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Antiviral Res.2013, 98(3):386-93Nat Prod Sci.2014, 20(3):182-190Faculty of Chem. & Nat. Resource ...2014...Am J Chin Med.2015, 30:1-22Int J Mol Med.2015, 35(5):1237-45Evid Based Complement Alternat Me...2016...Food Sci Biotechnol....2016...Am J Chin Med.2016, 44(8):1719-1735
J Pharm Biomed Anal.2017, 140:274-280Cell Physiol Biochem....2017...Cell Physiol Biochem....2017...Viruses.2017, 9(10)Chem Biol Interact.2018, 283:59-74South African J of Plant&Soil...2018...J Sep Sci.2018, 41(11):2488-2497Cancer Manag Res.2019, 11:483-500
Food Res Int.2019, 123:125-134Int J Mol Sci.2019, 20(3):E651Environ Toxicol Pharmacol....2019...Planta Med.2019, 85(3):217-224Food Chem.2020, 313:126079Appl. Sci.2020, 10(20), 7323.Drug Des Devel Ther.2020, 14:969-976.
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J Nat Med.2017, 71(2):457-462Evid Based Complement Alternat Med.2018, 2018:4259603Food Chem Toxicol.2020, 135:110863J Nat Med.2020, 74(3):550-560.Appl. Sci.2020, 10(23), 8729The Journal of Animal & Plant Sciences.2020, 30(6):1366-1373Evid Based Complement Alternat Med.2020, 2020:9416962.Biomolecules.2020, 10(2):E184Pharmacol Rep.2018, 70(6):1195-1201Korean J. of Horticultural Sci. & Tech. 2017, 793-804
Related Screening Libraries
||Nobiletin, a citrus flavonoid isolated from citrus peels like in tangerine, which has anti-inflammatory and anti-tumor activities, it could be a potential protective agent for the prevention and treatment of restenosis after angioplasty. Nobiletin downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), suppressed cell viability through AKT pathways. |
||Akt | NF-kB | NOS | COX | ERK | Bcl-2/Bax | Caspase | p38MAPK | MMP(e.g.TIMP) | AP-1 | HIF | VEGFR | ROS | p65 | TNF-α | Beta Amyloid | cAMP | PKA | AMPK | PGE | IL Receptor|
|Tumour Biol. 2014 Dec;35(12):11903-11. |
|Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells.[Pubmed: 25164609]|
|Nobiletin, a compound isolated from citrus fruits, is a polymethoxylated flavone derivative that was shown to have anti-inflammatory and anticancer activities in various solid tumors. The anticancer effect of Nobiletin on nonsolid tumor remains unclear.
METHODS AND RESULTS:
Herein, the molecular mechanisms by which Nobiletin exerts its anticancer effects on acute myeloid leukemia (AML) cells were investigated. The results showed that Nobiletin suppressed cell proliferation in various types of AML cell lines. Moreover, Nobiletin induced cell-cycle arrest of HL-60 AML cells at the G0/G1 phase by suppressing extracellular signal-regulated kinase (ERK) activity. Furthermore, Nobiletin effectively induced apoptosis of HL-60 cells through caspase-8, caspase-9, and caspases-3 activation concomitantly with a marked induction of p38 mitogen-activated protein kinase (MAPK) activation, but without affecting expression levels of Bcl-2, Bax, or Bid.
Taken together, our results suggest that Nobiletin inhibited HL-60 cell proliferation through inducing cell-cycle arrest and apoptosis and could serve as a potential additional chemotherapeutic agent for treating AML.
|Expert Opin Ther Targets. 2015 Mar;19(3):307-20. |
|Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2.[Pubmed: 25563790]|
|Nasopharyngeal carcinoma (NPC) is known for its high incidence of neck lymph node metastasis, which represents poor prognosis. Nobiletin is a citrus polymethoxyflavonoid that suppresses tumor growth and metastasis, both of which depend on angiogenesis in previous studies. However, the effect of Nobiletin on human NPC cells metastasis has not been clearly clarified.
METHODS AND RESULTS:
In this study, we determine the effects of Nobiletin on the migration and invasion in NPC cells.
