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烯酸衍生物通过抑制PTP1B活性和调节AMPK/TGF-β/Smads通路来缓解心脏纤维化

An-Hui Wang¹, Hao-Yue Ma¹, Yan-Liang Yi²

¹Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China; State Key Laboratory of Vascular Homeostasis and Remodeling, State Key Laboratory of Natural and Biomimetic Drugs, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University, Beijing, 100191, China; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing, 100191, China.

European journal of pharmacology

|December 7, 2023

概括

一种新的烯酸衍生物,B化合物,通过强烈抑制蛋白氨酸酸酶1B (PTP1B) 和调节关键信号通路,显著降低心脏纤维化,为心血管疾病提供了有前途的治疗策略.

科学领域:

心血管生物学心血管生物学
药理学药理学是指药理学的学科.
生物化学生物化学

背景情况:

心脏纤维化 (CF) 通过促进原沉积,有助于心血管疾病 (CVD).
蛋白氨酸酸酶1B (PTP1B) 通过AMPK/TGF-β/Smads通路恶化CF.
醇酸 (OA) 抑制PTP1B,并显示出抗心脏重塑作用.

研究的目的:

为了合成具有增强PTP1B抑制的新型OA衍生物.
评估OA衍生物的更强的PTP1B抑制是否会导致心脏重塑的更大预防.
为了比较化合物B与OA在缓解心脏纤维化的疗效.

主要方法:

合成了四种新的OA衍生品.
在体内研究使用异二醇 (ISO) 诱导的小鼠心脏纤维化模型.
在体外研究使用TGF-β/ISO诱导的3T3细胞.
分子对接,表面等离子体共振和PTP1B活性测试.
对AMPK激活和TGF-β/Smads信号抑制的评估.

主要成果:

与OA相比,化合物B在体内和体外都显示出更好的心脏纤维化抑制.
和化合物B直接结合并抑制PTP1B的活性.
化合物B与PTP1B具有相似的结合,但比OA具有更强的抑制作用.
化合物B显示出明显更大的AMPK激活和TGF-β/Smads抑制比OA.

结论:

甲酸衍生化合物B有效缓解心脏纤维化.
化合物B的增强治疗效果源于高级PTP1B抑制和下游途径调节.
化合物B代表了一种有前途的治疗剂,用于预防心脏重塑和治疗心血管疾病.

关键词:

在AMPK/TGF-β/Smads路径中.心脏纤维化是什么心脏纤维化烯酸衍生物的烯酸衍生物这就是PTP1B.

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