Nobiletin (CAS 478-01-3)

Nobiletin is a flavanoid with antioxidant and anti-inflammatory properties found in the rind of tangerines. The compound has been observed to inhibit the phosphorylation of MEK (mitogen-activated protein kinase). Nobiletin has also been documented to suppress the expression of MMP-1 (matrix metalloproteinases), MMP-3 and MMP-9 that are involved in the breakdown of the extracellular matrix during tumor metastasis. In vitro studies of Nobiletin on varying cancer cell lines and on the chick egg has shown the anti-angiogenic effects of Nobiletin through down regulation of ERK 1, ERK 2 and c-Jun N-terminal kinase, and transcriptional factors c-Jun and Stat3. The compound also suppressed proliferation, migration and tube formation on matrigel of HUVEC cells stimulated with growth supplement. Nobiletin has demonstrated to attenuate NF-κB transcriptional activation, NO and PGE₂ production, NOS2 (inducible nitric oxide synthase) and Cox-2 (cyclooxygenase-2) expression.

References:

1. The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice.  |  Minagawa, A., et al. 2001. Jpn J Cancer Res. 92: 1322-8. PMID: 11749698
2. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages.  |  Lin, N., et al. 2003. Biochem Pharmacol. 65: 2065-71. PMID: 12787887
3. Inhibition of cell proliferation by nobiletin, a dietary phytochemical, associated with apoptosis and characteristic gene expression, but lack of effect on early rat hepatocarcinogenesis in vivo.  |  Ohnishi, H., et al. 2004. Cancer Sci. 95: 936-42. PMID: 15596041
4. Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells.  |  Morley, KL., et al. 2007. Cancer Lett. 251: 168-78. PMID: 17197076
5. Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells.  |  Tang, M., et al. 2007. Cancer Sci. 98: 471-7. PMID: 17284254
6. Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes.  |  Saito, T., et al. 2007. Biochem Biophys Res Commun. 357: 371-6. PMID: 17433253
7. Nobiletin from citrus fruit peel inhibits the DNA-binding activity of NF-kappaB and ROS production in LPS-activated RAW 264.7 cells.  |  Choi, SY., et al. 2007. J Ethnopharmacol. 113: 149-55. PMID: 17611060
8. Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice.  |  Nakajima, A., et al. 2007. J Pharmacol Sci. 105: 122-6. PMID: 17895593
9. Nobiletin, a citrus flavonoid with neurotrophic action, augments protein kinase A-mediated phosphorylation of the AMPA receptor subunit, GluR1, and the postsynaptic receptor response to glutamate in murine hippocampus.  |  Matsuzaki, K., et al. 2008. Eur J Pharmacol. 578: 194-200. PMID: 17976577
10. A citrus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells.  |  Miyata, Y., et al. 2008. Biochem Biophys Res Commun. 366: 168-73. PMID: 18053806
11. Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo.  |  Kunimasa, K., et al. 2010. Cancer Sci. 101: 2462-9. PMID: 20670297
12. Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer′s Disease and Parkinson′s Disease.  |  Nakajima, A. and Ohizumi, Y. 2019. Int J Mol Sci. 20: PMID: 31295812
13. Antioxidant Nobiletin Enhances Oocyte Maturation and Subsequent Embryo Development and Quality.  |  Cajas, YN., et al. 2020. Int J Mol Sci. 21: PMID: 32727154