Anti-dementia Activity of Nobiletin, a Citrus Flavonoid: A Review of Animal Studies

Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function and has a detrimental impact worldwide. Despite intensive laboratory and clinical research over the last three decades, pharmacological options for the prevention and effective long-term treatment of AD are not currently available. Consequently, successful therapeutic and preventive treatments for AD are needed. When researching materials from natural resources having anti-dementia drug activity, we identified nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin exhibited memory-improving effects in various animal models of dementia and exerted a wide range of beneficial effects against pathological features of AD including amyloid-beta (Abeta) pathology, tau hyperphosphorylation, oxidative stress, cholinergic neurodegeneration and dysfunction of synaptic plasticity-related signaling, suggesting this natural compound could become a novel drug for the treatment and prevention of AD.

Endothelial dysfunction underlying the increased contractility in aorta from older rats

Aging is associated with marked changes in the cardiovascular system and is one of the most important independent risk factors for cardiovascular diseases. The purpose of this study was to elucidate whether smaller increases in age influences the vascular contractile effect of various stimuli in rat thoracic aorta. An additional aim was evaluate the contribution of vascular smooth muscle and endothelium in case there is an altered behavior of the contractility of the aorta in various age groups. Open rings of male Wistar rats of 7, 11 and 15 weeks were used in this study. The experiments were done in both endothelium-denuded as well as endothelium-intact preparations. Isometric contraction was measured by a force-displacement transducer. KC1-induced contraction was not different in endothelium-denuded preparations from the three groups of animals, however, phenylephrine [PE], PGF[2 alpha] and endothelin-1 [ET-1] produced an exaggerated contractile response in aorta from 15 week animals. Carbachol relaxed the contraction produced by PE in a concentration-dependent manner; however, the magnitude of relaxation was more marked in 7 week animals compared to that in 11 or 15 week rats. Our study shows for the first time that even a modest increase in age from 7 to 15 weeks produces changes in VSM as well endothelial cells resulting in exaggerated contractile response to agonists