Beneficial Effects Of Isoflavones Research Articles

A UPLC-MS/MS Based Rapid, Sensitive, and Non-Enzymatic Methodology for Quantitation of Dietary Isoflavones in Biological Fluids.

Dietary isoflavones, a type of phytoestrogens, have gained importance owing to their health-promoting benefits. However, the beneficial effects of isoflavones are mediated by smaller metabolites produced with the help of gut bacteria that are known to metabolize these phytoestrogenic compounds into Daidzein and Genistein and biologically active molecules such as S-Equol. Identifying and measuring these phytoestrogens and their metabolites is an important step towards understanding the significance of diet and gut microbiota in human health and diseases. We have overcome the reported difficulties in quantitation of these isoflavones and developed a simplified, sensitive, non-enzymatic, and sulfatases-free extraction methodology. We have subsequently used this method to quantify these metabolites in the urine of mice using UPLC-MS/MS. The extraction and quantitation method was validated for precision, linearity, accuracy, recoveries, limit of detection (LOD), and limit of quantification (LOQ). Linear calibration curves for Daidzein, Genistein, and S-Equol were set up by performing linear regression analysis and checked using the correlation coefficient (r2 > 0.995). LOQs for Daidzein, Genistein, and S-Equol were 2, 4, and 2 ng/mL, respectively. This UPLC-MS/MS swift method is suitable for quantifying isoflavones and the microbial-derived metabolite S-Equol in mice urine and is particularly useful for large numbers of samples.

Beneficial Effects of Isoflavones in the Kidney of Obese Rats Are Mediated by PPAR-Gamma Expression.

Several studies have demonstrated an important association between altered lipid metabolism and the development of kidney injury because of a high-fat diet. Fructose is also closely associated with renal injury. We opted for a combination of fructose and saturated fats in a diet (DH) that is a model known to induce renal damage in order to evaluate whether soy isoflavones could have promising use in the treatment of renal alterations. After two months of ingestion, there was an expansion of visceral fat, which was associated with long-term metabolic disorders, such as sustained hyperglycemia, insulin resistance, polyuria, dyslipidemia, and hypertension. Additionally, we found a decrease in renal blood flow and an increase in renal vascular resistance. Biochemical markers of chronic kidney disease were detected; there was an infiltration of inflammatory cells with an elevated expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β), the activation of the renin–angiotensin system, and oxidative/nitrosative stress. Notably, in rats exposed to the DH diet for 120 days, the concomitant treatment with isoflavones after 60 days was able to revert metabolic parameters, renal alterations, and oxidative/nitrosative stress. The beneficial effects of isoflavones in the kidney of the obese rats were found to be mediated by expression of peroxisome proliferator-activated receptor gamma (PPAR-γ).

The hypocholesterolemic and hormone modulation effects of isoflavones alone or co-fermented with probiotic bacteria in hypercholesterolemic rats model

This study aimed to investigate the beneficial effect of isoflavones alone or probiotics-co-fermented isoflavones on serum and hepatic lipid profile, serum steroid (SHs) and thyroid hormones (THs) of hypercholesterolemic rats (N = 48). Animals were fed for 8 weeks with probiotics-co-fermented isoflavones or isoflavones alone, beside high-fat-high-cholesterol diet. Serum was analyzed for cholesterols, triglycerides (TG), SHs and THs. Results demonstrated that the given treatments significantly decreased serum total-cholesterol (TC), low-density-lipoprotein-cholesterol (LDL-C), high-density-lipoprotein-cholesterol (HDL-C), LDL/HDL ratio, and increased TG, compared to controls. The probiotics-co-fermented isoflavones decreased TC, LDL-C and LDL/HDL ratio more effectively than isoflavones alone. Also, both isoflavones treatments induced a hyperthyroidism state, as the levels of T-T4, T-T3 and fT3 significantly increased. In addition, these treatments decreased testosterone and increased cortisol levels. Thus, isoflavones-containing-treatments, particularly probiotics-co-fermented isoflavones, could reduce CVD incidence by controlling lipid profile; and this control could in part be due to modulation of SHs and THs.

