Tangeretin natural supplement by Ray Sahelian, M.D.
March 6 2016

Tangeretin is one of the Citrus bioflavonoids. Tangeretin may play a role, like many flavonoids, in reducing the risk for certain cancers. It has also shown promise in protecting nerve cells.

Int Immunopharmacology Jan 21 2014. Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells.

Tangeritin and cancer
Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells.
Cancer Lett. 2007. Morley KL, Ferguson PJ, Koropatnick J. Cancer Research Laboratory Program, London Regional Cancer Program, Lawson Health Research Institute, London Health Sciences Centre, London, Ont., Canada.
Tangeretin and nobiletin are citrus flavonoids that are among the most effective at inhibiting cancer cell growth in vitro and in vivo. The antiproliferative activity of tangeretin and nobiletin was investigated in human breast cancer cell lines MDA-MB-435 and MCF-7 and human colon cancer line HT-29. Both flavonoids inhibited proliferation in a dose- and time-dependent manner, and blocked cell cycle progression at G1 in all three cell lines. Conclusion:  Thus, tangeretin and nobiletin could be effective cytostatic anticancer agents. Inhibition of proliferation of human cancers without inducing cell death may be advantageous in treating tumors as it would restrict proliferation in a manner less likely to induce cytotoxicity and death in normal, non-tumor tissues.

Virus infection protection
J Agric Food Chem. 2015. Tangeretin from Citrus reticulate Inhibits Respiratory Syncytial Virus Replication and Associated Inflammation in Vivo. This study demonstrates that tangeretin inhibited Respiratory Syncytial Virus replication and RSV-induced lung inflammation in vivo and may be useful in preventing and treating Respiratory Syncytial Virus infections and inflammation.

Tangeretin Research
A safety study of oral tangeretin and xanthohumol administration to laboratory mice.
In Vivo. 2005.
The detection of molecular targets for flavonoids in cell signalling has opened new perspectives for their application in medicine. Both tangeretin, a citrus methoxyflavone, and xanthohumol, the main prenylated chalcone present in hops (Humulus lupulus), act on the mitogen-activated protein kinase pathway and await further investigation for administration in vivo.  A safety study was designed in laboratory mice orally administered concentrates of purified tangeretin (1 x 10(-4) M) or xanthohumol at libitum for 4 weeks. A reduction of the circulating lymphocyte number was noticed for tangeretin, while all other parameters were unaffected by treatment with either tangeretin or xanthohumol. The parameters encompassed an integrity check of the following tissues and organs: bone marrow, liver, exocrine pancreas, kidneys, muscles, thyroid, ovaries and surrenal cortex. Furthermore, no differences were noted in the metabolism of proteins, lipids, carbohydrates and uric acid, as well as in ion concentrations. All data indicate that oral administration of tangeretin or xanthohumol to laboratory mice does not affect major organ functions and opens the gate for further safety studies in humans.

Tangeretin inhibits extracellular-signal-regulated kinase (ERK) phosphorylation.
FEBS Lett. 2005.
Tangeretin is a methoxyflavone from citrus fruits, which inhibits growth of human mammary cancer cells and cytolysis by natural killer cells. Attempting to unravel the flavonoid's action mechanism, we found that it inhibited extracellular-signal-regulated kinases 1/2 (ERK1/2) phosphorylation in a dose- and time-dependent way. In human T47D mammary cancer cells this inhibition was optimally observed after priming with estradiol. The spectrum of the intracellular signalling kinase inhibition was narrow and comparison of structural congeners showed that inhibition of ERK phosphorylation was not unique for tangeretin. Our data add tangeretin to the list of small kinase inhibitors with a restricted intracellular inhibition profile.

Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease.
Neuroreport. 2001.
Neuroprotective effects of a natural antioxidant tangeretin, a citrus flavonoid, were elucidated in the 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease (PD), after bioavailability studies. Following the chronic oral administration (10 mg/kg/day for 28 days), significant levels of tangeretin were detected in the hypothalamus, striatum and hippocampus (3.88, 2.36 and 2.00 ng/mg, respectively). The levels in the liver and plasma were 0.59 ng/mg and 0.11 ng/ml respectively. Unilateral infusion of the dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA; 8 microg), onto medial forebrain bundle significantly reduced the number of tyrosine hydroxylase positive (TH+) cells in the substantia nigra and decreased striatal dopamine content in the vehicle treated rats. Sub-chronic treatment of the rats with high doses of tangeretin (20 mg/kg/day for 4 days; p.o.) before 6-OHDA lesioning markedly reduced the loss of both TH+ cells and striatal dopamine content. These studies, for the first time, give evidence that tangeretin crosses the blood-brain barrier. The significant protection of striato-nigral integrity and functionality by tangeretin suggests its potential use as a neuroprotective agent.