大豆异黄酮雌激素样作用与骨质疏松的防治

此文综述了近年来大豆异黄酮防治骨质疏松作用的研究进展。大豆异黄酮作为一种植物雌激素可模拟雌激素作用于骨骼系统,调节骨吸收和骨形成,有防治骨质疏松的作用。同时,大豆异黄酮与雌激素作用又有不同,如对子宫等生殖器官作用小,有降低肿瘤及心血管病发生风险等有益作用,故值得进一步研究大豆异黄酮药理作用机制。     

大豆异黄酮的开发利用

介绍近年来大豆异黄酮的研究进展，包括大豆异黄酮的主要类型，及其抗肿瘤，防治心血管病，免疫系统作用，雌激素样作用等多种生物活性，其开发与利用具有广阔前景。     

大豆异黄酮预防心血管疾病的研究进展

大豆异黄酮是一类存在于豆类食物中的植物雌激素,由于其类雌激素样作用,富含大豆异黄酮豆类食品对心血管等疾病具有防治作用而备受研究者关注,本文就大豆异黄酮对心血管疾病在流行病学、动物实验和临床试验等近几年的研究进展情况作一概述。     

血管紧张素受体拮抗剂在糖尿病肾病治疗中的作用

糖尿病肾病的防治是糖尿病慢性并发症防治研究的一项重要课题。研究显示，血管紧张素受体拮抗剂能够降低尿蛋白排泄量，延缓肾动脉硬化及肾脏纤维化的进展，对肾脏具有显著的保护作用。目前认为，这一作用是通过多种途径实现的，除降低血压带来的益处外，还存在非血流动力学方面的作用，如抑制细胞外基质在肾脏局部的积聚、下调肾脏皮质转化生长因子-β的表达、减少肾脏细胞凋亡、改善肾组织的高代谢状态和抗过氧化酶活性等。近年来，一些重要的大型临床试验如RENAAL研究等证明了血管紧张素受体拮抗剂在糖尿病肾病防治中的地位与作用。     

大豆异黄酮的生产方法

大豆异黄酮是天然的保健物质，其具有弱雌性激素活性，可竞争性地与雌激素受体结合。当体内或细胞内雌激素活性增强时，它显示拮抗作用，当体内或细胞内雌激素水平低下时，它显示加强作用，所以大豆异黄酮对于与雌激素相关的一些病症都有防治和治疗的功效，如具有预防癌症和减少肿瘤数目，防治心脑血管疾病，预防骨质疏松症，改善妇女更年期综合征，延缓衰老等功能。     

大豆异黄酮防治动脉粥样硬化作用研究进展

大豆异黄酮具有弱的雌激素活性,可通过多种机制产生防治动脉粥样硬化作用。本文综述了大豆异黄酮防治动脉粥样硬化的研究进展。     

大豆异黄酮与心血管疾病

流行病学调查显示，日本人心血管疾病死亡率与美国人有显著差异。研究表明亚洲人心血管疾病的低发病率可能与亚洲人饮食中的大豆食品所含的异黄酮物质，主要是金雀异黄素和大豆苷元有关。本文就大豆异黄酮对于防治动脉粥样硬化和相应的心血管疾病的有益作用进行综述。     

大豆异黄酮对2型糖尿病大鼠血清中SOD MDA GSH及NO的影响

目的研究大豆异黄酮对2型糖尿病大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)及一氧化氮(NO)的影响。方法以高脂饲料喂养后的雄性SD大鼠腹腔注射小剂量链脲佐菌素(STZ)诱导2型糖尿病模型。将实验动物随机分为普食对照组、糖尿病对照组、大豆异黄酮250mg/kg、50mg/kg剂量干预组。检测各组喂养6周、10周的血糖水平,检测第10周后大鼠血清中SOD、MDA、GSH及NO的变化。结果与糖尿病对照组相比,大豆异黄酮250mg/kg剂量干预组大鼠血清中的SOD明显升高(P<0.05),MDA与NO明显下降(P<0.05);大豆异黄酮50mg/kg剂量干预组大鼠血清中GSH明显升高(P<0.05)。结论大豆异黄酮能改善2型糖尿病大鼠的抗氧化能力。     

