Pueraria isoflavones inhibit XOD and GLUT9 to decrease uric acid production and promote uric acid excretion, respectively

Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male Kunming mice were divided into the healthy group (carboxymethylcellulose sodium at a dose of 250 mg/kg), the model group (HUA mice were given carboxymethylcellulose sodium at a dose of 250 mg/kg), the low group (HUA mice were given pueraria isoflavone at a dose of 125 mg/kg), HUA mice were given pueraria isoflavones at a dose of 250 mg/kg once d frequency)and the high group (HUA mice were given pueraria isoflavones at a dose of 500 mg/kg once d frequency) dosage groups, with 8 mice in each group. The contents of uric acid (SUA), urea nitrogen (BUN) and creatinine (SCr) in serum and urine of each group were compared before and after intervention (30 d). Statistical differences of xanthine oxidase (XOD) and human glucose transporter 9(GLUT9), cy- clooxygenase- 2(COX-2), tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) contents in renal tissues of each group after intervention (30 d) were compared. Results: After intervention, kidney inflammatory factors (COX-2, TNF-α and IL-1β) in the model group were compared. Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were higher than those of healthy group(P<0.05). Renal inflammatory cytokines (COX-2, TNF-α and IL-1β) in low, medium and high dose groups;Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were lower than those of model group, and there were low > medium > high dose groups, the comparison between the two groups had statistical significance(P< 0.05). After intervention, the contents of 3 indicators in blood or urine(COX-2, TNF-α and IL-1β) all decreased compared with before intervention, and the differences in intra-group comparison were statistically significant (P<0.05). Conclusion: Pueraria isoflavones can treat HUA mice by inhibiting the expression of XOD and GLUT9, and then play a role in reducing uric acid pro- duction and promoting uric acid excretion, as well as alleviating the degree of disease inflammation.

ISOFLAVONES FROM ASTRAGALUS MEMBRANACEUS

Two new isoflavones (8, 3'-dihydroxy-7,4'-dimethoxyisoflavone, odoratin-7-0-[3-D-glu-copyranoside) and four known isoflavones (formononetin, 7,3'-dihydroxy-8,4'-dimethoxyisoflavone, calycosin, calycosin-7-0-(3-D-glucopyranoside) were isolated from the roots of Astragalus mem-branaceus (Fisch.) Bunge. Their structures were established by spectral analysis.

Process for the Preparation of Chromones, Isoflavones and Homoisoflavones Using Vilsmeier Reagent Generated from Phthaloyl Dichloride and DMF

Vilsmeier reagent formed from phthaloyl dichloride and DMF was found to be very effective for converting 2-hydroxyacetophenones, deoxybenzoins and dihydrochalcones into corresponding chromones, isoflavones and homoisoflavones with excellent yield. This method offers significant advantages such as efficiency and mild reaction conditions with shorter reaction time.

Inhibitory Effect of Isoflavones on Prostate Cancer Cells and PTEN Gene

Objective To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells. Methods LNCaP and PC-3 cells were exposed to genistein and daldzein and cell viability was determined by MTF assay and cytotoxicity of the drugs by LDH test. Flow cytometry （FCM） was used to assess the cell cycle in LNCaP and PC-3 cells. Reverse transcription-polymerase chain reaction （RT-PCR） was applied to examine the expression of PTEN gene （a tumor suppressor gene）, estrogen receptor alpha gene （ERα）, estrogen receptor beta gene （ERβ）, androgen receptor gene （AR） and vascular endothelial growth factor gene （VEGF）. Results The viability of PC-3 and LNCaP cells decreased with increasing concentrations and exposure time of genistein and daidzein. Genistein increased G2/M phase cells in PC 3 cells while decreased S phase cells in LNCaP cells in a dose-dependent manner. Daidzein exerted no influence on the cell cycle of LNCaP and PC-3 cells, but the apoptosis percentage of LNCaP cells was elevated significantly by daidzein, Genistein induced the expression of PTEN gene in PC-3 and LNCaP cells. Daidzein induced the expression of PTEN gene in LNCaP but not in PC-3 cells. The expression of VEGF, ERα and ERβ genes decreased and AR gene was not expressed after incubation with genistein and daldzein in PC-3 cells. In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of ERα and ERβ gene after incubation with genistein and daidzein. Conclusion Genistein and daidzein exert a timeand dose-dependent inhibitory effect on PC-3 and LNCaP cells. The down-regulation of ER gene by daidzein influences the growth of PC-3 ceils directly, The inhibition of PC-3 cells by genistein and that of LNCaP cells by genistein and daidzein may be via Alct pathway that is repressed by PTEN gene, which subsequently down-regulates the expression of AR and VEGF genes. Our results suggest that the expression of PTEN gene plays a key role and several pathways may be involved in the suppression of prostate cancer cells by genistein and daidzein.

