Nobiletin https://greenmedinfo.com/category/keywords/Nobiletin en Nobiletin and tangeretin may be beneficial in the treatment and prevention of Alzheimer`s and Parkinson's disease. https://greenmedinfo.com/article/nobiletin-and-tangeretin-may-be-beneficial-treatment-and-prevention-alzheimers n/a PMID:  CNS Neurol Disord Drug Targets. 2017 Mar 27. Epub 2017 Mar 27. PMID: 28474543 Abstract Title:  Neuroprotective Effects of Citrus Fruit-Derived Flavonoids, Nobiletin and Tangeretin in Alzheimer's and Parkinson`s disease. Abstract:  Neurodegenerative diseases, namely Alzheimer`s disease and Parkinson's disease represent a deleterious impact worldwide. Despite extensive preclinical and clinical research in neurodegenerative disorders, therapeutic strategies aimed at the prevention and chronic treatment of neurodegenerative conditions have not been successfully translated to the clinic. Therefore, the identification of novel pharmacological intervention derived from natural products is warranted. Nobiletin and tangeretin are important citrus flavonoids derived from the peel and other parts of Citrus L. genus, and have been shown to exhibit neuroprotective effects in several in vitro and in vivo studies. Apart from there antioxidant and anti-inflammatory effects, nobiletin and tangeretin have been shown to attenuate cholinergic deficits, reduce the abnormal accumulation of neurotoxic amyloid-beta peptides, reverse N-methyl-D-aspartate (NMDA) receptor hypofunction, ameliorate ischemic injury, inhibit hyperphosphorylation of tau protein, enhance neprilysin levels, modulate several signaling cascades, and protect against 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. Taken together, these naturally occurring phytochemicals may represent beneficial drug candidates for the treatment and prevention of Alzheimer`s and Parkinson's disease. https://greenmedinfo.com/article/nobiletin-and-tangeretin-may-be-beneficial-treatment-and-prevention-alzheimers#comments Alzheimer's Disease Nobiletin Parkinson's Disease Tangeretin Neuroprotective Agents Alzheimer's disease Neuroprotective Agents Nobiletin Parkinson's disease Tangeretin In Vitro Study Wed, 10 May 2017 00:54:15 +0000 greenmedinfo 147518 at https://greenmedinfo.com Nobiletin appears to be a promising novel prophylactic seed drug or functional food for Alzheimer's disease. https://greenmedinfo.com/article/nobiletin-appears-be-promising-novel-prophylactic-seed-drug-or-functional-food n/a PMID:  Biol Pharm Bull. 2018 ;41(4):451-457. PMID: 29607920 Abstract Title:  Nobiletin Reduces Intracellular and Extracellularβ-Amyloid in iPS Cell-Derived Alzheimer's Disease Model Neurons. Abstract:  Alzheimer's disease (AD) is the most common cause of dementia, with progressive memory impairment. Recently, neprilysin, aβ-amyloid (Aβ)-degrading enzyme has become featured as a drug target for AD. Previously, we identified nobiletin from citrus peels as a natural compound possessing anti-dementia activity. In addition, we demonstrated that nobiletin improved memory in memory-impaired animals and, further, that Aβlevels were markedly decreased in the brains of these animals. We demonstrated in vitro that nobiletin up-regulates neprilysin expression and activity in human neuroblastoma cells. However, the action of nobiletin with regard to Aβ degradation under in vitro AD pathological conditions remains unclear. In this study, we examined whether nobiletin could enhance the degradation of intra- and extracellular Aβ using human induced pluripotent stem cell-derived AD model neurons, which generate an excess of Aβdue to the familial AD presenilin-1 mutation. The neurons were treated in the presence or absence of nobiletin. The results of real-time quantitative RT-PCR indicated that neprilysin mRNA levels were significantly up-regulated by nobiletin. Furthermore, immunostaining with an anti-Aβ antibody revealed that nobiletin substantially reduced the intraneuronal content of Aβ. Interestingly, the results of Aβimmunoassays confirmed that nobiletin also significantly decreased the levels of Aβreleased into the cellular medium. These results suggest that nobiletin enhanced the reduction of intra- and that extracellular Aβ levels under AD pathologic conditions, and this is associated with the up-regulation of neprilysin