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.     

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for hERα and hERβ with IC₅₀ values of 1.20 ×10⁻⁷ g/ml and 1.00×10⁻⁷ g/ml, respectively. LNE induced 17β-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on hER α and β than other fractions. Our results indicate that LNE had higher binding affinities for hERβ than hERα, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.     

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.     

Understanding the role of estrogen in the development of benign prostatic hyperplasia

Introduction

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that affects ageing men. As the number of men affected by this condition will only continue to grow with the aging population, finding new strategies and new therapeutic options for its treatment is crucial. Androgenic hormones have been known to play an important role in the development of BPH and they have been a target in its medical treatment. Estrogens have also been implicated in BPH but in contrast to androgens, the functions of estrogens in the prostate are still obscure.

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.     

Endocrine disrupting compounds and prostate cancer

Prostate cancer is a major health concern and is treated based on its hormone dependence. Agents that alter hormone action can have substantial biological effects on prostate cancer development and progression. As such, there is significant interest in uncovering the potential effects of endocrine disrupting compound (EDC) exposure on prostate cancer. The present review is focused on agents that alter hormone action in the prostate and how they may impact cancer growth or treatment.     

The soya isoflavone content of rat diet can increase anxiety and stress hormone release in the male rat

Rationale. Most commercial rodent diets are formulated with soya protein and therefore contain soya isoflavones. Isoflavones form one of the main classes of phytoestrogens and have been found to exert both oestrogenic and anti-oestrogenic effects on the central nervous system. The effects have not been limited to reproductive behaviour, but include effects on learning and anxiety and actions on the hypothalamo-pituitary axis. It is therefore possible that the soya content of diet could have significant effects on brain and behaviour and be an important source of between-laboratory variability. Objectives. To determine whether behaviour in two animal tests of anxiety, and stress hormone production, would differ between rats that were fed a diet which was free of soya isoflavones and other phytoestrogens (iso-free) and those that were fed a diet which contained 150 μg/g of the isoflavones genistein and daidzein (iso-150). This controlled diet has an isoflavone concentration similar to that in the maintenance diet routinely used in our institution. Methods. Male rats were randomly allocated to the iso-free and iso-150 diets and their body weights and food and water consumption were recorded for 14 days. They were then maintained on the same diets, but housed singly for 4 days, before testing in the social interaction and elevated plus-maze tests of anxiety. Corticosterone concentrations in both dietary groups were determined under basal conditions and after the stress of the two tests of anxiety. Vasopressin and oxytocin concentrations were determined after brief handling stress. Results. The groups did not differ in food or water intake, body weight or oxytocin concentrations. Compared with the rats fed the iso-free diet, the rats fed the iso-150 diet spent significantly less time in active social interaction and made a significantly lower percentage of entries onto the open arms of the plus-maze, indicating anxiogenic effects in both animal tests. The groups did not differ in their basal corticosterone concentrations, but the iso-150 group had significantly elevated stress-induced corticosterone concentrations. Stress-induced plasma vasopressin concentrations were also significantly elevated in the iso-150 diet group compared with the iso-free rats. Conclusions. Major changes in behavioural measures of anxiety and in stress hormones can result from the soya isoflavone content of rat diet. These changes are as striking as those seen following drug administration and could form an important source of variation between laboratories. Electronic Publication     

补骨脂素对骨质疏松小鼠骨折修复的影响

目的观察补骨脂素对骨质疏松小鼠骨折修复的影响。方法 20只雌性C57BL/6小鼠在建立骨质疏松模型后,随机分为2组:模型组和补骨脂素组,每组10只。所有小鼠在右侧股骨中段建立横形骨折,骨折术后第1天,补骨脂素组按20 mg/kg/d体重量灌胃,每天一次,连续21天,模型组以等剂量生理盐水灌胃。术后21天处死,骨折标本行钼靶X线、组织学和生物力学等检测方法。结果骨折术后第21天,补骨脂素组较模型组骨痂密度变高、骨折线模糊,两组骨痂生成面积比较无明显差异。补骨脂素组软骨细胞数量较模型组明显减少,成骨细胞增生较活跃,软骨骨化形成编织骨。补骨脂素组破骨细胞密度更稀疏,2组中破骨细胞形态和细胞核数量见明显差异。补骨脂素组最大载荷比模型组明显升高。结论补骨脂素作为一种植物雌激素能有效改善骨质疏松小鼠骨痂愈合质量和生物力学性能。