Identification
- Summary
Isoflavone is a biologically active phytoestrogen found in high concentrations in soy and other legumes.
- Generic Name
- Isoflavone
- DrugBank Accession Number
- DB12007
- Background
Isoflavone is a soy phytoestrogen and a biologically active component of several agriculturally important legumes such as soy, peanut, green peas, chick peas and alfalfa 4. Soybean is an exceptionally rich source of dietary isoflavones, where the average isoflavone content is 1-2 mg/gram 4. The main soy isoflavones are mostly present in glycosylated forms and include Genistein, Daidzein, and glycitein, which accounts for approximately 50%, 40%, and 10%, respectively, of the total soybean isoflavone content 1. The clinical benefits of soy proteins have been studied and demonstrated for many years, with some evidence of soy products associated with a reduced incidences of coronary heart disease, atherosclerosis, type II diabetes mellitus, and breast and prostate cancer 2. While existing data are consistent or inadequate in supporting most of the suggested health benefits of consuming soy proteins and isoflavones 2, the trials investigating isoflavone as a potential treatment for atrophy, menopause, and postmenopausal symptoms are ongoing. Isoflavone is found as one of constituents in oral over-the-counter dietary supplements indicated for improved bone mass density and body fat regulation.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Isoflavone (DB12007)
- Weight
- Average: 222.243
Monoisotopic: 222.068079562 - Chemical Formula
- C15H10O2
- Synonyms
- 3-phenyl-4H-1-benzopyran-4-one
- 3-Phenylchromone
- Isoflavon
- External IDs
- NSC-135405
Pharmacology
- Indication
Indicated for over-the-counter use as a dietary supplement for increasing bone density and regulating blood fat.
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- Contraindications & Blackbox Warnings
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Isolated soy protein with isoflavones was shown to decrease LDL cholesterol levels in randomized trials assessed by the American Heart Association 2. In a study of postmenopausal women, daily dietary intake of 101 mg of aglycone isoflavones (indicating Genistein and Daidzein) was associated with lowered LDL cholesterol and apolipoprotein B levels by 8% and reduced systolic and diastolic blood pressure by 6.8% in hypertensive women 2. In a meta-analysis of randomized controlled trials of menopausal women, soy isoflavones attenuated bone loss of the spine and decreased the levels of deoxypyridinoline, a bone resorption marker, while increasing serum bone-specific alkaline phosphatase, a bone formation marker 2. The findings from studies investigating the effects of soy consumption on menopausal symptoms, breast cancer, and prostate cancer remain somewhat controversial and inconclusive. Consumption of soy isoflavones may decrease the markers of cancer development and progression in prostate cells, including prostate-specific antigen (PSA), testosterone, and androgen receptor in patients with prostate cancer but not in normal subjects 2. Although epidemiologic data in Asian women demonstrate that high soy food intake is associated with protection against breast cancer, soy foods have little effect on intermediary markers of breast cancer risk and postmenopausal soy intake may not reduce the risk of developing breast cancer 1. However, preliminary studies show that soy food intake reduces tumor recurrence in breast cancer patients 1. Soy isoflavones reported to interfere with thyroid peroxidase, which are involved in the production of thyroid hormones 4.
- Mechanism of action
Isoflavones are selective estrogen receptor modulators that exert estrogenic-like effects under certain experimental conditions 1, as they are structurally similar to mammalian 17β-estradiol. They may bind to both α and β isoforms of estrogen receptor (ER), but with binding affinities to ERβ approximately 20 times higher than that to ERα 2. The role of isoflavones on estrogen-dependent cancer has been studied, since they may mediate antiestrogenic actions by blocking the binding of endogenous estrogens and their receptor signalling 3. In cell culture, Genistein inhibited the proliferation of MDA-MB-231 human breast cancer cells, probably by arresting the cell cycle progression at the G2–M transition 3. In addition, genistein was shown to induce apoptosis, modify eicosanoid metabolism, and inhibit angiogenesis 3. There is an evidence that soy isoflavones may act on androgen receptors to inhibit tyrosine kinase activity, thereby blocking the growth and proliferation of cancer cells 3.
Isoflavones may not significantly contribute to the hypolipidemic effects of soy protein, but may exert coronary benefits by improving endothelial function; in clinical trials of postmenopausal women, isoflavones improved flow-mediated dilation in women with impaired endothelial function 1. Some observational data suggests that isoflavones improve endothelial function by increasing the number of circulating endothelial progenitor cells, which replace damaged endothelial cells 1. Isoflavone may modulate the key transcription factors involved in the regulation of lipid metabolism by acting on the peroxisome proliferator-activated receptors (PPAR) alpha and gamma, which are receptors that regulate the transcription of genes involved in lipid and glucose homeostasis and lipid metabolism 3. Multiple biological actions of isoflavones, such as favorable effect on the blood lipid profile and inhibition of LDL cholesterol oxidation, may lead to cardio protective effects 3.
