Effects of genistein and equol on human and rat testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities

The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid de- hydrogenase （3β-HSD） and 17β-hydroxysteroid dehydrogenase 3 （17β-HSD3） in human and rat testis microsomes. These enzymes （3β-HSD and 17β-HSD3）, along with two others （cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17α-hydroxylase/17-20 lyase）, catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3β-HSD activity （0.2 μmol L^-1 pregnenolone） with half-maximal inhibition or a half-maximal inhibitory concentration （IC50） of 87 ± 15 （human） and 636 ± 155 nmol L^-1 （rat）. Genistein＇s mode of action on 3β-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD＋. There was no difference in genistein＇s potency of 3β-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3β-HSD, genistein had lesser effects on human and rat 17β-HSD3 （0.1 μmol L^-1 androstenedione）, with an IC50 〉 100μmol L^-1. On the other hand, equol only inhibited human 3β-HSD by 42%, and had no effect on 3β-HSD and 17β-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3β- HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.     

大豆异黄酮对无菌小鼠脂代谢的影响

目的通过无菌(GF)小鼠模型研究大豆异黄酮(SI)对脂代谢的影响,探讨肠道菌群在大豆异黄酮调节脂代谢中的作用。方法用高脂饲料饲养GF小鼠,并选择低、中、高剂量SI对其进行干预,干预4周后,检测血液中血脂指标和抗氧化指标,称量肝脏、肠和心脏重量后进行比较。结果高脂饲料使GF小鼠血液中总胆固醇、甘油三酯水平升高,同时出现肝脏、肠重量增加,心脏重量减小,SI具有减小肠重量增加幅度和心脏重量降低幅度的保护作用。SI能提高高密度脂蛋白胆固醇(HDL-c)水平,但在GF小鼠实验中未见SI提升抗氧化功能的作用。结论 SI对高脂饮食下的心脏和肠道有保护作用,且能提高HDL-c,预防动脉粥样硬化的发生,提示SI对脂代谢的有益作用不完全依赖于其肠道菌群代谢产物雌马酚。     

大豆异黄酮代谢产物——雌马酚对更年期症状的影响研究

目的探讨大豆异黄酮代谢产物——雌马酚对妇女更年期症状的影响。方法经筛选的71名久居哈尔滨市45～55岁更年期妇女为调查对象,采用HPLC法检测其清晨第一次空腹尿样中雌马酚及其前体大豆异黄酮浓度,被调查者完成Kupperman评分问卷,用以评价其更年期症状严重程度,采用统计分析方法研究尿中雌马酚代谢与更年期症状的关系。结果尿中雌马酚浓度与更年期指数评分值之间存在数量上的负相关关系(P<0.05),按0.5μg/ml分组之后,负相关关系只表现在产雌马酚组。结论更年期妇女尿中雌马酚含量越高,更年期症状越轻。     

Development of ELISAs for the measurement of the dietary phytoestrogens daidzein and equol in human plasma

Microtitration plate ELISAs were developed for the isoflavone daidzein, a phytoestrogen found mainly in soya and the mammalian metabolite of daidzein, equol. The detection limits in assay buffer were 21 pg per well for daidzein and 70 pg per well for equol. The assays were both highly specific. Human plasma was extracted with an organic solvent and standard curves for daidzein and equol were obtained in the presence of the extract. Applications of the assays are discussed.     

Effects of Yeast Mannan Which Promotes Beneficial Bacteroides on the Intestinal Environment and Skin Condition: A Randomized,Double-Blind,Placebo-Controlled Study

Yeast mannan (YM) is an indigestible water-soluble polysaccharide of the yeast cell wall. In vitro fecal fermentation studies showed that YM could exhibit a notable prebiotic effect. The aim of this randomized, double-blind, placebo-controlled study was to assess the efficacy of YM intake on the intestinal environment and skin condition. One hundred and ten healthy female subjects aged 30–49 years were supplemented with YM or placebo for eight weeks. Skin dryness was set as the primary endpoint. No side effects were observed during the study. Microbiota analyses revealed that YM intake selectively increased the relative abundance of Bacteroides thetaiotaomicron and Bacteroides ovatus compared to that by placebo. Feces and urine analyses showed that YM intake lowered the concentration of fecal p-cresol, indole, and skatole, and elevated urinal equol levels compared to those in placebo. Furthermore, YM supplementation ameliorated subjective skin dryness. This study suggests that YM intake could promote beneficial Bacteroides and improve the intestinal environment and skin condition.     