Effects of Dietary Soy Isoflavones on Feed Intake,Growth Performance and Digestibility in Juvenile Japanese Flounder(Paralichthys olivaceus)

An 8-week feeding trial was conducted to investigate the effects of dietary soy isoflavones on feeding intake,growth performance,and digestion of juvenile Japanese flounder(Paralichthys olivaceus).Four isonitrogenous(49% crude protein) and isoenergetic(20.1 MJ kg-1) diets were formulated to contain four graded levels of soy isoflavones,namely,0,1,4 and 8 g soy isoflavones in 1 kg of diet.Each diet was randomly fed to triplicate tanks of fish(Initial average weight:2.58 g ± 0.01 g),and each tank was stocked with 35 fish.No significant difference was observed among diets with levels of 0,1 and 4 g kg-1 soy isoflavones in feed intake,weight gain,feed efficiency ratio(FER),proximate composition of fish whole body and apparent digestibility coefficients(ADC) of nutrients and energy(P>0.05).However,high dietary soy isoflavones level(8 g kg-1) significantly depressed weight gain,FER,whole-body crude lipid content of fish and ADC of nutrients(P<0.05).These results indicate that high level of dietary soy isoflavones(above 4 g kg-1) significantly depresses growth responses and FER of Japanese flounder.However,as the content of soy isoflavones in soybean meal is around 1 to 3 g kg-1,the adverse effects might be neglected when soybean products are used as a fish feed ingredient.

Developmental and Reproductive Toxicity of Soybean Isoflavones to Immature SD Rats

Objective To investigate the dose-dependent toxic effect of soybean isoflavone extracts （SIE） on reproductive development in immature rats. Methods Growing male and female rats （n=50 each, 4 weeks） were divided into five groups fed with a standard cereal-based diet and gastrogavaged daily with 0, 30, 150, 300, and 600 mg SIE / kg body weight, respectively, for 12 weeks. Body weight, organ weights, and serum level of estrogen and testosterone were measured. Results Oral administration of SIE had no effect on food intake but decreased food efficiency ratio （P〈0.01）. Suppression on body weight gain by SIE was dose-dependent and the effect was greater on male than on female rats （P〈0.01）. SIE at high doses exhibited hepatotoxicity by increasing a relative liver weight, and also caused a smaller uterus but a greater relative ovary in female rats, while leading to larger relative testis and epididymis in male rats. SIE could decrease progesterone concentrations in female rats, whereas in male rats it reduced not only total testosterone level but also sperm count compared with the control group （P〈0.05）. Conclusion SIE at a range of 50-1000 times of human intake level affects not only growth but also development of reproductive system in growing rats.

Estrogen Receptor α and β Expressions in Hypothalamus-pituitary-ovary Axis in Rats Exposed Lactationally to Soy Isoflavones and Bisphenol A

Objectives This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones （SIF） and bisphenol A （BPA） and to examine estrogen receptor α （ERα） and estrogen receptor β （ERβ） expressions in hypothalamus-pituitary-ovary axis and uterus.Methods Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group.Dams in different treatment groups received corn oil （control）,150 mg/kg BW of SIF,150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA,respectively,from postnatal day 5 to 11 （PND5-11） by gavage.On PND12 and PND70,10 female litters were killed and hypothalamus,pituitary,ovary and uterus were collected.ERα and ERβ expressions in these organs were detected with Western blotting assay.And vaginal opening time and estrus cycle were examined in animals fed for PND70.Results On PND12,the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats （P〈0.05）.But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA.On PND 70,however,the relative uterine weight in each treatment group was not statistically different from that in the control group （P〈0.05）.Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group （P〈0.05）.Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus,pituitary,ovary and uterus on PND12 and PND70.These regulation patterns for ERα and ERβ were different in different organs at different time points.Conclusion Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats,which disappeared in later life.But these data fail to suggest a possibility for synergic actions between SIF and BPA.It was also demonstrated that the uterotrophic effects of SIF and BPA exposure might,at least,involve modification of ERα or ERβ expressions in the hypothalamus-pituitary-ovary axis.

