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Stefan Poschner, Alexandra Maier-Salamon, Martin Zehl, Judith Wackerlig, Daniel Dobusch, Bettina Pachmann, Konstantin L Sterlini, Walter Jäger
The beneficial effect of dietary soy food intake, especially for women diagnosed with breast cancer, is controversial, as in vitro data has shown that the soy isoflavones genistein and daidzein may even stimulate the proliferation of estrogen-receptor alpha positive (ERα+) breast cancer cells at low concentrations. As genistein and daidzein are known to inhibit key enzymes in the steroid metabolism pathway, and thus may influence levels of active estrogens, we investigated the impacts of genistein and daidzein on the formation of estrogen metabolites, namely 17β-estradiol (E2), 17β-estradiol-3-(β-D-glucuronide) (E2-G), 17β-estradiol-3-sulfate (E2-S) and estrone-3-sulfate (E1-S) in estrogen-dependent ERα+ MCF-7 cells...
2017: Frontiers in Pharmacology
Fei Chang, Saisai Xue, Xiaqing Xie, Wei Fang, Zemin Fang, Yazhong Xiao
Complicated purification steps, together with the fact that β-glucosidase has to be tolerant to ethanol restricts the application of β-glucosidase in isoflavone aglycone hydrolyzing process. β-Glucosidase Bgl1A(A24S/F297Y) is a promising enzyme in hydrolyzing isoflavones. In this work, six different carbohydrate-binding modules (CBMs), which were from 3 families, were fused to the C-terminal of Bgl1A(A24S/F297Y), respectively, to simplify the enzyme preparation process. The fusion proteins were expressed in Escherichia coli and adsorbed onto cellulose...
October 15, 2017: Journal of Bioscience and Bioengineering
Prakash Parajuli, Ramesh Prasad Pandey, Thi Huyen Trang Nguyen, Dipesh Dhakal, Jae Kyung Sohng
Methylation is a common post-modification reaction that is observed during the biosynthesis of secondary metabolites produced by plants and microorganisms. Based on the sequence information from Streptomyces peucetius ATCC27952, a putative O-methyltransferase (OMT) gene SpOMT7740 was polymerase chain reaction amplified and cloned into E. coli BL21 (DE3) host to test the substrate promiscuity and conduct functional characterization. In vitro and in vivo reaction assays were carried out over various classes of substrates: flavonoids (flavonol, flavones, and isoflavonoid), chalcones, anthraquinones, anthracyclines, and sterol molecules, and the applications in synthesizing diverse classes of O-methoxy natural products were also illustrated...
October 18, 2017: Applied Biochemistry and Biotechnology
Keiichirou Nemoto, Abdelaziz Ramadan, Gen-Ichiro Arimura, Kenichiro Imai, Kentaro Tomii, Kazuo Shinozaki, Tatsuya Sawasaki
Gibberellin (GA) is a major hormone for plant growth and development. GA response is derived from the degradation of DELLA repressor proteins after GA-dependent complex formation of the GID1 GA receptor with DELLA. Genistein is a known tyrosine (Tyr) kinase inhibitor and inhibits DELLA degradation. However, the biological role of Tyr phosphorylation on the GA response remains unclear. Here, we demonstrate that GARU (GA receptor RING E3 ubiquitin ligase) mediates ubiquitin-dependent degradation of GID1, and that the TAGK2 plant Tyr-kinase is a target of genistein and inhibits GARU-GID1A interactions by phosphorylation of GARU at Tyr321...
October 17, 2017: Nature Communications
P Chanphai, H A Tajmir-Riahi
Dietary polyphenols are abundant micronutrients in our diet and paly major role in prevention of degenerative diseases. The binding efficacy of antioxidant polyphenols resveratrol, genistein and curcumin with PAMAM-G3 and PAMAM-G4 nanoparticles was investigated in aqueous solution at physiological conditions, using multiple spectroscopic methods, TEM images and docking studies. The polyphenol bindings are via hydrophilic, hydrophobic and H-bonding contacts with resveratrol forming more stable conjugates. As PAMAM size increased the loading efficacy and the stability of polyphenol-polymer conjugates were increased...
October 11, 2017: Journal of Biomolecular Structure & Dynamics
Lenka Applová, Jana Karlíčková, Michal Říha, Tomáš Filipský, Kateřina Macáková, Jiřina Spilková, Přemysl Mladěnka
BACKGROUND: One reason for the lower incidence of cardiovascular diseases in Asian countries may be the high intake of isoflavonoids and their antiplatelet effects may be an important factor. To date, there is limited comparison of a range of isoflavonoids and knowledge of their effects at different levels of platelet aggregation. PURPOSE: To screen the antiplatelet effects of a number of isoflavonoids on the arachidonic acid based aggregation pathway and investigate how the antiplatelet activity might occur...
