Genistein:4',5,7-Trihydroxyisoflavone.:Introduction and Its Benefit Applications.

Common Benefits of Genistein.

Genistein:4',5,7-Trihydroxyisoflavone CAS 446-72-0 EINECS ELINCS No 207-174-9 isoflavone,flavonoids,phytoestrogens,antioxidant photo picture image Properties: Genistein works on several fronts: it acts as a phytoestrogens and as an antioxidant.

Isoflavones comprise a class of organic compounds, often naturally occurring, related to the flavonoids.Many act as phytoestrogens in mammals. Being polyphenols, they are antioxidants.Some isoflavones and isoflavone-rich foods possess activity against cancer, including certain types of breast and prostate cancer.Isoflavones are produced almost exclusively by the members of the Fabaceae/Leguminosae (bean) family.

Because of their diversity, isoflavones can have diverse effects on human and animal health.Early evidence that plants produced estrogen-like compounds was manifested in the infertility among sheep that eat large amounts of clover in Australia.Similarly, California Quails fed on the leaves of high-isoflavone desert annuals during periods of food shortage had reduced fertility.Studies using chemically pure isoflavones or plant materials with known concentrations of these compounds have indicated both positive and negative effects of isoflavones on disease progression and fertility.

Phytoestrogens: The estrogenic activity of genistein has been confirmed in many studies. Of all the isoflavones, genistein has the strongest estrogenic activity.The estrogenic effect of genistein may also explain its protective action against osteoporosis.Genistein is also used to ease menopause symptoms, such as hot flushes.

Antioxidant: Some isoflavones act as antioxidants to counteract damaging effects of free radicals in tissues. Genistein has a converse effect in this area compared to other isoflavones; It stimulates a step in nitrate synthesis, which is oxidation.

Genistein is a strong antioxidant. Genistein removed damaging free radicals and reduces lipid peroxidation. Only oxidized LDL cholesterol is absorbed by the arterial cells. Prevention of the oxidation of LDL cholesterol will reduce the risk for arteriosclerosis. Gensistein prevents the formation of hearth attacks and strokes by acting as anticlotting agent. Genistein increases the activity of other antioxidant enzymes such as glutathione peroxidase, superoxide dismutase and glutathione reductase. Studies have shown that genistein can also influence the growth of cells which are not hormone-dependent. Genistein seems to inhibit the activity of tyrosine kinase, which plays an important role in cell growth. Reduction of tyrosine activity will result in a reduced cancer risk.

Antioxidant action:the antioxidant properties of genistein were demonstrated in HL-60 human leukaemia cells.Amonst tested isoflavones,genistein is the more potent inhibitor of TPA(12-O-tetradecanoylphorbol acetate) induced H2O2 formation by HL-60 cells,daidzein in second;genistein is equally the most potent in inhibiting O2 generation by xanthine/xanthine oxidate,daidzein showing a moderate inhibitory effect(Wei et al.,1995).Dietary administration of 250 ppm genistein for 30 days significantly enhances the activities of antioxidant enzymes in the skin and small intestine in mice,and pre-treatment with genistein by topical application significantly inhibits TPA-induced proto-oncogene expression in mouse skin in a dose-dependant manner.(Wei et al.,1995).The administration of soy proteins containing genistein and daidzein to prepubertal rhesus monkeys significantly reduced LDL-VLDL cholesterol concentrations(less than 30~40%) in both males and females,significantly increased HDLC(high-density lipoprotein cholesterol) in females(> 15%) and significantly lowered total plasma cholesterol/HDLC ratios.The phytoestrogens had no adverse effects on the reproductive system of either males or females as evaluated by hormone concentration and organ weights at necroscopy(Anthony et al.,1996,abstract only).In addition to its antioxidative potential during LDL(low density lipoproteins) oxidative processes,genistein exerted a cytoprotective effect on bovine aortic endothelial cell and human endothelial cell-mediated LDL from damage by oxidized lipoproteins.(Kapiotis et al.,1997).These findings support a beneficial action(of a soy diet) in preventing chronic vascular diseases and early atherogenic events.Results of recent research suggest that genistein is a potent inhibitor of UVR-induced skin carcinogenesis and could be used for chemoprevention of skin photo damage,photo aging and photo carcinogenesis.