Consumption of soybean,soy foods,soy isoflavones and breast cancer incidence:Differences between Chinese women and women in Western countries and possible mechanisms

Breast cancer is one of the most lethal diseases world-wide.However,there is a large difference in breast cancer incidence among Caucasian,Hispanic,African and Asian(e.g.Chinese)women with Caucasian women being the highest and Asian women being the lowest.It has been suggested that the dietary factors may account for approximately 50%of the breast cancer.One of such dietary components which are typical to Asian but not Caucasian diet is soy foods.A number of epidemiological studies have suggested that increasing soy consumption could be related to the decreased risk of occurrence and/or mortality of breast cancer.In this review,we first described briefly different types of soy products and their nutritional functions and consumption.Then,we described briefly soybean isoflavones,i.e.genistein(GEN),daidzein,glycitein,and presented several lines of evidence to demonstrate the possible association of soy flavone food consumption with incidence and prognosis of breast cancer;finally,we summarized several possible molecular mechanisms,including the effects of GEN as an agonist of ER,epigenetic and genome-wide effects,activation of peroxisome proliferator-activated receptors,induction of apoptosis and stimulation of autophagy,involved in the chemo-preventive effects of GEN on breast cancer.©2013 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Isoflavones’effects on pharmacokinetic profiles of main iridoids from Gardeniae Fructus in rats

Gardeniae Fructus(GF)and Semen Sojae Praeparatum(SSP)are both medicine food homologies and widely used in Chinese clinical prescriptions together.The research investigated the pharmacokinetics of four iridoids in normal rats and isolfavones-fed rats,which were administered with isolfavones from SSP for 7,14,21 and 28 consecutive days.A validated LC-MS/MS method was developed for determining shanzhiside,genipin-1-gentiobioside,geniposide and their metabolite genipin in rat plasma.Plasma samples were pretreated by solid-phase extraction using paeoniflorin as the internal standard.The chromatographic separation was performed on a Waters Atlantis T3(4.6 mm×150 mm,3 mm)column using a gradient mobile phase consisting of acetonitril and water(containing 0.06%acetic acid).The mass detection was under the multiple reaction monitoring(MRM)mode via polarity switching between negative and positive ionization modes.The calibration curves exhibited good linearity(r>0.997)for all components.The lower limit of quantitation was in the range of 1 e10 ng/m L.The intra-day and inter-day precisions(RSD)at three different levels were both less than 12.2%and the accuracies(RE)ranged fromà10.1%to 16.4%.The extraction recovery of them ranged from 53.8%to 99.7%.Pharmacokinetic results indicated the bioavailability of three iridoid glycosides and the metabolite,genipin in normal rats was higher than that in rats exposed to isoflavones.With the longer time of administration of isoflavones,plasma concentrations of iridoids decreased,while genipin sulfate,the phase II metabolite of genposide and genipin-1-gentiobioside,appeared the rising exposure.The pharmacokinetic profiles of main iridoids from GF were altered by isoflavones.

Two new C-glucofuranosyl isoflavones in puerarin injection

Two new C-glucofuranosyl isoflavones of impurities in puerarin injection were isolated. Their structures were detemained to be 8-C-α-glucofuranosyl-7, 4P-dihydroxyisoflavone and 8-C-β-glucofuranosyl-7, 4＇-dihydroxy- isoflavone by chemical and spectral analysis.

Soybean Seed Phenol, Lignin, and Isoflavones and Sugars Composition Altered by Foliar Boron Application in Soybean under Water Stress

