The effects of dihydromyricetin on cognitive dysfunction in type 2 diabetes mice

doi:10.12047/j.cjap.5478.2017.079

Abstract

Abstract: Objective: To observe the effects of dihydromyricetin(DHM) on cognitive dysfunction and expression of brain derived neurotrophic factor(BDNF) protein in hippocampus of type 2 diabetic mice(T2DM).Methods: Forty C57BL/6J mice were randomly divided into two groups, normal control group (n=8):normal diet feeding; T2DM model group (n=32):high-glucose and high-fat combined with 100 mg/kg streptozocin(STZ) treatment (five mice died during modeling and three failed). Twenty-four diabetic mice were modeled successfully and divided into three groups (T2DM group, T2DM+L-DHM group and T2DM+H-DHM group). Three groups mice were fed with high-glucose and high-fat diet, and treated with equal volume of normal saline, 125 mg/(kg·d) DHM or 250 mg/(kg·d) DHM for 16 weeks respectively. The control mice were fed with normal diet and treated with equal volume of saline (once a day, gavage) for 16 weeks. After 16 weeks, the body weight and fasting blood glucose were measured, intraperitoneal glucose tolerance test and related behavioral experiment were performed. Finally, the expression of BDNF protein in hippocampus of mice was detected by Western blot.Results: The model of type 2 diabetes mellitus was established successfully with high-glucose and high-fat combined with 100 mg/kg STZ. After 16 weeks, the body weight of T2DM group was significantly decreased, the fasting blood glucose was significantly increased and the glucose tolerance was significantly abnormal compared with the normal control group. Compared with T2DM group, the body weight of T2DM+DHM groups mice was increased, while the levels of fasting blood glucose were decreased. And H-DHM could significantly improve the abnormal glucose tolerance of T2DM mice. Behavior test results showed that the ability of learning and memory of T2DM mice was significant decreased compared with control group, but these phenomena were improved in T2DM+DHM groups mice, and T2DM+H-DHM group was more obvious. Western blot analysis showed that the expression of BDNF protein in hippocampus of T2DM group was significantly lower than that of control group, while T2DM+DHM group was significant increased compared with T2DM mice.Conclusion: Dihydromyricetin can improve the cognitive dysfunction in type 2 diabetic mice. The mechanism may be through hypoglycemic effect and activation of BDNF protein expression in hippocampus.

Key words: dihydromyricetin, type 2 diabetes, mouse, cognitive impairment, BDNF

ZHU Ze-mei, YANG Ji-hua, YANG Si-si, HE Jian-qin, ZHANG Kai-fang, FENG Shui-dong, LING Hong-yan. The effects of dihydromyricetin on cognitive dysfunction in type 2 diabetes mice[J]. CJAP, 2017, 33(4): 323-328.

References

[1] Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes-systematic overview of prospective observational studies[J]. Diabetologia, 2005, 48(12):2460-2469.
[2] Strachan MW, Reynolds RM, Frier BM, et al. The role of metabolic derangements and glucocorticoid excess in the aetiology of cognitive impairment in type 2 diabetes. Implications for future therapeutic strategies[J]. Diabetes Obes Metab, 2009, 11(5):407-414.
[3] Arvanitakis Z, Wilson RS, Bienias JL, et al. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function[J]. Arch Neurol, 2004, 61(5):661-666.
[4] Umegaki H. Type 2 diabetes as a risk factor for cognitive impairment:current insights[J]. Clin Interv Aging, 2014, 28(9):1011-1019.
[5] Spencer JP. The impact of fruit flavonoids on memory and cognition[J]. Br J Nutr, 2010, 104(Suppl 3):S40-S47.
[6] 朱蕾. 发酵藤茶黄酮类化学组成及其对糖尿病大鼠血糖、血脂的影响[J]. 湖北民族学院学报(医学版), 2015, 32(1):4-7.
[7] 逯凤肖, 郁建平, 秦, 等. 藤茶中二氢杨梅素对糖尿病小鼠血糖和血脂的影响[J]. 山地农业生物学报, 2015, 34(6):89-92.
[8] 郝小江, 李玲, 李顺林, 等. 滇产植物乌墨中胰岛素增敏活性成分[J]. 植物资源与环境学报, 2009, 31(5):469-473.
[9] Liang J, Lopez-Valdes HE, Martinez-Coria H, et al. Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of transgenic mouse models of Alzheimer's disease[J]. Neurochem Res, 2014, 39(6):1171-1181.
[10] Liu P, Zou D, Chen K, et al. Erratum to:Dihydromyricetin improves hypobaric hypoxia-induced memory impairment via modulation of SIRT3 signaling[J]. Mol Neurobiol, 2017, 54(3):2373-2374.
[11] Besheer J, Bevins RA. Impact of nicotine withdrawal on novelty reward and related behaviors[J]. Behav Neurosci, 2003, 117(2):327-340.
[12] Sharma S, Rakoczy S, Brown-Borg H. Assessment of spatial memory in mice[J]. Life Sci, 2010, 87(17-18):521-536.
[13] Luchsinger JA, Reitz C, Patel B, et al. Relation of diabetes to mild cognitive impairment[J]. Arch Neurol, 2007, 64(4):570-575.
[14] Xu W, Qiu C, Gatz M, et al. Mid-and late-life diabetes in relation to the risk of dementia:a population-based twin study[J]. Diabetes, 2009, 58(1):71-77.
[15] Xu W, Caracciolo B, Wang HX, et al. Accelerated progression from mild cognitive impairment to dementia in people with diabetes[J]. Diabetes, 2010, 59(11):2928-2935.
[16] 杜青,王宇红,赵洪庆,等. 糖尿病并发抑郁症大鼠海马血脑屏障结构的损伤及其机制[J]. 中国应用生理学杂志, 2016, 32(6):558-562.
[17] 董倩倩, 陈立峰. 二氢杨梅素药理研究进展[J]. 中南药学, 2005, 3(5):295-298.
[18] 要航, 赵彬, 黄燕华, 等. GABA减缓缺氧引起的神经营养素mRNA表达量的变化[J]. 中国应用生理学杂志, 1998, 14(4):289-292.
[19] Ying P, Chen L. Neurotrophic factors and diabetic neuropathies in brain[J]. Inter J Endocrinol Metab, 2006, 26(2):119-144.
[20] Borah A, Paul R, Choudhury S, et al. Neuroprotective potential of silymarin against CNS disorders:insight into the pathways and molecular mechanisms of action[J]. CNS Neurosci Ther, 2013, 19(11):847-853.