Protective effect of rhubarb derivatives on amyloid beta (1-42) peptide-induced apoptosis in IMR-32 cells: a case of nutrigenomic.
Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brains of patients with Alzheimer's disease (AD). In the last years considerable attention has been focused on identifying natural food products, such as phytochemicals that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of rhaponticin (3,3',5-trihydroxy-4'-methoxystilbene 3-O-d-glucoside) a stilbene glucoside extracted from rhubarb roots (Rhei rhizoma) and rhapontigenin, its aglycone metabolite, against amyloid beta (1-42)-dependent toxicity. The obtained results show that rhapontigenin maintains significant cell viability in a dose-dependent manner and it exerts a protective effect on mitochondrial functionality, as evidenced by mitochondrial oxygen consumption experiments. A similar behaviour, but to a lesser extent, has been shown by rhaponticin. The protective mechanism mediated by the two stilbenes could be related to their effect on bcl-2 gene family expression. Bax, a pro-apoptotic gene, resulted down-regulated by the treatment with rhaponticin and rhapontigenin compared with the results obtained in the presence of amyloid beta (1-42) peptide. Conversely, bcl-2, an anti-apoptotic gene, highly down-regulated by amyloid beta (1-42) treatment, resulted expressed in the presence of stilbenes similarly to that shown by control cells. The obtained results support the hypothesis that amyloid beta (1-42)-induced neurotoxicity occurs via bax over-expression, bcl-2 down-regulation, firstly indicating that rhaponticin and its aglycone moiety may alter this cell death pathway. Based on these studies, we suggest that rhaponticin and its main metabolite could be developed as agents for the management of AD.
Misiti
F
F
Department of Health and Motor Sciences, University of Cassino, V.le Bonomi, 03043 Cassino (FR), Italy.
Sampaolese
B
B
Mezzogori
D
D
Orsini
F
F
Pezzotti
M
M
Giardina
B
B
Clementi
M E
ME
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000378:metabolism; D012250:Rheum / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D013267:Stilbenes; C075222:amyloid beta-protein (1-42); C431126:rhapontigenin; C023538:rhapontin