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| Names | |
|---|---|
| IUPAC name 3,9-Dihydroxypterocarp-6a(11a)-en-6-one | |
| Systematic IUPAC name 3,9-Dihydroxy-6H-[1]benzofuro[3,2-c][1]benzopyran-6-one | |
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3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.006.842 |
| EC Number |
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| KEGG |
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| UNII | |
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| Properties | |
| C15H8O5 | |
| Molar mass | 268.224 g·mol−1 |
| Melting point | 385 °C (725 °F; 658 K) (decomposes)[1] |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Coumestrol is a naturalorganic compound in the class ofphytochemicals known ascoumestans. Coumestrol was first identified as a compound with estrogenic properties by E. M. Bickoff in ladinoclover andalfalfa in 1957.[2] It has garnered research interest because of its estrogenic activity and prevalence in some foods, includingsoybeans,brussels sprouts,spinach and a variety oflegumes. The highest concentrations of coumestrol are found inclover, Kala Chana (a type ofchick pea), andAlfalfa sprouts.[3]
Coumestrol is aphytoestrogen, mimicking thebiological activity ofestrogens. Phytoestrogens are able to pass through cell membranes due to their low molecular weight and stable structure, and they are able to interact with the enzymes and receptors of cells.[4] Coumestrol binds to theERα andERβ with similaraffinity to that ofestradiol (94% and 185% of therelative binding affinity of estradiol at the ERα and ERβ, respectively),[5] although the estrogenic activity of coumestrol at both receptors is much less than that of estradiol.[6] In any case, coumestrol has estrogenic activity that is 30 to 100 times greater than that of isoflavones.[7]
The chemical shape of coumestrol orients its twohydroxy groups in the same position as the two hydroxy groups in estradiol, allowing it toinhibit the activity ofaromatase and3α-hydroxysteroid dehydrogenase.[8] These enzymes are involved in the biosynthesis ofsteroid hormones, and inhibition of these enzymes results in the interference with hormonemetabolism.[9]
Levels of coumestrol within individual plants of the same species are variable. Studies of coumestrol levels in alfalfa suggest that there may be a positive correlation between coumestrol production and infection of the plant byviruses,bacteria, andfungi. Higher levels of coumestrol are also found in plants which had been damaged byaphids. Further study is required to fully explain the cause of the correlation between damage, infection, and coumestrol levels.[10]
According to theUnited States Department of Agriculture andIowa State University database onisoflavanes and coumestrol, coumestrol is found in the following food items:
| Food Item | Coumestrol Level (mg/100g) |
|---|---|
| Large, dryLima beans | 0.14 |
| RawPinto Beans | 1.80 |
| Dry Kala Chana | 6.13 |
| Alfalfa Sprouts | 1.60 |
| RawClover Sprouts | 14.08 |
| Soy Sprouts | 0.34 |
| MatureSoy Beans | 0.02 |
| Unfortified Original and VanillaSoy milk | 0.81 |
| Fortified Original and VanillaSoy milk | 0.12 |
| FirmTofu Prepared withCalcium Sulfate andMagnesium Chloride | 0.12 |
| Doughnuts with Soy Flour of Protein | 0.24 |
Based on extrapolation from studies done on animals, the maximum tolerable daily intake of coumestrol for human beings has been estimated at 22 μg per kg of body mass. This was calculated by extrapolating from the lowest level at which adverse effects were seen in animals. Although due to the variability of the human diet, the exact amount of coumestrol the average person consumes has not been calculated, studies of phytoestrogen intake suggest that most human diets result in a negligible intake of coumestrol relative to the maximum tolerable daily intake.[12]
 | This sectionis missing information about numbers for activity on receptors (rel. affinity, rel. agnoism), including aforementioned ERa/b, new PXR (PMID 18096694), and a somewhat surprising MAO-A (PMID 36145197). Please expand the section to include this information. Further details may exist on thetalk page.(October 2022) |
Because coumestrol is an estrogen mimic, it is anendocrine disruptor with the potential to affect all organ systems that are regulated hormonally via estrogens.
