Praeruptorin C alleviates cognitive impairment in type 2 diabetic mice through restoring PI3K/AKT/GSK3β pathway
Praeruptorin C alleviates cognitive impairment in type 2 diabetic mice through restoring PI3K/AKT/GSK3β pathway
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DOI：
10.1002/ptr.7949
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发表时间：
2023-07
影响因子：
7.2
通讯作者：
Long-fei Li;Ying Gao;Yuan Xu;Dan-jie Su;Qi Yang;An Liu;Saiying Wang;Xiu-Ling Tang;Jun Z
中科院分区：
文献类型：
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作者：
Long-fei Li;Ying Gao;Yuan Xu;Dan-jie Su;Qi Yang;An Liu;Saiying Wang;Xiu-Ling Tang;Jun Z
糖尿病脑病是糖尿病的常见后果，可引起认知功能障碍和神经精神障碍。白花前胡素C（Praeruptorin C，Pra‐C）来自传统中草药白花前胡（Peucedanum praeruptorum Dunn.）是潜在的抗氧化剂和神经保护剂。本研究旨在研究Pra‐C对糖尿病认知功能障碍影响的分子机制。采用新的物体识别实验和Morris水迷宫实验评价小鼠的行为学表现。进行电生理记录以监测海马中的突触可塑性。构建了推定Pra-C靶标的蛋白质-蛋白质相互作用网络，并进行了分子对接模拟以预测Pra-C作用的潜在机制。Western blotting检测蛋白表达水平。Pra‐C给药显著降低了2型糖尿病小鼠的体重和空腹血糖水平，并缓解了学习和记忆障碍。网络药理学和分子对接结果表明，Pra‐C影响PI 3 K/AKT/GSK 3 β信号通路。蛋白质印迹分析证实，Pra-C给药后，体内和体外磷酸化PI 3 K、AKT和GSK 3 β水平显著增加。Pra‐C通过激活PI 3 K/AKT/GSK 3 β通路减轻2型糖尿病小鼠的认知功能障碍。
Diabetic encephalopathy is a common consequence of diabetes mellitus that causes cognitive dysfunction and neuropsychiatric disorders. Praeruptorin C (Pra‐C) from the traditional Chinese medicinal herb Peucedanum praeruptorum Dunn. is a potential antioxidant and neuroprotective agent. This study was conducted to investigate the molecular mechanisms underlying the effect of Pra‐C on diabetic cognitive impairment. A novel object recognition test and the Morris water maze test were performed to assess the behavioral performance of mice. Electrophysiological recordings were made to monitor synaptic plasticity in the hippocampus. A protein–protein interaction network of putative Pra‐C targets was constructed, and molecular docking simulations were performed to predict the potential mechanisms of the action of Pra‐C. Protein expression levels were detected by western blotting. Pra‐C administration significantly lowered body weight and fasting blood glucose levels and alleviated learning and memory deficits in type 2 diabetic mice. Network pharmacology and molecular docking results suggested that Pra‐C affects the PI3K/AKT/GSK3β signaling pathway. Western blot analysis confirmed significant increases in phosphorylated PI3K, AKT, and GSK3β levels in vivo and in vitro upon Pra‐C administration. Pra‐C alleviated cognitive impairment in type 2 diabetic mice by activating PI3K/AKT/GSK3β pathway.