Taxifolin (5,7,3',4'-flavan-on-ol), also known as dihydroquercetin, belongs to the subclass flavanonols in the

flavonoid Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids ...

s, which in turn is a class of

polyphenol Polyphenols () are a large family of naturally occurring phenols. They are abundant in plants and structurally diverse. Polyphenols include phenolic acids, flavonoids, tannic acid, and ellagitannin, some of which have been used historically as ...

s. It is extracted from plants such as Siberian larch and milk thistle.

Stereocenters

Taxifolin has two

stereocenter In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...

s on the C-ring, as opposed to quercetin which has none. For example, (+)-taxifolin has (2''R'',3''R'')-configuration, making it one out of four stereoisomers that comprise two pairs of

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

Natural occurrences

Taxifolin is found in non-glutinous rice boiled with

adzuki bean ''Vigna angularis'', also known as the , azuki bean, aduki bean, red bean, or red mung bean, is an Annual plant, annual vine widely cultivated throughout East Asia for its small (approximately long) bean. The cultivars most familiar in East A ...

(adzuki-meshi). It can be found in conifers like the

Siberian larch ''Larix sibirica'', the Siberian larch or Russian larch, is a frost-hardy tree native to western Russia, from close to the Finnish border east to the Yenisei valley in central Siberia, where it hybridises with the Dahurian larch ''L. gmelinii ...

, ''Larix sibirica'', in Russia, in ''

Pinus roxburghii ''Pinus roxburghii'', commonly known as chir pine or longleaf Indian pine, is a species of pine tree Native plant, native to the Himalayas. It was named after William Roxburgh. Description ''Pinus roxburghii'' is a large tree reaching with a ...

'', in ''

Cedrus deodara ''Cedrus deodara'', the deodar cedar, Himalayan cedar, or deodar, is a species of cedar native to the Himalayas. Description It is a large evergreen coniferous tree reaching tall, exceptionally with a trunk up to in diameter. It has a conic ...

'' and in the Chinese yew, '' Taxus chinensis var. mairei''. It is also found in the silymarin extract from the milk thistle seeds. Taxifolin is present in

vinegar Vinegar () is an aqueous solution of diluted acetic acid and trace compounds that may include flavorings. Vinegar typically contains from 5% to 18% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting ...

s aged in cherry wood. Taxifolin, and flavonoids in general, can be found in many beverages and products. Specifically, taxifolin is found in plant-based foods like fruit, vegetables, wine, tea, and cocoa.

Pharmacology

Taxifolin is not

mutagenic In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...

and less

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

than the related compound

quercetin Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor ...

. It acts as a potential

chemopreventive Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a cu ...

agent by regulating genes via an ARE-dependent mechanism. Taxifolin has shown to inhibit the ovarian cancer cell growth in a dose-dependent manner. However, in this same study, taxifolin was the least effective flavonoid in the inhibition of VEGF expression. There is also a strong

correlation In statistics, correlation or dependence is any statistical relationship, whether causal or not, between two random variables or bivariate data. Although in the broadest sense, "correlation" may indicate any type of association, in statistics ...

(with a correlation coefficient of 0.93) between the antiproliferative effects of taxifolin derivatives on murine skin

fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...

s and human

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

cells. Taxifolin has shown to have anti-proliferative effects on many types of cancer cells by inhibiting cancer cell lipogenesis. By inhibiting the fatty acid synthase in cancer cells, taxifolin is able to prevent the growth and spread of cancer cells. Taxifolin also stops the effects of overexpression of P-glycoprotein, which prevents the development of chemoresistance. Taxifolin does this via inhibition of rhodamine 123 and doxorubicin. The capacity of taxifolin to stimulate fibril formation and promote stabilization of fibrillar forms of

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

can be used in medicine. Also taxifolin inhibited the cellular melanogenesis as effectively as arbutin, one of the most widely used hypopigmenting agents in cosmetics. Taxifolin also enhances the efficacy of conventional

