Skip to main content
Log in

Cell culture protection andin vivo neuroprotective capacity of flavonoids

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

An Erratum to this article was published on 19 September 2013

Abstract

Flavonoids are an important group of recognized antioxidants ubiquitous in fruits, vegetables and herbs. There are epidemiological evidences for the stroke-protecting capacity of flavonoids and while the neuroprotective power of complex extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized red wine have been demonstrated in several studies, neuroprotection by individual flavonoids has been poorly studiedin vivo.

The neuroprotective capacity of individual flavonoids was studied in PC12 cells in culture and in a model of permanent focal ischemia (permanent Middle Cerebral Artery Occlusion — pMCAO). In thein vivo experiments, flavonoids were administered in lecithin preparations to facilitate the crossing of the blood brain barrier.

The simultaneous incubation of PC12 cells with 200 μM hydrogen peroxide (H2O2) and different flavonoids for 30 min resulted in a conspicuous profile: quercetin, fisetin, luteolin and myricetin significantly increased cell survival while catechin, kaempherol and taxifolin did not.

Quercetin was detected in brain tissue 30 min and 1 h after intraperitoneal administration. When one of the protective flavonoids (quercetin) and one of those that failed to increase PC12 cell survival (catechin) were assessed for their protective capacity in the pMCAO model, administered i.p. 30 min after vessel occlusion, quercetin significantly decreased the brain ischemic lesion while catechin did not.

It is concluded that when administered in liposomal preparations, flavonoids structurally related to quercetin could become leads for the development of a new generation of molecules to be clinically effective in human brain ischemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Auddy B, M Ferreira, F Blasina, L Lafon, F Arredondo, F Dajas, P Tripathy, T Seal and B Mukherjee (2003) Screening of antioxidant activity of the Indian medicinal plants traditionally used for the management of neurodgenerative diseases.J. Ethnopharmacol. 84, 131–138.

    Article  PubMed  CAS  Google Scholar 

  • Azuma K, K Ippoushi, H Ito, H Higashio and J Terao (2002) Combination of lipids and emulsifiers enhances the absorption of orally administered quercetin in rats.J. Agriculture Food Chemistry,50, 1706–1712.

    Article  CAS  Google Scholar 

  • Bastianetto S and R Quirion (2002) Natural extracts as possible protective agents of brain aging.Neurobiol. Aging 23, 891–897.

    Article  PubMed  CAS  Google Scholar 

  • Bruggisser R, K von Daeniken, G Jundt, W Schaffner and H Tullberg-Reinert (2002) Ionterface of plant extracts, phytoestrogens and antioxidants with the MTT tetrazolium assay.Planta Med. 68, 445–448.

    Article  PubMed  CAS  Google Scholar 

  • Denizot F and R Lang (1986) Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability.J. Immunological Methods 89, 271–277.

    Article  CAS  Google Scholar 

  • Duthie G and A Crozier (2000) Plant derived phenolic antioxidants.Curr. Opin. Clin. Nutrition Metabolism 3, 477–451.

    Google Scholar 

  • Emmert D and L Kirchner (1999) The role of vitamin E in the prevention of heart disease.Arch. Family Med. 8, 537–542.

    Article  CAS  Google Scholar 

  • Esposito E, D Rotilio, V Di Matteo, C. Di Giulio, M Cacchio and S Algeri (2002) A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes.Neurobiol. Aging 23, 719–735.

    Article  PubMed  CAS  Google Scholar 

  • Fergusson L (2001) Role of plant polyphenols in genomic stability.Mutation Res. 475, 89–111.

    Google Scholar 

  • Fujiki H, T Horiuchi and K Yamashita (1986) Inhibition of tumor promotion by flavonoids, In: Cody V., E Middleton and JB Harborne, Eds.,Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-Activity Relationships (New York), pp 429–440.

  • Greene L and A Tischer (1976) Establishment of a noradrenergic clonal line of adrenal pheochromocytoma cells which respond to nerve growth factor.Proc. Natl. Acad. Sci. USA 73, 2424–2428.

    Article  PubMed  CAS  Google Scholar 

  • Harborne J and C Williams (2000) Advances in flavonoid research since 1992.Phytochemistry,55, 481–504.

    Article  PubMed  CAS  Google Scholar 

  • Ishige K, D Schubert and Y Sagara (2001) Flavonoids protect neuronal cells from oxidative stress by three different mechanisms.Free Radic. Biol. Med. 30, 433–446.

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa Y and M Kitamura (2000) Anti-apoptotic effect of quercetin: intervention in the JNK and ERK mediated apoptotic pathways.Kidney Int. 58, 1078–1087.

