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Drug Dev Res. 2019 Jul 13. doi: 10.1002/ddr.21567. [Epub ahead of print]

Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats.

Author information

1
Department of Orthopedics, Bin Zhou People's Hospital, Binzhou, Shandong Province, China.
2
Department of Internal Neurology, Bin Zhou People's Hospital, Binzhou, Shandong Province, China.
3
Innoscience Research Sdn Bhd, Subang Jaya, Selangor, Malaysia.
4
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Abstract

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) 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) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 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 Aβ1-42 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 Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.

KEYWORDS:

Alzheimer's disease; HO-1; Nrf2; quercetin; sitagliptin; β-amyloid

PMID:
31301179
DOI:
10.1002/ddr.21567

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