大豆异黄酮酊干预Ⅱ度烫伤模型小鼠创面的愈合

背景：雌激素具有促进创面愈合的作用,大豆异黄酮能与雌激素受体结合,具有明显的雌激素样效应。 目的：探索大豆异黄酮酊的制备、观察其对小鼠烫伤创面愈合的影响。 方法：用冷浸渍法制备大豆异黄酮酊,筛选最佳有效浓度。用昆明小鼠造Ⅱ度烫伤模型,随机分为6组。药物组分别应用0.100,0.361,1.000,3.610 g/L的大豆异黄酮酊局部涂抹;溶剂对照组应用体积分数75%乙醇局部涂抹;空白对照组不作任何处理。从第 3 天起,隔天记录创面面积、计算未愈合创面占原始创面的百分比,于造模后第 3,9,14 天取创面组织做病理切片,观察形态学改变和创面愈合情况。 结果与结论：大豆异黄酮酊的最佳效应浓度是3.61 g/mL。在创伤后第 5,7,9,11,13 天,大豆异黄酮酊组的未愈合创面占原始创面的百分比明显小于溶剂对照组和空白组(P < 0.05)。病理组织切片显示,第 9 天,大豆异黄酮酊组的成纤维细胞明显多于溶剂对照组和空白组,第 14 天,大豆异黄酮酊组的表皮生长情况比溶剂对照组和空白组好。表明以75%乙醇为溶剂制备大豆异黄酮酊是可行的;  3.61 g/L的大豆异黄酮酊对小鼠创面的愈合具有明显的促进用。     

Lack of effects of isoflavones on the lipid profile of Brazilian postmenopausal women

OBJECTIVE: To evaluate the effects of soy isoflavone supplementation on profile lipid and endogenous hormone levels. METHODS: In this double-blind, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of isoflavone (n = 25) or 40 mg of casein placebo (n = 22). Cardiovascular risk factors were assessed by evaluating lipid profile at baseline and after 6 mo of treatment. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone and beta-estradiol were measured. Urinary isoflavone concentrations (genistein and daidzein) were measured as markers of both compliance and absorption using high performance liquid chromatography. Baseline characteristics were compared by the unpaired Student's t-test. Within-group changes were determined by paired Student's t-test and comparison between the isoflavone and casein placebo groups were determined by analysis of variance. RESULTS: Lipid levels (low-density lipoprotein and total cholesterol) similarly decreased in both groups. High-density lipoprotein increased significantly in both groups and cannot thus be attributable to treatment; the reason for such variation is unknown and can be attributed to chance or to bias (even that of a real placebo effect in both groups or perhaps in spontaneous changes in exercise and dietary habits of patients after their inclusion). Furthermore, in both groups very low-density lipoprotein and triacylglycerol levels increased in a non-significant manner. CONCLUSION: The results of the present study do not support any biologically significant estrogenic effects of isoflavone on the parameters assessed. Further research will be necessary to definitively assess the safety and efficacy of isoflavone.     

大豆异黄酮补充剂对围绝经期女性外周IGFs水平影响的随访研究

目的 评价大豆异黄酮补充剂对围绝经期女性外周IGFs水平的影响。方法 2011年9月至2012年7月期间,序贯收集在成都市妇女儿童中心医院进行围绝经期保健的女性143名,年龄40～59岁。研究对象自愿选择是否服用大豆异黄酮补充剂分为服用组（根据其服用时间长短分为< 1个月、1个月、> 1个月）和对照组,电话随访并检测其外周IGFs水平。采用配对t检验比较2组随访前后外周IGFs水平;采用双重差分法分析服用大豆异黄酮补充剂对外周IGFs水平变化影响;同时,以随访后与随访前IGFs水平的差值作为IGFs水平变化值,采用协方差分析比较两组随访前后外周IGFs水平变化。结果 本次研究服用组女性IGF-1水平升高（> 1个月）,IGFBP-3水平下降,IGF-1:IGFBP-3摩尔比升高（P < 0.05）,而对照组女性随访前后外周IGFs水平变化差异均无统计学意义（P > 0.05）;双重差分结果和协方差分析结果均发现2组女性随访前后IGFs变化值无统计学差异（P > 0.05）。结论 本研究尚不支持大豆异黄酮对女性乳腺癌的保护作用是通过调节外周IGFs水平的假设,但存在样本量小,随访时间短的问题。     

Estrogen receptor‐β gene polymorphism and colorectal cancer risk: Effect modified by body mass index and isoflavone intake

