RESUMO
Alzheimer's disease (AD) is characterized by progressive cognitive decline, and the number of affected individuals has increased worldwide. However, there are no effective treatments for AD. Therefore, it is important to prevent the onset of dementia. Oxidative stress and endoplasmic reticulum (ER) stress are increased in the brains of AD patients, and are postulated to induce neuronal cell death and cognitive dysfunction. In this study, Centella asiatica, a traditional Indian medicinal herb, were fractionated and compared for their protective effects against glutamate and tunicamycin damage. Araliadiol was identified as a component from the fraction with the highest activity. Further, murine hippocampal cells (HT22) were damaged by glutamate, an oxidative stress inducer. C. asiatica and araliadiol suppressed cell death and reactive oxygen species production. HT22 cells were also injured by tunicamycin, an ER stress inducer. C. asiatica and araliadiol prevented cell death by mainly inhibiting PERK phosphorylation; additionally, C. asiatica also suppressed the expression levels of GRP94 and BiP. In Y-maze test, oral administration of araliadiol (10 mg/kg/day) for 7 days ameliorated the arm alternation ratio in mice with scopolamine-induced cognitive impairment. These results suggest that C. asiatica and its active component, araliadiol, have neuroprotective effects, which may prevent cognitive dysfunction.
Assuntos
Morte Celular/efeitos dos fármacos , Centella/química , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Triterpenos/administração & dosagem , Triterpenos/farmacologia , Administração Oral , Animais , Células Cultivadas , Chaperona BiP do Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Hipocampo/citologia , Hipocampo/patologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Triterpenos/isolamento & purificação , eIF-2 Quinase/metabolismoRESUMO
Huperzia serrata has been used as a Chinese folk medicine for many years. It contains huperzine A, which has a protective effect against memory deficits in animal models; however, it is unclear if H. serrata extract exerts any effects in Alzheimer's disease (AD) models. We used H. serrata collected in Japan and determined its huperzine A content using HPLC. We determined its inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. H. serrata extract (30 mg/kg/day) and donepezil (10 mg/kg/day) were orally administrated for 7 days. After repeated administration, we performed the Y-maze and passive avoidance tests. H. serrata extract contained 0.5% huperzine A; H. serrata extract inhibited AChE, but not BuChE. H. serrata extract ameliorated cognitive function in mice. These results indicate that Japanese H. serrata extract ameliorates cognitive function deficits by inhibiting AChE. Therefore, H. serrata extract may be valuable for the prevention or treatment of dementia in AD.