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.

本研究旨在探讨小檗碱 (BBR) 对 2 型糖尿病 (T2DM) 和阿尔茨海默病 (AD) 的保护作用，并探讨其潜在作用机制。我们建立了一个合并 AD 和 T2DM 的大鼠模型，并用它来研究 BBR (150 mg/kg) 对这些病理过程的影响。Morris水迷宫、生化分析、苏木精-伊红染色、免疫组织化学研究、免疫荧光染色、TUNEL测定、RT-qPCR和蛋白质印迹被用来揭示BBR对血糖、脂质变化、海马损伤和认知障碍的影响。结果表明，BBR可以缓解记忆缺陷，恢复神经细胞排列紊乱、神经元损伤，改善TUNEL阳性细胞，降低空腹血糖升高水平，阿尔茨海默病大鼠的甘油三酯、总胆固醇和糖基化血清蛋白水平。此外，BBR 处理减少了与内质网 (ER) 应激相关的 mRNA 的转录和蛋白质的表达。这些发现得出结论，BBR 可以通过抑制 ER 应激通路来保护神经元，从而在 AD 和 T2DM 的预防和治疗中发挥重要作用。