Abstract
This study is aimed to investigate the protective effect against type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) of Berberine (BBR), and the underlying mechanism of action is explored. We established a rat model of combined AD and T2DM and used it to investigate the effect of BBR (150 mg/kg) on the course of these pathologies. The Morris water maze, biochemical analysis, hematoxylin-eosin staining, immunohistochemical study, immunofluorescent staining, TUNEL assay, RT-qPCR and western blot were used to reveal the effect of BBR on blood glucose, lipid changes, hippocampal injuries and cognitive impairment. The results showed that BBR could alleviate memory deficits, restore the disordered arrangement of nerve cells, the damage of neurons, improve TUNEL-positive cells and decrease the elevated levels of fasting blood glucose, triglyceride, total cholesterol and glycosylated serum protein levels in Alzheimer diabetic rats. Moreover, BBR treatment reduces the transcription of mRNAs and expression of proteins related to endoplasmic reticulum (ER) stress. These findings conclude that BBR can protect neurons by inhibiting the pathway of ER stress and thereby play an essential role in the preventive and therapeutic of AD and T2DM.