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

such as

levofloxacin Levofloxacin, sold under the brand name Levaquin among others, is a broad-spectrum antibiotic of the fluoroquinolone drug class. It is the left-handed isomer of the medication ofloxacin. It is used to treat a number of bacterial infections ...

and ceftazidime ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'', which have potential for combinatory therapy of patients infected with methicillin-resistant ''Staphylococcus aureus'' (MRSA). Like other flavonoids, taxifolin is able to function as an antifungal agent by blocking multiple pathways that promote the growth and proliferation of fungi. Taxifolin has also been found to reduce inhibitor of intestinal mobility especially when antagonized by verapamil. Taxifolin has also been shown to be anti-hyperlipidemic by maintaining the normal lipid profile of the liver and keeping lipid excretion at normal levels. Taxifolin prevents hyperlipidemia by reducing the esterification of cellular cholesterol, phospholipid, and triacylglycerol synthesis. Taxifolin, as well as many other flavonoids, has been found to act as a non-selective

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.opioid receptors, albeit with somewhat weak

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

. Taxifolin shows promising pharmacological activities in the management of inflammation, tumors, microbial infections, oxidative stress, cardiovascular, and liver disorders Taxifolin has been found to act as an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the adiponectin receptor 2 (AdipoR2).

Metabolism

The enzyme taxifolin 8-monooxygenase uses taxifolin,

NADH Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require N ...

, H⁺, and O₂ to produce 2,3- dihydrogossypetin, NAD⁺, NADP⁺, and H₂O. The enzyme leucocyanidin oxygenase uses leucocyanidin, alpha-ketoglutarate, and O₂ to produce ''cis''-dihydroquercetin, taxifolin,

succinate Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into Fuma ...

, CO₂, and H₂O.

Glycosides

Astilbin is the 3-''O''- rhamnoside of taxifolin. Taxifolin deoxyhexose can be found in açai fruits. Taxifolin 3-''O''-glucoside isomers have been separated from ''

Chamaecyparis obtusa ''Chamaecyparis obtusa'' (Japanese cypress, hinoki cypress or hinoki; or , ) is a species of cypress native to central Japan in East Asia, and widely cultivated in the temperate climate, temperate northern hemisphere for its high-quality timber ...

''. (-)-2,3-''trans''-Dihydroquercetin-3'-''O''-β-D-glucopyranoside, a taxifolin glucoside has been extracted from the inner bark of ''

Pinus densiflora ''Pinus densiflora'', also called the Japanese red pine, the Japanese pine, or Korean red pine, is a species of pine tree native to East Asia and Siberia. In China, the plant is known as 赤松 (pinyin: chì sōng, literally "red pine"). Distrib ...

'' and can act as an oviposition stimulant in the cerambycid beetle '' Monochamus alternatus''. (2''S'',3''S'')-(-)-Taxifolin-3-''O''-β-D-glucopyranoside has been isolated from the root-sprouts of '' Agrimonia pilosa''. (2''R'',3''R'')-Taxifolin-3'-''O''-β-D-pyranoglucoside has been isolated from the rhizome of '' Smilax glabra''. Minor amount of taxifolin 4′-O-β-glucopyranoiside can be found in red onions. (2''R'',3''R'')-Taxifolin 3-''O''- arabinoside and (2''S'',3''S'')-taxifolin 3-''O''-arabinoside have been isolated from the leaves of '' Trachelospermum jasminoides'' (star jasmine).

Derived natural compounds

Dihydroquercetin
3-O-rhamnoside ( Astilbin) * (+)- Leucocyanidin can be synthesized from taxifolin by

sodium borohydride Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula (sometimes written as ). It is a white crystalline solid, usually encountered as an aqueous basic solution. Sodi ...

reduction.

References

{{Flavanonols Adiponectin receptor agonists Flavanonols Catechols Resorcinols Kappa-opioid receptor antagonists Mu-opioid receptor antagonists 3-Hydroxypropenals Wood extracts