Protective Effect of Buyang Huanwu Decoction on Diabetes-Induced Damage to Hippocampal Neurons by Regulating PI3K-AKT/Bcl-2 Pathway

Diabetic encephalopathy is one of the complications of diabetes, closely related to the degeneration and apoptosis of hippocampal neurons. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine prescription, which has the functions of benefit qi, activing blood circulation and dredging collaterals. To investigate the protective effect and mechanism of BHD on hippocampal neurons in diabetes, a high glucose (HG) induced PC12 cell injury model was established, cell proliferation and apoptosis were detected. The protein expression levels were detected by western blot. Rats with type 2 diabetes mellitus were fed high-fat-sugar diet and low dose of streptozotocin for 4 weeks to observe the body weight, fasting blood glucose, etc. The pathological changes of hippocampal CA1 region were observed through hematoxylin-eosin staining, and the expression of related proteins was detected. The results showed that, after BHD intervention, the degree of apoptosis of PC12 cells injured by HG was significantly reduced, and the cell proliferation was significantly increased. In model group, blood glucose increased significantly, weight loss, oral glucose tolerance was abnormal, while BHD group reversed the above changes. Most nerve cells in BHD group had relatively intact structure and less morphological changes. Immunohistochemistry showed that compared with the model group, the expression of Bcl-2 (B-cell lymphoma 2) in BHD group increased, while the expression of Bax (BCL2-associated X) and caspase-3 decreased. The expression of p-PI3K (phosphorylated phosphatidyl inositol 3-kinase), p-AKT (phosphorylated protein kinase B) and Bcl-2 decreased in model and HG group, while the expression of Bax, Caspase-3, and Cleaved Caspase-3 increased. After BHD intervention, p-PI3K, p-AKT, Bcl-2 expression increased, while Bax, Caspase-3 and Cleaved Caspase-3 expression decreased. In conclusion, BHD may play a protective role on diabetic hippocampal neurons by regulating mitochondria related apoptosis protein and up-regulating PI3K-AKT/Bcl-2 signaling pathway.