In utero and postnatal exposure to isoflavones results in a reduced responsivity of the mammary gland towards estradiol

Exposure scenarios during different stages of development of an organism are discussed to trigger adverse and beneficial effects of isoflavones (ISO). The aim of this study was to investigate how in utero and postnatal ISO exposure modulates the estrogen sensitivity of the mammary gland and to identify the underlying molecular mechanisms. Therefore, rats were exposed to either ISO-free (IDD), ISO-rich (IRD) or genistein-rich diet (GRD), up to young adulthood. Proliferative activity (PCNA expression) in the mammary gland at different ages and the estrogen sensitivity of the mammary gland to estradiol (E₂) or genistein (GEN) in adult ovariectomized animals was determined and compared with different treatments. Treatment with E₂ resulted in a significant lower proliferative and estrogenic response of the mammary gland in IRD and GRD compared with IDD. This correlates to a change in the gene expression pattern and a decrease in the ratio of estrogen receptor alpha (ERα) beta (ERβ Our results provide evidence that in utero and postnatal exposure to a diet rich in ISO but also to GEN reduces the sensitivity of the mammary gland toward estrogens and support the hypothesis that in utero and postnatal ISO exposure reduces the risk to develop breast cancer.

Isoflavones: effects on bone health

Background There are many effects described, both experimental and clinical, that assess the relationship between isoflavones and bone. It has been hypothesized that isoflavones may have a positive effect on bone health.Objective To review the effects of isoflavones on biochemical markers of bone remodeling, bone density and bone quality, and finally on fracture incidence.Methods A systematic review was carried out of in vitro, animal, and human studies involving isoflavones and bone health. An electronic search was made, based on Internet search engines, MEDLINE (1966–June 2010) and the Cochrane Controlled Clinical Trials Register. This search was further supplemented by a hand-search of reference lists of selected review papers.Results After crossing-cleaning the reference lists, 737 studies dealing with isoflavones and bone were identified. Of these, 36 were considered selectable. From in vitro and animal studies, isoflavones appear to stimulate osteoblastic bone formation and inhibit osteoclastic bone resorption. Reviewed data show evidence of a beneficial effect of isoflavones on bone health in peri- and postmenopausal women when high-isoflavone soy protein is incorporated in the diet. Inconsistencies observed among data from different studies are related to differences in study design, the variety of soy sources of isoflavones, time of analysis, and the variability in the bioavailability and metabolism of isoflavones.Conclusions Most of the studies suggested a positive relationship between isoflavones and bone health. Further well-controlled, randomized, double-blind, clinical trials with a larger sample population, longer duration, and examination of various dosages are needed to better elucidate the inter-relationship between isoflavones and bone loss and to clarify whether isoflavones could prevent bone fractures.

대두추출물을 처리한 조골세포 조건배양액은 RANKL에 의해 유도된 파골세포 분화를 억제

Soybean is of particular interest as a food supplement of isoflavones for inhibiting bone resorption in postmenopausal woman. These beneficial effects of isoflavones are caused by functioning as partial agonists or antagonists of estrogen, of which anti-resorptive effect is mediated indirectly through paracrine factors produced by osteoblasts that act on osteoclasts. In this study, the indirect effect of soybean on osteoclastic differentiation of RAW264.7 cells were investigated. The conditioned medium was collected from MC3T3-E1 osbeoblasts treated with 0.001 ㎎/mL~0.1 ㎎/mL soybean extracts for 6 days, mixed in 1:1 ratio with osteoclast medium, and then added into RAW264.7 cells with receptor activator of nuclear factor kappa B ligand (RANKL), a differentiation inducer for 3 days. Of paracrine factors in the conditioned medium, the protein expression of osteoprotegerin (OPG) with soybean extract was specifically higher in a dose dependent manner than with 10?? M~10?? M of estrogen, genistein or daidzein standards. In RAW264.7 cells, the conditioned medium with soybean inhibited RANKL induced osteoclastic differentiation as total number of multinucleated tartrateresistant alkaline phosphatase (TRAP)-positive osteoclasts and protein expression of MMP-9 were significantly decreased. Coupled with the low expression of estrogen receptor α and β proteins in RANKL treated RAW264.7 cells, we demonstrate that the conditioned medium of soybean treated osteoblasts inhibits RANKL induced differentiation of osteoclasts with the selective expression of OPG in osteoblasts.

