RESUMO
Alzheimer's disease (AD) is a neurodegenerative pathology, which is characterized by progressive and irreversible cognitive impairment. Most of the neuronal perturbations described in AD can be associated with soluble amyloid- ß oligomers (SO-Aß). There is a large amount of evidence demonstrating the neuroprotective effect of Nicotine neurotransmission in AD, mainly through nicotinic acetylcholine receptor (nAChR) activation and antiapoptotic PI3K/Akt/Bcl-2 pathway signaling. Using HPLC and GC/MS, we isolated and characterized two alkaloids obtained from C. scoparius, Lupanine (Lup), and 17- oxo-sparteine (17- ox), and examined their neuroprotective properties in a cellular model of SO-Aß toxicity. Our results showed that Lup and 17- ox (both at 0.03µM) prevented SO-Aß-induced toxicity in PC12 cells (Lup: 64±7%; 17- ox: 57±6%). Similar results were seen in hippocampal neurons where these alkaloids prevented SO-Aß neurotoxicity (Lup: 57±2%; 17- ox: 52±3%) and increased the frequency of spontaneous calcium transients (Lup: 60±4%; 17- Ox: 40±3%), suggesting an enhancing effect on neural network activity and synaptic activity potentiation. All of the neuroprotective effects elicited by both alkaloids were completely blocked by α-bungarotoxin. Additionally, we observed that the presence of both Lup and 17- ox increased Akt phosphorylation levels (52±4% and 35±7%, respectively) in cells treated with SO-Aß (3âh). Taken together, our results suggest that the activation of nAChR by Lup and 17- ox induces neuroprotection in different cellular models, and appears to be an interesting target for the development of new pharmacological tools and strategies against AD.
Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/toxicidade , Cytisus/química , Fármacos Neuroprotetores/farmacologia , Receptores Nicotínicos/efeitos dos fármacos , Esparteína/análogos & derivados , Esparteína/farmacologia , Animais , Sinalização do Cálcio/efeitos dos fármacos , Células HEK293 , Hipocampo/patologia , Humanos , Camundongos Endogâmicos C57BL , Rede Nervosa/efeitos dos fármacos , Neurônios/patologia , Proteína Oncogênica v-akt/metabolismo , Células PC12 , Ratos , Esparteína/química , Esparteína/isolamento & purificação , Sinapses/efeitos dos fármacosRESUMO
A new lupin alkaloid, (+)-sparteine N-16-oxide was isolated from Lygos raetam var. sarcocarpa, together with five known alkaloids: (+)-aphylline, (+)-17 oxosparteine, (-)-5,6-dehydrolupanine, (-)-N-formyl cytisine and (+)-ammodenderine. The structure of the new alkaloid including absolute configuration was determined by spectroscopic methods and chemical transformation.
Assuntos
Alcaloides/química , Óxidos N-Cíclicos/química , Extratos Vegetais , Esparteína/análogos & derivados , Alcaloides/isolamento & purificação , Óxidos N-Cíclicos/isolamento & purificação , Clima Desértico , Egito , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Esparteína/química , Esparteína/isolamento & purificaçãoRESUMO
TLC and GLC of an alkaloid extract of the aboveground portions of Lupinus argenteus Pursh. var. stenophyllus (Rydb.) Davis (Leguminosae) suggested the presence of sparteine, beta-isosparteine, delta5-dehydrolupanine, alpha-isolupanine, lupanine, thermopsine, and anagyrine. GLC-mass spectrometry confirmed these preliminary findings. Preparative TLC was used to isolate sparteine, and this alkaloid was further characterized by IR spectral analysis and derivatization.