expression. Collectively, nobiletin appears to be a promising novel prophylactic seed drug or functional food for AD. https://greenmedinfo.com/article/nobiletin-appears-be-promising-novel-prophylactic-seed-drug-or-functional-food#comments Alzheimer's Disease Nobiletin Neuroprotective Agents Prophylactic Agents Alzheimer's disease Neuroprotective Agents Nobiletin Prophylactic Agents Human In Vitro Mon, 09 Apr 2018 19:22:36 +0000 greenmedinfo 162381 at https://greenmedinfo.com Nobiletin could be used as an intervention that enhances circadian rhythms to combat metabolic disease via the circadian gene network. https://greenmedinfo.com/article/nobiletin-could-be-used-intervention-enhances-circadian-rhythms-combat-metabol n/a PMID:  Cell Metab. 2016 Apr 12 ;23(4):610-21. PMID: 27076076 Abstract Title:  The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome. Abstract:  Dysregulation of circadian rhythms is associated with metabolic dysfunction, yet it is unclear whether enhancing clock function can ameliorate metabolic disorders. In an unbiased chemical screen using fibroblasts expressing PER2::Luc, we identified Nobiletin (NOB), a natural polymethoxylated flavone, as a clock amplitude-enhancing small molecule. When administered to diet-induced obese (DIO) mice, NOB strongly counteracted metabolic syndrome and augmented energy expenditure and locomotor activity in a Clock gene-dependent manner. In db/db mutant mice, the clock is also required for the mitigating effects of NOB on metabolic disorders. In DIO mouse liver, NOB enhanced clock protein levels and elicited pronounced gene expression remodeling. We identified retinoid acid receptor-related orphan receptors as direct targets of NOB, revealing a pharmacological intervention that enhances circadian rhythms to combat metabolic disease via the circadian gene network. https://greenmedinfo.com/article/nobiletin-could-be-used-intervention-enhances-circadian-rhythms-combat-metabol#comments Metabolic Diseases Nobiletin Circadian Rhythm Gene Expression Regulation Metabolic Diseases Nobiletin Animal Study Fri, 02 Dec 2016 01:24:18 +0000 greenmedinfo 139767 at https://greenmedinfo.com Nobiletin might be useful for the prevention and treatment of nonalcoholic fatty liver diseases. https://greenmedinfo.com/article/nobiletin-might-be-useful-prevention-and-treatment-nonalcoholic-fatty-liver-di n/a PMID:  Evid Based Complement Alternat Med. 2018 ;2018:7420265. Epub 2018 Feb 7. PMID: 29552085 Abstract Title:  Nobiletin Inhibits Hepatic Lipogenesis via Activation of AMP-Activated Protein Kinase. Abstract:  We aimed to investigate the effects of nobiletin on hepatic lipogenesis in high glucose-induced lipid accumulation in HepG2 cells. Nobiletin, a citrus polymethoxyflavonoid with six methoxy groups, is present abundantly in the peels of citrus fruits. HepG2 cells were incubated in Dulbecco's modified Eagle's medium containing high glucose (25 mM) and subsequently treated with nobiletin at different concentrations (5, 25, and 50 M). Results showed that nobiletin markedly inhibited high glucose-induced hepatic lipid accumulation in HepG2 cells. In addition, it reduced the protein expression of lipogenic factors, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Nobiletin significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Pretreatment with compound C, an AMPK inhibitor, abolished the inhibitory effects of nobiletin on SREBP-1c and FAS expression. These results suggested that nobiletin might attenuate high glucose-induced lipid accumulation in HepG2 hepatocytes via modulation of AMPK signaling pathway. Therefore, nobiletin might be useful for the prevention and treatment of nonalcoholic fatty liver diseases. https://greenmedinfo.com/article/nobiletin-might-be-useful-prevention-and-treatment-nonalcoholic-fatty-liver-di#comments Nobiletin Nonalcoholic fatty liver disease (NAFLD) Nobiletin Nonalcoholic fatty liver disease (NAFLD) In Vitro Study Mon, 09 Apr 2018 20:04:11 +0000 greenmedinfo 162382 at https://greenmedinfo.com Nobiletin-ameliorated lipopolysaccharide-induced inflammation in acute lung injury. https://greenmedinfo.com/article/nobiletin-ameliorated-lipopolysaccharide-induced-inflammation-acute-lung-injur n/a PMID:  Inflammation. 