异黄酮衍生物的合成Ⅱ.7-氯和6-氯-7-甲氧基-3′-(N,N-二乙胺甲基)-4′-羟基异黄酮的合成

合成了7-氯和-6-氯-7-甲氧基-3′-(N,N-二乙胺甲基)-4′-羟基异黄酮(1478和1481)。它们的合成是由间-氯苯酚或3-羟基-4-氯苯酚与对-硝基苯乙酰氯反应,制得取代的脱氧安息香。它们与原甲酸乙酯环合得到取代的-4′-硝基异黄酮,再将化合物中的硝基用锌粉还原成氨基,再经重氮化和水解,得到取代的-4′-羟基异黄酮。它们经Mannich反应,最后制得7-氯和6-氯-7-甲氧基-3′-(N,N-二乙胺甲基)-4′-羟基异黄酮。它们耐氧作用不如已合成的7-甲氧基-3′-(N,N-二烷胺甲基)-4′-羟基异黄酮。     

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。     

双歧异黄酮奶粉抗氧化作用研究

目的:研究双歧异黄酮奶粉的抗氧化作用.方法:小鼠每4d注射阿霉素(ADR)5mg/kg,连续4次,制备小鼠高过氧化模型,同时实验组予双歧异黄酮奶粉灌胃(8.38,16.67,50.00g/kg),对照组予普通奶粉,测定小鼠的抗氧化能力.结果:双歧异黄酮奶粉能明显提高小鼠超氧化物歧化酶(S0D)活性,降低脂质过氧化物(LP0)含量.结论:双歧异黄酮奶粉具有抗氧化作用.     

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.     

乌蕨黄酮类化合物薄层成分分析

提取乌蕨(采自南安)地上部的黄酮类化合物,并测得其总黄酮含量为1.41%。将提取的黄酮样液进行薄层层析及紫外光谱分析,乌蕨黄酮类化合物只含有一种成分,且其紫外光谱特征与异黄酮的紫外光谱特征相似,据此推测乌蕨黄酮样液分离出的一种黄酮类化合物可能为异黄酮。     

In vitro and in vivo anti-photoaging effects of an isoflavone extract from soybean cake

Ethnopharmacological relevance

Soy has been used in traditional Chinese medicine for thousands of years for its health and nutritional benefits, as well as to treat and care for the skin. Advanced skin care research has shown that soy isoflavone and genistein are effective in reducing damage to the skin from the sun.

Aim of the study

To study the protective effects of isoflavone extract from soybean cake against the UVB-induced skin damage.

Materials and methods

The in vitro effects and possible mechanisms of soybean extract on UVB protection were determined in HaCaT cells. In the in vivo study, ICR-Foxn/^nu mice were irradiated with UVB. The epidermal thickness, catalase and the expressions of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) were detected to evaluate the antioxidant and anti-inflammatory activities of the isoflavone extract.

Results

Our in vitro studies showed that UVB-induced HaCaT cell death and the phosphorylation of p38, JNK, and ERK1/2 decreased in the presence of isoflavone extract. In the in vivo studies, we found that the topical application of isoflavone extract before UVB irritation decreased the epidermal thickness and the expressions of COX-2 and PCNA and increased catalase concentration. These results showed anti-photoaging effect of isoflavone extract from soybean cake involved the inhibition of UVB-induced apoptosis and inflammation.

Conclusions

It is shown that isoflavone extract from soybean cake may be functional cosmeceutical candidate for skin photoaging.     

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.