天然黄酮类化合物防治糖尿病肾病的研究进展

糖尿病肾病（DN）是一种严重的糖尿病并发症,其发病机制复杂而多样。现代药理研究表明,天然黄酮类化合物具有多种潜在药用价值,对糖尿病肾病的防治作用就是其中之一。黄酮类化合物抗糖尿病肾病的作用机制是多方面药理活性的综合结果,包括通过抗氧化应激与清除自由基、抗炎、改善血糖血脂紊乱、抗凋亡、调节血管舒张及改善血流动力学异常等途径来实现。在查阅近年来国内外发表的相关文献后,对黄酮类化合物在糖尿病肾病防治中的多种作用及相关机制进行综述,以期为糖尿病肾病防治药物的研发提供参考。     

益气补肾活血清热方对血压正常的早期糖尿病肾病患者临床疗效观察

糖尿病肾病(DN)是糖尿病的重要并发症之一。因此，必须重视对DN的防治。微量白蛋白尿是循环动力学和代谢因素诱发的肾脏损伤的早期敏感指标。本组观察了自拟方对血压正常的早期糖尿病肾病患者减少尿白蛋白排泄率和保护肾功能的作用。     

Non-digestive stachyose enhances bioavailability of isoflavones for improving hyperlipidemia and hyperglycemia in mice fed with high fat diet

This study examined the efficacy of non-digestive stachyose on enhancing the absorption of soy isoflavones to improve metabolic syndrome in C57/BL6 mice. UPLC-q/TOF-MS was employed to analyze the content of isoflavones in urine and faeces. Stachyose significantly increased urinary contents of total isoflavones, genistein, daidzein and glycitein in mice. Supplementation of stachyose, soybean isoflavones or a combination prevented high fat diet (HFD)-induced body weight gain, accumulated adipose, dyslipidemia and hyperglycemia in obese mice. Interestingly, co-supplementation of stachyose and isoflavones improved all the mentioned parameters more effectively than administration of stachyose or isoflavones alone. Histological observation of hepatic tissues also confirmed the beneficial effects of co-supplementation of stachyose and isoflavones. These findings suggest that co-ingestion of non-digestible oligosaccharides and polyphenols as normal diet is a promising potential strategy for managing or reducing the risk of metabolic syndrome, which will lead to new knowledge on whole soybean and have extensive application in development of healthy food.     

大豆异黄酮对去卵巢大鼠血液生化指标的影响

目的研究大豆异黄酮对去卵巢大鼠血液生化指标的影响。方法将4月龄雌性SD大鼠摘除卵巢，按体重分成6组，分别给予不同剂量的大豆异黄酮或／和钙粉。连续灌胃饲养二个半月后，断头处死，收集血样并测定生化指标，采集右股骨、右胫骨、子宫并称重。结果大豆异黄酮对大鼠体重和子宫重量均有影响，可抑制去卵巢大鼠的代偿性增重和促进子宫的生长。大豆异黄酮对去卵巢大鼠血清钙、磷和骨钙素的影响不大，碱性磷酸酶活性稍有降低，血清雌二醇和降钙素水平稍有提高，但这些实验给药组与模型B组的的大多未达到显著水平。结论大豆异黄酮对去卵巢大鼠血液生化指标有一定的调节作用，所起的作用类似于弱雌激素活性，大豆异黄酮与钙剂联合使用时调节作用更明显。     

大豆异黄酮的开发及市场前景

目的:为我国医药企业及研究机构开发大豆异黄酮产品提供参考。方法:对大豆异黄酮的国内、外市场及开发现状进行较详细的分析。结果与结论:大豆异黄酮具有开发价值,市场前景广阔。     

