标题：Activation of Nrf2 signaling by sitagliptin and quercetin combination against beta-amyloid induced Alzheimer's disease in rats
作者：Li, Yuping; Tian, Qiangyuan; Li, Zhe; Dang, Minyan; Lin, Yukiat; Hou, Xunyao
作者机构：[Li, Yuping; Li, Zhe] Bin Zhou Peoples Hosp, Dept Orthoped, Binzhou, Shandong, Peoples R China.; [Tian, Qiangyuan] Bin Zhou Peoples Hosp, Dept Inter 更多
通讯作者地址：[Hou, XY]Shandong Univ, Prov Hosp, Dept Senile Neurol, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China.
来源：DRUG DEVELOPMENT RESEARCH
关键词：Alzheimer's disease; HO-1; Nrf2; quercetin; sitagliptin; beta-amyloid
摘要：The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in beta-amyloid (A beta) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) A beta injected; (c) A beta injected + Sita 100; (d) A beta injected + QCR 100; and (e) A beta injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, A beta 1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced A beta 1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in A beta induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing A beta 1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.