Grape Seed Proanthocyanidins Combined with Aerobic Exercise Improve Learning and Memory Abilities in Type 2 Diabetes Mellitus Rats

Purpose To investigate the effects of grape seed proanthocyanidins (GSP) combined with aerobic exercise (AE) on learning and memory abilities in type 2 diabetes mellitus (T2DM) rats.

Methods T2DM rats were divided into model control (MC) group, AE group, GSP group and combined intervention (CI) group (AE+GSP), and the unmodeled rats were set as the normal control (NC) group. Rats in the AE group were given treadmill exercise, rats in the GSP group were given 200 mg/kg GSP by intragastric administration, and rats in the CI group were given treadmill exercise and intragastric administration at the same time. The changes of related indexes were detected after eight weeks.

Results Compared with the MC group, the escape latency, fasting blood glucose (FBG), fasting insulin (FINS), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglyceride (TG) contents in the AE, GSP and CI groups were decreased, target quadrant residence time, platform crossing times and high density lipoprotein cholesterol (HDL-C) content were increased; the malondialdehyde (MDA) content and Kelch-like ECH associated protein 1 (Keap1) expression in hippocampus were decreased, the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and expressions of nuclear factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were increased. Compared with the AE and GSP groups, the escape latency, FBG, FINS, LDL-C, TC and TG contents in the CI group were further decreased, the target quadrant residence time and platform crossing times were further increased, and the HDL-C content was only significantly higher than that in the AE group; the MDA content and Keap1 expression in hippocampus were further decreased, the activities of GSH-Px and SOD, T-AOC, and the expressions of Nrf2 and HO-1 were further increased.

Conclusion AE, GSP and CI can improve learning and memory abilities in T2DM rats. The mechanism is related to the regulation of the disorder of glucose and lipid metabolism and the anti-oxidative stress mediated by Keap1/Nrf2/HO-1 signaling pathway, and the CI showing superior better effects.