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

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.

The Protective Effect of DiDang Tang Against AlCl3-Induced Oxidative Stress and Apoptosis in PC12 Cells Through the Activation of SIRT1-Mediated Akt/Nrf2/HO-1 Pathway

“…Studies have reported translocation of Nrf2 from the cytosol to the nucleus, where it activates antioxidative enzymes, such as HO-1, and produces a notable antioxidative response to counteract escalated ROS-induced oxidative stress and protect against oxidative stress (Loboda et al, 2016;Xu et al, 2019). The Nrf2/HO-1 signaling pathway is considered as a protective molecular mechanism in several pathological processes, particularly oxidative stress, and this pathway is also involved in several neurodegeneration diseases, including AD and PD (Tufekci et al, 2011;Li Y. P. et al, 2019). Levels of Nrf2 localized to the nucleus and the expression level of HO-1 were both significantly higher in cells treated with DDT, the activation of Nrf2 we observe may in part be mediated via Akt, increasing antioxidant defenses ( Figure 6).…”

Quercetin in Animal Models of Alzheimer’s Disease: A Systematic Review of Preclinical Studies

“…They were Aβ-injection, lipopolysaccharide (LPS)-induced, pentylenetetrazole (PTZ)-induced, senescence accelerated mouse (SAM), and APP/PS1/tau-transgenic AD models. The Aβ injection model can induce Aβ accumulation and deposition in the brain, but as an acute toxicity model it cannot reproduce the progressive neurodegeneration process [18]. The drug-induced models (LPS and PTZ) display neurodegeneration and cognitive impairments, but they lack AD-related histological hallmarks [13,14].…”

“…et al [17] reported that quercetin treatment strongly prevented Aβ aggregation and partially decreased hyperphosphorylated tau in the CA1 region of the hippocampus and in the amygdala, without changes in the entorhinal cortex of AD mice. Li Y. et al [18] showed that quercetin treatment to AD rats reduced the β-amyloid accumulation in the CA1 region of hippocampus.…”

“…Rishitha N. et al [14] reported that the solid lipid nanoparticle of quercetin (SLN-Q) had an ameliorative effect on the decreased GSH levels in AD zebrafish brains in a dose-dependent manner. Li Y. et al [18] indicated that in quercetin-treated Meanwhile, three included studies measured Aβ levels in the CA1 regions and cortexes of mice's brains by immunohistochemistry (IHC). The following meta-analysis ( Figure 4) indicated that compared with the vehicle control group, Aβ immunoreactivity was significantly decreased in the quercetin treated group (p < 0.00001), with mean differences of −3.51 and −8.55 in the subgroups, and −4.68 in the overall outcome.…”

“…Rishitha N. et al [14] reported that the solid lipid nanoparticle of quercetin (SLN-Q) had an ameliorative effect on the decreased GSH levels in AD zebrafish brains in a dose-dependent manner. Li Y. et al [18] indicated that in quercetin-treated Three studies examined the anti-oxidative function of quercetin on animal AD models. Superoxide dismutase (SOD) and glutathione (GSH) are important antioxidant enzymes that prevent the brain tissue from oxidative injury.…”