November 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Pål A Olsvik, Kaja H Skjærven, Liv Søfteland
Screening has revealed that aquafeeds with high inclusion of plant material may contain small amounts of endocrine disrupting agricultural pesticides. In this work, bisphenol A (BPA) and genistein (GEN) were selected as model endocrine disrupting toxicants with impact on DNA methylation in fish. Atlantic salmon hepatocytes were exposed in vitro to four concentrations of BPA and GEN (0.1, 1.0, 10 and 100 μM) for 48 h. Toxicity endpoints included cytotoxicity, global DNA methylation, targeted transcriptomics and metabolomic screening (100 μM)...
September 17, 2017: Chemosphere
Tareisha L Dunlap, Caitlin E Howell, Nita Mukand, Shao-Nong Chen, Guido F Pauli, Birgit Maria Dietz, Judy L Bolton
Many women consider botanical dietary supplements (BDSs) as safe alternatives to hormone therapy for menopausal symptoms. However, the effect of BDSs on breast cancer risk is largely unknown. In the estrogen chemical carcinogenesis pathway, P450 1B1 metabolizes estrogens to 4-hydroxylated catechols, which are oxidized to genotoxic quinones that initiate and promote breast cancer. In contrast, P450 1A1 catalyzed 2-hydroxylation represents a detoxification pathway. The current study evaluated the effects of red clover, a popular BDS used for women's health, and its isoflavones, biochanin A (BA), formononetin (FN), genistein (GN), and daidzein (DZ), on estrogen metabolism...
October 6, 2017: Chemical Research in Toxicology
Pyung-Gang Lee, Joonwon Kim, Eun-Jung Kim, Sang-Hyuk Lee, Kwon-Young Choi, Romas J Kazlauskas, Byung-Gee Kim
Equols are isoflavandiols formed by reduction of soy isoflavones such as daidzein and genistein by gut microorganisms. These phytoestrogens are of interest for their various biological effects. We report biosynthesis from genistein to (-)-5-hydroxy-equol in recombinant E. coli expressing three reductases (daidzein reductase DZNR, dihidrodaidzein reductase DHDR, tetrahydrodaidzein reductase THDR) and a racemase (dihydrodaidzein racemase, DDRC) originating from the gut bacterium, Slackia isoflavoniconvertens...
October 6, 2017: ACS Chemical Biology
Da-Hye Lee, Min Jung Kim, Jiyun Ahn, Sang Hee Lee, Hyunjung Lee, Jin Hee Kim, So-Hyun Park, Young-Jin Jang, Tae-Youl Ha, Chang Hwa Jung
SCOPE: Cheonggukjang (CGJ) is a soybean-based quick-fermented food popular in Korea that contains a variety of biologically active compounds including isoflavones and saponins. Isoflavone bioavailability may be important for the bone health of postmenopausal women; therefore, the aim of this study was to evaluate the influence of fermentation on the isoflavone metabolite nutrikinetic profile after single dose CGJ or unfermented soybean administration in ovariectomized (OVX) and sham mice...
October 5, 2017: Molecular Nutrition & Food Research
Rui Zhang, Jian Xu, Jian Zhao, Yuzhe Chen
This study aimed to investigate the protective potential of genistein in dextran sulfate sodium (DSS)-induced colonic injury in vitro and in vivo models. The results showed that DSS exposure caused growth suppression, colonic injury, inflammation, and barrier dysfunction in mice. Dietary genistein alleviated DSS-caused colonic injury via reducing colonic weight, rectal bleeding, and diarrhea ratio. Meanwhile, genistein reduced colonic inflammatory response via downregulating cytokines expression and improved colonic permeability and barrier in DSS-challenged mice...
September 22, 2017: Oncotarget
Jace W Jones, Isabel L Jackson, Zeljko Vujaskovic, Michael D Kaytor, Maureen A Kane
PURPOSE: Biomarkers serve a number of purposes during drug development including defining the natural history of injury/disease, serving as a secondary endpoint or trigger for intervention, and/or aiding in the selection of an effective dose in humans. BIO 300 is a patent-protected pharmaceutical formulation of nanoparticles of synthetic genistein being developed by Humanetics Corporation. The primary goal of this metabolomic discovery experiment was to identify biomarkers that correlate with radiation-induced lung injury and BIO 300 efficacy for mitigating tissue damage based upon the primary endpoint of survival...
October 2, 2017: Pharmaceutical Research
Yalong Lu, Dehui Lin, Wenfeng Li, Xingbin Yang
This study was designed to explore the molecular mechanism of stachyose in enhancing the gastrointestinal stability and absorption of soybean genistein in mice. Male Kunming mice in each group (n = 8) were administered by intragastric gavage with saline, stachyose (250 mg/kg·bw), genistein (100 mg/kg·bw), and stachyose (50, 250, and 500 mg/kg·bw) together with genistein (100 mg/kg·bw) for 4 consecutive weeks, respectively, and then their urine, feces, blood, gut, and liver were collected. UPLC-qTOF/MS analysis showed that levels of genistein and its metabolites (dihydrogenistein, genistein 7-sulfate sodium salt, genistein 4'-β-D-glucuronide, and genistein 7-β-D-glucuronide) in serum and urine were increased with an increase in stachyose dosages in mice...
