Neuroprotective effects of chalcones from Myracrodruon urundeuva on 6-hydroxydopamine-induced cytotoxicity in rat mesencephalic cells.
In the present work, we showed that a chalcone-enriched fraction (CEF) isolated from the stem bark of a Brazilian medicinal plant, Myracrodruon urundeuva, presents neuroprotective actions on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death, in rat mesencephalic cells. In the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium] assay, which is an index of cell viability, CEF (1-100 microg/ml) reversed in a concentration-dependent manner the 6-OHDA-induced cell death. While cells exposed to 6-OHDA (40 microM) showed an increased concentration of thiobarbituric acid reactive substances (TBARS), the pretreatment with CEF (10-100 microg/ml) significantly decreased the 6-OHDA-induced TBARS formation, indicative of a neuroprotection against lipoperoxidation. Furthermore, the drastic increase of nitrite levels induced by 6-OHDA, indicative of nitric oxide formation and free radicals production, was prevented by CEF. Double staining with acridine orange/ethidium bromide showed that cultures exposed to 6-OHDA (40 and 200 microM) presented an increase of apoptotic and necrotic cell numbers in a concentration-dependent manner. CEF (100 microg/ml) protected cells from apoptosis and necrosis and increased number of cells presenting a normal morphology. The immunohistochemical analysis for tyrosine hydroxylase (TH) positive neurons indicated that 6-OHDA (40 and 200 microM) caused a concentration-dependent loss of TH+ and TH- neurons. CEF protected both cells types from 6-OHDA-induced cell death. All together, our results demonstrated neuroprotective effects of chalcones, which are able to reduce oxidative stress and apoptotic injury caused by 6-OHDA. Our findings suggest that chalcones could provide benefits, along with other therapies, in neurodegenerative injuries, such as Parkinson's disease.
Nobre-Júnior
Hélio V
HV
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
Oliveira
Ricardo A
RA
Maia
Flavio D
FD
Nogueira
Marcelle A S
MA
de Moraes
Manoel Odorico
MO
Bandeira
Mary Anne M
MA
Andrade
Geanne M
GM
Viana
Glauce S B
GS
D027926:Anacardiaceae; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D003603:Cytotoxins / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D047188:Chalcones; D003603:Cytotoxins; D018696:Neuroprotective Agents; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine