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Isoflavones (soy isoflavones) are a type of phytoestrogens, the most abundant in soybeans, mainly daidzein (didzein) and genistein, both of which are structurally similar to estrogen as aromatic rings: non-steroidal compounds. The soy isoflavones in soybeans are usually in the active form without glycoside conjugation and are only broken down by the glucosidase enzyme of intestinal flora to form biologically active non-glucoside isoflavones. Naturally, biochanin A and formononetin play roles as precursors of the soy isoflavones, daidzein and genistein, both of which enter the intestinal flora: Genistein can further metabolize p-methylphenol, the principle of daidzein, which can be broken down into the more active equol (equol), O-dimethylangoracin (O-DMA). Intestinal flora decomposes conjugated isoflavones, which are easily absorbed by the body and are secreted directly from the bile to the intestinal tract and eliminated from the body; deglucosidized isoflavones undergo enterohepatic circulation and metabolism, and are combined with glycosides to form biologically active compounds. . Soy isoflavone content varies among soybean varieties, origin, harvest season, fungal infection and treatment "Gang of Four" intake among this population. The average intake of isoflavones by Japanese residents is 20-30 mg/day, while residents in Europe, the United States and other developed countries have low intakes of isoflavones. Since the major factors affecting the intestinal flora of the large intestine, such as gender, dietary fat and fiber, and levels of endogenous estrogen in the metabolism of isoflavones, soy isoflavone metabolism will have the same degree of influence, therefore, even if the isoflavones are the same The intake and plasma isoflavone concentrations of different individuals vary greatly, which may be one of the reasons for the different or even opposite findings of researchers in different plants.
Soy isoflavones have two or three hydroxyl groups and aromatic rings. This structure is relatively stable, easily passes through cell membranes, and is conducive to binding and receptor proteins and enzymes. Isoflavones bind to the estrogen receptor (ER) and have estrogenic and antiestrogenic activity similar to the structural characteristics of estrogens. The protective effects of isoflavones on physical health, as well as the prevention and treatment of disease, are mostly measured by two important biological activities. The final activity of isoflavones in cells and the body is mainly determined by the local concentration of endogenous estrogen levels and the ER levels of tissues and organs. Isoflavones have weak estrogenic activity, usually only estrogen 1,000-300,000. Higher concentrations of isoflavones compete with estrogen for estrogen receptors, thus exhibiting anti-estrogenic activity. The biological activities of soy isoflavones include antioxidant activity, inhibiting cell proliferation and differentiation, anti-tumor angiogenesis, and promoting the synthesis of sex hormone binding globulin (SHBG).
Concerns and in-depth research on soy isoflavones and human health caused by soy diet on the incidence of diseases, epidemiological surveys in Asia (especially Japan), breast cancer, cardiovascular disease, menopause The incidence of hot flashes is significantly lower than in Europe and the United States and other countries (regions), but this difference is considered to be closely related to high-fiber diets and high-fat diets in Europe, the United States, and Asia, but as research deepens, The role of phytoestrogens (soy isoflavones) in the development of these diseases has attracted increasing attention from researchers. Most scholars believe that the main reason for the difference in intake of soy isoflavones is the cause of this disease. So far, a large number of epidemiological surveys, clinical trials, animal experiments and in vitro experiments have confirmed that soy isoflavones are beneficial to women. It plays an important role in the pathogenesis and prevention of osteoporosis, postmenopausal vascular disease, breast cancer, and menopausal hot flashes.
After women enter menopause, the ovarian function declines, the synthesis and secretion of estrogen, and the decrease in estrogen will lead to fat and cholesterol metabolism. Postmenopausal women often have increased fat, cardiovascular and cerebrovascular diseases and cholesterol, and the incidence of cardiovascular diseases. increase in rates and mortality.
According to statistics, the incidence of coronary heart disease in postmenopausal women increases by 2 to 3 times. Premenopausal and postmenopausal women who use estrogen replacement therapy (ERT) have a reduced risk of cardiovascular disease: 35% to 50%. Research shows that soy isoflavones, which have only estrogenic activity, can play an important role in epidemiology. Survey results show that mortality from coronary heart disease in the United States is as high as 10% in women aged 40 to 69 and the incidence of cardiovascular disease in Japanese women. Detailed data analysis in the same age group found that soy protein rates reduced atherosclerosis primarily due to differences in mortality rates between Shengzhou and developed industrial countries, compared with coronary heart disease mortality rates, similar conclusions. But due to the huge differences in lifestyles and food cultures in Asia, Europe, the United States and other countries, it still cannot be ruled out that other factors or food ingredients play a role in coronary heart disease. The epidemic in Okazaki also has different Perceptions and needs are the subject of further research.
Results from clinical trials, animal experiments and in vitro studies further affirm the role of soy isoflavones in vascular disease. Dietary intervention trial found that daily intake of 45 mg of isoflavones increased blood cholesterol in women with normal blood cholesterol Porter 66 6-month intervention trial test group of postmenopausal women with hypercholesterolemia Taking 40 grams of soy protein every day, it was found that total plasma cholesterol dropped by about 0.40mmol/L, and the proportion of total cholesterol decreased, while high-density lipoprotein (HDL) increased by 0.065mmol/L year-on-year. After the experiment, the proportion of high-density lipoprotein cholesterol 0.5, the results showed that soy isoflavones lower plasma cholesterol. 38-year-old Anderson, a meta-analysis of 34 studies on the relationship between soy isoflavones, blood lipids or cholesterol, found that in these trials, the average intake of soy isoflavones and soy protein confirmed the hypolipidemia effect. Intake was 479/day, while total serum cholesterol decreased by an average of 0.59 mmOI/L (9.3%). 11 The AYlthOYly research team used macaques to study the effects of soy protein on high-fat diet-induced cardiovascular disease. The blood lipid parameters were divided into three groups of female macaques, a diet with casein as a protein source, and a diet (ethanol extract) to eliminate isoflavones. Soy Protein as a Source of Protein The Illinois group feeds crudely extracted soy protein as a source of H mass for eggs (143 mg of isoflavones per day in Phase 1). Some experimental results are shown in Table 1. It can be seen that soy protein containing isoflavones can effectively reduce total cholesterol and low-density lipoprotein (LDL). Very low-density lipoprotein (VLDL) levels and inhibits atherosclerotic plaque formation. In this study, there was only small evidence of a protective effect of soy isoflavones against cardiovascular disease, but it was also suggested that soy protein H and isoflavones exert a lipid-lowering component. The mechanism of action of soy isoflavones in cardiovascular disease has been extensively studied in the past 20 years. Researchers AnthOYly summarized the diversity of its mechanisms of action as follows:
(1) LDL Receptor regulation. Soy isoflavones can enhance the occurrence of LDL receptors (upregulate ON) and increase the activity of LDL receptors, thereby facilitating the removal of cholesterol, (2) antioxidant properties. In vitro studies have shown that soy protein has a reduced volume of LDL particles and protects against excessive oxidation of LDL. This effect of isoflavones can reduce the deposition of LDL particles, thereby reducing the incidence of atherosclerosis in the coronary artery wall. (3) Inhibit the proliferation of vascular smooth muscle cells. Cell culture with genistein at 25 mm/l reduces the activity of basal fibroblast growth factor (bFGF) and fibrinogen-type plasminogen activator, thereby inhibiting the proliferation of smooth muscle cells and having an important role in the development of arteriogenesis In the development of atherosclerosis, such cells have an antithrombotic effect in their proliferation (4). Protein tyrosine phosphorylation is closely related to platelet activity. Genistein reduces tyrosine egg platelet H by inhibiting the phosphorylation of tyrosine kinase, thereby reducing platelet activity, its deposition and accumulation on the blood vessel wall. , to reduce and prevent the occurrence of atherosclerosis.
Nakajima studies the dyes flavonoids and daidzein that can block blood flow. Bolt Prime AZ binds to its receptor, causing platelet isoflavone unresponsiveness. Therefore, this mechanism requires further study. Recently, some scholars have begun to pay attention to the role of lipoprotein H(a)(ILP(a)) in the protective mechanism of isoflavones. LPB) is an independent risk factor for coronary heart disease, and the impact of diet, drugs, and postmenopausal women to
Estrogen treatment can significantly reduce the concentration of this substance, Okazaki changes, soybean 000 indigenous and estrogenic activity of genistein and estrogen receptor binding properties, some scholars speculate that isoflavones can reduce LP ( a) To reduce the risk of coronary heart disease, studies need to be conducted to confirm that Transformed Growth Steel PL (TGF 61) abnormally reduces the risk factors of coronary heart disease, and genistein can induce the formation of TGF PL, which Pathways are also thought to be mechanisms by which isoflavones may act
Breast cancer
University's investigation into the prevalence of soy intake and breast cancer incidence. Other long-term epidemiological surveys have found that soy milk intake is inversely associated with breast cancer incidence, and Japanese and Chinese immigrants to the United States still have lower breast cancer incidence than ten residents in controlled studies, which may The early and mid-term soybean intake is approximately: Wu Si case, in different countries after 1990, a comparative analysis found that both in developed countries such as Europe and the United States, in Asia and other countries, with the daily soybean intake of residents The relative risk of breast cancer decreased with each year of increased soy consumption. Results: Rats fed feed containing soy protein and then exposed to chemical carcinogens found that soy protein could prevent tumor formation. Provided strong epidemiological evidence that the incidence of breast cancer in Sichuan was eliminated after the removal of isoflavones from soy protein and ethanol, and this study confirmed that genistein and daidzein can inhibit. The production of DNA adducts induced by 7,12-dimethylphenidate is more convincing in the study of soy isoflavones in breast cancer. For 7, U-dimethyl prognosis, it was found that genistein can prolong the latency period of cancer, and has a significant reduction effect on the incidence of breast cancer in mice in adulthood, indicating that early exposure to isoflavones is beneficial to preventing cancer later in life. In part, this can also be used to explain why the incidence of breast cancer in Asian immigrants to the United States (in the early stages of high soy isoflavone intake) is still lower than in the United States. BR /gt;
Cell culture. The experimental results further confirmed the inhibitory effect of soy isoflavones on breast cancer. Soy isoflavones also revealed the cancer-suppressing mechanism. Current research shows that soy isoflavones (genistein) are involved in estrogen receptor dependence and anti-cancer. Cellular action of estrogen receptor-positive compounds, estrogen or estrogen, on non-oestrogen receptor-dependent mechanisms of fines in human breast cancer (MCF-7) lines. Similar effect. MCF-7 cell culture found that low concentrations of genistein can promote cell proliferation, but when the concentration of genistein and genistein is greater than 10 mmol, it inhibits cell proliferation. In the presence of estrogen, the former can competitively bind to the core of the estrogen receptor, thereby avoiding the formation of estrogen and mutagenic DNA adducts. These studies indicate that the inhibition of soy isoflavones on breast cancer is mediated by ER channels. However, another study showed that 2. SX 10-5?IX-4mol Some genistein can inhibit human breast cancer MCF-7 cells. The researchers believe that the benefit of this concentration range is the inhibition of tyrosine kinase and DNA topoisomerase in the concentration range. Tyrosine kinases are closely related to epidermal growth factor, insulin-like growth factor, and platelet-derived growth prisoner cell growth factor receptors. They play an important role in preventing cell proliferation and transformation by inhibiting the proliferation of cancer cells by tyrosine kinases. Flavonoid; genistein inhibits the 11-type DNA topoisomerase binding of cancer cells to proteins until DNA strand breaks, causing cancer cell death.
Genistein acts by interfering with receptor signaling pathways and DNA-dependent inhibition of non-ER. Genistein can interfere with the activity of EZ to reduce ERmRNA expression and allow the endogenous estrogen in the body to decrease. This antiestrogenic effect is one of the anti-cancer mechanisms.
Genistein has antioxidant effects and inhibits superoxide production. In human polymorphonuclear lymphocytes (neutrophils) and HL-60 cells, genistein can strongly inhibit the inhibition of H202 12-0 phenol production induced by the tumor-promoting phorbol 13-vinyl acetate (TP) The concentration range is 1 to 15mmol. According to some dose-effect relationships, genistein can inhibit the production of superoxide anions by HL-60 cells. Since hydrogen peroxide and hydrogen peroxide are harmful in inducing cancer, the antioxidant effect of flavonoids is one of the mechanisms of anti-cancer action.
Research shows that genistein can affect the activity of hormone metabolism enzymes. Aromatase is an androgen to estrogen enzyme 17β estrone decarboxylase converting enzyme to estrone. Through the inhibition of these metabolic activities of estradiol, genistein, cells can reduce the concentrations of estrone and estradiol. By inhibiting Sichuan enzyme, soybean isoflavones can also change the type and content of estrogen metabolites in the body, thus preventing estrogen from forming DNA adducts in cells to inhibit carcinogenesis. Human experiments have confirmed this . 12 Premenopausal women taking soy protein equivalent to 10, 15, and 129 mg/day of soy isoflavones had significant decreases in urinary concentrations of 4 EI, (OH) 4 (OH) EZ I 6 (OH) estrogen metabolites lasting 100, The adducts between said metabolites and DNA are genotoxic and are considered to be risk factors for breast cancer. According to this result, Xu et al.'s influence on the metabolism of estrogen is one of the anti-cancer mechanisms of soy isoflavones. Some scholars believe that isoflavones. Promotes the synthesis of sex hormone binding globulin and prolongs the menstrual cycle, but its possible anti-cancer mechanism
Postmenopausal hot flashes, osteoporosis
Female menopause, estrogen. Hormone levels can cause a series of hot flashes and sweating that are characteristic of menopause. The continued loss of bone is a natural process of aging, and the incidence of osteoporosis is higher in older women than in men. The level of estrogen in the body decreases rapidly, thereby accelerating bone stigma and estrogen receptors in osteoclasts. Estrogen and estrogen receptors combine to reduce osteoclast activity, thereby limiting bone resorption and benefiting postmenopausal bone quality. Prevention and treatment of porosis. Epidemiological survey results show that 25% of menopausal women in Japan complain of hot flashes and sweating symptoms, but in North America this is as high as 85% in Japan and in Europe. Compared with the incidence of osteoporosis in postmenopausal women in the United States, the incidence of osteoporosis is significantly lower than that in Europe, the United States, and other countries (regions). In the past 10 years, scholars from various countries have conducted a large number of clinical trials and animal studies. The experiment sought to find a relationship between soy intake and the incidence of osteoporosis and hot flashes in postmenopausal women. Albertazzi studied 104 postmenopausal women each with a soy protein dietary intervention. Experiments have finally found that some % of patients' hot flash symptoms disappear, significantly higher: Experimental results show that soy protein significantly improves the effect of postmenopausal women's hot flash symptoms. Some other experiments also observed vaginal cytology and. The effects of soy protein on hot flashes have been inconsistent across trial populations, in the form of soy products, and in a recent clinical trial testing the association of soy isoflavones with hypercholesterolemia in postmenopausal women. Porter's Dietary Intervention Experiment 66 women were divided into three groups, the control group, one group consumed 56 mg of isoflavones per day, and the other group consumed 90 mg of isoflavones per day. Subject l continuous 60 And the bone density results found that the bone mineral content and bone mineral density of the subjects who consumed 90 mg of isoflavones per day increased by 2%, which was a significant difference compared with the control group.
Clinical use of isoflavones. Based on flavonoids (isoflavonoids) to reduce postmenopausal bone loss there is strong evidence of a relationship between isoflavones and osteoporosis.
Isoflavones are synthesized from soybean isoflavones, which can be used as a treatment drug for acute ovarian dysfunction and osteoporosis. Taking 200 to 600 mm each time can effectively increase bone mass and reduce bone loss. This may be related to intestinal bacteria converting daidzein into many metabolites, including daidzein. Currently, a large number of studies mainly focusing on castrated rats as model animal experiments have shown that soy isoflavones reduce bone loss and promote bone formation. The above-mentioned chronic diseases are hormone-dependent diseases. Otherwise studies have shown that soy isoflavones protect against non-hormone-dependent disease or injury. The antioxidant properties of soy isoflavones can protect DNA from ultraviolet damage and can prevent liver damage caused by ischemia-reperfusion type diabetes 11 and improve kidney function and proteinuria. In short, a large number of epidemiological and clinical experiments and animal studies and In vitro experiments have confirmed the protective effects of soy isoflavones in women suffering from chronic diseases. Needless to say, increasing the intake of soybeans and soy products is beneficial to human health as an aging society, postmenopausal women, causes The whole society is concerned that ERT is a promising treatment for low estrogen-related diseases. Soy isoflavones in women who receive ERT will increase the risk of breast cancer, menopausal and postmenopausal women with estrogen-dependent diseases, and have good application prospects.
However, in-depth research on the relationship between soy isoflavones and diseases is still needed. So far, there are opposing views on the effect of soy protein on blood cholesterol: the relationship between isoflavones and cancer. Relationships can be inferred only from human cell lines and animal experiments, and more human intervention examinations are needed. The relationship between soy isoflavones, hot flashes, and osteoporosis requires more human experiments to further confirm its mechanism. In-depth interactions between soy isoflavones and other food ingredients have not yet been reported, per "Daily Recommendations The amount has not yet been determined, so there is still a lot of work to be done to study the effects and mechanisms of soy isoflavones in detail.