Nobiletin is an extract from citrus peel - Has anyone tried it or know more?


1. Neuroscience. 2013 Dec 4;259C:126-141. doi: 10.1016/j.neuroscience.2013.11.051.
[Epub ahead of print]

Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced
Parkinson model mice.

Yabuki Y(1), Ohizumi Y(2), Yokosuka A(3), Mimaki Y(3), Fukunaga K(4).

Author information:
(1)Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku
University, Sendai, Japan.
(2)School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan;
Department of Anti-dementia Functional Food Development, Graduate School of
Engineering, Tohoku University, Sendai, Japan; Laboratory of Kampo Medicines,
Yokohama College of Pharmacy, Yokohama, Japan; Kasei Fukushi Research Center,
Tohoku Fukushi University, Sendai, Japan.
(3)Laboratory of Medicinal Plant Science, School of Pharmacy, Tokyo University of
Pharmacy and Life Science, Tokyo, Japan.
(4)Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku
University, Sendai, Japan. Electronic address: kfukunaga@m.tohoku.ac.jp.

Nobiletin, a polymethoxylated flavonoid found in citrus fruit peel, reportedly
improves memory impairment in rodent models. Here we report its effect on
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor and cognitive
deficits. Nobiletin administration (50mg/kg i.p.) for 2 consecutive weeks
improved motor deficits seen in MPTP-induced Parkinson model mice by 2weeks, an
effect that continued until 2weeks after drug withdrawal. Drug treatment promoted
similar rescue of MPTP-induced cognitive impairment at equivalent time points.
Nonetheless, nobiletin treatment did not block loss of dopaminergic neurons seen
in the MPTP-treated mouse midbrain, nor did it rescue decreased tyrosine
hydroxylase (TH) protein levels seen in the striatum or hippocampal CA1 region of
these mice. Interestingly, nobiletin administration (50mg/kg i.p.) rescued
reduced levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
autophosphorylation and phosphorylation at Thr-34 of dopamine- and cAMP-regulated
phosphoprotein-32 (DARPP-32) in striatum and hippocampal CA1 to levels seen in
sham-operated mice. Likewise, CaMKII- and cAMP kinase-dependent TH
phosphorylation was significantly restored by nobiletin treatment. MPTP-induced
reduction of dopamine contents in the striatum and hippocampal CA1 region was
improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal
administration of nobiletin also enhanced dopamine release in striatum and
hippocampal CA1, an effect partially inhibited by treatment with nifedipine (a
L-type Ca(2+) channel inhibitor) or NNC 55-0396 (a T-type Ca(2+) channel
inhibitor) and completely abolished by combined treatment with both. Overall, our
study describes a novel nobiletin activity in brain and suggests that nobiletin
rescues motor and cognitive dysfunction in MPTP-induced Parkinson model mice, in
part by enhancing dopamine release.

Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

PMID: 24316474 [PubMed - as supplied by publisher]

1. Curr Opin Lipidol. 2013 Feb;24(1):34-40. doi: 10.1097/MOL.0b013e32835c07fd.

Citrus flavonoids and lipid metabolism.

Assini JM, Mulvihill EE, Huff MW.

Author information:
Department of Biochemistry, Department of Medicine, The University of Western
Ontario, London, Ontario, Canada.

PURPOSE OF REVIEW: Citrus flavonoids are polyphenolic compounds with powerful
biological properties. This review aims to summarize recent advances towards
understanding the ability of citrus flavonoids to regulate lipid metabolism and
other metabolic parameters relevant to the metabolic syndrome, type 2 diabetes
and cardiovascular disease.
RECENT FINDINGS: Citrus flavonoids, including naringenin, hesperidin, nobiletin
and tangeretin, have emerged as promising therapeutic agents for the treatment of
metabolic dysregulation. Epidemiological studies report that intake of citrus
flavonoid-containing foods attenuates cardiovascular diseases. Experimental and a
limited number of clinical studies reveal lipid-lowering, insulin-sensitizing,
antihypertensive and anti-inflammatory properties. In animal models, citrus
flavonoid supplements prevent hepatic steatosis, dyslipidemia and insulin
sensitivity primarily through inhibition of hepatic fatty acid synthesis and
increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response
in metabolically important tissues including liver, adipose tissue, kidney and
the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have
not been completely established. In mouse models, citrus flavonoids show marked
suppression of atherogenesis through improved metabolic parameters and also
through direct impact on the vessel wall.
SUMMARY: These recent studies suggest an important role of citrus flavonoids in
the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity and
atherosclerosis. The favorable outcomes are achieved through multiple mechanisms.
Human studies focussed on dose, bioavailability, efficacy and safety are required
to propel the use of these promising therapeutic agents into the clinical arena.

PMID: 23254473 [PubMed - indexed for MEDLINE]

Some familiar names-


1. Biol Pharm Bull. 2010;33(11):1814-21.

Anti-neuroinflammatory activity of nobiletin on suppression of microglial
activation.

Cui Y, Wu J, Jung SC, Park DB, Maeng YH, Hong JY, Kim SJ, Lee SR, Kim SJ, Kim SJ,
Eun SY.

Author information:
Institute of Medical Science, Jeju National University School of Medicine, 66
Jejudaehakno, Jeju-si, Jeju-do 690–756, Republic of Korea.

A growing body of evidence suggests that nobiletin (5,6,7,8,3',4'-hexamethoxy
flavone) from the peel of citrus fruits, enhances the damaged cognitive function
in disease animal models. However, the neuroprotective mechanism has not been
clearly elucidated. Since nobiletin has shown anti-inflammatory effects in
several tissues, we investigated whether nobiletin suppresses excessive
microglial activation implicated in neurotoxicity in lipopolysaccharide
(LPS)-stimulated BV-2 microglia cell culture models. Release of nitric oxide
(NO), the major inflammatory mediator in microglia, was markedly suppressed in a
dose-dependent manner following nobiletin treatment (1-50 µM) in LPS-stimulated
BV-2 microglia cells. The inhibitory effect of nobiletin was similar to that of
minocycline, a well-known microglial inactivator. Nobiletin significantly
inhibited the release of the pro-inflammatory cytokine tumor necrosis factor
(TNF-α) and interleukin-1β (IL-1β). LPS-induced phosphorylations of extracellular
signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38
mitogen-activated protein kinases (MAPKs) were also significantly inhibited by
nobiletin treatment. In addition, nobiletin markedly inhibited the LPS-induced
pro-inflammatory transcription factor nuclear factor κB (NF-κB) signaling pathway
by suppressing nuclear NF-κB translocation from the cytoplasm and subsequent
expression of NF-κB in the nucleus. Taken together, these results may contribute
to further exploration of the therapeutic potential and molecular mechanism of
nobiletin in relation to neuroinflammation and neurodegenerative diseases.

PMID: 21048305 [PubMed - indexed for MEDLINE]