Medicinal Potential of Isoflavonoids: Polyphenols That May Cure Diabetes

In recent years, there is emerging evidence that isoflavonoids, either dietary or obtained from traditional medicinal plants, could play an important role as a supplementary drug in the management of type 2 diabetes mellitus (T2DM) due to their reported pronounced biological effects in relation to multiple metabolic factors associated with diabetes. Hence, in this regard, we have comprehensively reviewed the potential biological effects of isoflavonoids, particularly biochanin A, genistein, daidzein, glycitein, and formononetin on metabolic disorders and long-term complications induced by T2DM in order to understand whether they can be future candidates as a safe antidiabetic agent. Based on in-depth in vitro and in vivo studies evaluations, isoflavonoids have been found to activate gene expression through the stimulation of peroxisome proliferator-activated receptors (PPARs) (α, γ), modulate carbohydrate metabolism, regulate hyperglycemia, induce dyslipidemia, lessen insulin resistance, and modify adipocyte differentiation and tissue metabolism. Moreover, these natural compounds have also been found to attenuate oxidative stress through the oxidative signaling process and inflammatory mechanism. Hence, isoflavonoids have been envisioned to be able to prevent and slow down the progression of long-term diabetes complications including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Further thoroughgoing investigations in human clinical studies are strongly recommended to obtain the optimum and specific dose and regimen required for supplementation with isoflavonoids and derivatives in diabetic patients.     

染料木素分子印迹聚合物的制备及其识别性能

以染料木素为模板分子、4-乙烯基吡啶(4-VP)为功能单体、乙二醇二甲基双丙烯酸酯(EGDMA)为交联剂、四氢呋喃(THF)为溶剂,采用本体聚合法制备了染料木素的分子印迹聚合物;采用静态平衡结合实验研究了该分子印迹聚合物对染料木素的结合能力和选择性能.结果表明,与化学组成相同的相应非印迹聚合物相比,染料木素分子印迹聚合物对染料木素的吸附性能和选择性更好.利用所合成的分子印迹聚合物作为固相萃取材料填充固相萃取小柱,可以选择性地从豆奶粉中分离、富集染料木素;此外,该分子印迹聚合物还有望用于其他豆制品的分析检验.     

Genistein activates endothelial nitric oxide synthase in broiler pulmonary arterial endothelial cells by an Akt-dependent mechanism

Deregulation of endothelial nitric oxide synthase (eNOS) plays an important role in the development of multiple cardiovascular diseases. Our recent study demonstrated that genistein supplementation attenuates pulmonary arterial hypertension in broilers by restoration of endothelial function. In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser(1179) which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases observed in animal models.     

Interaction of isoflavones with different structures and transferrin

Transferrin, as a drug carrier, holds promise for targeted drug delivering into cancer cells where transferrin receptors (TfRs) are overexpressed. In the present study, the influence of structure characteristics of isoflavones have been explored, which are critical for binding to transferrin. Three isoflavones, daidzein, puerarin, and genistein, with characteristic daidzein core structures were selected for the study of the effects of substituent group on the A-ring on interaction with transferrin. The results demonstrated that daidzein-bound transferrin with an affinity almost 7 or more than 20 times higher than that of puerarin or genistein attributed to the addition of C(8)-glycosyl or C(5)-hydroxyl on the aromatic A-ring. Our docking study indicated that daidzein had strong hydrogen bond and hydrophobic interactions with transferrin, which believed to contribute to its higher binding affinity. Furthermore, daidzein binding induced fewer structures changes of transferrin than that by puerarin or genistein, suggesting that daidzein binding result in less disturbance of normal biological function of transferrin. Together these findings not only corroborated that daidzein was a superior ligand for transferrin, but also provided substantive information for possible modification and design methods of isoflavone.     

新型含1,2,3-三氮唑的染料木素糖缀合物的合成

以染料木素为起始原料,经两步反应制得中间体7-O-炔丙基染料木素(3);以CuI为催化剂,3与叠氮乙酰基糖经Click反应合成了7-O-［1-(2,3,4,6-四-O-乙酰基-β-D-糖苷)1H-1,2,3-三氮唑-4-甲基］-染料木素(5a~5c); 5a~5c经去乙酰基制得三种含1,2,3-三氮唑的氮苷染料木素糖缀合物(6a~6c)。3, 5和6均为新化合物,其结构经¹H NMR, ¹³C NMR和HR-MS表征。     

An alternative approach to controlled release of oxprenolol from the implantable delivery system based on biodegradable copolymer and genistein

This paper describes the development of covalent star-shaped poly(L-lactide/?-caprolactone) random copolymer-oxprenolol (OXP) conjugates as a potential approach to controlling drug release from implantable delivery systems. We prepared synthesized materials containing 14–17 mol% OXP, which were conjugated via an ester bond. The conjugates, which were composed of biodegradable copolyester chains, natural genistein as a central core and drug, were characterized by hydrogen nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectroscopy (FTIR) and viscosity methods. We evaluated the cyto- and genotoxicity of the synthesized copolymeric matrices, followed by the conjugates, with bacterial luminescence, protozoan and Salmonella typhimurium TA1535 assays. Furthermore, we performed in vitro mammalian assays of the obtained products with V79 cells. We found that the in vitro release of OXP from the obtained star-shaped conjugates was dependent on the structure of the synthesized biodegradable matrices.     

A high concentration of genistein down-regulates activin A, Smad3 and other TGF-β pathway genes in human uterine leiomyoma cells

Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis™, we identified genes (up- or down-regulated, ≥ 1.5 fold, P ≤ 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 µg/ml) in UtLM cells. Downregulation of TGF-β signaling pathway genes, activin A, activin B, Smad3, TGF-β2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-β pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.     

银杏叶提取物中染料木素的分离纯化及结构鉴定

对银杏叶提取物进行酸水解,然后利用正相硅胶柱色谱及重结晶法从银杏叶水解物中分离出染料木素,经紫外光谱（UV）、质谱（MSn）、核磁共振（1H NMR、13C NMR）等波谱学方法鉴定证实了其结构。高效液相色谱分析表明,所提纯的染料木素纯度达到了98%以上。     

Biotransformation of soy flour isoflavones by Aspergillus niger NRRL 3122 β-glucosidase enzyme

β-glucosidase enzyme produced from Aspergillus niger NRRL 3122 has been partially purified and characterised. Its molecular weight was 180 KDa. The optimal pH and temperature were 3.98 and 55 °C, respectively. It promoted the hydrolysis of soy flour isoflavone glycosides to their aglycone. Two-level Plackett–Burman design was applied and effective variables for genistein production were determined. Reaction time had a significant positive effect, and pH had a significant negative effect. They were further evaluated using Box–Behnken model. Accordingly, the optimal combination of the major reaction affecting factors was reaction time, 5 h and pH, 4. The concentration of genistein increased by 11.73 folds using this optimal combination. The antioxidant activity of the non-biotransformed and biotransformed soy flour extracts was determined by DPPH method. It was found that biotransformation increased the antioxidant activity by four folds.     

染料木素磺酸钠制备及其抗脂质过氧化作用

染料木素磺酸钠制备及其抗脂质过氧化作用;染料木素;染料木素磺酸钠;水溶性;抗脂质体过氧化