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对天然表观遗传修饰剂进行查,以管理血糖记忆和糖尿病病
Kriti Kushwaha1, Sourbh Suren Garg2, Debojyoti Mandal3
1Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India.
Journal of drug targeting
|May 15, 2024
概括
短暂的高血糖发作会导致代谢记忆,恶化糖尿病病. 贝利费龙 (UMB) 和饮食逆转 (DR) 通过增加基因组乙化,改善大鼠的葡萄糖和脂质概况来缓解这一问题.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 糖尿病学 糖尿病学
背景情况:
- 短暂的高血糖发作诱导代谢记忆 (MM),通过表观遗传变化加剧糖尿病病 (DN).
- 目前仅专注于高血糖的治疗方法不足以阻止DN的进展.
- 表观遗传修饰,特别是基因组乙化,在MM和DN中起着至关重要的作用.
研究的目的:
- 为了确定针对糖尿病脏病的表观遗传轴的新型植物化学物质.
- 为了评估Umbeliferone (UMB) 和饮食逆转 (DR) 在改善高脂肪饮食诱导的MM和DN的疗效.
主要方法:
- 结构相似性搜索确定了UMB作为潜在的表观遗传修饰剂.
- 与SIRT1和ADME研究的分子对接评估了UMB的药理动力学特性.
- 在体外进行了抗氧化剂 (DPPH) 和细胞毒性 (MTT) 试验.
- 在Sprague-Dawley大鼠的体内研究调查了UMB和DR对高血糖,MM和DN标志物的影响.
- 西方斑点分析测量了基因素乙化水平.
主要成果:
- UMB与已知的表观遗传修饰剂具有显著的结构相似性,并且具有有利的ADME特性.
- UMB表现出抗氧化活性,并没有诱导细胞死亡.
- 在体外,UMB改善了高葡萄糖诱导的氧化应激和MM.
- 在老鼠中同时接受UMB和DR治疗,降低了血糖,脂质概况和/肝损伤.
- UMB治疗增加了基因素乙化水平,抵消了高血糖引起的下降.
结论:
- UMB是一种有前途的植物化学物质,具有作为治疗糖尿病病的表观遗传修饰剂的潜力.
- 结合UMB和饮食逆转有效地减轻高脂肪饮食诱导的新陈代谢记忆和大鼠糖尿病病.
- 恢复基因素乙化是UMB改善DN和MM的一个关键机制.
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