RESUMO
Alzheimer's disease (AD) is the leading cause of dementia, affecting approximately 33.5 million people worldwide. Aging is the main risk factor associated with AD. Drug discovery based on nutraceutical molecules for prevention and treatment of AD is a growing topic. In this sense, carotenoids are phytochemicals present mainly in fruits and vegetables with reported benefits for human health. In this research, the anti-amyloidogenic activity of three carotenoids, cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin, was assessed. Cryptocapsin showed the highest bioactivity, while cryptocapsin-5,6-epoxide and zeaxanthin exhibited similar activity on anti-aggregation assays. Molecular modeling analysis revealed that the evaluated carotenoids might follow two mechanisms for inhibiting Aß aggregation: by preventing the formation of the fibril and through disruption of the Aß aggregates. Our studies provided evidence that cryptocapsin, cryptocapsin-5,6-epoxide, and zeaxanthin have anti-amyloidogenic potential and could be used for prevention and treatment of AD.
Assuntos
Doença de Alzheimer/fisiopatologia , Amiloide/efeitos dos fármacos , Carotenoides/farmacologia , Descoberta de Drogas , Humanos , Modelos Moleculares , Zeaxantinas/farmacologiaRESUMO
PURPOSE: To evaluate the safety profile of solutions containing lutein and zeaxanthin alone or associated with brilliant blue (BB). METHODS: Twenty-eight New Zealand rabbits were used to evaluate 4 concentrations of the various dye solutions: 0.5% lutein/zeaxanthin; 0.5% lutein/zeaxanthin associated with 0.0125% BB; 0.3% lutein/zeaxanthin associated with 0.025% BB; and 0.25% lutein/zeaxanthin associated with 0.05% BB. The pHs of the dye solutions ranged from 6.5 to 7.2 and the osmolarities from 280 to 320 mOsm/mL. Each rabbit had 0.1 mL of one of the dyeing solutions injected into the vitreous cavity of the right eye, while balanced salt solution (BSS) was injected into the left eye as the control. Scotopic electroretinography responses were recorded in all eyes at different time points. The animals were sacrificed at 1 and 7 days after injection; the eyes were analyzed by light and transmission electron microscopy. RESULTS: No significant (P>0.05) differences were seen in the a- and b-wave amplitudes among groups at any given point in time. Light and electron microscopy findings showed no significant abnormalities either, and were similar to the histological findings after intravitreal BSS injection. CONCLUSIONS: Lutein and zeaxanthin alone or in association with BB showed a good safety profile in this experimental model.