Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice.
ABSTRACT We have recently reported that nobiletin, a citrus flavonoid, improves impaired memory in olfactory-bulbectomized (OBX) mice, which have been widely utilized as a useful paradigm that shares some major clinical features of Alzheimer's disease. Here, we examined the effects of nobiletin on OBX-induced cholinergic neurodegeneration in mice. OBX mice showed reduced acetylcholinesterase (AChE) staining and choline acetyltransferase (ChAT) expression in the hippocampus. An 11-day administration of nobiletin rescued OBX-induced decrease in the density of AChE-staining and ChAT expression in the hippocampus. These results suggest that nobiletin rescues OBX-induced cholinergic neurodegeneration, accompanied by improvement of impaired memory in OBX mice.
Article: Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines ( Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand.[show abstract] [hide abstract]
ABSTRACT: Polymethoxylated flavones (PMFs) and flavanone glycosides (FGs) were analyzed in hand-pressed juice and the peeled fruit of 'Sainampueng' tangerines ( Citrus reticulata Blanco cv. Sainampueng) grown in northern Thailand. The tangerines were collected from a citrus cluster of small orchard farmers and were cultivated as either agrochemical-based (AB), agrochemical-safe (AS), or organic grown fruits. Juice samples were also measured on contents of carotenoids, ascorbic acid, and tocopherols. The peel-deriving PMFs tangeretin, nobiletin, and sinensetin were found with high concentrations in juice as a result of simple squeezing, whereas amounts of those PMFs were negligibly low in peeled tangerine fruit. In contrast, the mean concentrations of the FGs narirutin, hesperidin, and didymin were several fold higher in peeled fruit than in tangerine juice and significantly higher in organic than AS and AB tangerines. Narirutin and hesperidin in juice from organic produces as well as narirutin in juice from AS produces were significantly higher than respective mean concentrations in juice from AB produces. beta-Cryptroxanthin was the predominant carotenoid beside zeaxanthin, lutein, lycopene, and beta-carotene in tangerine juice. Ascorbic acid concentrations were not predicted by the type of cultivation, whereas alpha-tocopherol was significantly higher in juice from organic than AS produces. In summary, hand-pressed juice of C. reticulata Blanco cv. Sainampueng serves as a rich source of PMFs, FGs, carotenoids, and antioxidants: 4-5 tangerine fruits ( approximately 80 g of each fruit) giving one glass of 200 mL hand-pressed juice would provide more than 5 mg of nobiletin and tangeretin and 36 mg of hesperidin, narirutin, and didymin, as well as 30 mg of ascorbic acid, >1 mg of provitamin A active beta-cryptoxanthin, and 200 microg of alpha-tocopherol.Journal of Agricultural and Food Chemistry 05/2010; 58(10):6069-74. · 2.82 Impact Factor
Article: Nobiletin, a citrus flavonoid, suppresses invasion and migration involving FAK/PI3K/Akt and small GTPase signals in human gastric adenocarcinoma AGS cells.[show abstract] [hide abstract]
ABSTRACT: Nobiletin, a compound isolated from citrus fruits, is a polymethoxylated flavone derivative shown to have anti-inflammatory, antitumor, and neuroprotective properties. This study has investigated that nobiletin exerted inhibitory effects on the cell adhesion, invasion, and migration abilities of a highly metastatic AGS cells under non-cytotoxic concentrations. Data also showed nobiletin could inhibit the activation of focal adhesion kinase (FAK) and phosphoinositide-3-kinase/Akt (PI3K/Akt) involved in the downregulation of the enzyme activities, protein expressions, messenger RNA levels of matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-2 (MMP-9). Also, our data revealed that nobiletin inhibited FAK/PI3K/Akt with concurrent reduction in the protein expressions of Ras, c-Raf, Rac-1, Cdc42, and RhoA by western blotting, whereas the protein level of RhoB increased progressively. Otherwise, nobiletin-treated AGS cells showed tremendously decreased in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), the nuclear level of NF-κB, and the binding ability of NF-κB to NF-κB response element. Furthermore, nobiletin significantly decreased the levels of phospho-Akt and MMP-2/9 in Akt1-cDNA-transfected cells concomitantly with a marked reduction in cell invasion and migration. These results suggest that nobiletin can reduce invasion and migration of AGS cells, and such a characteristic may be of great value in the development of a potential cancer therapy.Molecular and Cellular Biochemistry 10/2010; 347(1-2):103-15. · 2.06 Impact Factor