北京地区成人雌马酚代谢表型与血清性激素关系研究

目的确定北京地区成人雌马酚代谢表型与血清性激素的关系。方法应用现况调查方法,调查北京市区180名20～72岁志愿者生活方式及膳食营养素摄入量;采用高效液相色谱法(HPLC)分析负荷大豆异黄酮(Iso)前后尿中雌马酚等大豆异黄酮24h排泄量,分析雌马酚代谢表型与血清性激素的关系。结果男性血清总睾酮浓度,女性血清雌二醇和孕酮浓度,在产雌马酚者与非产生者间差异无显著性(P>0.05)。在男性产雌马酚者中,日常膳食情况下的尿液总大豆异黄酮、大豆素、雌马酚、邻脱甲基安哥拉柴檀素、黄豆黄素和双氢黄豆黄素24h排泄量与血清总睾酮浓度呈负相关(r=-0.29～-0.36,P<0.05);而女性日常膳食情况下的尿液大豆异黄酮代谢产物24h排泄量与血清雌二醇和孕激素相关性无统计学意义(P>0.05),且与雌马酚代谢表型无关。结论日常膳食Iso暴露与男性血清总睾酮水平有关。     

雌马酚对PC12细胞缺氧/复氧损伤的保护作用及其机制

目的探讨雌马酚对PC12细胞缺氧/复氧损伤的保护作用及机制。方法以PC12细胞为研究对象,构建体外神经元缺氧/ 复氧损伤模型,用雌马酚进行干预。MTT法检测细胞活力,比色法测定细胞培养上清液中乳酸脱氢酶（LDH）活性和丙二醛（MDA）含量,免疫细胞化学法检测活性氧（ROS）含量,Western blotting 检测缺氧/复氧损伤的PC12 细胞内NADPH氧化酶2 （gp91phox）和磷酸化Src（p-Src）激酶的表达。结果雌马酚可有效减轻缺氧/复氧引起的PC12细胞损伤,降低缺氧/复氧损伤细胞培养上清液中LDH的活性和MDA的含量,明显抑制ROS的生成及gp91phox和p-Src的表达。结论雌马酚通过抑制p-Src激酶和gp91phox表达,减少ROS生成,从而对PC12细胞缺氧/复氧损伤产生保护作用。     

Counts of Slackia sp. strain NATTS in Intestinal Flora are Correlated to Serum Concentrations of Equol both in Prostate Cancer Cases and Controls in Japanese Men

Background: Isoflavones, which are included in soybeans, have been suggested to protect against prostatecancer. Equol, one of isoflavones, is an intestinally derived bacterial metabolite of daidzein. A newly identifiedequol-producing bacterium, Slackia sp. strain NATTS, with a high equol-producing activity was isolated fromhuman feces in Japanese adults. Counts of Slackia sp. strain NATTS in intestinal flora have not been assessedwith regard to prostate cancer risk. In this study, we investigated the association of serum isoflavones andcounts of Slackia sp. strain NATTS with prostate cancer risk in a case-control study. Materials and Methods:Concentrations of isoflavones and counts of Slackia sp. strain NATTS in feces were measured from 44 patientswith prostate cancer and 28 hospital controls. The risk of prostate cancer was evaluated in terms of odds ratios(ORs) and 95% confidence intervals (CIs) by the logistic regression analysis. Results: The detection proportions ofSlackia sp. strain NATTS in cases and controls were 34.1% and 25.0%, respectively. Counts of Slackia sp. strainNATTS were significantly correlated with serum concentrations of equol both in cases and controls (Spearmancorrelation coefficients, rs=0.639 and rs=0.572, p<0.01, respectively). Serum concentrations of genistein, daidzein,glycitein, and equol were not significantly associated with risk of prostate cancer. Conclusions: This study foundthat counts of Slackia sp. strain NATTS correlated with serum concentrations of equol both in prostate cancercases and controls, but serum isoflavone concentrations were not associated with risk of prostate cancer in ourpatients.     

Higher Consumption of Green Tea may Enhance Equol Production

Background: Our previous case-control study revealed that Japanese living in Japan and Koreans living in ‍Korea can be divided into equol producers who have an ability to metabolize daidzein to equol and non-producers, ‍and that the incidence of prostate cancer is higher in the latter group. In the present study, we examined relationships ‍between type of food intake and the capacity for equol production in Japanese subjects. ‍Methods: The subjects were the individuals analyzed for the ability to produce equol in our previous study and ‍newly registered cases. From December 2000 to December 2002, 276 hospitalized patients were interviewed face-toface ‍and blood samples were collected before breakfast. These included 122 patients with prostate cancer and 154 ‍age-matched controls. Result: The frequency of equol producers (0.5 ng/ml or more) among cases and controls was ‍29% and 45%, respectively (p = 0.004). The consumption of soybeans and green tea were significantly higher in ‍equol producers than in the non-producers (p<0.05). By contrast, the consumption of selenium and fiber was ‍significantly lower in equol producers (p<0.05). Conclusion: Our results suggest that higher consumption of soybean ‍and green tea are strongly related to the establishment of a capacity for equol production.