Tangerines and Tangeretin: The Appeal Is in the Peel

Tangerines and Tangeretin: The Appeal Is in the Peel

Tangerines are a citrus fruit that are smaller and sweeter than oranges. Named for Tangier, Morocco, where they were once sourced, the fruit is an excellent source of vitamin C and fiber. The frequently discarded peel of citrus fruit is known for its beneficial bioflavonoid content. Tangerine peel contains a significant amount of the polymethoxy flavonoid tangeretin, which has antioxidant and other beneficial effects in the body.

Researchers have studied tangeretin in cells, animals and humans. We will explore some of their findings.

Heath Benefits of Tangeretin

Tangeretin has been investigated regarding potential benefits in a number of health areas. In a mouse model of bone loss, tangeretin suppressed the formation of osteoclasts (which absorb bone tissue) induced by an inflammatory compound.1 Research in rodents has also shown effects against asthma.2 And in rats with chronic kidney disease, tangeretin’s antioxidant and anti-inflammatory effects improved renal function, as well as memory and cognitive impairments.3

In hamsters with diet-induced high cholesterol levels, polymethoxylated flavones that included tangeretin were associated with a reduction in serum total and very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol.4 In human liver cells, tangeretin reduced apolipoprotein B, cholesterol and triglyceride synthesis.5 Other research has shown that tangeretin significantly inhibited proliferation and migration of rat aortic smooth muscle cells without inducing cell death.6 This finding indicates a potential use for tangeretin in the prevention and treatment of vascular diseases, including atherosclerosis. Tangeretin has also shown an ability to inhibit platelet adhesion and clot formation.7

Other data show that tangeretin can increase uptake of glucose in mouse fat cells via three pathways, which might explain the antidiabetic effect of this type of flavonoid.8 More research involving fat cells has found that tangeretin increased the secretion of adiponectin (an insulin-sensitizing factor), while decreasing insulin-resistance factor MCP1.9 In diabetic rats, tangeretin lowered glucose and hemoglobin A1c while helping normalize the activity of enzymes involved in carbohydrate metabolism, with effects comparable to that of antidiabetic drug glibenclamide.10 In vitro and in mice, tangeretin was found to exert antidiabetic effects through activation of AMPK, an enzyme found in every cell of the body that decreases with aging.11 AMPK promotes healthy cellular metabolism and encourages the body to burn stored abdominal fat. Tangeretin was also shown to inhibit the formation of new fat cells.12

Like many flavonoids, tangeretin has shown anticancer effects. In 1991, it was discovered that, of all citrus flavonoids tested, tangeretin had the greatest inhibitory effect against tumor invasion.13 In human squamous cell carcinoma, tangeretin inhibited cell growth five and seven days after treatment at all concentrations tested, while two other flavonoids showed no effect.14 In human leukemia cells, tangeretin induced apoptosis (programmed cell death), with no toxicity in normal white blood cells.15

Tangeretin also showed antiproliferative activity against human lung carcinoma, mouse melanoma, human T-cell leukemia, and human gastric cancer cells that was at least 10 times of that exerted against normal cell lines.16 In addition, tangeretin can inhibit growth of human colorectal carcinoma cells by blocking cell cycle progression.17 An ability to inhibit mutagenesis and metastasis are other anticancer mechanisms attributed to tangeretin.18 In an animal model of lung metastatic melanoma, tangeretin lowered the percentage of three indexes of metastasis in comparison with a control substance.19

“There are two general approaches to the use of flavonoids or other polyphenols as cancer chemopreventive agents,” Thomas Walle writes in an article titled, Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? “One is to choose diets rich in such compounds, including verification of their possible effectiveness followed by attempts to deduce potential mechanisms . . . The other more common and simplest approach is to identify dietary components with potential cancer chemopreventive properties through testing of individual compounds first in vitro and then in vivo. The ultimate goal here is to arrive at food supplements, which may serve to reinforce the dietary contribution.”20

Unique and Synergistic Properties

Unlike many compounds, tangeretin can cross the blood-brain barrier to exert its effects in the brain. In a rat model of Parkinson’s disease in which the disease was induced by injection of a neurotoxin, tangeretin helped protect against loss of brain cells involved in the production of dopamine and decrease in brain striatal dopamine content, suggesting its potential use as a neuroprotective agent.21 Another study involving a rat model of the disease resulted in improved motor function and cognition and a reduction in memory impairment in animals treated with tangeretin. Tangeretin-treated animals experienced protection against dopaminergic degeneration and hippocampal neuron loss, and had lower expression of inflammatory mediators and cytokines.22 In a study that evaluated the effects of tangerine peel extract or a combination of the flavonoids tangeretin, hesperidin and nobiletin, both inhibited inflammation induced by lipopolysaccharide administration in cultured microglia cells (which are the primary immune cells of the central nervous system), leading the authors of the report to conclude that tangerine peel possesses a potent anti-neuroinflammatory capacity.23 Research has also uncovered potent antioxidant effects for tangeretin in microglia.24

A Fruitful Future for Tangeretin

Tangeretin has been shown to: decrease cholinergic deficits; reduce the abnormal accumulation of amyloid-beta; reverse N-methyl- D-aspartate receptor hypofunction; improve ischemic injury; inhibit hyperphosphorylation of tau protein; and more, according to N. Braidy and colleagues in the journal CNS & Neurological Disorders Drug Targets. The authors suggest that “tangeretin and other citrus flavonoids could represent beneficial drug candidates for the treatment and prevention of Alzheimer's and Parkinson's disease.”25 Future research will add evidence to these and other potential targeted uses for tangeretin.

The chemical structure of tangeretin indicates potential for superior oral bioavailability.26 Research in mice has shown that tangeretin does not adversely affect the function of major organs.27 Women treated with the drug tamoxifen for cancer should avoid supplementing with tangeretin.28

References

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  18. Calomme M et al. Planta Med. 1996 Jun;62(3):222-6.
  19. Conesa DM et al. J Agric Food Chem. 2005 Aug 24;53(17):6791-7.
  20. Walle T et al. Semin Cancer Biol. 2007 Oct;17(5):354-62.
  21. Datla KP et al. Neuroreport. 2001 Dec 4;12(17):3871-5.
  22. Yang JS et al. Inflammopharmacology. 2017 Aug;25(4):471-484.
  23. Ho SC et al. Food Chem Toxicol. 2014 Sep;71:176-82.
  24. Lee et al. J Neuroimmune Pharmacol. 2016 Jun;11(2):294-305
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  27. In Vivo. 2005 Jan-Feb;19(1):103-7.
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