The multiple faces of quercetin in neuroprotection.
This review discusses the most recent data on the potential of quercetin to confer neuroprotection. Unfortunately, most of the in vitro studies have used quercetin aglycone, which is not detectable in the plasma or in the brain after oral intake. Moreover, quercetin metabolites and glycosides seem to be less neuroprotective and penetrate the BBB less efficiently than aglycone. Surprisingly, quercetin has beneficial effects on various in vivo models of neural disorders, particularly in cerebrovascular insults; contrasting data also do exist. This may be due to an increase of BBB permeability, described in many of these animal models, which would facilitate quercetin brain penetration. Although quercetin causes no significant toxicity in several animal studies, the risk for neurotoxicity is not negligible because of its narrow therapeutic dose-range in vitro. Notably, this risk may be even higher in the case of increased quercetin access to the brain, which may occur pathologically or artificially (e.g., by liposomal preparations). Based on the referred literature, we doubt that quercetin possesses any significant efficacy in neurodegenerative disorders. Instead, therapeutic trials should focus more on the quercetin efficacy in cerebrovascular insults rather than neurodegeneration.
Ossola
Bernardino
B
University of Helsinki, Division of Pharmacology & Toxicology PO Box 56, (Viikinkaari 5E), Helsinki FIN-00014, Finland.
Kääriäinen
Tiina M
TM
Männistö
Pekka T
PT
D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000209:etiology; D011794:Quercetin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D008081:Liposomes; D018696:Neuroprotective Agents; D011794:Quercetin