    Article  PubMed  CAS  Google Scholar 

  • Jiang D, N Jha, R Boonplueang and JK Andersen (2001) Caspase 3 inhibition attenuates hydrogen peroxide-induced DNA fragmentation but not cell death in neuronal PC12 cells.J. Neurochem. 76, 1745–1755.

    Article  PubMed  CAS  Google Scholar 

  • Kelli S, M Hertog, E Feskens and D Kromhout (1996) Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study.Arch. Int. Med. 156, 637–642.

    Article  Google Scholar 

  • Koh J and D Choi (1987) Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay.J. Neurosci. Meth. 20, 83–90.

    Article  CAS  Google Scholar 

  • Lee EJ, HY Chen, TW Wu, TY Chen, IA Ayoub and KI Maynard (2002) Acute administration ofGinkgo biloba extract (Egb 761) affords neuroprotection against permanent and transient focal cerebral ischemia in Sprague-Dawley rats.J. Neurosci. Res. 68, 636–645.

    Article  PubMed  CAS  Google Scholar 

  • Mealing GAR, TH Lanthorn, DL Small, MA Black, NB Laferriere and P Morley (1997) Antangonism ofN-methyl-d-aspartate-evoked currents in rat cortical cultures by ARL 15896AR.J. Pharmacol. Exp. Ther. 281, 376–383.

    PubMed  CAS  Google Scholar 

  • Nakayama T, M Yamada, T Osawa and S Kawakishi (1993) Suppression of active oxygen-induced citotoxicity by flavonoids.Biochem. Pharmacol. 45, 265–267.

    Article  PubMed  CAS  Google Scholar 

  • Oyama Y, PA Fuchs, N Katayama and K Noda (1994) Myricetin and quercetin, the flavonoid constituents ofGinkgo biloba extract, greatly reduce oxidative metabolisms in both resting and Ca(2+)-loaded brain neurons.Brain Res. 635, 125–129.

    Article  PubMed  CAS  Google Scholar 

  • Preston E and J Webster (2000) Spectrophotometric measurement of experimental brain injury.J. Neurosci. Meth. 94, 187–192.

    Article  CAS  Google Scholar 

  • Rice Evans C (2001) Flavonoid antioxidants.Curr. Med. Chem. 8, 797–807.

    Google Scholar 

  • Shafer T and W Atchinson (1991) Transmitter, ion channel and receptor properties of pheochromocytoma (PC12) cells: a model for neurotoxical studies.Neurotoxicology 12, 473–492.

    PubMed  CAS  Google Scholar 

  • Shutenko Z, Y Henry, E Pinard, J Seylaz, P Potier, F Berthet, P Girard and R Sercombe (1999) Influence of the antioxidant quercetinin vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia y reperfusion.Biochem. Pharmacol. 57, 199–208.

    Article  PubMed  CAS  Google Scholar 

  • Sladowski D, SJ Steer, RH Clothier and M Balls (1993) An improved MTT assay.J. Immunol. Meth. 157, 203–207.

    Article  CAS  Google Scholar 

  • Sydserff SG, AJ Cross and AR Green (1995) The neuroprotective effect of chlormethiazole on ischaemic neuronal damage following permanent middle cerebral artery ischaemia in the rat.Neurodegeneration 4, 323–328.

    Article  PubMed  CAS  Google Scholar 

  • Wang H and J Joseph (1999) Structure-activity relationship of quercetin in antagonizing hydrogen peroxide-induced calcium dysregulation in PC12 cells.Free Radic. Biol. Med. 27, 683–694.

    Article  PubMed  CAS  Google Scholar 

  • Wang R, J Zhou and XC Tang (2002) Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells.Brain Res. Mol. Brain Res. 107, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Yamakawa H, Y Ito, T Naganawa, Y Banno, S Nakashima, S Yoshimura, M Sawada, Y Nishimura, Y Nozawa and N Sakai (2000) Activation of caspase-9 and −3 during H2O2-induced apoptosis of PC12 cells independent of ceramide formation.Neurological Res. 22, 56–64.

    Google Scholar 

  • Yokoo T and M Kitamura (1997) Unexnpected protection of glomerular mesangial cells from oxidant triggered apoptosis by bioflavonoid quercetina.Am. J. Physiol. 273, F206-F212.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Federico Dajas.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s12640-013-9424-1.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dajas, F., Rivera, F., Blasina, F. et al. Cell culture protection andin vivo neuroprotective capacity of flavonoids. neurotox res 5, 425–432 (2003). https://doi.org/10.1007/BF03033172

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033172

Keywords

Navigation