糖尿病肾病相关药物研究进展

糖尿病肾病(DN)是糖尿病重要微血管并发症,其病理特征性表现为肾小球周边部位出现嗜酸性K-W结节,是糖尿病性肾病具有诊断意义的改变。但仅出现于约10%～20%的糖尿病性肾病患者。糖尿病性肾病其他病理改变特点包括肾小球基膜增厚,肾小球上皮细胞足突融合以及由于细胞外系膜基质增多所致肾小球增大。疾病晚期可出现肾小管萎缩肾内纤维化。糖尿病病程10年以上者约50%并发糖尿病肾病,每年新增终末期肾病中,糖尿病导致者所占比例逐年增高。近年关于血管紧张素转换酶抑制剂(ACEI)治疗糖尿病肾病的研究较多。其外内皮素拮抗剂等,被认为有一定的肾脏保护作用,基因治疗亦给糖尿病肾病带来新希望。现就有关内容综述如下。     

Enhancement of β-secretase inhibition and antioxidant activities of tempeh,a fermented soybean cake through enrichment of bioactive aglycones

Abstract

Context: Soybean and its fermented products are the most common source of isoflavones in human food.

Objective: The present study quantifies the major glycosides and aglycones in soybean and its fermented product tempeh isoflavone extracts. The comparision of antioxidant effects and BACE1 inhibitory activity between the isoflavones of soybean and tempeh were also established.

Materials and methods: The major isoflavones such as daidzein and genistein (aglycones), and their sugar conjugates (glycosides) daidzin and genistin in soybean and tempeh isoflavones were quantified using HPLC analysis. Comparative studies on BACE 1 (β-site amyloid precursor protein cleaving enzyme 1 or β-secretase 1) inhibition and free-radical scavenging activities (diphenyl-1-picrylhydrazyl (DPPH) and ferrous ion chelating ability) were conducted.

Results: The amount of actives (mg/100?g) in soybean isoflavone compared with tempeh isoflavone is as follows: daidzein 16.72?mg/100?g versus 38.91?mg/100?g, genistein 11.10?mg/100?g versus 24.03?mg/100?g, daidzin 6.16?mg/100?g versus 0.69?mg/100?g, and genistin 24.61?mg/100?g versus 6.57?mg/100?g. The IC₅₀ values of soybean and tempeh isoflavones against BACE1 were 10.87 and 5.47?mg/ml, respectively. The tempeh isoflavone had a more potent DPPH free-radical scavenging activity (IC₅₀?=?2.67?mg/ml) than the soybean isoflavone (IC₅₀?=?10?mg/ml). The ferrous ion chelating ability of the isoflavones was practically similar (IC₅₀?=?10.40?mg/ml, soybean and 11.13?mg/ml, tempeh).

Discussion and conclusion: The present study indicates that tempeh is a healthy supplement to alleviate oxidative stress through the enrichment of aglycones.     

阿伐他汀伍用大豆异黄酮预防大鼠脂质代谢紊乱的作用

目的探讨阿伐他汀(AT)伍用大豆异黄酮(SI)调节大鼠脂质代谢紊乱的药效学及相关分子机制以提供联合疗法的科学依据。方法采用喂养法建立食物性高脂血症大鼠模型,正常对照组和模型组给予蒸馏水,其他供试组给予不同剂量的药物:AT 20 mg.kg-1,AT伍用SI(40 mg.kg-1+120 mg.kg-1,20 mg.kg-1+60 mg.kg-1,10 mg.kg-1+30mg.kg-1),每日给药一次,连续给药12周。酶法测定血清中各项脂蛋白含量;制作冰冻切片进行病理学观察;RT-PCR检测肝脏组织低密度脂蛋白受体(LDLR)和载脂蛋白apoA-1的mRNA表达,W estern印迹检测LDLR蛋白表达变化。结果AT伍用SI(40 mg.kg-1+120 mg.kg-1,20 mg.kg-1+60 mg.kg-1)与单用AT 20 mg.kg-1相比,明显降低血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)(P<0.05),明显升高高密度脂蛋白(HDL-C)(P<0.05);AT伍用SI(10 mg.kg-1+30 mg.kg-1)与单用AT 20 mg.kg-1相比,对指标TC,TG及LDL-C的作用具有药效等效性,明显升高HDL-C(P<0.05);能够减少肝脏对脂蛋白颗粒的蓄积,RT-PCR实验和W estern印迹实验表明能够增强大鼠肝脏LDLR mRNA和蛋白的表达,并上调HDL-C代谢相关蛋白apoA-1 mRNA的表达。结论AT伍用SI对高脂血症大鼠的血脂和脂蛋白代谢紊乱有预防作用,该脂质代谢紊乱调节作用机制与上调LDLR和apo-A1 mRNA表达及促进LDLR蛋白表达有相关性。     