Anti-Cancer: Genistein seems to reduce the risk for some hormone related cancers, principally breast cancer and prostate cancer. Epidemiological studies show that consumption of isoflavones may protect against breast and prostate cancer. High dietary intake of soy products China are linked with low incidence of these cancers. There are lots of theories to explain the anti-cancer action of genistein: inhibition of angiogenesis, inhibition of tyrosine kinases, antioxidant property, and anti-estrogen action (it is known that estrogen increases risk for certain cancers). Genistein binds with estrogen receptors, preventing the estrogen from binding and initiating cancer growth.

Some isoflavones have been found to have antiangiogenic effects (blocking formation of new blood vessels), and may block the uncontrolled cell growth associated with cancer, most likely by inhibiting the activity of substances in the body that regulate cell division and cell survival (growth factors). However, Genistein has the effect of promoting breast cancer in one study.

Studies show that gastrointestinal cancer occurs less frequently among North Americans who do not learn to eat meat. North Americans who go to other continents without learning to eat vegetables show more digestive tract cancer than neighbours.
Timing of phytoestrogen use is important.
Genistein makes some cells more sensitive to radio-therapy.

Though research is still ongoing, some recent studies have indicated that soy's phytoestrogens could be contributive factors in some forms of breast cancer, penile birth defects, and infantile leukemia.

Some studies have raised the concern that genistein might increase the risk of leukemia, because it inhibits the enzyme topoisomerase which results in double strand DNA breaks, which are, in turn, mutagenic. Some cancer patients whose chemotherapy drugs inhibited topoisomerase later developed leukemia. An animal study suggested that GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.

Regardless, soy's phytoestrogens, or isoflavones, have been definitely shown to depress thyroid function and to cause infertility in every animal species studied so far.

Genistein's chief method of activity is as a tyrosine kinase inhibitor. Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades. Genistein has been used to selectively target pre B-cells via conjugation with an antibody. This highly successful study in mice has promising benefits for future chemotherapy.

Atherosclerosis: Genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte-endothelium interaction, thereby modulating vascular inflammation, a major event in the pathogenesis of atherosclerosis.

Effects in males: Isoflavones can act like estrogen, stimulating development and maintenance of female characteristics or they can block cells from using cousins of estrogen. In vitro studies have proven genistein to induce apoptosis of testicular cells at certain levels, thus raising concerns about effects it could have on male fertility.

Soy is also rich in estrogenic compounds such as genistein and daidzein; however, research is conflicting as to whether or not it can cause increases in estrogen in males.

Molecular function: Genistein influences several targets in living cells. One important function is the inhibition of several tyrosine kinases. Genistein also inhibits the mammalian hexose transporter GLUT1 and contraction of several types of smooth muscles. Genistein can bind to the CFTR channel, potentiating its opening at low concentration and inhibiting it a higher doses.

Hot flash Treatment:

Hot flashes (also known as hot flushes, or night sweats if they happen at night) are a symptom of the changing hormone levels that are considered to be characteristic of menopause.

Hot flashes, a common symptom of menopause and perimenopause, are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from two to thirty minutes for each occurrence. The sensation of heat usually begins in the face or face and chest, although it may appear elsewhere such as the back of the neck, and it can spread throughout the whole body. Some women pass out if the effects are strong enough. In addition to being an internal sensation, the surface of the skin, especially on the face, becomes hot to the touch. This is the origin of the alternative term "hot flush," since the sensation of heat is often accompanied by visible reddening of the face. Excessive flushing can lead to rosacea.

The hot-flash event may be repeated a few times each week or constantly throughout the day, with the frequency reducing over time. Hot flashes may begin to appear several years before menopause starts and last for years afterwards. Some women undergoing menopause never have hot flashes. Others have mild or infrequent flashes. The worst sufferers experience dozens of hot flashes each day. In addition, hot flashes are often more frequent and more intense during hot weather or in an overheated room, the surrounding heat apparently making the hot flashes themselves both more probable and more severe.

Severe hot flashes can make it difficult to get a full night's sleep (often characterized as insomnia), which in turn can affect mood, impair concentration, and cause other physical problems. When hot flashes occur at night, they are called "night sweats." As estrogen is typically lowest at night, some women get night sweats without having any hot flashes during the daytime.