Nobiletin significantly inhibited migration/invasion capacities of HONE-1 and NPC-BM cell lines. The results of gelatin zymography and western blotting revealed that the activities and protein levels of the MMP-2 were inhibited by Nobiletin. Nobiletin also showed that inhibits phosphorylation of ERK1/2. Tests of the real-time PCR and promoter assays evaluated the inhibitory effects of Nobiletin on MMP-2 expression in human NPC cells. Nobiletin inhibits MMP-2 expression, up-regulating tissue inhibitor of metalloproteinase-2 and down-regulation of the transcription factors of NF-κB and activator protein 1 (AP-1) signaling pathways. Finally, an administration of Nobiletin effectively suppressed the tumor formation and metastasis in the NPC xenograft model in vivo.
Nobiletin may have potential use as a chemo-preventive agent against nasopharyngeal cancer metastasis.
|Biochem Pharmacol. 2003 Jun 15;65(12):2065-71. |
|Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages.[Pubmed: 12787887]|
|We previously reported that Nobiletin (5,6,7,8,3',4'-hexamethoxy flavone), 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].
METHODS AND RESULTS:
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 (<64 microM). 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.
|Mol Nutr Food Res. 2015 May;59(5):829-42. |
|Citrus nobiletin ameliorates experimental colitis by reducing inflammation and restoring impaired intestinal barrier function.[Pubmed: 25655748]|
|Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract. Citrus Nobiletin can exert robust anti-inflammatory effects in vivo and in vitro. We evaluated the impact of Nobiletin on the excessive inflammatory response and impaired barrier function in a rodent colitis model.
METHODS AND RESULTS:
Colitis was established by infusion with 1 mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol (40% v/v) in rats at a 125 mg/kg dose. Caco-2 cell monolayer exposed to LPSs is used as a culture model for intestinal permeability measurements. Nobiletin decreased rat epithelial proinflammatory cytokines and mediators production. Nobiletin restored impaired barrier function in colitic rats and Caco-2 monolayer. Nobiletin decreased protein expressions of Akt, nuclear factor-kappa B (NF-κB), and myosin light chain kinase (MLCK) isolated from rat intestinal epithelial tissue and Caco-2 cell, respectively. PI3K inhibitor or siRNA targeting of either Akt or NF-κB mitigated the impact of Nobiletin on MLCK expression and barrier function in Caco-2 monolayer, respectively.
Nobiletin exerted anti-inflammatory effects in TNBS-induced colitis through the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression. Nobiletin restored barrier function, which had been damaged after TNBS administration, through the inhibition of the Akt-NF-κB-MLCK pathway.
||The peels of Citrus nobilis Lour.
||Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
||Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
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||The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.
ChemFaces New Products and Compounds
Recently, ChemFaces products have been cited in many studies from excellent and top scientific journals
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)PMID: 29328914
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)PMID: 32004475
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)PMID: 29149595
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)PMID: 29553709
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)PMID: 28005066
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)PMID: 30417089
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|Cancer Res. 2000 Sep 15;60(18):5059-66. |
|Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice.[Pubmed: 11016629]|
|The intake of citrus fruits has been suggested as a way to prevent the development of some types of human cancer. Nitric oxide (NO) is closely associated with the processes of epithelial carcinogenesis.
We attempted a search for NO generation inhibitors in Citrus unshiu.
METHODS AND RESULTS:
The active constituent was traced by an activity-guiding separation. NO and superoxide (O2-) generation was induced by a combination of lipopolysaccharide and IFN-gamma in mouse macrophage RAW 264.7 cells, and by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocyte HL-60, respectively. Expression of inducible NO synthase and cyclooxygenase 2 proteins were detected by Western blotting. The in vivo anti-inflammatory and antitumor promoting activities were evaluated by topical TPA application to ICR mouse skin with measurement of edema formation, epidermal thickness, leukocyte infiltration, hydrogen peroxide production, and the rate of proliferating cell nuclear antigen-stained cells. As a result, Nobiletin, a polymethoxyflavonoid, was identified as an inhibitor of both NO and O2- generation. Nobiletin significantly inhibited two distinct stages of skin inflammation induced by double TPA application [first stage priming (leukocyte infiltration) and second stage activation (oxidative insult by leukocytes)] by decreasing the inflammatory parameters. It also suppressed the expression of cyclooxygenase-2 and inducible NO synthase proteins and prostaglandin E2 release. Nobiletin inhibited dimethylbenz[a]anthracene (0.19 micromol)/TPA (1.6 nmol)-induced skin tumor formation at doses of 160 and 320 nmol by reducing the number of tumors per mouse by 61.2% (P < 0.001) and 75.7% (P < 0.001), respectively.
