Effect of Astragalus and Anemarrhenae on diabetic cognitive impairment and hippocampal JAK2/STAT3 signaling pathway in rats
Objective To determine the combined impact of Astragalus and Anemarrhenae(HQ-ZM)on diabetic cognitive impairment(DCI)rats,evaluate its neuroprotective effect,and elucidate the underlying mechanism.Methods The rats in the blank group were given a standard diet,while the remaining rats were subjected to a high-fat and high-sugar diet along with intraperitoneal injection of streptozotocin(STZ,35 mg·kg-1)to establish diabetes cognitive impairment(DCI)rat model.Once the modeling was successfully finished,the rats were randomly divided into a model group(Model),an Astragalus-Anemarrhenae low-dose group[HQ-ZM-L,2.4 g/(kg·d)],an Astragalus-Anemarrhenae high-dose group[HQ-ZM-H,4.8 g/(kg·d)],and a metformin group[Met,0.02 g/(kg·d)],with 6 rats in each group.Their respective treatments lasted 30 days.During the administration,the body weight and fasting blood glucose(FBG)levels of the rats were measured weekly.After the administration,the spatial memory of the DCI rats was tested with the Morris water maze.After the test,the whole brains of the rats were taken for pathological sections.The morphological changes in the rat hippocampus tissue were observed with hematoxylin-eosin(HE)staining.Insulin(INS)in the rat hippocampal serum was detected by ELISA.Furthermore,the levels of interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.The expression of JAK2,STAT3,p-JAK2,and p-STAT3 proteins in the rat hippocampus tissue was detected with Western blot.Results Compared with the blank group,the body weight of rats in the model group was greatly decreased,and the FBG was significantly increased;the escape latency was significantly prolonged,and the number of platform crossings was significantly reduced;the morphology of the hippocampal nerve cells was destroyed;the levels of IL-1β,TNF-α and MDA were significantly increased,while the content of INS and SOD was significantly decreased;the expression levels of p-JAK2 and p-STAT3 proteins in the hippocampal tissue of the rats were increased.Compared with the model group,the body weight and FBG of rats in the treatment groups were controlled;the escape latency was much shortened,and the number of platform crossings as well as the activity time and distance in the target area were increased;the morphological destruction of the hippocampal nerve cells of the rats was greatly improved;the levels of IL-1β,TNF-α,and MDA were decreased,and the content of INS and SOD was increased;and the expression levels of p-JAK2 and p-STAT3 proteins were decreased.Conclusion Combination of Astragalus and Anemarrhenae can improve the cognitive impairment in DCI rats,whose mechanism may be related to inhibiting JAK2/STAT3 protein phosphorylation levels,reducing inflammatory responses,and repairing the hippocampal nerve damage in rats.
Astragalus and Anemarrhenaediabetic cognitive impairmentJAK2STAT3