Genistein has been shown to have antioxidant properties on hydrogen peroxide production in vitro and blocks the formation of oxygen free radicals 3. Studies also suggest that at micromolar concentrations, genistein increases glucose-stimulated insulin secretion in cell lines and mouse pancreatic islets via a cAMP-dependent protein kinase mechanism 3. Based on the findings of experimental studies, genistein may exert a positive effect on bone formation by decreasing osteoclastic resorption factor, such as collagen C-telopeptide, and increasing osteoblastic formation markers, such as bone-alkaline phosphatase 3. In vitro, it antagonized the catabolic effects of parathyroid hormone (PTH) in osteoblasts by reversing the PTH-induced increase in soluble receptor activator of nuclear factor-xB ligand and decrease in osteoprotegerin expression 3.
Target Actions Organism UPeroxisome proliferator-activated receptor alpha agonistHumans UPeroxisome proliferator-activated receptor gamma agonistHumans - Absorption
Following oral ingestion, serum isoflavone concentrations increase in a dose-dependent manner 1. Isoflavones are metabolized by gut microflora, where they need to undergo deglycosylation in order to be absorbed in the intestine 4. After oral ingestion, glycosylated isoflavones are rapidly deglycosylated, absorbed and metabolized in intestinal enterocytes and liver, entering the systemic circulation predominantly as conjugates with limited bioavailability 4. In humans, the mean time to reach peak plasma concentrations (Tmax) for conjugated and unconjugated genistein and daidzein are approximately 5-6 and 6-8 hours, respectively 4.
- Volume of distribution
Isoflavones are readily distributed to all tissues, and they are known to cross the placental barrier and blood brain barrier 4. They are also distributed to the extra-vascular compartments. In a human study, the volume of distribution of daidzein and genistein were 336.25 L and 258.76 L, respectively 4.
- Protein binding
No pharmacokinetic data available.
- Metabolism
The conversion of glycosylated isoflavones to de glycosylated isoflavones begins in the oral cavity, wherein oral microflora and oral epithelium exhibit β-glucosidase activity 4. Further conversion is mediated by intestinal lactase phlorizin hydrolase on the luminal side of the intestinal brush border to form aglycones that diffuses into the enterocytes 4. The glycosylated isoflavones may also be converted to aglycone in the large intestines by the resident intestinal microflora. Isoflavone aglycones that enter the intestinal cell via passive diffusion are rapidly conjugated into sulfate or glucuronide conjugates 4.
Under the anaerobic, reductive conditions of the colon, genistein undergoes reduction to form dihydrogenistein and further to 5-hydroxyequol, while daidzein is reduced to dihydrodaidzein and equol 4. Microbial cleavage of the Ring-C of isoflavones produces deoxybenzoin metabolites (DOBs), which retains similar biological activity as unchanged isoflavones and are passively absorbed 4. There is a large interindividual variation in isoflavone metabolism, leading to circulating concentrations of isoflavone metabolites and parent isoflavones varying up to hundreds-fold 1. About 25% of the non-Asian and 50% of the Asian population host the intestinal bacteria that convert the daidzein into the isoflavonoid equol, which is a beneficial isoflavonoid 1.
- Route of elimination
Renal excretion is the predominant route of elimination for dietary isoflavones, where approximately 10-60% of total administered dose is excreted in urine 4. Glucuronide conjugates account for the majority (70-90%) of the isoflavone content in urine, followed by sulphate conjugates (10-25%) and aglycone forms (1-10%) 4. Fecal excretion is minimal, which accounts for 1-4% of the dietary isoflavone ingested 4.
- Half-life
The half-life of isoflavones is between 4 and 8 h 1. Daidzein has a longer intestinal half-life than genistein due to more rapid degradation of genistein 3. Individual half-life of daidzein and genistein in a human pharmacokinetic study were 7.75 h and 7.77 h, respectively 4.
- Clearance
In a human study, the clearance rate for daidzein and genistein were 30.09 L/h and 21.85 L/h, respectively 4.
