RESUMO
Phosphatidylcholine is one of the major phospholipids comprising cellular membrane and is known to have several health-promoting activities, including the improvement of brain function and liver repair. In this paper, we examine the in vivo effect of dietary supplementation with phosphatidylcholine on the response to environmental stressors and aging in C. elegans. Treatment with phosphatidylcholine significantly increased the survival of worms under oxidative stress conditions. However, there was no significant difference in response to stresses caused by heat shock or ultraviolet irradiation. Oxidative stress is believed to be one of the major causal factors of aging. Then, we examined the effect of phosphatidylcholine on lifespan and age-related physiological changes. Phosphatidylcholine showed a lifespan-extending effect and a reduction in fertility, possibly as a tradeoff for long lifespan. Age-related decline of motility was also significantly delayed by supplementation with phosphatidylcholine. Interestingly, the expressions of well-known longevity-assuring genes, hsp-16.2 and sod-3, were significantly upregulated by dietary intervention with phosphatidylcholine. DAF-16, a transcription factor modulating stress response genes, was accumulated in the nucleus by phosphatidylcholine treatment. Increase of the ROS level with phosphatidylcholine suggests that the antioxidant and lifespan-extending effects are due to the hormetic effect of phosphatidylcholine. Phosphatidylcholine also showed a protective effect against amyloid beta-induced toxicity in Alzheimer's disease model animals. Experiments with long-lived mutants revealed that the lifespan-extending effect of phosphatidylcholine specifically overlapped with that of reduced insulin/IGF-1-like signaling and required DAF-16. These findings showed the antioxidant and antiaging activities of phosphatidylcholine for the first time in vivo. Further studies focusing on the identification of underlying cellular mechanisms involved in the antiaging effect will increase the possibility of using phosphatidylcholine for the development of antiaging therapeutics.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Longevidade/efeitos dos fármacos , Fosfatidilcolinas/farmacologia , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos da radiação , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Proteínas de Caenorhabditis elegans/genética , Núcleo Celular/metabolismo , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/genética , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Interferência de RNA , RNA de Cadeia Dupla/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta , Regulação para Cima/efeitos dos fármacosRESUMO
Recently, there have been reports that chronic insomnia acts as an insult in the brain, causing memory loss through the production of ROS, inflammation, and, Alzheimer's disease if persistent. Insomnia remains the leading cause of sleep disturbance and as such has serious implications for public health. Patients with Alzheimer's disease are also known to suffer from severe sleep disturbance. Meanwhile, vitexin is a key ingredient in Passiflora incarnata L (passion flower, PF) extract, which is known to help with sleep. This medicinal plant has been used as a folk remedy for sedation, anxiety and sleep since centuries ago, but the standardization work has not been done and the extent of the effect has not been clearly demonstrated. For this reason, we tried to test the possibility that repeated administration of PF could improve the memory by promoting hippocampal neurogenesis at the DBA/2 mice known have inherited sleep disorders, as well as preventive effects of Alzheimer's disease. Here, we found that vitexin, which is the main bioactive component of ethanol extracts from leaves and fruits (ratio; 8:2) of PF, confirmed the improvement of neurogenesis (DCX) of DBA/2 mice repeated PF oral administration by immunohistochemistry (IHC) and western blot analysis. PF-treated group showed increased the neurotrophic factor (BDNF) in the hippocampus compared with that of vehicle-treated group, but the inflammation markers Iba-1 (microglial marker) and COX-2 were inconsistent between the groups. However, we found COX-2 signal is essential for hippocampal neurogenesis according to the additional IHC experiments using COX-2 inhibitor and pIkappaB have shown. In addition, although prescription sleeping pills have been reported to show significant changes in appetite and metabolic rate from time to time, no changes in the feeding behavior, body weight, metabolic rate and body composition of the animals were observed by administration of PF. Interestingly, we found that short-term oral administration of PF displayed improved memory according to the water maze test. Quantitative analysis of Tau protein, which is a marker of Alzheimer's disease, was performed in the SD rats and DBA/2 mice by repeated PF oral administration and pTau/Tau values were significantly decreased in PF-treated group than vehicle-treated group. In conclusion, our results suggest that PF lead high hippocampal neurogenesis in the animals even in inherited sleep-disturbed animals. The increased hippocampal neurogenesis functionally enhanced memory and learning functions by repeated PF oral administration. These results identify PF as a potential therapy for enhancing memory functions and prevention of Alzheimer's disease through actions on the hippocampus.