DOCSLIB.ORG

The Isoflavone Genistein Inhibits Proliferation and Increases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Isoflavone Genistein Inhibits Proliferation and Increases TheIsoflavone Genistein Inhibits Proliferationand Increases HistamineContent inHuman Leukemic MastCells Michael G.Alexandrakis, M.D.,* Despina S.Kyriakou, M.D.,* Duraisamy Kempuraj, Ph.D.,# Man Huang, M.D., Ph.D.,# WilliamBoucher, B.Pharm.,# Dimitris Seretakis, M.D.,* and Theoharis C.Theoharides, Ph.D.,M.D.# ABSTRACT Mastcells exposed to allergens or otherstimuli 2 can release Mastcells are involved in allergic inflammation and some rare manypotent and rapidly acting mediators of inflammation, disorderssuch as systemic mastocytosis and mast cell leukemia. includinghistamine, proteases, prostaglandins, leukotrienes, 1,3–5 Certainnaturally occurring flavonoids have been shown to inhibit andcytokines. Themediator most readily associated 6 mastcell activation and promotematuration of secretory granules. withthe mast cell is histamine. Histamineplays an impor- Here,we report that the isoflavone genistein inhibited the growth tantrole in the pathogenesis of various allergic disorders, ofhuman leukemic mast cells (HMC-1) by 68.8,51.6, and 30.2% includingvasodilatation and increased vasopermeability. In at 102 4 , 1025 , and 1026 M,respectively,at day 3 (p , 0.001). addition,mast cells and histamine are involved in thepatho- Genisteinat 10 24 Mincreasedthe histamine content per 2 3 105 physiologyof irritable bowel syndrome 7 andinterstitial cellsat day 3 from5.9 6 1.2 mg/mL to 11.1 6 1.3 mg/mL (n 5 6; cystitis,8 sterileinflammatory conditions associated with p , 0.0001).These results indicate that genistein can inhibit pain,and worsened by stress. 9 proliferationand induce maturation of HMC-1 cells. (Allergyand Flavonoidsare lowmolecular weight benzo- g-pyrone AsthmaProc 24:373– 377, 2003) derivativesubiquitous in plants with a widespectrum of biologicactivities, such as inflammatory and immune re- astcells are primary effector cells in immediate hy- sponses,including inhibition of mastcells. 10 Genisteinis a M persensitivityresponses and their numbers are in- naturalisoflavonoid phytoestrogen present in various plant creasedin a widespectrum of pathological conditions. 1 foods,especially soy. This isoflavone has a heterocyclic, diphenolicstructure similar to estrogen; 11 atmicromolar concentrations,genistein was foundto have an inhibitory effecton protein tyrosine kinases (PTK), presumablyat the Fromthe *Department of Hematology, University Hospital of 12 Heraklion,School of Medicine University of Crete, Greece, and levelof theadenosine triphosphate binding site. Although #Departmentof Pharmacology and Experimental Therapeutics, thebiologic effects of genistein have not been fully clari- fied,genistein could induce cell cycle arrest and apoptosis TuftsUniversity School of Medicine, Boston Massachusetts 13,14 Supportedby ThetaBiomedical Consulting and Development Co., inleukemic cells andalso affect the growth and cell Inc.,Brookline, Massachusetts cycleprogression of human leukemic MOLT-4 and HL-60 15 Addresscorrespondence and reprint requests to T.C. Theoharides, cells. Apossibleinterpretation of these observations is the Ph.D.,M.D., Department of Pharmacology and Experimental abilityof genistein to inhibitthe activities of topoisomerases Therapeutics,Tufts University School of Medicine, 136 Harrison andtyrosine kinases and to induce differentiation in the 16 Ave.,Boston, MA 02111 humanleukemia cells HL-60 and K-562. Inaddition, genisteinat 150 mMwas shownto be an inhibitor of Allergy andAsthma Proc. 373 angiogenesis, 17 in vivo.10 Severalstudies have shown that Inhibition (%) genisteincan induce apoptosis in breast, stomach, lung, head,and neck, as well as prostate cancer cell lines by 1 2 number oflive cells in treatment group 5 3 100. modulationof cellcycle and apoptosis of regulatorymole- number oflive cells in nontreatment group cules.18–20 Genisteinhas been observed to inducethe differentiation Stainingof HMC-1 Cells ofhuman myelogenous leukemia K562 cells. 