Low activities of intestinal lactase suppress the early phase absorption of soy isoflavones in Japanese adults

The contribution of lactase to isoflavone bioavailability has not been clarified. We evaluated the association between lactase activity and the bioavailability of isoflavone glucosides in Japanese adults. Twenty-six Japanese adult participants completed a study that included tests of breath hydrogen after a lactose load, orocecal transit time, and isoflavone glucoside absorption. Lactose malabsorbers were defined as those with an increase in breath hydrogen level (DeltaH(2)) of more than 20 ppm after a load of lactose (20 g). Participants ingested 200 ml soymilk, and serum isoflavones were analyzed until 480 min. Serum daidzein and genistein levels increased rapidly until 60 min, then slowly increased. The increases of serum isoflavones in the early phase, but not the later phase, were suppressed in lactose malabsorbers. DeltaH(2 max) after a load of lactose inversely correlated with serum daidzein levels at 30 min. The percentage of equol producers tended to be greater among lactose malabsorbers (P=0.067). Lactase may be involved in absorption of isoflavone glucosides in the small intestine, but the bacterial deglycosylation in the large intestine compensates the reduction of isoflavone absorption. The beneficial effect of isoflavones may not be impaired by low lactase activity.

Pharmacokinetics of an Equol Supplement in Humans

Equol, a metabolite of daidzein, is considered to be the most effective estrogen modifier in the human body. The production of equol depends on an individual's intestinal flora, however, so an equol supplement has been developed for nonproducers. To examine the pharmacokinetics in humans of a newly developed equol supplement made from fermented soy germ by Lactococcus sp. Equol supplements were given to 18 adults (20-22 yr) in three doses (one 10-mg dose, one 30-mg dose, or three 10-mg doses per day) to investigate the pharmacokinetics and physiological effects. Equol reached a peak in plasma at 30 or 60 min after supplement intake, and the average plasma half-life was 83 min. Plasma concentrations of equol were always higher in females than in males. Less than 5% of the highest plasma concentration remained in the plasma after 2 days. Up to 56% of the orally administered equol was excreted in urine within 1 day. This short-term, high-dose equol exposure yielded no observable adverse effect in both feeling and biochemical markers. For equol nonproducers, this newly developed equol supplement may yield more beneficial effects of isoflavones.

Soy isoflavones affect platelet thromboxane A 2 receptor density but not plasma lipids in menopausal women

Objectives It has been suggested that isoflavones protect the cardiovascular system, in part by improving lipid profile. The purpose of the present research was to examine the effect of a 12-week soy isoflavone supplementation on lipoprotein status and platelet thromboxane A 2 receptor density. Methods Twenty-nine healthy postmenopausal women were invited to take part in a randomised study to receive either 100 mg/day isoflavone supplement ( n = 15) or identical placebo capsules ( n = 14). Blood samples obtained at baseline and after 12 weeks were analysed for isoflavones, total cholesterol, high density lipoprotein cholesterol, triglycerides, glucose, insulin, estradiol, testosterone, gonadotrophins, sex hormone-binding globulin (SHBG) and platelet thromboxane A 2 receptor density. Blood pressure measurements, body mass index, subcutaneous fat at entrance and at the end of treatment were also registered. Changes in variables between groups were compared by ANOVA for repeated measures. Results Blood pressure, body mass index, subcutaneous fat, insulin, serum lipoprotein, sex hormones and SHBG did not differ among groups. However, platelet thromboxane A 2 receptor density declined significantly (from 181.9 ± 30.9 to 115.2 ± 16.2 fmol/10 8 platelets) in the experimental group, remaining mostly unchanged in the placebo group (176.3 ± 27.3 to 170.4 ± 28.2 fmol/10 8 platelets). The dissociation constant ( K d) values were unchanged. The change in platelet thromboxane A 2 receptors correlated negatively with isoflavones serum concentration ( r = −0.59, p < 0.001). Conclusions In this study we demonstrated that the beneficial effects of isoflavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors.