Estrogen receptor (ER)‐β signaling has generally been implicated in protection against colorectal cancer. The ER‐β gene cytosine‐adenine (ESR2 CA) repeat polymorphism was reported to be associated with colorectal cancer, although showing contradicting results probably caused by ethnicity or age distribution of the subjects. We investigated the association between this polymorphism and the colorectal cancer risk in a community‐based case‐control study in Japan (685 cases/778 controls), including only subjects younger than 75. The effect modifications of the body mass index (BMI) and isoflavone intake were also examined. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein‐labeled primers. CA repeat alleles were classified into short (S) allele (<22 repeats) and long (L) allele (≥22 repeats). Subjects were divided into three genotype groups (SS/SL/LL). The risk of colon cancer, but not of rectal cancer, was increased with an increasing number of L alleles among postmenopausal women; age‐adjusted odds ratio (OR) for SL and LL genotypes compared with the SS genotype were 1.78 and 2.91, respectively (trend p = 0.002). Increased risks of colon cancer associated with the L allele were more evident among postmenopausal women with low BMI (<25 kg m^?2) or with high isoflavone intake. Such associations were not observed among men or premenopausal women. Having longer ESR2 CA repeat increases colon cancer risk among postmenopausal women younger than 75, possibly with modification of BMI and isoflavone intake. Aging and estrogenic condition may be important in the colon cancer pathogenesis associated with ESR2 CA repeat polymorphism.     

Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN,p27kip1, p57kip2, and PUMA

Pancreatic cancer is the fourth leading cause of cancer related death in the US and exhibits aggressive features with short survival rate and high mortality. Therefore, it is important to understand the molecular mechanism(s) involved in the aggressive growth of pancreatic cancers, and further design novel targeted therapies for its treatment with better treatment outcome. In the present study, we found that the expression of miR-221 was significantly up-regulated in pancreatic cancer cell lines and tumor tissues compared to normal pancreatic duct epithelial cells and normal pancreas tissues. Moreover, we found that the pancreatic cancer patients with high miR-221 expression had a relatively shorter survival compared to those with lower expression, suggesting that miR-221 could be an oncogenic miRNA and a prognostic factor for poor survival of patients. Interestingly, transfection of miR-221 inhibitor suppressed the proliferative capacity of pancreatic cancer cells with concomitant up-regulation of PTEN, p27^kip1, p57^kip2, and PUMA, which are the tumor suppressors and the predicted targets of miR-221. Most importantly, we found that the treatment of pancreatic cancer cells with isoflavone mixture (G2535), formulated 3,3’-diindolylmethane (BR-DIM), or synthetic curcumin analogue (CDF) could down-regulate the expression of miR-221 and consequently up-regulate the expression of PTEN, p27^kip1, p57^kip2, and PUMA, leading to the inhibition of cell proliferation and migration of MiaPaCa-2 and Panc-1 cells. These results provide experimental evidence in support of the oncogenic role of miR-221 and also demonstrate the role of isoflavone, BR-DIM, and CDF as potential non-toxic agents that are capable of down-regulation of miR-221. Therefore, these agents combined with conventional chemotherapeutics could be useful in designing novel targeted therapeutic strategy for the treatment of pancreatic cancer for which there is no curative therapy.     

壮药两粤黄檀化学成分研究(I)

目的 研究壮药两粤黄檀Dalbergia benthami的化学成分。方法 通过硅胶、凝胶、HPLC等柱色谱及重结晶方法进行分离和纯化,根据理化性质和波谱数据对化合物结构进行鉴定。结果 从两粤黄檀乙醇提取物中分离得到14个化合物,分别鉴定为4''-羟基-6-羟甲基-5,7-二甲氧基异黄酮（1）、β-谷甾醇（2）、胡萝卜苷（3）、豆甾醇（4）、大鱼藤树酸（5）、robustin（6）、4-hydroxy-3-（3''-hydroxy-4''-methoxyphenyl）-5-methoxy-2",2"-dimethylpyrano-（5",6"：6,7）-coumarin（7）、大鱼藤树素甲醚（8）、大鱼藤树酸甲酯（9）、4''-羟基-5,7-二甲氧基-6-（3-甲基-2-丁烯基）-异黄酮（10）、芒柄花黄素（11）、伪赝靛苷元（12）、毛蕊异黄酮（13）、豆甾醇-3-O-β-D-葡萄糖苷（14）。结论 化合物1为新化合物,命名为两粤黄檀酮;所有化合物均为首次从该属植物中分离得到。     

