Department of Nutritional Physiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Bizen Chemical Co. Ltd., Okayama, 709-0716, Japan.
Biosci Biotechnol Biochem. 2022 Sep 23;86(10):1448-1458. doi: 10.1093/bbb/zbac140.
This study investigated the effect of morin, a flavonoid, on dexamethasone-induced muscle atrophy in C57BL/6J female mice. Dexamethasone (10 mg/kg body weight) for 10 days significantly reduced body weight, gastrocnemius and tibialis anterior muscle mass, and muscle protein in mice. Dexamethasone significantly upregulated muscle atrophy-associated ubiquitin ligases, including atrogin-1 and MuRF-1, and the upstream transcription factors FoxO3a and Klf15. Additionally, dexamethasone significantly induced the expression of oxidative stress-sensitive ubiquitin ligase Cbl-b and the accumulation of the oxidative stress markers malondialdehyde and advanced protein oxidation products in both the plasma and skeletal muscle samples. Intriguingly, morin treatment (20 mg/kg body weight) for 17 days effectively attenuated the loss of muscle mass and muscle protein and suppressed the expression of ubiquitin ligases while reducing the expression of upstream transcriptional factors. Therefore, morin might act as a potential therapeutic agent to attenuate muscle atrophy by modulating atrophy-inducing genes and preventing oxidative stress.
本研究探讨了黄酮类化合物桑色素对 C57BL/6J 雌性小鼠地塞米松诱导的肌肉萎缩的影响。地塞米松（10mg/kg 体重）连续给药 10 天，可显著降低小鼠的体重、比目鱼肌和胫骨前肌的质量以及肌肉蛋白含量。地塞米松可显著上调肌肉萎缩相关的泛素连接酶，包括肌萎缩蛋白 1（atrogin-1）和 MuRF1，以及上游转录因子 FoxO3a 和 Klf15。此外，地塞米松还可显著诱导氧化应激敏感的泛素连接酶 Cbl-b 的表达，并增加血浆和骨骼肌样本中丙二醛和高级蛋白氧化产物等氧化应激标志物的积累。有趣的是，桑色素（20mg/kg 体重）连续给药 17 天可有效减轻肌肉质量和肌肉蛋白的丢失，抑制泛素连接酶的表达，同时降低上游转录因子的表达。因此，桑色素可能通过调节萎缩诱导基因和预防氧化应激，作为一种潜在的治疗药物来减轻肌肉萎缩。
