Investigation of in vitro activities of Crocus sativus styles extract relevant to Alzheimer's disease

Crocus sativus styles are one of the widely known spices (saffron) and consist of unusually polar carotenoids (crocins). Traditionally, saffron has been used for the treatment of cognitive diseases. Alzheimer's disease is characterized pathologically by deposition of amyloid β-peptide (Aβ) fibrils and a diminution of cholinergic activity. The only available drugs for symptomatic therapy of Alzheimer's disease are acetylcholinesterase inhibitors. To identify agents inhibiting the pathogenesis of Alzheimer's disease, we examined in vitro the effect on Aβ 1–40 fibrillogenesis and on the activity of acetylcholinesterase of the water-methanol (50:50, v/v) extract of C. sativus styles. The effects on Aβ-aggregation and fibrillogenesis were studied by thioflavine T-based fluorescence assay and by DNA binding shift assay [1]. The extract inhibited Aβ fibrillogenesis in a dose and time-dependent manner. The main carotenoid constituent, trans -crocin-4, the digentibiosyl ester of crocetin, inhibited Aβ fibrillogenesis at lower concentrations than dimethylcrocetin, revealing that the action of the carotenoid is enhanced by the presence of the sugars [1]. Inhibition of the activity of acetylcholinesterase was studied with a colorimetric assay and the results showed that although the extract exhibited low dose-independant inhibitory values, crocetin and dimethylcrocetin had IC50 values in the low micromolar range, suggesting that the sugars obstruct their inhibitory activity on acetylcholinesterase. Our findings reveal that C. sativus style constituents may have a potential for prevention/treatment of Alzheimer's disease. Acknowledgements: This project is co-funded from the European Union by 75% and from the Hellenic State by 25% through the Reinforcement Programme of Human Research Menpower (PENED) 2003/03ED/665 and by GlaxoSmithKline S.A. References: [1] Papandreou et al. (2006) J. Agric. Food Chem. 54: 8762.