从机制上讲，光滑素可抑制糖皮质激素受体的核转位。Glabridin直接与糖皮质激素受体结合，从而抑制地塞米松与受体蛋白的结合。Glabridin还抑制地塞米松诱导的p38和FOXO3a的磷酸化，作为诱导C2C12肌管泛素连接酶的上游。此外，通过敲除糖皮质激素受体，而不是通过p38敲除，可以消除光滑霉素对蛋白质降解的抑制作用。这些结果表明，光滑素抑制地塞米松诱导的肌肉萎缩的机制主要是通过抑制地塞米松与肌管中糖皮质激素受体的结合来实现的。口服光滑素可阻止地塞米松诱导的小鼠胫骨前肌蛋白质降解。已证实，光滑素可抑制地塞米松诱导的小鼠肌肉糖皮质激素受体核移位和FOXO3a的磷酸化。这些发现表明，光滑素是一种有效的预防糖皮质激素诱导的骨骼肌萎缩的食物成分。
Prevention of muscle wasting is known to contribute to improving the quality of life and extending a healthy life. Recently, we have reported that licorice flavonoid oil containing glabridin, which is a prenylated isoflavone, enhances muscle mass in mice. In this study, we investigated the prevention effect of glabridin on dexamethasone-induced muscle atrophy and clarified its mechanism in cultured myotubes and in muscle of mice. Treatment with glabridin to C2C12 myotubes inhibited dexamethasone-induced protein degradation through dexamethasone-induced expression of ubiquitin ligases, MuRF1 and Cbl-b, but not atrogin-1. Mechanistically, glabridin inhibited nuclear translocation of the glucocorticoid receptor. Glabridin directly bound to the glucocorticoid receptor, resulting in the inhibition of binding between dexamethasone and the receptor protein. Glabridin also inhibited dexamethasone-induced phosphorylation of p38 and FoxO3a, as the upstream for the induction of ubiquitin ligases in C2C12 myotubes. Moreover, the glabridin-induced inhibition of protein degradation was eliminated by knockdown of the glucocorticoid receptor, but not by p38 knockdown. These data indicated that the inhibitory mechanism of glabridin against dexamethasone-induced muscle atrophy was mainly mediated by the inhibition of binding between dexamethasone and the glucocorticoid receptor in myotubes. Oral administration of glabridin prevented dexamethasone-induced protein degradation in the tibialis anterior muscle of mice. It was confirmed that glabridin inhibited dexamethasone-induced nuclear translocation of the glucocorticoid receptor and phosphorylation of FoxO3a in the muscle of mice. These findings suggest that glabridin is an effective food ingredient for the prevention of glucocorticoid-induced skeletal muscle atrophy.