Methoxylated Flavones
OTHER NAME(S): 5-Methyl-7-Methoxy Isoflavone, Bioflavonoid, Bioflavonoïde, Bioflavonoid Complex, Bioflavonoid Concentrate, Bioflavonoid Extract, Citrus Bioflavones, Citrus Bioflavonoid Extract, Citrus Bioflavonoid, Citrus Bioflavonoids, Citrus Flavones, Citrus Flavonoids, Citrus Polymethoxylated Flavones, Complexe de Bioflavonoïde, Concentré de Bioflavonoïde, Extrait de Bioflavonoïde, Flavonoids, Flavonoïdes, Flavonoïdes Méthoxylés, Gardenin D, Heptamethoxyflavones, Hexamethoxyflavones, Methoxyflavones, Méthoxyflavones, Methoxylated flavonoids, Nobiletin, Nobilétine, Pentamethoxyflavones, PMF, Polyméthoxyflavones, Polymethoxylated Flavones, Sinensetin, Sinensétine, Tangeretin, Tangerétine, Tetramethoxyflavones, 5,6,7,8,4'-pentamethoxyflavone, Tangeretin, 5,6,7,3',4'-pentamethoxyflavone, Sinensetin, 5,6,7,8,3',4'-hexamethoxyflavone, nobiletin, 3,5,6,7,8,3',4'-heptamethoxyflavone, heptamethoxyflavone, Bioflavonoids, Bioflavonoids, Bioflavonoids, Bioflavonoids, Flavonoid, 5-Methyl-7-Methoxy-Isoflavone, Polymethoxylated Flavonoids, 5-methyl 7-methoxy isoflavone, 5-Methyl-7-Methoxyflavone, Flavonas Metoxiladas, Flavones Méthoxylées
Overview
Flavonoids are pigments found in plants. They are responsible for many of the yellow, red, and orange colors in plants. Flavonoids are divided into groups based on slight differences in chemical structure. Flavones are one of the groups. Methoxylated flavones are a subdivision of that group. Methoxylated flavones are found in especially large amounts in citrus fruits.
Over 4000 different flavonoids have been identified from various plant sources. Common food sources include red wine, stems, flowers, fruits, vegetables, nuts, seeds, herbs, spices, coffee, and teas.
Methoxylated flavones are used for poor circulation in the legs (venous insufficiency), varicose veins (enlarged veins that appear on the skin), heart disease, high cholesterol, cataracts, cancer, and other conditions, but there is no good scientific research to support any of these uses.
Methoxylated flavones are natural antioxidants and might reduce inflammation (swelling). They might also affect the way the liver processes cholesterol and other blood fats. Scientists think methoxylated flavones might also reduce the spread of cancer cells. But more information is needed.
Methoxylated flavones are natural antioxidants and might reduce inflammation (swelling). They might also affect the way the liver processes cholesterol and other blood fats. Scientists think methoxylated flavones might also reduce the spread of cancer cells. But more information is needed.
Uses
Insufficient Evidence for
- Poor circulation that can cause the legs to swell (chronic venous insufficiency or CVI).
- Varicose veins.
- Heart disease.
- High cholesterol.
- Cataracts.
- Cancer.
- Other conditions.
More evidence is needed to rate the effectiveness of methoxylated flavones for these uses.
Side Effects
When taken by mouth: Methoxylated flavones are a normal part of the diet. They are LIKELY SAFE when consumed as part of food. But there isn't enough reliable information to know if it is safe to take methoxylated flavones in amounts greater than those commonly found in food.
Precautions
When taken by mouth: Methoxylated flavones are a normal part of the diet. They are LIKELY SAFE when consumed as part of food. But there isn't enough reliable information to know if it is safe to take methoxylated flavones in amounts greater than those commonly found in food.
Pregnancy and breast-feeding: Methoxylated flavones are LIKLEY SAFE for pregnant and breast-feeding women when used as part of the diet. But there isn't enough reliable information to know if methoxylated flavones are safe to use in amounts greater than those commonly found in foods when pregnant or breast-feeding. Stay on the safe side and stick to food amounts.
Surgery: Methoxylated flavones can slow blood clotting. There is some concern that they might increase the risk of bleeding during and after surgery. Stop taking methoxylated flavones supplements at least 2 weeks before a scheduled surgery.
Interactions
Moderate Interaction
Be cautious with this combination
- Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates) interacts with Methoxylated FlavonesSome medications are changed and broken down by the liver. Methoxylated flavones might increase how quickly the liver breaks down some medications. Taking methoxylated flavones along with some medications that are changed by the liver might decrease the effects of some medications. Before taking methoxylated flavones, talk to your healthcare provider if you take any medications that are changed by the liver. Some of these medications that are changed by the liver include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), and others.
- Medications moved by pumps in cells (P-Glycoprotein substrates) interacts with Methoxylated FlavonesSome medications are moved by pumps in cells. Some methoxylated flavones might change how these pumps work and increase how much of some medications get absorbed by the body. Some medications that are moved by these pumps include etoposide, paclitaxel, vinblastine, vincristine, vindesine, ketoconazole, itraconazole, amprenavir, indinavir, nelfinavir, saquinavir, cimetidine, ranitidine, diltiazem, verapamil, corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.
- Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs) interacts with Methoxylated FlavonesSome methoxylated flavones might slow blood clotting. Taking methoxylated flavones along with medications that also slow clotting might increase the chances of bruising and bleeding. Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
- Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) interacts with Methoxylated FlavonesSome medications are changed and broken down by the liver. Methoxylated flavones might decrease how quickly the liver breaks down some medications. Taking methoxylated flavones along with some medications that are changed by the liver might increase the effects and side effects of some medications. Before taking methoxylated flavones, talk to your healthcare provider if you take any medications that are changed by the liver. Some medications changed by the liver include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), and many others.
- Medications moved by pumps in cells (Organic anion-transporting polypeptide substrates) interacts with Methoxylated FlavonesSome medications are moved in and out of cells by pumps. Methoxylated flavones might change how these pumps work and change how much medication stays in the body. In some cases, this might change the effects and side effects of a medication.
Dosing
The appropriate dose of methoxylated flavones depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for methoxylated flavones. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.
References
- Middleton E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000;52:673-751.
- Robbins RC. Effect of methoxylated flavones on erythrocyte aggregation and sedimentation in blood of normal subjects: Evidence of a dietary role for flavonoids. Internat J Vit Nutr Res 1973;43:494-503.
- Robbins RC. Stabilization of flow properties of blood with phenylbenzo-y-pyrone derivatives (Flavonoids). Internat J Vit Nutr Res 1977;47:373-82.
- Robbins RC. Action in human blood of methoxylated flavones which confer disease resistance on both plants and animals: Concept of a dietary conditioned mechanism of defense against disease. Internat J Vit Nutr Res 1975;45:51-60.
- Robbins RC. Specificities between blood cell adhesion in human diseases and antiadhesion action in vitro of methoxylated flavones. J Clin Pharmacol 1973;13:401-7.
- Robbins RC. In vitro effects of penta-, hexa-, and hepta-methoxylated flavones on aggregation of cells in blood from hospitalized patients. J Clin Pharmacol 1973;13:271-5.
- Manthey JA, Guthrie N. Antiproliferative effects of citrus flavonoids against six human cancer cell lines. J Agric Food Chem 2002;50:5837-43.
- Kurowska EM, Manthey JA. Hypolipidemic Effects and Absorption of Citrus Polymethoxylated Flavones in Hamsters with Diet-Induced Hypercholesterolemia. J Agric Food Chem 2004;52:2879-86.
- Takanaga H, Ohnishi A, Yamada S, et al. Polymethoxylated flavones in orange juice are inhibitors of P-glycoprotein but not cytochrome P450 3A4. J Pharmacol Exp Ther 2000;293:230-6.
- Manthey JA, Cesar TB, Jackson E, Mertens-Talcott S. Pharmacokinetic study of nobiletin and tangeretin in rat serum by high-performance liquid chromatography-electrospray ionization-mass spectrometry. J Agric Food Chem 2011;59(1):145-51.
- Ayatollahi AM, Ghanadian M, Att-Ur-Rahman R, Mesaik MA, Khalid AS, Adeli F. Methoxylated flavones from Salvia Mirzayanii Rech. f. and Esfand with immunosuppressive properties. Iran J Pharm Res 2015;14(3):955-60.
- Wudtiwai B, Sripanidkulchai B, Kongtawelert P, Banjerdpongchai R. Methoxyflavone derivatives modulate the effect of TRAIL-induced apoptosis in human leukemic cell lines. J Hematol Oncol 2011;4:52.
- Feng SL, Yuan ZW, Yao XJ, et al. Tangeretin, a citrus pentamethoxyflavone, antagonizes ABCB1-mediated multidrug resistance by inhibiting its transport function. Pharmacol Res 2016;110:193-204.
- Duan L, Dou LL, Yu KY, et al. Polymethoxyflavones in peel of Citrus reticulata 'Chachi' and their biological activities. Food Chem. 2017 Nov 1;234:254-261.
- Seo SH, Lee YC, Moon HI. Acetyl-cholinesterase Inhibitory Activity of Methoxyflavones Isolated from Kaempferia parviflora. Nat Prod Commun. 2017 Jan;12(1):21-22.
- Li Y, Ning J, Wang Y, et al. Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
- Surichan S, Arroo RR, Tsatsakis AM, Androutsopoulos VP. Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1-mediated metabolism to the product 4' hydroxy tangeretin. Toxicol In Vitro. 2018 Aug;50:274-284.
- Hamada Y, Nakajima M, Tsuzuki K, et al. Heptamethoxyflavone Reduces Phosphodiesterase Activity and T-Cell Growth in vitro. Int Arch Allergy Immunol. 2017;174(3-4):113-120.
- Yoshizaki N, Hashizume R, Masaki H. A polymethoxyflavone mixture extracted from orange peels, mainly containing nobiletin, 3,3',4',5,6,7,8-heptamethoxyflavone and tangeretin, suppresses melanogenesis through the acidification of cell organelles, including melanosomes. J Dermatol Sci. 2017 Oct;88(1):78-84.
- Wang H, Dong L, Qu F, et al. Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism. Pharm Biol. 2020 Dec;58(1):352-356.
- Bajraktari-Sylejmani G, Weiss J. Potential risk of food-drug interactions: Citrus polymethoxyflavones and flavanones as inhibitors of the organic anion transporting polypeptides (OATP) 1B1, 1B3, and 2B1. Eur J Drug Metab Pharmacokinet. 2020;45(6):809-815.