肠道菌群参与糖尿病肾病的机制研究进展

随着糖尿病患病率升高,糖尿病肾病的预防和治疗已成为世界性难题。糖尿病肾病发生发展的分子机制目前尚不明确,但近年来诸多研究表明,肠道菌群在糖尿病肾病的进展中发挥重要作用。综述了肠道菌群参与糖尿病肾病的机制研究进展。     

In vitro and in vivo evaluation of topical delivery and potential dermal use of soy isoflavones genistein and daidzein

Genistein, daidzein, and glycitein are soy isoflavones. These compounds can be used to protect the skin from oxidative stress induced by UVB radiation. To this end, the feasibility of skin absorption of soy isoflavones was evaluated in the present study. As assayed by flow cytometry, UVB-induced H(2)O(2) production in keratinocytes was inhibited by genistein and daidzein, confirming that these two compounds can act as free radical scavengers when keratinocytes are photodamaged. Glycitein showed no protective activity against photodamage. The effects of vehicles on the in vitro topical delivery from saturated solutions such as aqueous buffers and soybean oil were investigated. The isoflavones in a non-ionized form (pH 6) showed higher skin deposition compared to the ionized form (pH 10.8). Soybean oil reduced the isoflavone amount retained in the skin, especially for genistein. Genistein generally exhibited greater skin absorption than did daidzein. However, daidzein permeation was enhanced when an aglycone mixture was used as the active ingredient. An eutectic effect was proposed as the enhancing mechanism. In vivo skin deposition showed a linear correlation with the in vitro results. The safety profiles suggested no or only negligible stratum corneum disruption and skin erythema by topical application of soy isoflavones. It was concluded that topical delivery may serve as a potent route for soy isoflavones against photoaging and photodamage.     

Small Molecule Inhibiting Nuclear Factor‐kB Ameliorates Oxidative Stress and Suppresses Renal Inflammation in Early Stage of Alloxan‐Induced Diabetic Nephropathy in Rat

Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus which ultimately gives rise to cardiovascular diseases. Prolonged hyperglycaemia and chronic renal inflammation are the two key players in the development and progression of diabetic nephropathy. Nuclear factor kB (NF‐kB)‐mediated inflammatory cascade is a strong contributor to the renovascular inflammation in diabetic nephropathy. Here, we studied the effects of piceatannol, a potent NF‐kB inhibitor, on various oxidative stress markers and NF‐kB dependent diabetic renoinflammatory cascades in rat induced by alloxan (ALX). Experimental diabetes was induced in male Wistar rats by a single intraperitoneal dose, 150 mg/kg body‐weight (b.w.) of ALX. Diabetic rats were treated with Piceatannol (PCTNL) at a dose of 30 and 50 mg/kg b.w. After 14 days of oral treatment, PCTNL significantly restored blood sugar level, glomerular filtration rate, serum markers and plasma lipids. PCTNL administration also reversed the declined activity of cellular antioxidant machineries namely superoxide dismutase and glutathione and the elevated levels of malondialdehyde and nitric oxide. Moreover, piceatannol‐treated groups showed marked inhibition of renal pro‐inflammatory cytokines and NF‐kB p65/p50 binding to DNA. Renal histopathological investigations also supported its ameliorative effects against diabetic kidney damage. Importantly, effects were more prominent at a dose of 50 mg/kg, and in terms of body‐weight gain, PCTNL failed to effect significantly. However, overall findings clearly demonstrated that PCTNL provides remarkable renoprotection in diabetes by abrogating oxidative stress and NF‐kB activation – and might be helpful in early stage of diabetic nephropathy.