异黄酮改构化合物F11雌激素效应初步研究

目的初步研究异黄改构化合物F11的雌激素效应。方法构建去双卵巢大鼠动物模型,经腹腔注射F11[15、50、150 mg/(kg.d)3个剂量组(F11-15组、F11-50组、F11-150组)]共10周,同时设置阴性对照组,阳性对照组(E2)和假手术组,统计分析各组大鼠子宫湿质量/体质量情况,HE染色观察用药前后阴道涂片和子宫内膜变化情况;Westernblot检测子宫内膜组织ERα和ERβ的表达情况。结果 F11-50及F11-150组大鼠子宫湿质量/体质量显著高于阴性对照组(P<0.05),且F11-150组与E2和假手术组无显著差别(P>0.05)。阴性对照组大鼠阴道涂片以炎细胞为主,F11各组以角化上皮细胞为主,与E2和假手术组相似;F11各组较阴性对照组子宫内膜腺体数目增多,腺腔增大,F11-150组与E2和假手术组相似。F11各组ERα及ERβ蛋白表达均强于阴性对照组(P<0.05),其中ERα表达弱于E2和假手术组(P<0.01),而F11-150组ERβ的表达强于E2和假手术组(P<0.05)。结论 F11在增加去双卵巢大鼠子宫湿质量、阴道上皮成熟及子宫内膜ER的表达等方面均表现出雌激素效应,该效应主要通过ERβ介导。     

葛根总黄酮治疗去势大鼠鼻粘膜萎缩的研究

目的 :探讨葛根总黄酮治疗去势大鼠鼻粘膜萎缩的效果。方法 :将 6 0只成年雌性大鼠随机等分为 4组 :第 1组 :为正常对照组 ;第 2组 :行去势处理 ;第 3组 :于去势后以维尼安治疗。第 4组 :于去势后以葛根总黄酮治疗。对各组动物鼻中隔粘膜进行光镜、电镜观察 ;抽血测定血清雌二醇水平。结果 :去势后 30 d鼻粘膜呈萎缩性改变 ;经维尼安、葛根总黄酮胃灌注治疗 30 d后 ,鼻粘膜可恢复正常的形态结构。去势 30 d后动物血清雌二醇水平与正常组比较明显下降 ,差异有显著性意义 (P <0 .0 5 ) ;经维尼安治疗 ,血清雌二醇水平更趋于下降 (P <0 .0 5 ) ;经葛根总黄酮治疗后 ,血清雌二醇水平可恢复正常 (P >0 .0 5 )。结论 :葛根总黄酮可恢复去势大鼠的雌激素水平 ,对由于雌激素水平下降所致的鼻粘膜萎缩有较好的治疗作用。     

Isoflavone consumption and subsequent risk of hepatocellular carcinoma in a population‐based prospective cohort of Japanese men and women

The incidence of hepatocellular carcinoma (HCC) is much higher in men than in women. Several experiment and epidemiological studies have suggested that estrogen might play an inhibitory role in the development of HCC. Because isoflavones have a similar structure as 17β‐estradiol and appear to have an anti‐estrogenic effect in women and estrogenic effect in men, we hypothesized that the effect of isoflavones on HCC differs by sex. We investigated the association between isoflavones (genistein and daidzein) and soy products and HCC in Japan in a population‐based prospective study in 19,998 Japanese (7,215 men and 12,783 women) aged 40–69 years. During 11.8 years of follow‐up, 101 subjects (69 men and 32 women) were newly diagnosed with HCC. Case patients were grouped according to consumption of isoflavones and soy products and stratified by hepatitis virus infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC were calculated by Cox proportional‐hazards modeling. In women, genistein and daidzein were dose‐dependently associated with an increased risk of HCC, with multivariable HRs for the highest versus lowest tertile of 3.19 (95%CI = 1.13–9.00, p_trend = 0.03) and 3.90 (95% CI = 1.30–11.69, p_trend = 0.01), respectively. No association between isoflavones and HCC was observed in men. These results persisted when analysis was restricted to subjects positive for either or both hepatitis C and B virus. In conclusion, isoflavone consumption may be associated with an increased risk of HCC in women. Women with hepatitis virus infection may be advised to abstain from isoflavone consumption. Further studies are warranted to confirm these findings. © 2008 Wiley‐Liss, Inc.     

A Comparative Analysis of Genistein and Daidzein in Affecting Lipid Metabolism in Rat Liver

Effects of soy isoflavones, genistein and daidzein, on the hepatic gene expression profile and indices for lipid metabolism were compared in rats. In the first experiment (Expt. 1), animals were fed diets containing 2 g/kg of either genistein or daidzein, or a control diet free of isoflavone for 14 days. In the second experiment (Expt. 2), rats were fed diets containing 1 or 2 g/kg of genistein, or an isoflavone-free diet for 16 days. Genistein at a dietary level of 2 g/kg reduced serum triacylglycerol concentrations in both experiments, and serum concentrations of cholesterol in Expt. 2. However, daidzein at 2 g/kg did not decrease serum lipid concentrations in Expt. 1. A DNA microarray analysis in Expt. 1 showed that genistein was stronger than daidzein in affecting gene expression in liver, targeting many genes involved in lipid and carbohydrate metabolism. Detailed analyses indicated that alterations in the expression of genes related to lipogenesis are primarily responsible for the serum lipid-lowering effect of genistein. This notion was supported by analyses of the activity of enzymes involved in lipogenesis in Expt. 2.