2017: Food & Nutrition Research
Shreya Patel, James A Hartman, William G Helferich, Jodi A Flaws
Genistein is a phytoestrogen found in soy and soy-based products. Previously, we found that genistein adversely affected estradiol levels and follicle growth in vitro. Proper hormone production and follicle growth are key regulators of normal fertility. Therefore, we hypothesized that genistein adversely affects female fertility and pregnancy outcomes. To test this hypothesis, we dosed sexually mature female CD-1 mice (35days) with 0, 300, 500, or 1000ppm genistein for 30, 60, 150, and 240days. At the end of the dosing periods, we measured mating rate, pregnancy rate, fertility rate, gestation time, parturition time, pup mortality, litter size, average pup weight, and estradiol and progesterone levels...
September 29, 2017: Reproductive Toxicology
Johanna Rienks, Janett Barbaresko, Ute Nöthlings
Context: Isoflavones have been suggested to play a role in disease prevention. The accuracy of assessing exposure to isoflavones might be improved by using them as biomarkers. Objective: A systematic review of observational studies on the association of isoflavone biomarkers with the risk of chronic disease and mortality was conducted. Meta-analyses of specific biomarker and disease combinations were performed. Data Sources: PubMed and Web of Science databases were searched...
August 1, 2017: Nutrition Reviews
Sabrina B Cepeda, Marisa J Sandoval, María B Rauschemberger, Virginia L Massheimer
Although soy phytoestrogen are proposed to prevent or improve postmenopausal vascular and bone diseases, the currently available data are controversial and unclear. In this study we evaluated the molecular and biochemical action of genistein on the cellular events involved in vascular calcification. Rat monocytes, aortic vascular cell and osteoblasts cultures in vitro exposed to Gen were employed. Gen down regulated the expression of cell adhesion molecules involved in stable leukocyte attachment. Using flow cytometry we found that the PE significantly diminished monocyte integrins CD11b, CD11c and CD18 expression either under basal and pro-inflammatory environment...
August 24, 2017: Journal of Nutritional Biochemistry
Isabel L Jackson, Andrew Zodda, Ganga Gurung, Radmila Pavlovic, Michael D Kaytor, Michael A Kuskowski, Zeljko Vujaskovic
BACKGROUND AND PURPOSE: BIO 300 nanosuspension (Humanetics Corporation) is being developed as a medical countermeasure (MCM) for the mitigation of the delayed effects of acute radiation exposure (DEARE), specifically pneumonitis and fibrosis of the lung. The objective of this study was to determine the best dose and treatment duration of BIO 300 to mitigate lung injury and improve the likelihood for survival in C57L/J mice exposed to whole thorax lung irradiation (WTLI). EXPERIMENTAL APPROACH: Age and sex-matched C57L/J mice received a single dose of 11...
September 30, 2017: British Journal of Pharmacology
Xiaoyan Zhou, Jinxiao Zhu, Tao Bian, Ruiqian Wang, Fei Gao
The Runt-related transcription factor (RUNX) gene family consists of three members, RUNX1, -2 and -3, which heterodimerize with a common protein, core-binding factor β, and contain the highly conserved Runt-homology domain. RUNX1 and -2 have essential roles in hematopoiesis and osteogenesis. Runx3 protein regulates cell lineage decisions in neurogenesis and thymopoiesis. The aim of the present study was to determine the expression features of the Runx3 protein in a murine asthma model. In vivo, Runx3 protein and mRNA were found to be almost equivalently expressed in the murine lung tissue of the control, ovalbumin (OVA) and genistein groups; however, the nuclear Runx3 protein was abated in lung tissue in OVA-immunized and challenged mice...
September 2017: Experimental and Therapeutic Medicine
Jiansong Fang, Zengrui Wu, Chuipu Cai, Qi Wang, Yun Tang, Feixiong Cheng
Natural products with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for natural products at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we proposed a systems pharmacology infrastructure to predict new drug targets and anticancer indications of natural products. Specifically, we reconstructed a global drug-target network with 7,314 interactions connecting 751 targets and 2,388 natural products and built predictive network models via a balanced substructure-drug-target network-based inference approach...
October 13, 2017: Journal of Chemical Information and Modeling
Masumeh Sanaei, Fraidoon Kavoosi, Shekoufeh Atashpour, Soheila Haghighat
Introduction: The flavonoids comprise a diverse group of polyphenolic compounds with antioxidant activity that is present in edible plants like soybeans and soy products. In vivo studies have concentrated on the effects of flavonoids on cancer and genistein (GE), a soy-derived isoflavone, has been reported to reduce prostate, colon, hepatic and breast adenocarcinoma risk. Tamoxifen (TAM) is an important drug for cancer treatment worldwide, which can induce apoptosis in various cancers, including examples in the liver, breast and ovaries...
September 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
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