- Adverse Effects
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No toxicokinetic data available.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Isoflavone which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Isoflavone which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Isoflavone which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Isoflavone which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Isoflavone which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Not Available
Products
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Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as isoflavones. These are polycyclic compounds containing a 2-isoflavene skeleton which bears a ketone group at the C4 carbon atom.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Isoflavonoids
- Sub Class
- Isoflav-2-enes
- Direct Parent
- Isoflavones
- Alternative Parents
- Chromones / Pyranones and derivatives / Benzene and substituted derivatives / Heteroaromatic compounds / Oxacyclic compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- 1-benzopyran / Aromatic heteropolycyclic compound / Benzenoid / Benzopyran / Chromone / Heteroaromatic compound / Hydrocarbon derivative / Isoflavone / Monocyclic benzene moiety / Organic oxide
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- isoflavones (CHEBI:18220) / Isoflavonoids (LMPK12050000) / a small molecule (ISOFLAVONE)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- OVO2KUW8H8
- CAS number
- 574-12-9
- InChI Key
- GOMNOOKGLZYEJT-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H10O2/c16-15-12-8-4-5-9-14(12)17-10-13(15)11-6-2-1-3-7-11/h1-10H
- IUPAC Name
- 3-phenyl-4H-chromen-4-one
- SMILES
- O=C1C(=COC2=CC=CC=C12)C1=CC=CC=C1
References
- General References
- Messina M: Soy foods, isoflavones, and the health of postmenopausal women. Am J Clin Nutr. 2014 Jul;100 Suppl 1:423S-30S. doi: 10.3945/ajcn.113.071464. Epub 2014 Jun 4. [Article]
- Xiao CW: Health effects of soy protein and isoflavones in humans. J Nutr. 2008 Jun;138(6):1244S-9S. doi: 10.1093/jn/138.6.1244S. [Article]
- Kalaiselvan V, Kalaivani M, Vijayakumar A, Sureshkumar K, Venkateskumar K: Current knowledge and future direction of research on soy isoflavones as a therapeutic agents. Pharmacogn Rev. 2010 Jul;4(8):111-7. doi: 10.4103/0973-7847.70900. [Article]
- Chandrasekharan S: Pharmacokinetics of Dietary Isoflavones Journal of Steroids & Hormonal Science. [Article]
- INVIMA Product Registration: Trifoliom (red clover extract 40%) capsules for oral use [Link]
- External Links
- KEGG Compound
- C00799
- PubChem Compound
- 72304
- PubChem Substance
- 347828325
- ChemSpider
- 65255
- ChEBI
- 18220
- ChEMBL
- CHEMBL366460
- ZINC
- ZINC000000895390
- Wikipedia
- Isoflavone
- MSDS
- Download (46.8 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Asthma 1 4 Completed Treatment Hot Flashes 1 3 Unknown Status Treatment Menopause 1 3 Unknown Status Treatment Postmenopausal 1 3 Unknown Status Treatment Postmenopausal Syndrome 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, coated Oral Capsule, coated Oral 40 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00843 mg/mL ALOGPS logP 3.51 ALOGPS logP 3.34 Chemaxon logS -4.4 ALOGPS pKa (Strongest Basic) -5.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 26.3 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 65.74 m3·mol-1 Chemaxon Polarizability 23.64 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 155.5904799 predictedDarkChem Lite v0.1.0 [M-H]- 155.4759799 predictedDarkChem Lite v0.1.0 [M-H]- 150.09846 predictedDeepCCS 1.0 (2019) [M+H]+ 156.2032799 predictedDarkChem Lite v0.1.0 [M+H]+ 156.5694799 predictedDarkChem Lite v0.1.0 [M+H]+ 152.49403 predictedDeepCCS 1.0 (2019) [M+Na]+ 155.7536799 predictedDarkChem Lite v0.1.0 [M+Na]+ 155.7340799 predictedDarkChem Lite v0.1.0 [M+Na]+ 158.45177 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
- Gene Name
- PPARA
- Uniprot ID
- Q07869
- Uniprot Name
- Peroxisome proliferator-activated receptor alpha
- Molecular Weight
- 52224.595 Da
References
- Mezei O, Banz WJ, Steger RW, Peluso MR, Winters TA, Shay N: Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J Nutr. 2003 May;133(5):1238-43. doi: 10.1093/jn/133.5.1238. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
- Gene Name
- PPARG
- Uniprot ID
- P37231
- Uniprot Name
- Peroxisome proliferator-activated receptor gamma
- Molecular Weight
- 57619.58 Da
References
- Mezei O, Banz WJ, Steger RW, Peluso MR, Winters TA, Shay N: Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J Nutr. 2003 May;133(5):1238-43. doi: 10.1093/jn/133.5.1238. [Article]
Drug created at October 20, 2016 21:10 / Updated at May 21, 2021 10:22