脱脂豆粉对去卵巢大鼠骨质量的保护作用

目的 探讨脱脂豆粉对去卵巢大鼠骨质量减低的预防作用。方法 ３０只３月龄ＳＤ大鼠随机分为３组：假手术（ｓｈａｍ,Ｓ）组、脱脂粉（ｌｉｐｉｄ－ｆｒｅｅ ｓｏｙ ｐｏｗｄｅｒ,ＳＰ）组和酪蛋白（ｃａｓｅｉｎ,Ｃ）组。８周后测骨密度（ＢＭＤ）等指标。结果 ①ＳＰ组的腰椎ＢＭＤ低于Ｓ组（Ｐ〈０．０５）,股骨ＢＭＤ与Ｓ组无差异,两者均高于Ｃ组（Ｐ均〈０．０５）。②ＳＰ组腰椎的抗压强底低于Ｓ组（Ｐ〈０．０１）,股骨的抗弯强度与Ｓ组无差异,两者均高于Ｃ组（Ｐ均〈０．０１）。③ＳＰ组和Ｃ组的子宫重量均代于Ｓ组（Ｐ均〈０．０５）。结论 脱脂豆粉可以预防去卵巢大鼠股骨及部分预防其腰椎骨质量的降低,对子宫无不良影响。     

Role of phytoestrogens in prevention and management of type 2 diabetes

Type 2 diabetes(T2D)has become a major public health threat across the globe.It has been widely acknowledged that diet plays an important role in the development and management of T2D.Phytoestrogens are polyphenols that are structurally similar to endogenous estrogen and have weak estrogenic properties.Emerging evidence from pre-clinical models has suggested that phytoestrogens may have anti-diabetic function via both estrogendependent and estrogen-independent pathways.In the current review,we have summarized the evidence linking two major types of phytoestrogens,isoflavones and lignans,and T2D from epidemiological studies and clinical trials.The cross-sectional and prospective cohort studies have reported inconsistent results,which may due to the large variations in different populations and measurement errors in dietary intakes.Long-term intervention studies using isoflavone supplements have reported potential beneficial effects on glycemic parameters in postmenopausal women,while results from short-term smallsize clinical trials are conflicting.Taken together,the current evidence from different study designs is complex and inconsistent.Although the widespread use of phytoestrogens could not be recommended yet,habitual consumption of phytoestrogens,particularly their intact food sources like soy and whole flaxseed,could be considered as a component of overall healthy dietary pattern for prevention and management of T2D.     

Association of dietary isoflavone consumption with subclinical cardiovascular disease in middle-aged and elderly Chinese people

Background and aimsThe association between isoflavone (ISF) consumption and cardiovascular disease (CVD) remains controversial because of limited evidence. Carotid atherosclerosis is an established indicator of subclinical CVD. The study aimed to investigate the relationship between dietary ISF intake and subclinical CVD in middle-aged and elderly adults.Methods and resultsA total of 873 subjects aged 40–70 years without CVD were enrolled in this cross-sectional study. A restricted cubic spline was used to investigate the association between ISF intake and subclinical CVD risk. The odds ratio (OR) and 95% confidence interval of the risk of subclinical CVD for ISF were estimated by two-segmented logistic regression analysis. In Model 2, there was a non-linear association between ISF intake and the risk of subclinical CVD among women (P_non-linear = 0.002), with an inverse association below the change point. The nadir for the risk of subclinical CVD among women was 7.26 mg/day (energy-adjusted). Below the change point, an increase of 1 mg ISF/day reduced the risk of subclinical CVD by 15%. There was no significant association between ISF intake and subclinical CVD risk above the change point (OR = 1.01 [0.99, 1.04]). ISF intake was not associated with subclinical CVD risk in men (Model 2: P_non-linear = 0.224).ConclusionsBelow the change point (7.26 mg/day), women with a higher intake of ISF had a significantly lower risk of subclinical CVD. Encouraging the consumption of ISF-rich foods may help to lower CVD risk in middle-aged and elderly women.Trial registrationThis study is registered at http://www.chictr.org.cn (ChiCTR 1900022445).     

Isoflavones and Prostate Cancer: A Review of Some Critical Issues

Objective:

The purpose of this review is to discuss some critical issues of isoflavones protective against the development of prostate cancer (PCa).

Data Sources:

Data cited in this review were obtained primarily from PubMed and Embase from 1975 to 2015.

Study Selection:

Articles were selected with the search terms “isoflavone”, “Phytoestrogen”, “soy”, “genistin”, and “PCa”.

Results:

Isoflavones do not play an important role on prostate-specific antigen levels reduction in PCa patients or healthy men. The effect of isoflavones on sex hormone levels and PCa risk may be determined by equol converting bacteria in the intestine, specific polymorphic variation and concentrations of isoflavones. The intake of various types of phytoestrogens with lower concentrations in the daily diet may produce synergistic effects against PCa. Moreover, prostate tissue may concentrate isoflavones to potentially anti-carcinogenic levels. In addition, it is noteworthy that isoflavones may act as an agonist in PCa.

Conclusions:

Isoflavones play a protective role against the development of PCa. However, careful consideration should be given when isoflavones are used in the prevention and treatment of PCa.     

大豆异黄酮对大鼠骨密度及骨代谢生化指标的影响

目的 研究植物雌激素-大豆异黄酮对大鼠骨密度及骨代谢生化指标的影响。方法 将断乳Wister大鼠按体重随机分为4组，分别给予基础饲料和不同剂量的大豆异黄酮。每周称体重，调整给食量。12周后处死大鼠，取脏器称重，计算脏体比值；剥离股骨，测骨矿物质含量(BMC)、骨密度(BMD)和骨钙、骨磷的含量；对血清中骨形成生化指标碱性磷酸酶、骨钙素和骨吸收生化指标抗酒石酸酸性磷酸酶进行检测，同时测定雌激素-雌二醇(E2)的含量。结果 具有弱雌激素样作用的大豆异黄酮对实验大鼠的子宫、卵巢无刺激作用。与对照组相比，给予大豆异黄酮能提高BMC、BMD及骨钙含量，并随剂量的增加而增大。大豆异黄酮可影响骨代谢，高剂量的大豆异黄酮(41．6mg／kg)同时抑制骨形成和骨吸收，使骨转化率降低，但对骨吸收的作用大于骨形成。给予大豆异黄酮组血清雌激素水平大于对照组。结论 大豆异黄酮通过调整骨代谢生化指标的活性，提高大鼠的骨钙含量和骨密度，可预防骨质疏松的发生。     

Reproductive safety studies with genistein in rats.

Genistein is a phytoestrogen that occurs naturally in the diet and is found in a wide variety of plant-derived foods especially in soybeans and soy-based foods. There is wide spread interest in genistein and related phytoestrogens as chemopreventive agents for a variety of human diseases and cancers based on epidemiologic evidence of reduced cancer rates in populations with a high intake of soy. Soy, and hence its constituents, such as genistein, have been consumed at high levels in several Asian populations for many centuries without any apparent adverse effects and to the contrary, many health benefits have been associated with the ingestion of soy based foods. Concern has been raised, however, of potential adverse effects due to the estrogenic and other activities of the isoflavones and thus a comprehensive series of safety studies was performed with genistein. To assess the teratogenic and fetal toxic potential of genistein, several studies were conducted. Genistein was tested in an in vitro rat whole embryo culture assay (WEC), which is a preliminary screen, for fetotoxic and teratogenic potential, over a concentration range of from 1 to 100 microg/mL. Treatment related anomalies were observed at concentrations of >or= 10 microg and at 100 microg/mL, all embryos were malformed. Two in vivo embryo fetal developmental safety studies were conducted with genistein by oral administration (gavage and dietary admix) in which there was no evidence for a teratogenic effect. In an oral (gavage) embryonic and fetal development pilot study, genistein was administered to rats at dose levels of 0, 20, 150 and 1000 mg/kg/day from days 6-20 of gestation to females that were allowed to litter and rear their offspring up to day 7 of lactation. A slight maternal toxicity at 1000 mg/kg/day was observed as indicated by decreased body weight and food consumption and at this dose, adverse effects in the pups were observed including increased pup mortality, poor general condition, reduced pup body weights, and reduced pup milk uptake. At the high dose of 1000 mg/kg, no external malformations were noted, however some minor visceral and skeletal variations were observed. At the low dose of 20 mg/kg/day, an increased mortality, reduced milk uptake, a decreased % male sex ratio, and decreased body weights during lactation were observed. Due to lack of effects at the mid dose and the small number of animals, a relationship to treatment was considered unlikely. In an oral (dietary admix) Prenatal developmental safety study, genistein was administered to rats at dose levels of 0, 5, 50, 100 and 500 mg/kg/day from day 5-21 of gestation. At 500 mg/kg, maternal body weight and food consumption were markedly reduced. The incidence of resorptions was markedly increased with a corresponding decrease in the number of live fetuses per dam. Fetal body weights were also reduced. No treatment-related teratogenic effects were noted during external, visceral and skeletal examination of fetuses or in body weight normalized anogenital distance. On the basis of these studies, it is concluded that genistein has no teratogenic potential in vivo at very high doses of up to 1000 mg/kg/day by oral gavage in the embryo-fetal toxicity pilot study or up to 500 mg/kg/day by dietary admix in the Prenatal developmental study even though these doses were maternally toxic and fetal-toxic. In vitro, genistein had teratogenic potential at high concentrations in the WEC screening assay, however this was not predictive of the in vivo findings. On the basis of the definitive Prenatal development study, the NOAEL for maternal toxicity and adverse effects on embryonic development was considered to be 100 mg/kg/day when administered orally by dietary admix.     