Previous research showed that foliar boron (B) application at flowering or seed-fill growth stages altered seed protein, oil, and fatty acids. The objective of this research was to investigate the effects of foliar B fertilizer on seed phenolics (phenol, lignin, and isoflavones) and sugars concentrations. A repeated greenhouse experiment was conducted on soybean [(Glycine max(L.) Merr.)] under watered and water-stressed conditions. Soybean plants were divided into different sets, and each set was subjected to one of the following treatments: W = plants were watered with no foliar B;WB = plants were watered and received foliar B;WS = plants were water-stressed with no foliar B;WSB = plants were waterstressed and received foliar B. Foliar B was applied at rate of 0.45 kg/ha twice at flowering and twice at seed-fill stages. The results showed that total phenol and lignin concentrations were higher in seed collected from water-stressed plants compared with those collected from watered plants whether B was applied or not. The higher total phenol and lignin concentration in seed collected of water-stressed plants may be due to B-deficiency in plant tissues. Application of B resulted in higher concentrations of total seed B and isoflavones under watered and water-stressed plants. Higher cell wall B was higher in water-stressed plants than in watered plants, having an opposite trend to total B. Application of B resulted in higher seed sucrose in watered and water-stressed plants, but raffinose and stachyose were significantly higher under water-stressed plants. The research demonstrated that foliar B fertilizer altered seed phenol, lignin, isoflavones, and sugars, suggesting that B involved in phenolics and sugar metabolism. The higher cell wall B in waterstressed plants than in watered plants supports previous research that B has mainly a structural role. The higher sucrose resulting from foliar B in watered plants is desirable as sucrose contributes to seed quality. The increase of raffinose and stachyose concentrations in seed of water-stressed plants is undesirable as raffinose, and especially stachyose may be involved in water stress/drought tolerance. The current knowledge would help soybean breeders select for higher phenolic compounds and desirable sugars for higher seed qualities under drought conditions.

Effects of soybean isoflavones on reproductive parameters in Chinese mini-pig boars

Background： Soybean isoflavones are structurally similar to mammalian estrogens and therefore may act as estrogen agonists or antagonists. However, it has not been determined if they have any negative effects on reproductive parameters in male livestock. Therefore, the objective of this study was to evaluate the effects of soybean isofiavones on male reproduction using Chinese mini-pig boars as a model. Fifty Xiang boars were randomly divided into five groups and fed diets containing 0, 125, 250, or 500 ppm soybean isoflavones or 0.5 ppm diethylstilbestrol for 60 days. Results： Dietary supplementation with 250 ppm of soy isoflavones markedly increased the testis index （P 〈 0.05）, fructose content （P 〈 0.05）, and o-glycosidase content in testicular tissue （P 〈 0.01）, as well as increased the number of viable germ cells （P 〈 0.01） and the level of Bcl-2 protein （P 〈 0.01）. However, 500 ppm of soybean isoflavones significantly reduced both testis and epididymis indexes （P 〈 0.0S） and lactate dehydrogenase levels （P 〈 0.01）, as well as reduced serum LH and testosterone levels （P 〈 0.05）. High levels of soybean isoflavones also increased malondialdehyde levels （P 〈 0.05）, as well as increased the numbers of early and late apoptotic germ cells （P 〈 0.01） and the level of Bax proteins （P 〈 0.05） in the testis. Conclusions： The results of this study indicate that consumption of soy isoflavones at dietary levels up to 250 ppm did not adversely affect reproductive parameters in Chinese mini-pig boars whereas higher levels of soy isoflavones may adversely affect male reproduction.

A value-added cooking process to improve the quality of soybean:Protecting its isoflavones and antioxidant activity

This study investigated the effects of domestic cooking process on the variations of soybean isoflavones,aiming at understanding the conversion of-glucosides and aglycones isoflavones during the process and the relation with antioxidant activity.It was found that-glucosides isoflavones was significantly increased from 223.01(raw)to 727.29 mg/g(frying at 160◦C for 2 min),but boiling showed only a slight increase to 258.14 mg/g.The process for the mixed cooking of soybeans with vegetables was also evaluated,which is quite common in home cuisine.The results showed all bioactive ingredients were aggressively destroyed by over processing,but interestingly,green pepper and kelp exhibited isoflavones generation potentials for soybean.In addition,cooking from 60 to 160◦C for 2 or 5 min,showed a significantly decrease on FRAP.However,in the case of fried soybeans which treated at 120◦C or 160◦C,when extending the heating time to 5 min,their FRAP activity got a significant increase.The present study may provide a practical guidance for healthy soybean cooking,by using frying around 120◦C for 5 min and mixed with some vegetables such as green peppers or kelp.

