异黄酮衍生物对心肌缺血损伤的保护作用

】在４种实验动物模型上，评价了１１个异黄酮衍生物抗小鼠常压耐缺氧作用和抗大鼠心肌缺血作用。结果表明，１４４１、１４６１和１５１９这３个化合物具有明确的对抗急性心肌缺血的作用。     

鹰嘴豆中3种异黄酮及其乙氧基化衍生物体外协同降糖活性研究＊

目的：通过对鹰嘴豆中3种异黄酮类化合物染料木素、鹰嘴豆芽素A、刺芒柄花素进行乙氧基化结构修饰,研究其降糖活性及协同降糖活性。方法：对上述3种异黄酮类化合物进行乙氧基化结构修饰,并研究该3种异黄酮类化合物及其衍生物降糖活性,并对化合物进行组合给药,研究其之间存在的协同降糖活性,选择胰岛素抵抗HepG2细胞作为降糖活性筛选模型。结果：获得4个乙氧基化产物,3个母体异黄酮衍生物中染料木素的降糖活性优于鹰嘴豆芽素A和刺芒柄花素,差异具有统计学意义（P<0.05）,3个母体异黄酮衍生物最大给药剂量与阳性药盐酸二甲双胍相比,效果不如盐酸二甲双胍,差异均具有统计学意义（P<0.05或P<0.01）。衍生物中化合物a和d之间差异无统计学意义（P>0.05）,化合物b和c降糖效果均不如化合物a和d,差异具有统计学意义（P<0.05）,其中化合物d较修饰前降糖活性有明显提高（P<0.05）。组合5的降糖活性与盐酸二甲双胍相当,差异无统计学意义（P>0.05）。结论：本研究发现,通过化合物组合,化合物之间可以起到协同作用,发挥更好的降糖效果,为开发具有自主知识产权的降糖药物提供一定的基础。     

Soy Isoflavone Glycitin (4'‐Hydroxy‐6‐Methoxyisoflavone‐7‐D‐Glucoside) Promotes Human Dermal Fibroblast Cell Proliferation and Migration via TGF‐β Signaling

Glycitin is a soy isoflavone that exhibits antioxidant, antiallergic, and anti‐osteoporosis activities. We investigated the effects of glycitin on dermal fibroblast proliferation and migration. Treatment of primary dermal fibroblasts with glycitin increased cell proliferation and migration. In addition, treatment with 20 μM glycitin for 24 h induced the synthesis of collagen type I and type III at both the mRNA and protein levels. Fibronectin was also increased by 20% after treatment. Matrix metalloproteinase‐1 collagenase was decreased in the media after 24‐h incubation with glycitin, and the synthesis of transforming growth factor‐beta (TGF‐β) mRNA increased approximately twofold in cells following glycitin treatment. Phosphorylation of Smad2 and Smad3 increased after 1 h of glycitin treatment, and phosphorylation continued for 24 h. Furthermore, the phosphorylated form of AKT was increased in glycitin‐treated cells after 3 h and remained higher for 24 h. Thus, glycitin treatment produces anti‐aging effects including increased total collagen in the culture media, decreased elastase, and decreased β‐galactosidase. Together, these results indicate that glycitin stimulates TGF‐β secretion, and the subsequent autocrine actions of TGF‐β induce proliferation of fibroblasts, ultimately protecting skin cells from aging and wrinkling. Copyright © 2015 John Wiley & Sons, Ltd.     

Therapeutic effects of isoflavones on impaired salivary secretion

Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.     

Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue,skeletal muscle and liver of male Huanjiang mini-pigs

Although a growing body of evidence suggests that soy isoflavones help regulate lipid metabolism, the underlying mechanism has not yet been thoroughly clarified. The present study was undertaken to determine the effects of soy isoflavones on the expression of genes involved in lipid metabolism in different adipose tissue depots, skeletal muscle and liver of male Huanjiang mini-pigs, as well as the expression of adipokines and myokines. A total of 36 male Huanjiang mini-pigs were fed basal diet (control, Con), low-dose soy isoflavones (LSI) and high-dose soy isoflavones (HSI). The results showed that LSI and HSI regulated the expression of genes involved in the anabolism and catabolism of fatty acids in dorsal subcutaneous (DSA), abdominal subcutaneous (ASA) and perirenal (PRA) adipose tissue depots, as well as longissimus dorsi muscle (LDM) and liver. LSI and HSI also regulated the expression of adipokines in DSA, ASA and PRA, and the expression of myokines in LDM in male Huanjiang mini-pigs. In addition, soy isoflavones regulated plasma glucose, leptin and adiponectin contents after treatment for two months. Our results indicate that soy isoflavones, by regulating the expression of adipokines and myokines, may regulate the metabolism of lipids and could have potential therapeutic applications in lipid abnormalities.     

