Ameliorative Effect of Quercetin on Neurochemical and Behavioral Deficits in Rotenone Rat Model of Parkinson's Disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease)

Abstract

Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death.

Neuroprotective Effects of Quercetin in Alzheimer’s Disease

“…It also inhibits lipid peroxidation and platelet aggregation, and it stimulates mitochondrial biogenesis [32]. Several studies have reported on the neuroprotective effects of quercetin, both in vitro and in vivo models of neurodegenerative disorders, such as cognitive impairment [33], ischemia, traumatic injury [34], Parkinson's disease (PD) [35], and Huntington's disease (HD) [36]. The aim of the present review is to provide a summary of the recent literature exploring the relationship between quercetin and cognitive performance.…”

Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression

“…Quercetin also has a role in rotenone-induced neurotoxicity in PD. Moreover, quercetin treatment reverses impaired autophagic activity and results in the protection of the brain against oxidative stress [186]. Furthermore, quercetin reduces PKCε/p38MAPK mediated ROS production through the activation of the ERK1/2 pathway to protect neurons from oxidative stress [187] and it is indicated that GSK-β and p38 inhibition or PKC activation results in Nrf2 phosphorylation under quercetin treatment [188].…”

Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

“…In turn, flavonoids can be sub-classified into flavonols, flavones, flavanols, flavanones, anthocyanidins, and isoflavonoids, according to the structure of the heterocycle C ring. Examples of compounds which are mostly investigated for their potential neuroprotective effects include quercetin, kaempferol and myricetin (flavonols) [ 50 , 51 , 52 , 53 , 54 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ], scutellarin, baicalein, and apigenin (flavones) [ 50 , 55 , 56 , 61 , 87 , 88 , 89 , 90 ], catechins, epicatechin, and epigallocatechin gallate (EGCG, flavanols), as well as genistein (isoflavonoid), and silymarin (flavonolignan) [ 63 , 91 , 92 , 93 , 94 , 95 , 96 ]. The stilbene group is best exemplified by resveratrol, a well-known phenolic compound found in red wine, grape, and virgin olive oil, which has shown remarkable neuroprotective and anti-aging properties in a plethora of experimental models [ 50 , 58 , 59 , 65 , 69 , 97 , 98 , 99 , 100 , 101 , 102 ].…”