Nobiletin

Nobiletin is a polymethoxylated flavonoid that has been found in C. unshiu and has diverse biological activities.^1,2,3 It reduces LPS- and IFN-γ-induced increases in inducible nitric oxide synthase (iNOS) protein levels and NO production in RAW 264.7 cells when used at concentrations of 25, 50, and 100 µM.¹ Nobiletin decreases proliferation of A549 lung, B16/4A5 melanoma, CCRF-HSB-2 leukemia, and TGBC11TKB gastric cancer cell lines with IC₅₀ values of 22, 18, 13, and 8.3 µM, respectively.² Dietary administration of nobiletin (0.3% w/w) reduces body weight, hepatic steatosis, and plasma LDL and HDL cholesterol levels in mice fed a high-fat, high-cholesterol diet for 18 weeks.³ It also inhibits increases in plasma glucose levels in an intraperitoneal glucose tolerance test in the same model.

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1. Murakami, A., Nakamura, Y., Torikai, K., et al. Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res. 60(18), 5059-5066 (2000).

2. Kawaii, S., Tomono, Y., Katase, E., et al. Antiproliferative activity of flavonoids on several cancer cell lines. Biosci. Biotechnol. Biochem. 63(5), 896-899 (1999).

3. Morrow, N.M., Burke, A.C., Samsoondar, J.P., et al. The citrus flavonoid nobiletin confers protection frommetabolic dysregulation in high-fat-fed mice independent of AMPK. J. Lipid Res. 61(3), 387-402 (2020).