大豆异黄酮的生物学作用及其临床应用的研究进展

大豆异黄酮(SIF)是一种天然的雌激素,是大豆生长过程中形成的次级代谢产物,自然界中主要以游离型的糖苷配基和结合型的糖苷两种形式存在,且具有多种的生物学作用及临床应用。主要包括:抗动脉粥样硬化、抗肿瘤、预防骨质疏松、神经保护和抗神经退变的作用、抗菌消炎、提高免疫力的作用、防辐射及雌激素样作用。随着对SIF研究的逐渐深入并日趋成熟,SIF的应用将会越来越广泛。     

Genistein potentiates activity of the cation channel TRPC5 independently of tyrosine kinases

Background and purpose:

TRPC5 is a Ca²⁺-permeable channel with multiple modes of activation. We have explored the effects of genistein, a plant-derived isoflavone, on TRPC5 activity, and the mechanism(s) involved.

Experimental approach:

Effects of genistein on TRPC5 channels were investigated in TRPC5-over-expressing human embryonic kidney 293 (HEK) cells and bovine aortic endothelial cells (BAECs) using fluorescent Ca²⁺ imaging and electrophysiological techniques.

Key results:

In TRPC5-over-expressing HEK cells, genistein stimulated TRPC5-mediated Ca²⁺ influx, concentration dependently (EC₅₀= 93 µM). Genistein and lanthanum activated TRPC5 channels synergistically. Effects of genistein on TRPC5 channels were mimicked by daidzein (100 µM), a genistein analogue inactive as a tyrosine kinase inhibitor, but not by known tyrosine kinase inhibitors herbimycin (2 µM), PP2 (20 µM) and lavendustin A (10 µM). Action of genistein on TRPC5 channels was not affected by an oestrogen receptor inhibitor ICI-182780 (50 µM) or a phospholipase C inhibitor {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 (10 µM), suggesting genistein did not act through oestrogen receptors or phospholipase C. In BAECs, genistein (100 µM) stimulated TRPC5-mediated Ca²⁺ influx. In patch clamp studies, both genistein (50 µM) and daidzein (50 µM) augmented TRPC5-mediated whole-cell cation current in TRPC5 over-expressing HEK cells. Genistein stimulated TRPC5 channel activity in excised inside-out membrane patch, suggesting that its action was relatively direct and did not require cytosolic factors.

Conclusions and implications:

The present study is the first to demonstrate stimulation of a TRP channel by isoflavones. Genistein is a lipophilic compound able to stimulate TRPC5 activity in TRPC5-over-expressing HEK cells and in native vascular endothelial cells.     

异黄酮对高频电磁场致雌性性腺毒性的保护作用

目的探讨异黄酮(IF)对亚慢性暴露高频电磁场(HF-EMF)雌性性腺毒性的保护效应。方法大鼠每天ig给予IF150mg·kg-1后分别全身暴露HF-EMF0(IF对照组),25,100,400和1600V·m-18h,每周5d,连续8周。第48天开始观察大鼠动情周期的变化,56d后取血清和卵巢,血清采用放免法测定黄体生成素(LH),卵泡刺激素(FSH),雌激素(E2)和孕激素(P4),卵巢采用HE染色法计算各级卵泡数目构成比和电镜观察卵巢细胞超微结构。结果与IF对照组比较,EMF1600V·m-1组动情间期时间由68±7延长至(104±8)h(P<0.01);黄体数目构成比由13.50%上升至19.25%(P<0.01),而初/次级卵泡由26.4%下降至22.7%,成熟卵泡构成比由2.8%下降至1.3%(P<0.01),HF-EMF400V·m-1和HF-EMF1600V·m-1组闭锁卵泡构成比均显著上升(P<0.01);HF-EMF1600V·m-1组的LH水平从8.2±0.7增加至(12.8±1.2)μmol·L-1·min-1(P<0.01),FSH,E2和P4有变化,但无统计学差异;电镜观察HF-EMF1600V·m-1组卵巢细胞核异染色质增多,线粒体出现水肿,线粒体嵴变短而少等。结论 IF对暴露HF-EMF25～400V·m-1的雌性性腺毒性有较好的保护效应。     

红车轴草异黄酮对维甲酸致小鼠骨质疏松的预防作用

目的研究红车轴草异黄酮对维甲酸致小鼠骨质疏松的预防作用,并探讨其主要作用机制。方法维甲酸(90mg.kg-1)致小鼠骨质疏松模型,红车轴草异黄酮(50、100、200mg·kg-1)灌胃给药,实验过程监测体重,2周后以比色法测定血清钙、磷含量和碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)活性,竞争放射免疫法测定血清中骨钙素(BGP)和雌二醇(E2)含量,取股骨进行骨组织形态学观察。结果维甲酸可引起高转换型骨质疏松,红车轴草异黄酮可升高E2值,降低P、ALP、TRAP、BGP水平。结论红车轴草异黄酮对维甲酸致小鼠骨质疏松有一定的预防作用,其机制可能与其减缓雌激素水平降低,抑制骨高转换有关。