2018 Mar 14. Epub 2018 Mar 14. PMID: 29541888 Abstract Title:  Nobiletin-Ameliorated Lipopolysaccharide-Induced Inflammation in Acute Lung Injury by Suppression of NF-κB Pathway In Vivo and Vitro. Abstract:  Nobiletin (NOB), a citrus polymethoxy flavonoid, has been reported to exhibit anti-inflammatory, anti-cancer, and anti-insulin resistance activities. Although the anti-inflammatory activity of NOB already reported, its involvement in lung protection has not been reported. Thus, this study aimed to investigate the anti-inflammatory response of NOB in lipopolysaccharide (LPS)-stimulated A549 cells and LPS-induced acute lung injury (ALI) in mice. The animals were pre-treated with NOB (5, 10, and 20 mg/kg) or DEX (5 mg/kg) at 12 and 1 h before intranasal instillation of LPS. The severity of pulmonary injury was evaluated 6 h after LPS administration. Results suggested that treatment with NOB dramatically attenuated lung histopathological changes, wet-to-dry (W/D) ratio, myeloperoxidase (MPO) activity, the numbers of inflammatory cells, and TNF-α, IL-6, and NO in BALF induced by LPS. Furthermore, NOB also significantly inhibited the expression of iNOS and the phosphorylation of NF-κBp65 and IκBα. In vitro, NOB inhibited NF-κB activation and TNF-α, IL-6 production in LPS-stimulated A549 cells. Taken together, these results indicated that NOB exhibited a protective effect on ALI, and the possible mechanism is involved in inhibiting NF-κB activation, subsequently inhibiting LPS-induced inflammatory response. https://greenmedinfo.com/article/nobiletin-ameliorated-lipopolysaccharide-induced-inflammation-acute-lung-injur#comments Lipopolysaccharide-Induced Toxicity Lung Injury: Acute Nobiletin Anti-Inflammatory Agents Interleukin-6 Downregulation NF-kappaB Inhibitor Tumor Necrosis Factor (TNF) Alpha Inhibitor Anti-Inflammatory Agents Lipopolysaccharide-Induced Toxicity Lung Injury: Acute Nobiletin In Vitro Study Mon, 09 Apr 2018 22:39:50 +0000 greenmedinfo 162384 at https://greenmedinfo.com The observations of this study indicate protective effects of nobiletin against cadmium-induced neurotoxicity. https://greenmedinfo.com/article/observations-study-indicate-protective-effects-nobiletin-against-cadmium-induc n/a PMID:  Neurol Res. 2018 Jan 16:1-10. Epub 2018 Jan 16. PMID: 29334873 Abstract Title:  Nobiletin prevents cadmium-induced neuronal apoptosis by inhibiting reactive oxygen species and modulating JNK/ERK1/2 and Akt/mTOR networks in rats. Abstract:  Objectives Cadmium (Cd), an extremely noxious environmental pollutant is known to induce oxidative stress leading to neurodegenerative diseases. Nobiletin, a citrus flavonoid is reported to possess various pharmacological properties. This study investigates the effects of nobiletin over Cd-induced neuronal apoptosis in rodent experimental model. Methods To separate group of male Sprague Dawley rats, Cd (2 mL/kg/day) was subcutaneously injected for one month which results in a dose level of 1 mg/kg Cd. Couple of days prior to Cd injection, the treatment group rats regularly received nobiletin (50, 100, or 200 mg/kg b.wt) orally through the study period. Results Cd-induced ROS levels and malondialdehyde (MDA) content were inhibited by nobiletin and improved glutathione levels. Nobiletin reduced neuronal apoptosis induced by Cd and raised cleaved caspase-3 levels. Intriguingly, nobiletin blocked JNK and Erk1/2 phosphorylation and down-regulated the pathways. Raised expression of kinases - MKKand ASK1 were reduced by nobiletin. Discussion The suppressed expression of phosphatases - PP2A and PP5 were up-regulated on nobiletin treatment. Nobiletin significantly blocked the activation of Akt/mTOR signaling. Enhanced phosphorylation of S6K1, Akt, and 4E-BP1 induced by Cd was significantly inhibited by nobiletin. The raised levels of raptor and rictor proteins were remarkably down-regulated on nobiletin treatment. Collectively, the observations of this study indicate protective effects of nobiletin against Cd-induced neurotoxicity. https://greenmedinfo.com/article/observations-study-indicate-protective-effects-nobiletin-against-cadmium-induc#comments Cadmium Poisoning Nobiletin Antioxidants Cadmium Neuroprotective Agents Antioxidants Cadmium Poisoning Neuroprotective Agents Nobiletin Animal Study Tue, 23 Jan 2018 16:51:43 +0000 greenmedinfo 158687 at https://greenmedinfo.com