Department of Physiology, School of Medicine, University of South China, Hengyang 421001, China.
Department of Medicine, Changde Vocational Technical College, Changde 415000, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Mar 1;50(3):298-306. doi: 10.1093/abbs/gmy003.
Type 2 diabetes mellitus (T2DM) leads to cognitive impairment (CI), but there have been no effective pharmacotherapies or drugs for cognitive dysfunction in T2DM. Dihydromyricetin (DHM) is a natural flavonoid compound extracted from the leaves of Ampelopsis grossedentata and has various pharmacological effects including anti-oxidant and anti-diabetes. Thus, we investigated the effects of DHM on CI in T2DM mouse model and its possible mechanism. To induce T2DM, mice were fed with high-sugar and high-fat diet for 8 weeks, followed by a low dose streptozotocin (STZ) administration. After the successful induction of T2DM mouse model, mice were treated respectively with equal volume of saline (T2DM group), 125 mg/kg/d DHM (L-DHM group), or 250 mg/kg/d DHM (H-DHM group). After 16 weeks of DHM administration, the body weight (BW), fasting blood glucose, blood lipids, intraperitoneal glucose tolerance (IPGT), and cognitive function were determined. Then, alterations in the expressions of oxidative stress markers and brain-derived neurotrophic factor (BDNF) in the hippocampus were investigated. Our findings demonstrated that DHM could significantly ameliorate CI and reverse aberrant glucose and lipid metabolism in T2DM mice, likely through the suppression of oxidative stress and enhancement of BDNF-mediated neuroprotection. In conclusion, our results suggest that DHM is a promising candidate for the treatment of T2DM-induced cognitive dysfunction.
2 型糖尿病（T2DM）可导致认知障碍（CI），但目前尚无针对 T2DM 患者认知功能障碍的有效药物治疗方法。二氢杨梅素（DHM）是从葡萄科蛇葡萄属的显齿蛇葡萄茎叶中提取的一种天然黄酮类化合物，具有抗氧化、抗糖尿病等多种药理作用。因此，我们研究了 DHM 对 T2DM 小鼠模型认知障碍的影响及其可能的机制。为了诱导 T2DM，小鼠连续 8 周给予高糖高脂饮食，随后给予低剂量链脲佐菌素（STZ）注射。成功诱导 T2DM 小鼠模型后，分别给予等体积生理盐水（T2DM 组）、125mg/kg/d DHM（L-DHM 组）或 250mg/kg/d DHM（H-DHM 组）处理。DHM 给药 16 周后，测定体重（BW）、空腹血糖、血脂、腹腔葡萄糖耐量（IPGT）和认知功能，然后检测海马氧化应激标志物和脑源性神经营养因子（BDNF）的表达变化。研究结果表明，DHM 可显著改善 T2DM 小鼠的 CI，并逆转异常的葡萄糖和脂质代谢，其机制可能与抑制氧化应激和增强 BDNF 介导的神经保护作用有关。综上所述，本研究结果提示 DHM 可能是治疗 T2DM 诱导认知功能障碍的一种有前途的候选药物。
