Daidzein (7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) is a naturally occurring compound found exclusively in soybeans and other

legumes A legume () is a plant in the family Fabaceae (or Leguminosae), or the fruit or seed of such a plant. When used as a dry grain, the seed is also called a pulse. Legumes are grown agriculturally, primarily for human consumption, for livestock fo ...

and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones are produced in plants through the

phenylpropanoid pathway The phenylpropanoids are a diverse family of organic compounds that are synthesized by plants from the amino acids phenylalanine and tyrosine. Their name is derived from the six-carbon, aromatic phenyl group and the three-carbon propene tail of ...

of secondary metabolism and are used as signal carriers, and defense responses to pathogenic attacks. In humans, recent research has shown the viability of using daidzein in medicine for

menopausal Menopause, also known as the climacteric, is the time in women's lives when Menstruation, menstrual periods stop permanently, and they are no longer fertility, able to bear children. Menopause usually occurs between the age of 47 and 54. Medic ...

relief,

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

blood cholesterol Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a protein capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence ...

, and lowering the risk of some hormone-related

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s, and

heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

. Despite the known health benefits, the use of both puerarin and daidzein is limited by their poor

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

and low water

solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubil ...

Natural occurrence

Daidzein and other isoflavone compounds, such as

genistein Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen. It was first isolated in 1899 from the dyer's bro ...

, are present in a number of

plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...

s and

herb In general use, herbs are a widely distributed and widespread group of plants, excluding vegetables and other plants consumed for macronutrients, with savory or aromatic properties that are used for flavoring and garnishing food, for medicinal ...

s like kwao krua (''

Pueraria mirifica ''Pueraria mirifica'', also known as กวาวเครือ Kwao Krua (among other names), is a plant found in northern and north eastern Thailand and Myanmar. In Thailand, the plant is known as “Kwao Krua Kao”, the 'Kao' meaning white ...

'') and

kudzu Kudzu (; also called Japanese arrowroot or Chinese arrowroot) is a group of climbing, coiling, and trailing deciduous perennial vines native to much of East Asia, Southeast Asia, and some Pacific islands, but invasive species, invasive in many ...

. It can also be found in ''

Maackia amurensis ''Maackia amurensis'', commonly known as the Amur maackia, is a species of tree in the family Fabaceae that can grow 15 metres (49 ft) tall. The species epithet and common names are from the Amur River region, where the tree originated; it o ...

'' cell cultures. Daidzein can be found in food such as

soybean The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu an ...

s and soy products like

tofu Tofu (), also known as bean curd in English, is a food prepared by coagulating soy milk and then pressing the resulting curds into solid white blocks of varying softness; it can be ''silken'', ''soft'', ''firm'', ''extra firm'' or ''super firm ...

and

textured vegetable protein Textured or texturized vegetable protein (TVP), also known as textured soy protein (TSP), soy meat, or soya chunks is a defatted soy flour product, a by-product of extracting soybean oil. It is often used as a meat analogue or meat extender. I ...

. Soy isoflavones are a group of compounds found in and isolated from the soybean. Of note, total isoflavones in soybeans are—in general—37 percent daidzein, 57 percent genistein and 6 percent

glycitein Glycitein is an O-methylated isoflavone which accounts for 5-10% of the total isoflavones in soy food products. Glycitein is a phytoestrogen A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine sy ...

, according to

USDA The United States Department of Agriculture (USDA) is the federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, and food. It aims to meet the needs of com ...

data. Soy germ contains 41.7 percent daidzein.

Biosynthesis

History

The

isoflavonoid Isoflavonoids are a class of flavonoid phenolic compounds, many of which are biologically active. Isoflavonoids and their derivatives are sometimes referred to as phytoestrogens, as many isoflavonoid compounds have biological effects via the estro ...

pathway has long been studied because of its prevalence in a wide variety of plant species, including as pigmentation in many flowers, as well as serving as signals in plants and microbes. The isoflavone synthase (IFS) enzyme was suggested to be a P-450 oxygenase family, and this was confirmed by Shinichi Ayabe's laboratory in 1999. IFS exists in two isoforms that can use both

liquiritigenin Liquiritigenin is a flavanone that was isolated from ''Glycyrrhiza uralensis'', and is found in a variety of plants, including ''Glycyrrhiza glabra'' (licorice). It is an estrogenic compound which acts as a selective agonist of the ERβ subtype ...

and

naringenin Naringenin is a flavorless, colorless flavanone, a type of flavonoid. It is the predominant flavanone in grapefruit, and is found in a variety of fruits and herbs. Structure Naringenin has the skeleton structure of a flavanone with three hyd ...

to give daidzein and

respectively.

