Quercetin Exhibits α7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents

Neurotoxicity Research - Tập 39 - Trang 1859-1879 - 2021
Niraj Kumar Singh1, Debapriya Garabadu1,2
1Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, India
2Department of Pharmacology, School of Health Sciences, Central University of Punjab, Bathinda, India

Tóm tắt

The objective of the present study was to investigate the α7nAChR-mediated Nrf2-dependant protective activity against streptozotocin (STZ)-induced brain mitochondrial toxicity in Alzheimer’s disease (AD)-like rats. STZ (3 mg/kg) was injected through an intracerebroventricular route to induce AD-like dementia. Repeated Quercetin (50 mg/kg, i.p.) administration attenuated cognitive impairments in the STZ-challenged animals during Morris water-maze and Y-maze tests. Quercetin significantly mitigated the STZ-induced increase in cholinergic dysfunction, such as the increase in acetylcholinesterase activity, decrease in acetylcholine level, and activity of choline acetyltransferase, and increase in amyloid-beta aggregation and mitochondrial toxicity in respect of mitochondrial bioenergetics, integrity, and oxidative stress in memory-challenged rat hippocampus, prefrontal cortex and, amygdala. Further, Quercetin significantly attenuated STZ-induced reduction in the α7nAChRs and HO-1 expression levels in the selected rat brain regions. On the contrary, trigonelline (10 mg/kg, i.p.) and methyllycaconitine (2 mg/kg; i.p.) abolished the neuroprotective effects of Quercetin against STZ-induced behavioral, molecular, and biochemical alterations in the AD-like animals. Hence, Quercetin exhibits α7nAChR/Nrf2/HO-1-mediated neuroprotection against STZ-challenged AD-like animals. Thus, Quercetin could be considered as a potential therapeutic option in the management of AD.

Tài liệu tham khảo

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