Baicalein alters PI3K/Akt/GSK3β signaling pathway in rats with diabetes-associated cognitive deficits.
Our present investigation focused on assessing the neuroprotective potential of baicalein (BAC) against diabetes-associated cognitive deficit (DACD) using a diabetic model and further figure out the potential molecular mechanisms. Diabetic rat model was established by streptozotocin (STZ). Vehicle or BAC by the doses of 2 and 4 mg/kg was intraperitoneally injected once a day for seven consecutive weeks. Memory function was evaluated by Morris water maze test and avoidance passive test. The activities of acetylcholinesterase (AChE), choline acetylase (ChAT), caspase-9 and caspase-3 in STZ-induced diabetic rats' hippocampus were detected via responsive commercial kits. Western blot assay were used to determine the protein levels of phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-Akt (p-Akt), and phospho-glycogen synthase kinase-3β (p-GSK3β). Our results showed that BAC remarkably increased body weight and ChAT activity, decreased blood glucose level and AChE activity as well as improved cognitive deficits in diabetic rats. Additionally, it was also found that treatment with BAC to diabetes obviously stimulated the p-PI3K and p-Akt and inhibited the level of p-GSK3β. Furthermore, the neuronal apoptosis was also prevented after BAC treatment by decreasing caspase-9 and caspase-3 activities in diabetic rats' hippocampus. It is concluded that BAC exerted beneficial effects against DACD in rats and its neuroprotection might be linked with activating PI3K and Akt phosphorylation accompanied with suppressing the phosphorylated level of GSK3β. These results hint that BAC is likely to be served as an adjuvant therapy to conventional anti-hyperglycemic regimens as well as DACD.
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian 116011, China.
Zhonghua
Z
Qi
Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University Dalian 116011, China.
Yinghui
Y
Xu
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian 116011, China.
Zhanhua
Z
Liang
Department of Neurology, The First Affiliated Hospital of Dalian Medical University Dalian 116011, China.
Sheng
S
Li
Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University Dalian 116011, China.
Jie
J
Wang
Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University Dalian 116011, China.
Yi
Y
Wei
Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University Dalian 116011, China.
Bin
B
Dong
Akt; Baicalein; diabetes-associated cognitive decline; glycogen synthase kinase-3β; neuroprotection; phosphatidylinositol 3-kinase