Coumestrol and other phytoestrogens have been shown to have an effect on sexual behavior in rats by antagonizing the action of estrogen within the brain; male rats that nursed from females with coumestrol in their diets were both less likely to mount a female rat and less likely to ejaculate, despite producing normal levels oftestosterone. Exposure produced similar decreases of sexual behavior in female rats, as a result of the disruption of estrogen dependent gene expression in the brain. Effects were seen in three areas of thehypothalamus, theventromedial nucleus, theparaventricular nucleus, and themedial preoptic area, all of which play a role in sexual behavior and sexual activity.[13][14] Female rats that were exposed to coumestrolneonatally did not adopt thelordosis position as much as those that were not exposed to coumestrol.[15]
Coumestrol has been shown to accelerate the onset of puberty in mice.[12] Exposure to coumestrol immediately after birth resulted in an initial increase in uterine weight. However, continued exposure inhibited the growth of theuterus and decreased levels ofestrogen receptors within uterine tissue. The rats also showed altered vaginal development includingcornification andmetaplasia of vaginal tissue, and delayed opening of the vagina.[14] Whenneonatal female mice were treated with coumestrol, similar reproductive irregularities occurred, and at 22 months old, atypicalcollagen distribution was observed in the uterine wall.[15] When 2 day old maleWistar rats are injected with coumestrol daily, they exhibit a decrease in size in thelumens of theirseminiferous tubules and germ cells go through increased rates ofapoptosis. When bulls graze on pastures containing coumestrol, metaplasia occurs in theprostate andbulbourethral glands, and sperm maturation is suppressed. Female cows that consumed alfalfa experienced lower pregnancy rates and spontaneous abortions, as well as abnormal estrogen levels during pregnancy.[16] A high coumestrol diet has also been shown to induce early development of thevulva andudder of female lambs. In addition to these anatomical abnormalities, exposure to coumestrol has also been shown to alter theestrus cycle of a number of animals, including cows and sheep, resulting in lower rates of fertility.[10]
Coumestrol has been shown to decreasebone resorption and promote themineralization of bonein vitro andin vivo; daily injections of coumestrol were shown to reduce bone loss in rats who had undergone anovariectomy.[14]
Coumestrol has been shown to haveclastogenic properties at a certain concentration.[specify]. Studies have shown that coumestrol is amutagen and induces formation ofmicronuclei in hamster cells of the V79 cell line as well as humanlymphoblastoid cells in a dose-dependent manner. Exposure to coumestrol also causes single stranded breaks in hamster DNA, compromising genome stability.[17]
Studies have shown that coumestrol has beneficial properties on carbohydrate metabolism inovariectomized rats, decreasing glycogen levels in skeletal muscle. There is also data indicating that coumestrol lowers plasma cholesterol levels in chicks. These results point to a possibility of coumestrol having a positive role to play against human obesity and diabetes in the future.[18]
Coumestrol and other phytoestrogens are sometimes used as a substitute for hormone therapy in the treatment ofmenopausal symptoms such as hot flashes and night sweats. However, studies have indicated that phytoestrogen-enriched foods and supplements are not necessarily effective against these symptoms.[19] In addition, studies indicate that coumestrol and other phytoestrogens have an antiestrogenic effect in the brain and, as a result, do not produce the mental health benefits which are seen in estrogen replacement therapy.[13]
Coumestrol and other phytoestrogens have also been investigated as a possible substitute for hormone therapy andchemotherapy inbreast cancer patients. The results of various studies regarding the use of phytoestrogens in treating breast cancer have been somewhat contradictory and ambiguous, and as a result, researchers cannot clearly define phytoestrogens like coumestrol as beingchemoprotective agents or potentially having negative effects, such as inducing further growth of existing breast cancer tumors by activatingERα receptors.[20]Researchers atGeorgetown University Medical Center have investigated this matter and concluded that phytoestrogens may be used as an effective treatment for breast cancer because of theirapoptotic properties, but that it is only safe to do so after menopause, when women have a much lower level of estrogen in their bodies, or when used conjunctively with anti-estrogen therapies.[21]
Most research on the biological effects of coumestrol has been conducted on animals because of ethical concerns. There is a need for more human studies to better understand potential human health impacts due to exposure.[18]In addition, further research is required to fully understand the biosynthesis pathway of coumestrol, although it is believed to be similar to that offlavones and isoflavones. Further research is required to understand the exact nature of the relationship between the levels of coumestrol in a plant and the plant's response to pathogens.[10]
