在成年和老老鼠中,BIO101刺激肌细胞分化并改善肌肉功能
Maria Serova1, Blaise Didry-Barca1, Robin Deloux1
1Biophytis, Sorbonne Université, Paris, France.
Journal of cachexia, sarcopenia and muscle
|December 8, 2023
概括
BIO101是一种20-基乙,通过激活AKT/mTOR通路,促进肌肉生长和再生. 这种化合物在细胞和动物模型中显示出治疗缩症和肌肉消耗障碍的前景.
科学领域:
- 肌肉生物学和再生医学
- 药理学和药物发现
背景情况:
- 由于蛋白质合成和降解的不平衡,肌肉衰老会损害再生,这种失衡主要由AKT/mTOR途径调节.
- 骨肌肉的合成和再生能力是萨尔科佩尼亚和肌肉衰竭疾病的治疗点.
- BIO101 (20-hydroxyecdysone) 激活了MAS受体,增强了蛋白质的合成.
研究的目的:
- 为了在体外评估BIO101对C2C12肌肉细胞的合成代谢和促差异化作用.
- 调查BIO101对成年和老年小鼠模型的体内影响.
主要方法:
- 评估了BIO101对C2C12细胞分化的影响,使用肌源性转录因子和AKT/mTOR通路激酶的西布洛特.
- 向成年小鼠口服BIO101 (50毫克/公斤/天) 持续28天,向老年小鼠 (22个月) 持续14周.
- 在接受治疗的小鼠中测量了体重和肌肉重量,跑步能力和肌肉收缩能力.
主要成果:
- 通过AKT/mTOR激活,BIO101治疗使C2C12神经管直径增加了26%.
- 增强MyoD和myogenin的表达,分别增加了39%和53%的融合指数和每个myotube的核.
- 慢性口服BIO101给药改善了成年和老老鼠的体力表现,与AKT/mTOR激活一致.
结论:
- BIO101表现出显著的合成代谢和促使差异化的特性.
- 这些发现支持BIO101作为治疗萨尔科佩尼亚和其他肌肉衰竭疾病的潜在治疗剂.
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