Effects of the flavonoid casticin from Brazilian Croton betulaster in cerebral cortical progenitors in vitro: direct and indirect action through astrocytes.
Neurodegenerative diseases are a major constraint on the social and economic development of many countries. Evidence has suggested that phytochemicals have an impact on brain pathology; however, both their mechanisms of action and their cell targets are incompletely known. Here, we investigated the effects of the flavonoid casticin, extracted from Croton betulaster, a common plant in the state of Bahia in Brazil, on rat cerebral cortex neurons in vitro. Treatment of neural progenitors with 10 microM casticin increased the neuronal population positive for the neuronal marker beta-tubulin III and the neuronal transcriptional factor Tbr2 by approximately 20%. This event was followed by a 50% decrease in neuronal death. Pools of astrocyte (GFAP and S100beta), neural (nestin), and oligodendrocyte (Olig2 and NG2) progenitors were not affected by casticin. Neither neuronal commitment nor proliferation of progenitors was affected by casticin, suggesting a neuroprotective effect of this compound. Culture of neural progenitors on casticin-treated astrocyte monolayers increased the neuronal population by 40%. This effect was reproduced by conditioned medium derived from casticin-treated astrocytes, suggesting the involvement of a soluble factor. ELISA assays of the conditioned medium revealed a 20% increase in interleukin-6 level in response to casticin. In contrast to the direct effect, neuronal death was unaffected, but a 52% decrease in the death of nestin-positive progenitors was observed. Together our data suggest that casticin influences the neuronal population by two mechanisms: 1) directly, by decreasing neuronal death, and 2) indirectly, via astrocytes, by modulating the pool of neuronal progenitors.
de Sampaio e Spohr
Tânia Cristina Leite
TC
Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Stipursky
Joice
J
Sasaki
Adriana Campos
AC
Barbosa
Pedro Rocha
PR
Martins
Vanessa
V
Benjamim
Cláudia Farias
CF
Roque
Nidia Franca
NF
Costa
Sílvia Lima
SL
Gomes
Flávia Carvalho Alcantara
FC
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D029802:Croton; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
D016207:Cytokines; D005419:Flavonoids; D015850:Interleukin-6; D018696:Neuroprotective Agents; D010936:Plant Extracts; C054133:casticin