Soy Isoflavones: No Effects on Bone Mineral Content and Bone Mineral Density in Healthy, Menstruating Young Adult Women after One Year

Background: The effects of isoflavone-enriched soy protein on human bone mineral content (mass) and density in healthy, menstruating young adult females have not been examined in a comparative prospective investigation. Peri- and post-menopausal women have been reported to show beneficial effects of isoflavones on bone measurements. Therefore, young women may also be able to improve their accrual of peak bone mineral content (BMC) and bone mineral density (BMD) during the early adult years of bone consolidation with an isoflavone-enriched diet.Objectives: In this controlled, double-blind intervention, we tested the hypothesis that an isoflavone-rich soy protein diet increases BMC and BMD in young adult females over a period of one year in comparison to a control group receiving soy protein that has isoflavones removed.Design: Young healthy women of any ethnic background, 21 to 25 years of age, were divided into two groups, placebo (n = 13) and supplement (n = 15). The soy protein supplement was enriched with isoflavones (∼90 mg of total isoflavones/day), whereas the control protein diet was isoflavone-deficient, even though it contained the same amount of soy protein and other ingredients as the isoflavone-rich diet. Dual-energy x-ray absorptiometric (DXA) measurements of BMC and BMD were made at baseline and at 6 and 12 months. DXA estimates of body composition, including fat mass and lean body mass, were generated from whole-body BMC measurements. BMI was calculated as weight (kg) over height (m) squared. Physical activity was assessed, and three-day dietary records were taken at entry (baseline) and at 6 and 12 months.Results: No changes in BMD after 12 months were found in either the isoflavone-treated (treatment) group or the isoflavone-deficient (control) group. Other variables also remained essentially constant over the 12-month period, including normal menstrual patterns in both the treatment and control groups.Conclusions: The isoflavone-rich soy preparation had no effects on BMC and BMD over a 12-month period in young healthy adult females with normal menses. An isoflavone-rich supplement appears to have little or no effect on bone in young adult women with normal ovarian function, at least over this 12-month study period.

Soya and health 2002 – clinical evidence, dietetic applications

Soya and health 2002 – clinical evidence, dietetic applications

Isoflavones protect against diesel engine exhaust injury in organotypic culture of lung tissue

The wide range of potential health beneficial effects of isoflavones, including a chemoprentive action, have prompted us to study the potential benefits of genistein and daidzein in an experimental model of environmental pollution impact on lung tissue. A diesel engine placed was used to generate reproducible emissions including both gaseous and particulate matters that are commonly found in urban atmospheres. Isoflavones were added to culture medium of rat lung slices 2 h prior to their exposure to pollutants for 3 h. Intracellular ATP and GSH levels, TNFα production, nucleosome assay and TUNEL labeling were monitored. Isoflavones showed almost total in vitro protection against inflammatory and pro-apoptotic responses in lung slices. Isoflavones 0.3 and 1 μmol/l protected against exhaust induced GSH depletion. Isoflavones 0.3 μmol/l appeared to exert the most beneficial effects. In conclusion, this study points out the potential interest of soy isoflavones consumption in polluted areas. Further studies should be undertaken to verify that similar effects could be obtained after in vivo administration of isoflavones.