Nobiletin (natural herbal medicine listings)
January 17 2016 by Ray Sahelian, M.D.

Nobiletin is one of the citrus bioflavonoids. Limited laboratory and rodent studies indicate nobiletin to have antiinflammatory and antioxidnat properties.

Sytrinol has polymethoxylated flavones (PMFs) that decrease apoprotein B, a structural protein needed for endogenous synthesis of LKL cholesterol. PMFs (tangeritin and nobiletin) decrease diacylglycerol acetyl transferase, a liver enzyme needed for endogenous synthesis of triblycerides.

Dementia, Alzheimer's disease
Clin Psychopharmacol Neurosci. 2014. 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-β (Aβ) 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.

Parkinson's disease
Neuroscience. Feb 2014. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice.

Nobiletin research
Yakugaku Zasshi. 2010. Preventive action of nobiletin, a constituent of Auarantii Nobilis pericarpium with anti-dementia activity, against amyloid-beta peptide-induced neurotoxicity expression and memory impairment].

Antagonistic effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats and relevant mechanisms.
Life Sci. 2005; Department of Pharmacology, Nanjing Medical University, Nanjing, PR China.
Eosinophils are known to be the important effector cells in asthmatic airway inflammation. The purpose of this study was to investigate the effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats, and explore its possible mechanisms. Animals were actively sensitized by subcutaneous injection of ovalbumin (OVA). The inflammation in lung tissues of asthmatic rats was observed by hematoxylin and eosin (HE) staining. These results indicated that nobiletin could inhibit the eosinophilic airway inflammation. Lowering the levels of Eotaxin, relieving airway infiltration of eosinophils and promoting apoptosis of eosinophils by enhancing expression of Fas mRNA may be important mechanisms for nobiletin to antagonize eosinophilic airway inflammation of asthmatic rats.

Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin.
Biofactors. 2002.
Nobiletin, a polymethoxyflavonoid, is an effective anti-inflammatory and cancer preventive phytochemical found in citrus fruits. We compared the absorption and metabolism characteristics of nobiletin with those of luteolin (LT) in male rats. Each flavonoid (67 micromol/kg of body weight) was given separately by gastric intubation, and then concentrations were measured at 1, 4, and 24 hours after administration. In the digestive organs, Nobiletin showed a notable tendency for localizing into the mucous membrane and muscularis from 1 to 4 hours, in contrast to LT, though both nobiletin and LT were completely excreted within 24 hours. Further, significant amounts of nobiletin were detected in the whole liver and kidney specimens, whereas LT accumulation was slight. Although serum concentrations of nobiletin from 1 to 4 hours were comparable to those of LT, urinary concentrations of LT were significantly higher from 4 to 24 hours. Following glucuronidase/sulfatase treatments of urinary materials, we detected 3 types of mono-demethylated nobiletin, including 3'-demethyl-NOB, and two di-demethylated types, as well as 3'-demethyl-NOB alone in serum samples using liquid chromatography-mass spectral analysis. Our results suggest that the metabolic properties of polymethoxyflavonoids are distinct from those of other general flavonoids, because of their wide distribution and accumulation in tissue.

Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages.
Biochem Pharmacol. 2003.
We previously reported that nobiletin, a citrus polymethoxy flavonoid, effectively interferes with the production of promatrix metalloproteinase (proMMP)-9/progelatinase B in rabbit synovial fibroblasts [J. Rheumatol. 27 (2000) 20]. In this paper, we further examine the effects of nobiletin on the production of cyclooxygenases (COXs), prostaglandin (PG) E(2), and proinflammatory cytokines in human synovial fibroblasts and the mouse macrophage J774A.1 cell line. Nobiletin suppressed the interleukin (IL)-1-induced production of PGE(2) in human synovial cells in a dose-dependent manner. Additionally, it selectively downregulated COX-2, but not COX-1 mRNA expression. Nobiletin also interfered with the lipopolysaccharide-induced production of PGE(2) and the gene expression of proinflammatory cytokines including IL-1alpha, IL-1beta, TNF-alpha and IL-6 in mouse J774A.1 macrophages. In addition, nobiletin downregulated the IL-1-induced gene expression and production of proMMP-1/procollagenase-1 and proMMP-3/prostromelysin-1 in human synovial fibroblasts. In contrast, production of the endogenous MMP inhibitor, TIMP-1, was augmented by nobiletin. These anti-inflammatory actions of nobiletin are very similar to those of anti-inflammatory steroids such as dexamethasone, and the upregulation of TIMP-1 production is a unique action of nobiletin. Therefore, these results further support the notion that nobiletin is likely to be a candidate for characterization as a novel immunomodulatory and anti-inflammatory drug.

Can nobiletin be taken with saw palmetto herb or CoQ10 nutrient?
   There is not enough research to know for sure, but I don't see any obvious reasons it could not if used in low dosages.

5-HTP for mood stabilizing


Nobiletin as a tyrosinase inhibitor from the peel of Citrus fruit.
Biol Pharm Bull. 2002.
A tyrosinase inhibitor was isolated from the peel of Citrus fruit by activity-guided fractionation, and identified as 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) by comparison with reported spectral data. Nobiletin exhibited more potency than Kojic acid used as a positive control, and it was found to be potentially an effective inhibitor of the production of melanin.