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

flavanonol The flavanonols (with two "o"s a.k.a. 3-hydroxyflavanone or 2,3-dihydroflavonol) are a class of flavonoids that use the 3-hydroxy-2,3-dihydro-2-phenylchromen-4-one (IUPAC name) backbone. Some examples include: * Taxifolin (or Dihydroquercetin) * ...

s 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 organic compounds characterized by multiples of phenol units. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some ...

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 c ...

s on the C-ring, as opposed to quercetin which has none. For example, (+)-taxifolin has (2R,3R)-configuration, making it 1 out of 4

stereoisomers In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms ...

that comprise 2 pairs of

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...

Natural occurrences

Taxifolin is found in non-glutinous rice boiled with adzuki bean (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 to the Himalayas. It was named after William Roxburgh. Description ''Pinus roxburghii'' is a large tree reaching with a trunk diameter ...

'', 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 Silibinin ( INN), also known as silybin (both from ''Silybum'', the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of f ...

extract from the milk thistle seeds. Taxifolin is present in

vinegar Vinegar is an aqueous solution of acetic acid and trace compounds that may include flavorings. Vinegar typically contains 5–8% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting simple sugars to eth ...

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 i ...

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 sub ...

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 to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

agent by regulating genes via an ARE-dependent mechanism. Taxifolin has shown to inhibit the

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

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 statistic ...

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

fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...

s and human

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...

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.Das, A.; Baidya, R.; Chakraborty, T.; Samanta, A. K.; Roy, S. Pharmacological basis and new insights of taxifolin: A comprehensive review. ''Biomedicine & Pharmacotherapy'' 2021'', 142'', 17. 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 found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...

can be used in medicine. Also taxifolin inhibited the cellular

melanogenesis Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hear ...

as effectively as

arbutin Arbutin is a glycoside; a glycosylated hydroquinone extracted from the bearberry plant in the genus ''Arctostaphylos'' among many other medicinal plants, primarily in the family Ericaceae. Applied topically, it inhibits tyrosinase and thus prev ...

, one of the most widely used hypopigmenting agents in cosmetics. However, arbutin acts as quercetin extremely mutagenic,

carcinogenic A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...

and toxic. 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 bacterial infections, and antibiotic medications are widely used in the treatment and preventio ...

levofloxacin Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori (in combination with other medications), ...

and

ceftazidime Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, ...

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

'', which have potential for combinatory therapy of patients infected with methicillin-resistant ''Staphylococcus aureus'' (MRSA). Taxifolin can act as an anti-flammant because of its ability to inhibit the synthesis of cyclooxygenase by blocking prostaglandin synthesis. Cyclooxygenases converts to prostaglandin precursors. Saftar Asmi, K., et al. “Therapeutic Aspects of Taxifolin – An Update.” Therapeutic Aspects of Taxifolin – An Update - Journal of Advanced Pharmacy Education and Research, SPER Publications and Solutions Pvt. Ltd., 2017, https://japer.in/article/therapeutic-aspects-of-taxifolin-an-update. 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 chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

of the

opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin ...

s, albeit with somewhat weak affinity. 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 to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

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 aden ...

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 NA ...

, H⁺, and O₂ to produce 2,3- dihydrogossypetin, NAD⁺, NADP⁺, and H₂O. The enzyme

leucocyanidin oxygenase In enzymology, a leucocyanidin oxygenase () is an enzyme that catalyzes the chemical reaction :leucocyanidin + 2-oxoglutarate + O2 \rightleftharpoons cis- and trans-dihydroquercetins + succinate + CO2 + 2 H2O The 3 substrates of this enzyme are ...

uses

leucocyanidin Leucocyanidin is a colorless chemical compound that is a member of the class of natural products known as leucoanthocyanidins. Chemistry (+)-Leucocyanidin can be synthesized from (+)- dihydroquercetin by reduction with sodium borohydride. Mol ...

, alpha-ketoglutarate, and O₂ to produce ''cis''-dihydroquercetin, taxifolin,

succinate Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

, CO₂, and H₂O.

Glycosides

Astilbin Astilbin is a flavanonol, a type of flavonoid. Astilbin is the (2R-trans)-isomer; neoisoastilbin is the (2S-cis)-isomer and isoastilbin is the (2R-cis)-isomer. Natural occurrences Astilbin can be found in Hypericum perforatum, St John's wort ('' ...

is the 3-''O''-

rhamnoside Rhamnose (Rha, Rham) is a naturally occurring deoxy sugar. It can be classified as either a methyl-pentose or a 6-deoxy-hexose. Rhamnose predominantly occurs in nature in its L-form, L-form as L-rhamnose (6-deoxy-L-mannose). This is unusual, since ...

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; ja, 檜 or , ) is a species of cypress native to central Japan in East Asia, and widely cultivated in the temperate northern hemisphere for its high-quality timber and or ...

''. (-)-2,3-''trans''-Dihydroquercetin-3'-''O''-β-D-glucopyranoside, a taxifolin

glucoside A glucoside is a glycoside that is derived from glucose. Glucosides are common in plants, but rare in animals. Glucose is produced when a glucoside is hydrolysed by purely chemical means, or decomposed by fermentation or enzymes. The name was ...

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. Distribution and habitat ''P. densiflora'' has a home range that includes Japan, the Korean Peninsula, ...

'' 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 onion Red onions (also known as purple or blue onions in some mainland European countries, though not the UK) are cultivars of the onion ('' Allium cepa''), and have purplish-red skin and white flesh tinged with red. They are most commonly used in c ...

s. (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 ''Trachelospermum jasminoides'' is a species of flowering plant in the family Apocynaceae, native to eastern and southeastern Asia (Japan, Korea, southern China and Vietnam).Flora of China''Trachelospermum jasminoides''/ref> Common names include ...

'' (star jasmine).

Derived natural compounds

* Dihydroquercetin-3-O-rhamnoside (

) * (+)-

Leucocyanidin Leucocyanidin is a colorless chemical compound that is a member of the class of natural products known as leucoanthocyanidins. Chemistry (+)-Leucocyanidin can be synthesized from (+)- dihydroquercetin by reduction with sodium borohydride. Mol ...

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 Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds applica ...

reduction.

References

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