Effects of Soy Isoflavones on the Sex Hormone Level and Pathological Changes in the Perimenopausal Syndrome Animal Model

[Objectives] To observe the effect of soy isoflavones on the perimenopausal syndrome model of female rats,and to find its mechanism,in order to provide experimental evidence for the clinical treatment of menopausal syndrome. [Methods]50 female SD rats were randomly divided into five groups,with 10 rats in each group,respectively,for the normal control group,sham operation group,model group,diethylstilbestrol group,soy isoflavone treated group,except the normal control group and sham operation group,the other groups were ovariectomized rats,the formation model of perimenopausal rats treated with normal saline,diethylstilbestrol,soy isoflavone by gavage,normal control group and sham operation group were given the same dose of normal saline and soy isoflavone by gavage. After 6 weeks of continuous treatment,abdominal aorta was taken blood,the serum was isolated,and radioimmunoassay method to measure E_2( Eestradiol),P( Progesterone),T( Testosterone). And removal of the pituitary gland,uterine and adrenal prepared pathological section,experimental effect was observed by light microscopy,using immunohistochemical method to observe the brain pituitary FSH( Follicle-Stimulating Hormone) and LH( Luteinizing Hormone) levels. [Results] Radiation immune analysis results showed that soy isoflavone could significantly improve serum E_2 level in ovariectomized rats,compared with the model group,the statistical analysis showed significant difference( P < 0. 05),but the serum P and T level had little effect. The pathological results showed that( i) uterus: the uterine wall and endometrial thickness of soy isoflavone group was between that of model group and sham operation group,the surface epithelium was columnar,glands increased;( ii) pituitary gland: soy isoflavone ovariectomized group cells were between model group and normal group;( iii) adrenal gland: soy isoflavone group adrenal tissue did not change significantly. Immunohistochemical results showed that soy isoflavone group pituitary tissues of FSH and LH cells compared with the model group decreased significantly. [Conclusions] The soy isoflavones could make the uterus wall and endometria of perimenopausal syndrome animal model thicken,improve the serum level of E_2 in ovariectomized rats,and decrease the level of FSH and LH,but had little effect on the adrenal tissues,level of T and P.

Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease

Fatty liver disease(FLD) is a growing public health problem worldwide. There is an urgent requirement for alternative and natural medicine to treat this disease. As phytochemicals, isoflavones have attracted considerable attention for the prevention of FLD. Numerous studies have revealed that isoflavones protect against FLD through various pathways which modulate fatty acid β-oxidation, lipid synthesis, and oxidative stress. Recently, the aldose reductase(AR)/polyol pathwayhas been reported to be involved in the development of FLD by modulating hepatic fructose production, peroxisome proliferator-activated receptor(PPAR)α activity, cytochrome P450(CYP)2E1 expression, and gut bacterial endotoxin-induced cytokine release. It has been reported that some isoflavones are potent AR inhibitors. Here, we review the anti-FLD actions of isoflavones and the proposed mechanism whereby isoflavones protect against FLD, with regard to the AR/polyol pathway. We propose that isoflavones block the AR/polyol pathway and in turn reduce fructose production and subsequent fat accumulation in the liver in diabetic or high-glucose-diet mice. In addition, in rodents with alcoholic liver disease or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, inhibition of AR by isoflavones may improve PPARα-mediated fatty acid oxidation, reduce hepatic steatosis, and attenuate CYP2E1-mediated oxidative stress or AR/gut bacterial endotoxin-mediated cytokine overproduction, to alleviate progression of FLD.

Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate

Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.

Molecular docking studies of human MCT8 protein with soy isoflavones in Allan-Herndon-Dudley syndrome(AHDS)

Monocarboxylate transporter-8 （MCT8） is a specific thyroid hormone transporter, essential for the uptake of thyroid hormone into target tissues. Mutations in the MCT8 gene have been identified as the cause of Allan-Herndon-Dudley syndrome （AHDS）. It has been reported that soy isoflavones influence thyroid hormone system and can interact with thyroid hormone transporter proteins. Therefore, the present study aimed to find out whether soy isoflavones （genistein, daidzein and glycitein） can be used as a natural inhibitor to target MCT8 in AHDS. Docking studies were performed for soy isoflavones in order to evaluate their binding affinity to MCT8 protein using AutoDock4 （version 4.2.6） and AutoDock Vina. After docking, the ligands were ranked according to their binding energy and the best lead compound was selected based on the least binding energy. The docking results indicated that daidzein possesses the lowest binding energy against MCT8. Moreover, it was found that the residues PRO-338, HIS-341, and GLU-348 were involved in hydrogen bond interactions with genistein and daidzein. This study suggests that daidzein is a promising natural inhibitor to target MCT8 in AHDS.