PAMPA permeability, plasma protein binding, blood partition, pharmacokinetics and metabolism of formononetin, a methoxylated isoflavone

Formononetin (FMN) is a methoxylated isoflavone which is the major constituent in red clover and in commercially available extracts of this plant. In this study, we investigated the parallel artificial membrane permeability assay (PAMPA) permeability, protein binding, blood uptake characteristics, pharmacokinetics and metabolism of FMN. The permeability study samples were analyzed by HPLC-PDA method; whereas the pharmacokinetic study, protein binding and whole blood partitioning samples were analyzed by LC-MS/MS method. The PAMPA permeability of FMN was found to be high at pH 4.0 and 7.0. Plasma protein binding of FMN was found to be 93.61 ± 0.44% and 96.14 ± 0.15% at the tested concentration of 50 and 150 ng/mL, respectively. FMN reached equilibrium fast between red blood cells (RBCs) and plasma, and the partition coefficients between RBCs and plasma (K_RBC/PL) were independent of the initial rat blood concentrations of FMN. The bioavailability of unchanged/free FMN was found to be poor, i.e. approximately 3%. FMN was found to have a high clearance (5.13 L/h/kg) and a large apparent volume of distribution (14.16 L/kg). Circulating conjugates (glucuronides/sulfates) of FMN and daidzein (DZN) were quantified using enzymatic hydrolysis of plasma samples. The levels of isoflavone glucuronides/sulfates were found to be much greater than that of the corresponding aglycones.     

大豆异黄酮对代谢综合征大鼠胰岛素抵抗及脂联素水平的影响

目的研究大豆异黄酮(SIF)对膳食诱导型代谢综合征(MS)大鼠胰岛素抵抗(IR)及脂联素(ADPN)水平的影响及可能的作用机制。方法采用高脂、高糖、高盐饲料喂养复制MS大鼠模型。成模的47只MS大鼠再随机分为4组:模型组、西药组、大豆异黄酮低剂量组、大豆异黄酮高剂量组,药物干预4周。用生化法测大鼠血脂;用试纸法检测大鼠血糖;用放免法检测药物干预前后血浆脂联素水平。结果药物干预4周末,模型组大鼠FBG、FINS、HOMA-IR较空白组显著升高(P<0.01)。与模型组比较,西药组与SIF高剂量组大鼠FBG、FINS、HOMA-IR均降低(P<0.01或P<0.05),两组治疗效果相似,无显著性差异(P>0.05);SIF高剂量组大鼠TG、TC均显著降低(P<0.01);西药组大鼠TG、TC、HDL-C无显著性变化(P>0.05)。SIF低剂量组大鼠仅TC降低(P<0.05),余代谢指标无显著性差异(P>0.05)。药物干预4周末,与MS模型组相比,SIF高剂量组大鼠血清脂联素浓度增高(P<0.01)。结论 SIF具有调节MS模型大鼠血脂、胰岛素抵抗及血清脂联素的作用。