21 Other fla- ellswere grownon Lab-Tek culture chamber slides voneshave been reported to induce maturation of rat baso- (NUNK, Naperville,IL). After washingwith phos- philicleukemia cells. 22 Thiseffect, as well as the inhibition C phate-bufferedsaline, cells were fixedfor 5minuteswith ofmast cell activation has been associated with particular 10%formaldehyde in 10% acetic acid (pH 2.5).Cells were structuralrequirements, especially of the B ring. 23 stainedfor 5minuteswith 0.5% toluidine blue (pH 2.5), Inthis study, we investigatedthe effect of genistein on washedwith deionized water, and air dried. Cells were thegrowth of human leukemic mast cells (HMC-1) and photographedusing an Olympus light microscope (Olym- cellularconcentrations of histamine. These results suggest pusOptical Co., Tokyo, Japan). thatgenistein may be an effective agent in the prevention and/orfor thetreatment of human mast cell disorders. HistamineMeasurement MATERIALS AND METHODS istaminewas assayedby aluminescencespectrometer (Perkin-Elmer,Norwalk, CT) witha lowerdetection Genistein(4 * ,5,7-Trihydroxyisoflavone) H levelof 5ng/mL.HMC-1 cells were washedand harvested hiscompound was purchasedfrom Sigma(St. Louis, bycentrifugation at 400 3 g for 5minutesin 1.5-mL T MO) andwas dissolvedin propylene glycol, to make Eppendorftubes. Then, cells were resuspendendin water. a0.1M solution;then, it was filter-sterilizedand diluted Thissuspension was sonicatedin a Branson1200 ultra- 24 withculture medium to get the final concentrations 10 – sounddevice (Sonifier, Model W185D, Heat Systems — 26 10 M. Ultrasonics,Inc., Plainview, NY) for 10minutes, vortexed for 5minutes,and pelleted by 10-minute centrifugation at CellCulture 6000 3 g speedin an Eppendorf Microfuge. The total MC-124 was culturedin Iscove ’smodifiedDulbecco ’s amountof histamine in the cell pellet is expressed as mi- H medium(Gibco, Grand Island, NY) supplemented crograms/2 3 105 mastcells/ mL. with10% fetal calf serum and 1.2 mM ofmonothioglycerol 2 (Sigma)in 25-cm tissueculture flasks (Becton Dickinson Statistics Labware,Franklin Lakes, NJ). Thecells were incubatedat heresults are expressed as mean 6 SDofeither num- 37°Cina humidifiedincubator with 5% CO and 95% air. 2 berof cell or of the histamine present in the cell After 3daysof culture,cells were collectedand centrifuged T pellet.Comparisons were madeand probability was calcu- for 5minutesat 1000 rpm. Cells then were resuspendedin latedwith the nonparametric Mann-Whitney U test using culturemedium and plated in 12-well flat-bottom culture analysisof variance. Values of p , 0.05were considered plates(Costar, Cambridge, MA) ata densityof 2 3 105 statisticallysignificant. cell/mL.Genistein was addedin concentrations (10 24– 1025 M);cells cultured in mediumalone served as control. RESULTS Determinationof CellViability Effects ofGenistein on Cell Proliferation ellswith or without genistein were harvested,washed MC-1cells were culturedfor 3,4, and 5 daysin the C inphosphate-buffered saline and pelleted by centrif- H presenceor absenceof genisteinat 10 2 4, 1025, and ugationfor 5minutesat 400 3 g atroom temperature. Next, 1026 M.A concentration-dependentinhibition of growth cellswere resuspendedin Iscove ’smodifiedDulbecco ’s was observedon the 3rd, 4th, and 5th day of culture. Cell mediumsupplemented as aforementioned. Trypan blue viabilityon day 3 remainedhigh with lower than 10% (0.1%)exclusion tests were performedat theend of culture trypan blue–positivecells in cultures treated with any for cellviability. genisteinconcentration. On day 3 thenumber of cells (3103)was decreasedfrom 977.4 6 68.9in the untreated Determinationof Inhibitionof Cell Proliferation conditionto 304.6 6 53.9 at 1024 Mgenistein,to 472.6 6 heinhibition is expressed as the percentage of the 79.8 at 1025 M and 681.8 6 96.2 at 1026 M;the corre- T numberof live cells counted from eachtreatment spondingdegree of inhibition on proliferation of HMC-1 groupsubtracted from thetotal number of thenontreatment cells(Tables I andII) was 68.8%( p , 0.001) at 1024 M groupand then divided by thetotal number of cellsfrom the genistein,51.6% ( p , 0.001) at 1025 M,and 30.2% ( p , nontreatmentgroup, according to the formula: 0.002) at 1026 M,respectively. 