Pathway

Daidzein is an isoflavonoid derived from the

shikimate pathway The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) ...

that forms an oxygen containing heterocycle through a cytochrome P-450-dependent enzyme that is

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 NAD ...

dependent. The biosynthesis of daidzein begins with L-phenylalanine and undergoes a general phenylpropanoid pathway where the shikimate derived aromatic ring is shifted to the adjacent carbon of the heterocycle. The process begins with phenylalanine ligase (PAL) cleaving the amino group from L-Phe forming the unsaturated carboxylic acid,

cinnamic acid Cinnamic acid is an organic compound with the formula C6H5-CH=CH- COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxylic acid, it occurs n ...

. Cinnamic acid is then hydroxylated by membrane protein cinnamate-4-hydroxylase (C4H) to form p-coumaric acid. P-coumaric acid then acts as the starter unit which gets loaded with

coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...

by 4-coumaroyl:CoA-ligase (4CL). The starter unit (A) then undergoes three iterations of

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and commi ...

resulting in (B), which enzymes

chalcone synthase Chalcone synthase or naringenin-chalcone synthase (CHS) is an enzyme ubiquitous to higher plants and belongs to a family of polyketide synthase enzymes (PKS) known as type III PKS. Type III PKSs are associated with the production of chalcones, a ...

(CHS) and chalcone reductase (CHR) modify to obtain trihydroxychalcone. CHR is NADPH dependent.

Chalcone isomerase In enzymology, a chalcone isomerase () is an enzyme that catalyzes the chemical reaction :a chalcone \rightleftharpoons a flavanone Hence, this enzyme has one substrate, a chalcone, and one product, a flavanone. This enzyme belongs to the ...

(CHI) then isomerizes trihydroxychalcone to

, the precursor to daidzein. A radical mechanism has been proposed in order to obtain daidzein from liquiritigenin, where an iron-containing enzyme, as well as NADPH and oxygen cofactors are used by a 2-hydroxyisoflavone synthase to oxidize liquiritigenin to a radical intermediate (C). A 1,2 aryl migration follows to form (D), which is subsequently oxidized to (E). Lastly, dehydration of the hydroxy group on C2 occurs through a 2-hydroxyisoflavanone dehydratase (specifically '' GmHID1'') to give daidzein. Daidzein v2

Research

Daidzein 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 ago ...

of the

GPER G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the ''GPER'' gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible ...

(GPR30).

Pathogen interactions

Because daidzein is a defensive factor, ''

Pseudomonas syringae ''Pseudomonas syringae'' is a rod-shaped, Gram-negative bacterium with polar flagella. As a plant pathogen, it can infect a wide range of species, and exists as over 50 different pathovars, all of which are available to researchers from internat ...

'' produces the HopZ1b effector which degrades a ''GmHID1'' product.

Derivatives

Glyceollin Glyceollins are a family of prenylated pterocarpans found in ineffective types of nodule in soybean in response to symbiotic infection. It possesses two chiral centers and can be asymmetrically synthesized chemically at a gram level scale. Mol ...

, a type of

phytoalexin Phytoalexins are antimicrobial substances, some of which are antioxidative as well. They are defined, not by their having any particular chemical structure or character, but by the fact that they are defensively synthesized ''de novo'' by plants t ...

Glycosides

Daidzin Daidzin is a natural organic compound in the class of phytochemicals known as isoflavones. Daidzin can be found in Japanese plant kudzu (''Pueraria lobata'', Fabaceae) and from soybean leaves. Daidzin is the 7-O-glucoside A glucoside is a gly ...

is the 7-O-

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 o ...

of daidzein. *

Puerarin Puerarin, one of several known isoflavones, is found in a number of plants and herbs, such as the root of '' Pueraria'' (''Radix puerariae'') notably of the kudzu plant. Puerarin is the 8-''C''-glucoside A glucoside is a glycoside that is der ...

is the 8-C-glucoside of daidzein.

Plants containing daidzein

* ''Maackia amurensis'' * ''Pueraria montana'' var. ''lobata'''''' * ''

Pueraria thomsonii ''Pueraria'' is a genus of 15–20 species of legumes native to Asia. The best known member is kudzu, also called Japanese arrowroot. The genus is named after 19th century Swiss botanist Marc Nicolas Puerari. The genus, as traditionally circum ...

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...

, titlestyle = background:#ccccff , list1 = {{Estrogen receptor modulators {{Estrogen-related receptor modulators {{Glycine receptor modulators {{PPAR modulators 3α-Hydroxysteroid dehydrogenase inhibitors Isoflavones Glycine receptor antagonists GPER agonists Phytoestrogens Selective ERβ agonists