The present study suggests that Nobiletin is a functionally novel and possible chemopreventive agent in inflammation-associated tumorigenesis.
|Aliment Pharmacol Ther. 2004 Jul;20 Suppl 1:95-101. |
|Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation.[Pubmed: 15298613 ]|
|To demonstrate the antitumour effects of Nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), a citrus flavonoid extracted from Citrus depressa Hayata, on human gastric cancer cell lines TMK-1, MKN-45, MKN-74 and KATO-III.
METHODS AND RESULTS:
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the TdT-mediated dUTP biotin nick-end labelling (TUNEL) method and cell-cycle analysis revealed that Nobiletin acted on these cells in several ways, namely by direct cytotoxicity, induction of apoptosis and modulation of cell cycle. The efficacy of combined treatment of Nobiletin with a conventional anticancer drug, CDDP, was also examined. Treatment with Nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control.
Although the effective dose and administration route of Nobiletin require further investigation, our study represents a potential successful linking of this compound with the treatment of gastric cancer.
|Drug Dev Res. 2014 Dec;75(8):489-96. |
|Nobiletin Inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in a rat carotid artery injury model.[Pubmed: 25452110]|
|Preclinical Research The abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of neointimal hyperplasia after vascular injury. Nobiletin, a citrus bioflavonoid, exhibits anti-inflammatory and anti-oxidative activities.
METHODS AND RESULTS:
The present study evalutaed whether Nobiletin could inhibit platelet-derived growth factor (PDGF)-BB- stimulated VSMC proliferation and migration and decrease neointimal hyperplasia in a rat carotid artery injury model. Cultured VSMCs from rat thoracic aortas were treated with Nobiletin before being stimulated with 20 ng/ml PDGF-BB, and rats were subjected to carotid artery injury. Nobiletin inhibited PDGF-BB-induced VSMC proliferation and migration, attenuated reactive oxygen species (ROS) production and reduced phosphorylation of ERK1/2 and the expression of nuclear NF-κB p65 in PDGF-BB-stimulated VSMCs. Nobiletin decreased the intima area and the ratio of neointima to media in balloon-injured rat carotid arteries. Serum levels of TNF-α and IL-6 in Nobiletin-treated rats were decreased.
These results indicated that Nobiletin could be a potential protective agent for the prevention and treatment of restenosis after angioplasty.
|J Pharmacol Exp Ther. 2008 Sep;326(3):739-44. |
|Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's disease.[Pubmed: 18544674 ]|
|Increasing evidence suggests that the elevation of beta-amyloid (Abeta) peptides in the brain is central to the pathogenesis of Alzheimer's disease (AD).
METHODS AND RESULTS:
Our recent studies have demonstrated that Nobiletin, a polymethoxylated flavone from citrus peels, enhances cAMP/protein kinase A/extracellular signal-regulated kinase/cAMP response element-binding protein signaling in cultured hippocampal neurons and ameliorates Abeta-induced memory impairment in AD model rats.
For the first time, we report that this natural compound improves memory deficits in amyloid precursor protein (APP) transgenic mice that overexpress human APP695 harboring the double Swedish and London mutations [APP-SL 7-5 transgenic (Tg) mice]. Our enzyme-linked immunosorbent assay (ELISA) also showed that administration of Nobiletin to the transgenic mice for 4 months markedly reduced quantity of guanidine-soluble Abeta(1-40) and Abeta(1-42) in the brain. Furthermore, consistent with the results of ELISA, by immunohistochemistry with anti-Abeta antibody, it was evidently shown that the administration of Nobiletin decreased the Abeta burden and plaques in the hippocampus of APP-SL 7-5 Tg mice.
METHODS AND RESULTS:
These findings suggest that this natural compound has potential to become a novel drug for fundamental treatment of AD.