Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish.
Flavonoids have been reported to be potent antioxidants and beneficial in the treatment of oxidative stress-related diseases. Quercetin, a major flavonoid naturally occurring in plants, deserves attention because of its beneficial effects observed in various in vitro and in vivo neural damage models; however, the actions of quercetin are paradoxical. In an effort to confirm the neuroprotective effect of quercetin and to elucidate its mechanism of action, the neuroprotective effects of quercetin in PC12 cells and in zebrafish models were investigated. In this study, the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), was used to induce neural damage in PC12 cells and zebrafish models. Pretreatment with quercetin offered neuroprotection against 6-OHDA-induced PC12 cell death. Moreover, quercetin could prevent 6-OHDA-induced PC12 cell apoptosis and 6-OHDA-stimulated dopaminergic neuron loss in zebrafish. Interestingly, quercetin was able to protect, but not rescue the dopaminergic neuron damage when zebrafish were treated with quercetin at different maturation stages of the blood brain barrier. A mechanistic study showed that quercetin could inhibit NO over-production and iNOS over-expression in PC12 cells and could down-regulate the over-expression of pro-inflammatory genes (e.g. IL-1ß, TNF-α and COX-2) in zebrafish, suggesting that these genes play a role in the neuroprotective effect of quercetin. The objective of this study was to provide a scientific rationale for the clinical use of quercetin, leading to its development as an effective therapeutic agent for the treatment of Parkinson's disease.
Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, PR China.
Zai Jun
ZJ
Zhang
Lorita Chi Veng
LC
Cheang
Mei Wei
MW
Wang
Simon Ming-Yuen
SM
Lee
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D015027:Zebrafish / Q000378:metabolism*
D018663:Adrenergic Agents; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D016627:Oxidopamine; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat