nobiletin benefits
Nobiletin Extract, Pill, Supplement and Source
What is nobiletin? Nobiletin Source?
A polymethoxylated flavone extracted from citrus peels. Nobiletin is incorporated in some diet pills or
supplements. Retails promote nobiletin as an agent to fight diabetes and heart disease. Nobiletin is also
available in some citrus bioflavonoids supplements or pills.

Nobiletin Benefits - Alzheimer's disease
Increasing evidence suggests that the elevation of beta-amyloid (Abeta) peptides in the brain is central to the
pathogenesis of Alzheimer's disease. Onozuka H's studies at Tohoku University, Japan, demonstrated that
nobiletin, a polymethoxylated flavone from citrus peels, enhanced cAMP/protein kinase A/extracellular
signal-regulated kinase/cAMP response element-binding protein signaling in cultured hippocampal neurons
and ameliorated Abeta-induced memory impairment in Alzheimer's disease model rats. Nobiletin was also
shown to improve impaired memory in olfactory-bulbectomized mice. In addition, Nakajima A and co-workers
at Tohoku University, Japan, demonstrated that nobiletin was able to rescue OBX-induced cholinergic
neuro-degeneration, accompanied by improvement of impaired memory in OBX mice. These findings suggest
that this natural compound has potential to become a novel drug for fundamental treatment of Alzheimer's
disease. [1]

Nobiletin Benefits - Osteoarthritis
Nobiletin may have benefits of promoting joint health. Aggrecanase-1/a disintegrin and metalloproteinase with
thrombospondin-like motifs (ADAMTS)-4 and aggrecanase-2/ADAMTS-5 have been shown to play crucial
roles in cartilage destruction in rheumatoid arthritis and osteoarthritis. Imada K and co-workers found
nobiletin interfered with the interleukin (IL)-1beta-mediated ADAMTS-4 and -5 mRNA expression in cultured
human synovial fibroblasts. Furthermore, they also observed intraperitoneal administration of nobiletin
suppressed ADAMTS-4 and -5 mRNA expression in the joint tissues of collagen-induced arthritic mice. [2]
Murakami A and co-workers from Kyoto University, Japan, observed nobiletin significantly suppressed the
reduction of whole bone mineral density in ovariectomized mice. [3]

Nobiletin Benefits - Cancers
Nobiletin has been found to dose-dependently suppress the proliferation of human lung adenocarcinoma cell
line A549 cells. It is very likely that nobiletin induced p53-mediated cell cycle arrest and apoptosis via
modulated the Bax:Bcl-2 protein ratio. [4] The activation of mitogen-activated protein/extracellular
signal-regulated kinase (MEK) is well known to be associated with tumor invasion and metastasis. Nobiletin
has also shown to directly inhibit MEK activity and decrease the sequential phosphorylation of extracellular
regulated kinases, exhibiting the antitumor metastatic activity by suppressing matrix metalloproteinase
expression in human fibrosarcoma HT-1080 cells. [5]

Note: Clinical studies are needed to support nobiletin health claims.

ALL RIGHTS RESERVED  This article can not be used as medical advice. Please, consult with your doctor before using any
drug and supplement products.

[1] Onozuka H, et al, Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's
disease. J Pharmacol Exp Ther. 2008 Sep;326(3):739-44. Epub 2008 Jun 10. [2] Imada K, et al, Nobiletin, a citrus polymethoxy flavonoid,
suppresses gene expression and production of aggrecanases-1 and -2 in collagen-induced arthritic mice. Biochem Biophys Res Commun. 2008
Aug 22;373(2):181-5. Epub 2008 Jun 9. [3] Murakami A, et al Citrus nobiletin suppresses bone loss in ovariectomized ddY mice and
collagen-induced arthritis in DBA/1J mice: possible involvement of receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis
regulation. Biofactors. 2007;30(3):179-92. [4] Luo G, Guan X, Zhou L. Apoptotic effect of citrus fruit extract nobiletin on lung cancer cell line
A549 in vitro and in vivo. Cancer Biol Ther. 2008 Jun;7(6):966-73. Epub 2008 Mar 21. [5] Miyata Y et al, A citrus polymethoxyflavonoid, nobiletin,
is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells. Biochem Biophys Res Commun. 2008 Feb
1;366(1):168-73. Epub 2007 Nov 29. [6] Nakajima A, et al, Nobiletin, a citrus flavonoid that improves memory impairment, rescues
bulbectomy-induced cholinergic neurodegeneration in mice. J Pharmacol Sci. 2007 Sep;105(1):122-6.