Objective  To investigate effects of tea polyphenols (TP) combined with proanthocyanidins (PCs) on avoidance memory and protein expressions of B-cell leukemia/lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), dynamin-related protein 1 (Drp1), and optic dominant atrophy 1 (Opa1) and mechanism of the effects in Alzheimer′s disease (AD) model rats.

  Methods  The AD rat model was constructed by ovariectomy combined with intraperitoneal injection of D-galactose (100 mg/kg). Totally 60 female Wistar rats were randomly divided into a sham control, model, TP, PCs, TP plus PCs, and vitamin E (V_E) group. The avoidance task was measured with shuttle box test. Transmission electron microscopy was used to observe changes in ultrastructure of nuclear and mitochondrion. The protein expressions of Bax, Bcl-2,Drp1, and Opa1 were detected by Western blot.

  Results  Compared to the sham control rats, the AD model rats had significantly increased escape latency but increased rates of active avoidance response and total avoidance response (P < 0.05 for all). In comparison with those for the AD model rats, the escape latency declined but the rates of active avoidance response and total avoidance response increased significantly for the rats of TP, PCs, TP plus PCs, and V_E group (all P < 0.05). Meanwhile, compared to those in the rats of TP and PCs group, significantly decreased escape latency and increased active avoidance response rate were observed in the rats of TP plus PCs group (both P < 0.05). In contrast to those in the rats of sham group, significantly up-regulated protein expression of Bax and Drp1, down-regulated protein expression of Bcl-2 and Opa1, and declined ratio of Bcl-2/Bax were measured in hippocampus in the AD model rats (all P < 0.05); whereas, compared to those in the AD model rats, significantly down-regulated Bax and Drp1, up-regulated Opa1, and increased ratio of Bcl-2/Bax were measured in the rats of of TP, PCs, TP plus PCs, and V_E group (P < 0.05 for all). Moreover, Bax protein expression was significantly down-regulated in hippocampus of rats of TP plus PCs group when compared to the rats of TP group (P < 0.05).

  Conclusion  Solo and combined administration of TP and PCs could improve the avoidance memory in AD rats, with a stronger of combined administration, through the regulation of protein expression of fusion and fission of mitochondrion and apoptosis.