Hesperidin, a Flavone Glycoside, as Mediator of Neuronal Survival
- 456 Downloads
Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5,000 different flavonoids have been described. The biological activities of flavonoids cover a very broad spectrum, from anticancer and antibacterial activities to inhibition of bone reabsorption and neuroprotection effect. Although emerging evidence suggests that flavonoids have an important role on brain development, little is known about their mechanisms of action. In the present work, we performed a screening of flavonoid actions by analyzing the effects of these substances (hesperidin and rutin) on neural progenitors and neuronal morphogenesis in vitro. We demonstrated that treatment of neural progenitors with the flavonoid hesperidin enhanced neuronal population as revealed by an 80% increase in the number of β-tubulin III cells. This effect was mainly due to modulation of neuronal progenitor survival. Pools of astrocyte and oligodendrocyte progenitors were not affected by hesperidin whereas rutin had no effect on neuronal population. We also demonstrated that the flavonoid hesperidin modulates neuronal cell death by activating MAPK and PI3K pathways. This opens the possibility of using flavonoids for potential new therapeutic strategies for neurodegenerative diseases.
KeywordsFlavonoids Neurons Survival PI3 and MAP kinase pathways
We thank Adiel Batista do Nascimento, Marcelo Meloni and Severino Gomes for technical assistance. We are also indebted to David M. Kahn for the English revision of the manuscript. This study was supported by grants from the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
- 1.Beecher GR (2003) Overview of dietary flavonoids: nomenclature, occurrence and intake. J Nutr 133:3248–3254Google Scholar
- 20.Spohr TC, Stipursky J, Sasaki AC et al (2010) Effects of the flavonoid casticin from Brazilian Cróton betulaster in cerebral cortical progenitors in vitro: direct and indirect action through astrocytes. J Neurosci Res 15:530–541Google Scholar
- 26.Spencer JP (2008a) Flavonoids: modulators of brain function? Br J Nutr 99:60–77Google Scholar
- 34.Viola H, Marder M, Wasowski C et al (2000) 6, 3’-Dibromoflavone and 6-nitro-3’-bromoflavone: new additions to the 6, 3’-disubstituted flavone family of high-affinity ligands of the brain benzodiazepine binding site with agonistic properties. Biochem Biophys Res Commun 273:694–698PubMedCrossRefGoogle Scholar