Isoflavones are commonly found in legumes such as soy and red clover. The two soy isoflavones implicated in relieving menopausal symptoms are genistein and daidzein, and are also known as phytoestrogens. The half life of these molecules is about eight hours, which might explain why some studies have not consistently shown effectiveness of soy products for menopausal symptoms. Although red clover (Trifolium pratense) contains isoflavones similar to soy, the effectiveness of this herb for menopausal symptoms at relatively low concentrations points to a different mechanism of action.

Other phytoestrogens:It is believed that dietary changes that include a higher consumption of phytoestrogens from sources such as soy, red clover, ginseng, and yam may relieve hot flashes.

Ginseng - Very few studies exist on the effect of ginseng for relief of menopausal symptoms; however, hundreds of years of anecdotal evidence exists using ginseng as part of tonics made by Chinese herbalists.In a large double-blinded randomized controlled trial, reduction in hot flashes was not statistically significant but showed a strong trend towards improvement.

Lifestyle changes:Lifestyle changes may help alleviate hot flashes.These include avoiding caffeine, hot drinks, chocolate, spicy or hot foods and alcohol.Some evidence exists that regular exercise can reduce hot flashes and that yoga can help by teaching women to control their body's response to the stresses that can lead to bothersome hot flashes.

Endocrine activity:

Studies in which the effects on human cancer cells in vitro and on rats and mice uterus in vivo have been developed to assess the estrogenic activity of isoflavonoids.

In vitro.The relative estrogenic potencies of isoflavonoids (coumestrol,genistein,daidzein) and estradiol were estimated by an assay in vitro based on the estrogen-specific enhancement of alkaline phosphatase(AlkP) activity in human endometrial adenocarcinoma cells.The results indicate that estradiol and isoflavonoids exert their effects on AlkP by similar interaction with the estrogen receptor(ER),with potencies depending on binding affinities.Antiestrogens 4-hydroxytamoxifen and ICI 164384 suppressed their effects(Markiewicz et al.,1993).In a study comparing the effects of flavonoids(genistein,kampferol,quercetin) with estradiol and tamoxifen on human breast cancer cells MCF-7 grown in vitro,genistein behaved as a potent estrogen agonist(estrogenic action determined by binding with estrogen receptor ER,and by induction of the estrogen-regulated antigen pS2 protein) at concentration within the in vivo blood levels of genistein found in Asians consuming a soy-rich diet(10 nmol-20 umol) genistein had cell growth-inhibitory actions (Zava et Duwe,1997).Amonst other phytoestrogens,daidzein and genistein demonstrated agonistic effects on estrogen-dependant gene expression in MCF-7 human breast cancer cells.In combination,phytoestrogens stimulated the activity observed for individual ones(Willard et Frawley,1998,abstract only).

In vivo.short-term administration(5-21 d) of genistein at 750mg/g in the diet exerts estrogenic effects in the uterus,mammary gland and hypothalamus/pituitary axis of ovariectomized Sprague-Dawley rats.The relative binding of genistein to the estrogen receptor (ER) was ~1% that of estradiol(Santell et al.,1997).Genistein has been reported to exhibit estrogenic activity in mice(Bickoff et al.,1962).However,there is a difference in the response of different mouse strain.In a 4 days study,the administration of genistein by stomach tube to Swiss CD-1 mice(total dose:6 and 8 mg) did not cause any significant effect on uterus weight,nor on body weight gain.A significant increase in uterus weight was observed in mice treated with the positive control DES(total doses:0.6 and 0.8 ug)(Farmakalidis et Murphy,1984).

Other Uses:

Genistein is receiving much attention as a candidate therapeutic agent in cancer prevention.Experimental and epidemiological studies support the view that dietary consumption of soy food prevent angiogenesis,cancer as well as diseases and symptoms associated with estrogen deficiency.Consumption of soybeans in China and other asia area has been linked with the low incidence of breast,prostate and colon cancers.In these countries,it is estimated that 120 mg of isoflavones(genistein and daidzein representing >90% of the soy bean isoflavone content) are consumed each day in the form of tofu,soy-milk and other soy products when the average non-vegetarian diet in western countries provides only 1-5 mg of isoflavones daily.