The Role Study Of Dihydromyricetin Improve Cognitive Dysfunction In Type 2 Diabetes Mice

[Objective] To observe the effect of dihydromyricetin on cognitive dysfunction in type 2 diabetes(T2DM) mice and investigate its possible mechanism.[Methods] C57BL/6J mices were randomly divided into 2 group, Control group: mices were fed with normal diets; T2 DM model group: mices were fed with high-sugar and high-fat diets plus 100 mg/kg STZ. After T2 DM model was successful estabolished, normal control mices were fed with normal diets, at the same time, treated with equal volume of saline(once a day, gavage) for 16 weeks. T2 DM model mices were randomly divided into 3 group: 1).T2 DM group: mices were fed with high-sugar and high-fat diets,at the same time, treated with equal volume of saline(once a day, gavage) for 16 weeks. 2). T2DM+L-DHM group: mices were fed with high-sugar and high-fat diets,at the same time, treated with 125 mg/kg/day dihydromyricetin(once a day, gavage) for 16 weeks. 3). T2DM+H-DHM group: mices were fed with high-sugar and high-fat diets,at the same time, treated with 250 mg/kg/day dihydromyricetin(once a day, gavage) for 16 weeks. During the experiment, the weight and fasting blood glucose were measured weekly. After 16 weeks of treatment, intraperitoneal injections of glucose tolerance test and cognitive functions related behavioral indexes were measured, in order to observe the effect of DHM on cognitive function in type 2 diabetes mice. Finally, the associated protein expression of PI3K/Akt/CREB signal pathway in mice hippocampal of each group was detected by Western Blot to explore the influence of DHM on memory-related protein expression levels.[Results] High-sugar and high-fat diets plus 100 mg/kg STZ treated mices can successfully estabolished T2 DM model. With the extension of time, the body weight of T2 DM mice decreased continuously, while the fasting blood glucose increased. After T2 DM mices were treated with L-DHM and H-DHM for 16 weeks, the body weight of T2 DM mices significantly increased, while the fasting blood glucose significantly decreased. Compared with control group, the glucose tolerance was significant abnormal in the T2DM+H-DHM group, H-DHM can significantly improved the abnormal glucose tolerance of T2 DM mice, while L-DHM has no significant effect. Y maze experimental results showed that the spontaneous alternative percentage(SA%)of T2 DM mices was significant lower than control mices. Compared with T2 DM group, SA% significantly increased in the T2DM+L-DHM group and SA% further increased in the T2DM+H-DHM group. In Novel object recognition test, the discrimination index of T2DM+L-DHM group and T2DM+H-DHM group was markedly increased than T2 DM mice. In Shuttle box test, positive avoidance time of T2 DM group was significantly increased than control group, while the number of active avoidance significantly decreased. Compared with T2 DM group, positive avoidance time was significantly decreased and the number of active avoidance was enhanced in the T2DM+L-DHM group and T2DM+H-DHM group. In step-through test, the latency to enter the lit-box and the percent of time spent in the lit-box were dramatically decreased in T2 DM group compared with control group, and compared with T2 DM group, the latency to enter the lit-box and the percent of time spent in the lit-box were dramatically increased in the T2DM+L-DHM group and T2DM+H-DHM group. In the water maze space exploration experiments,compared with control group, the number of crossing platform and the percentage of time spent on targeted quadrant were significantly decreased in the T2 DM group, L-DHM and H-DHM can significantly increased the number of crossing platform and the percentage of time spent on targeted quadrant of T2 DM mice. Western Blot analysis showed that the protein expression of PI3 K, Akt, CREB and BDNF were significantly decreased in the T2 DM group compared with control group, while L-DHM can significantly increased the protein exprssion of PI3 K and BDNF of T2 DM mice, H-DHM can significantly restored the protein exprssion of PI3 K, Akt, CREB and BDNF of T2 DM mice.[Conclusion] Dihydromyricitin may amolirates cognitive deficts of T2 DM mice via reducing blood glucose level, and restores its protein expression of the PI3K/Akt/CREB/BDNF signaling pathway in the hippocampus.