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发现了一种天然的小分子AMP激活激酶激活剂,可以缓解非酒精性脂肪肝炎

Jin Chen^1,2,3, Li Xu^1,2, Xue-Qing Zhang^1,2

¹Key Laboratory of Marine Drugs, the Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 China.

Marine life science & technology

|June 5, 2023

概括

研究人员发现了海洋化合物候选素A,激活AMP激活激酶 (AMPK). 这种AMPK激活剂通过减少肝脂肪,炎症和纤维化,显示出治疗非酒精性脂肪肝炎 (NASH) 的潜力.

科学领域:

生物化学生化学
药理学药理学是指药理学的学科.
肝病学肝病学是一种肝病学.

背景情况:

非酒精性脂肪肝炎 (NASH) 是一种进展性肝病,导致肝硬化和癌症,目前没有批准的治疗方法.
AMP激活激酶 (AMPK) 是一种关键的代谢调节剂,其激活剂正在研究用于治疗NASH等代谢疾病.
海洋天然产品是新型治疗化合物的丰富来源.

研究的目的:

从海洋自然化合物库中识别和描述AMPK的新型激活剂.
在NASH的临床前模型中研究已识别的化合物候选素A (CHNQD-0803) 的治疗潜力.

主要方法:

对海洋天然化合物库进行AMPK活动的选.
生物化学试验以通过CHNQD-0803.3确定AMPK的直接结合和激活.
脂肪沉积,炎症和纤维化的体外细胞模型.
在体内小鼠模型 (MCD饮食) 治疗非酒精性脂肪肝炎.

主要成果:

甘素A (CHNQD-0803) 被确定为一种强大的AMPK激活剂,直接结合并激活AMPK.
CHNQD-0803通过 in vitro 抑制脂肪生成基因来减少脂肪沉积.
在NASH小鼠模型中,CHNQD-0803通过NF-κB-TNFα通路抑制炎症,改善肝损伤和纤维化.

结论:

甘素A是一种新型,强大的AMPK激活剂,具有直接结合和激活特性.
CHNQD-0803通过准关键的病理途径,证明了NASH的显著治疗潜力.
这种来自海洋的化合物代表了未来NASH药物开发的有希望的候选人.

关键词:

这就是AMPKK.纤维化纤维化纤维化炎症炎症是一种炎症.脂质代谢脂质代谢是一种美国海军陆战队的毒品纳什·纳什 (Nash Nash) 是一个名为纳什的城市.

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