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. 2023 Oct;37(10):4838-4850.
doi: 10.1002/ptr.7949. Epub 2023 Jul 17.

Praeruptorin C alleviates cognitive impairment in type 2 diabetic mice through restoring PI3K/AKT/GSK3β pathway

Long-Fei Li  1 , Ying Gao  1 , Yuan Xu  1 , Dan-Jie Su  1 , Qi Yang  1 , An Liu  1 , Sai-Ying Wang  1 , Xiu-Ling Tang  1 , Jun Zhao  1 , Li Luo  1 , Tao Yan  1 , Yu-Mei Wu  2 , Shui-Bing Liu  2 , Ming-Gao Zhao  1 , Le Yang  1
Affiliations

Praeruptorin C alleviates cognitive impairment in type 2 diabetic mice through restoring PI3K/AKT/GSK3β pathway

Long-Fei Li et al. Phytother Res. 2023 Oct.

Abstract

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.

Keywords: PI3K/AKT/GSK3β pathway; cognitive impairment; diabetic encephalopathy; long-term potentiation; praeruptorin C.

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