Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice.
Journal of Pharmacological Sciences. 2007 September;105(1):122-6
Previous studies by Nakajima et al have demonstrated that nobiletin improves impaired memory in mice with lesioning of the olfactory bulb. These olfactory-bulbectomized mice are used as a model of Alzheimer's disease, since they have clinical features of Alzheimer's disease. Olfactory-bulbectomized mice show a reduced acetylcholinesterase (terminates signal transmission) staining and choline acetyltransferase (marker motor neurons) expression in the hippocampus. The researchers found that both effects were reversed after the administration of nobiletin. They concluded that nobiletin rescues neurodegeneration and improves impaired memory in olfactory-bulbectomized mice.
Nobiletin, a citrus flavonoid, reverses learning impairment associated with N-methyl-D-aspartate receptor antagonism by activation of extracellular signal-regulated kinase signaling.
The Journal of Pharmacology and Experimental Therapeutics. 2007 May;321(2):784-90.
Previous studies have demonstrated that memorization requires extracellular signal-regulated kinase signalling via N-methyl-D-aspartate (NDMA) receptors. The NMDA receptor is an ionotropic receptor for glutamate. Activation of this receptor results in the opening of an ion channel. The regulation of extracellular signal-regulated kinase signalling by phytochemicals may be a potential target for the treatment of the cognitive dysfunction. This is the first study showing that nobiletin reverses learning impairment induced with a NMDA receptor antagonist by activation of extracellular signal-regulated kinase signalling in the hippocampus. This effect of nobiletin may result in the development on new drugs to treat neurological disorders, such as cognitive impairment, caused by inadequate functioning of extracellular signal-regulated kinase signalling via NDMA receptors.
Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer disease model rats.
Neuroscience Letters. 2006 June 12;400(3):230-4
Alzheimer disease is a neurodegenerative disease that mainly affects people over the age of 65.
Clinical signs of Alzheimer disease are characterized by progressive cognitive deterioration, declining activities of daily living, neuropsychiatric symptoms and behavioural changes. Plaques containing beta-amyloid peptide are formed in the brain years before the clinical signs are observed. Previous in-vitro studies with cultured hippocampus neurons have shown that beta-amyloid peptide inhibit PKA/CREB-dependent signalling pathway and long-term potentiation (long-lasting enhancement in communication between two neurons that that underlie learning and memory). This study investigated the effect of nobiletin on the inhibition of phosphorylation of CREB proteins (transcription factors which bind to certain DNA sequences and thereby regulating the transcription of certain genes) in cultured hippocampus neurons. The researchers found that pre-treatment with nobiletin reversed beta-amyloid peptide induced decrease in CREB phosphorylation. An in-vivo experiment with rats showed that nobiletin had protective effects on beta-amyloid peptide induced impairment of learning ability. The study concluded that nobiletin is a potential candidate for treatment of Alzheimer disease.
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