Dietary isoflavones,the modulator of breast carcinogenesis:Current landscape and future perspectives

Breast cancer is a frightful disease and serious concern in women around the world causing significant health care burden in both developed and developing countries. Extensive research work has shown that breast cancer provides strong resistance to chemical agents, U V radiation,and hormonal treatments. It is generally accepted that cell genetics is not the only main reason for breast cancer and genetic risk factors, for example, mutations in RRCAI and BRCA2 genes constitute 5%-10% of all breast cancer rates. Other related factors include age, gender,race, ethnicity, weight, reproductive factors, exo-and endogenous hormonal exposures, oral contraceptives use, ultraviolet radiation, diet, and night work(circadian disruption). Many studies have revealed that dietary isoflavones regulate breast cancer occurrence, recurrence and prognosis. Dietary isoflavones have long been part of Asian population diet and there is a significant increase as compared to dietary isoflavones intake among other populations. Dietary isoflavones are natural phytoestrogens having both estrogenic and anti-estrogenic potentials on breast cancer cells in culture, animal models and in experimental trials. This literature survey provides a comprehensive overview on the tumor preventive and tumor promoting potentials of dietary isoflavones on breast cancer. In addition, this paper provides a literature review of dietary isoflavones and their effects on up-regulation and down-regulation of different signaling pathways, genes and proteins. Finally, future perspectives of dietary isoflavones and breast cancer researchers are also critically discussed, which will provide a deeper insight regarding the inner molecular mechanisms of action.

Soybean Seed Protein, Oil, Fatty Acids, and Isoflavones Altered by Potassium Fertilizer Rates in the Midsouth

Previous research has shown that the effect of potassium fertilizer on soybean ([Glycine max (L.) Merr.] seed composition (protein, oil, fatty acids, and isoflavones) is still largely unknown. Therefore, the objective of this research was to investigate the effects of potassium application on seed protein, oil, fatty acids, and isoflavones under Midsouth environmental conditions. A three-year experiment was conducted in two locations (Milan, TN and Jackson, TN). Potassium (K) rates were applied in the form of K2O at a rate of 0 (Control, C), 45 (T1), 90 (T2), 134 (T3), and 179 (T4) kg·ha-1 in a randomized complete block design. The results showed that increasing the K application rate did not result in consistent effects on yield. However, increasing K application rate did increase protein, oleic acid, and individual and total isoflavone concentrations at both locations in 2008 and 2009. In Jackson in 2010, the increase of K rate did not change oleic acid, but resulted in an increase in glycitein and genistein isoflavone concentrations. In 2010, increasing K application rate increased protein concentrations, decreased individual and total isoflavones, and did not change oleic acid concentration at Milan. At the highest rate of K, 179 kg·ha-1, yield and some seed composition constituents were negatively impacted. Generally, K concentration in leaves at V5, R1, R3, and seed at harvest maturity stage (R8) increased with the increase of K rate applications. The research demonstrated that K application can alter seed composition, but this alteration depended on location, environmental stress factors, mainly heat and drought, K level in soil, and K application rate. Higher rates of K application may negatively impact seed composition constituents.

Effect of total isoflavones from pueraria lobata on the expressions of preproenkephalin, prodynorphin and D2 dopamine receptor mRNA in PC12 cells induced by MPP^+

Objective： The aim of the study was to observe the effect of total isoflavones from pueraria Iobata （TIP） on D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions in Parkinson＇s disease （PD） model cells induced by 1-methyl-4-phenylpyridinium ion （MPP^＋）. Methods： TIP was dissolved in 0.1 M NaOH and added to the culture medium at a final concentrations of 50 mg/L, 100 mg/L and 200 mg/L. Some cells （control） were exposed to 0.001 M NaOH. TIP was added to PC12 cells 30 min prior to the administration of MPP^＋. TIP and MPP^＋ remained in the culture medium for 96 h. D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions were assayed by real-time quantitative reverse transcription-PCR. Results： The D2 dopamine receptor mRNA and preproenkephalin mRNA expressions were up-regulated in MPP^＋ group compared with the control group, and prodynorphin mRNA expression was down-regulated in that. The D2 dopamine receptor mRNA expression being down-regulated and prodynorphin mRNA expression being up-regulated in TIP group compared with the MPP^＋ group. And there was no effect of TIP on preproenkephalin gene expression in PC12 cells induced by MPP^＋. Conclusion： The results suggest that TIP down-regulates the D2 dopamine receptor mRNA expression, up-regulates prodynorphin mRNA expression and not affects preproenkephalin gene expression in PC12 cells induced by MPP^＋.