374 September-October 2003, Vol.24, No. 5 TABLE I InhibitoryEffect ofGenistein on HMC-1 CellProliferation Genistein Day 3 Day 4 Day 5 Cells 3 103 Inhibition Cells 3 103 Inhibition Cells 3 103 Inhibition (% Total) (% Total) (% Total) Control 977.4 6 68.90 — 1012.8 6 97.3 — 723.3 6 37.7 — 1026 M 681.8 6 96.2# 30.2 763.0 6 92.4# 24.7 600.5 6 72.6§ 16.9 1025 M 472.6 6 79.7* 51.6 580.0 6 69.5* 42.7 470.0 6 63.9* 35.0 1024 M 304.6 6 53.9* 68.8 377.5 6 33.3* 62.6 382.0 6 39.7* 47.1 n 5 6 *p , 0.0001; #p , 0.002; §p , 0.005using Mann-Whitney U test. cells/mL at10 25 M and to 10.1 6 4.5 mg/mL at 1024 M TABLE II (p , 0.02). Effect ofGenistein on Total Histamine Content of HMC-1 Cells DISCUSSION TotalHistamine urresults clearly show that genistein inhibits HMC-1 5 (mg/2 3 10 Mast Cells/mL) O cellproliferation and induces accumulation of hista- Day 3 Day 4 Day 5 minein a dose-dependentmanner. HMC-1 was derived 24 Genistein (n 5 6) (n 5 8) (n 5 8) from apatientwith mast cell leukemia. HMC-1cells have lesshistamine than human mast cells in general. 23 Previous Control 5.9 6 1.2 5.8 6 2.4 6.1 6 1.7 studieshave shown that HMC-1 expresses a phenotypeand 1025 M 9.5 6 2.3 9.7 6 1.8 8.3 6 2.0* severalmarkers, i.e.,tryptase,histamine, heparin, and chon- p , 0.002* p , 0.02* p , 0.05* 1024 M 11.1 6 1.3 10.1 6 4.5 10.1 6 4.5 droitinsulfate, similar to that of human mast cells, and p , 0.0001* p , 0.01* p , 0.02* releasesor expressesthe mRNA ofanumberof chemokines andcytokines that are known to besecreted by humanmast *UsingMann-Whitney U test. cells.25,26 Flavonoidsare molecules rich in plants, fruits, andseeds with potent antioxidant effects. 10 Flavonoidsare lowmolecular weight benzo- g-pyronederivatives with a Onday 4, cell viability was alsohigh at 91.4%. The widespectrum of biologicactivities including regulation of 3 numberof cells( 310 )atthe respective genistein concen- inflammatoryand immune responses, especially inhibition 24 25 26 trationsof 10 , 10 , and 10 Mwas decreasedfrom ofmastcell activation.
Load more

Recommended publications
  • 1 1 2 3 4 5 6 7 Bioactive Phenolic Compounds of Soybean
    * Manuscript Click here to view linked References 1 Bioactive phenolic compounds of soybean ( Glycine max cv. Merit): modifications by 2 different microbial fermentations 3 4 5 M. Dueñas 2; T. Hernández 1; S. Robredo 1; *I. Estrella 1; R. Muñoz 1 6 7 1Instituto de Fermentaciones Industriales. C.S.I.C. Juan de la Cierva 3, 28006-Madrid. Spain. Fax: 34-915644853. 8 [email protected] 9 2Grupo de Investigación en Polifenoles, Unidad de Nutrición y Bromatología, Facultad de Farmacia, Universidad de 10 Salamanca. Campus Miguel de Unamuno. 37007 Salamanca. Spain. 11 12 *Corresponding author 13 14 Running title: Changes in phenolic compounds of soybeans by microbial fermentations 15 16 17 Abstract 18 Phenolic compounds of soybeans ( Glycine max ) are partially responsible of their beneficial 19 health effects. The most abundant phenolics in soybeans are isoflavones, mainly daidzein, 20 glycitein, and genistein and several derivatives of them. Other phenolic compounds are also 21 present but they have been minimally studied. In this work, the soybean seeds were fermented by 22 the microbiota present on the seeds or by inoculation with Aspergillus oryzae, Rhizopus oryzae or 23 Bacillus subtilis . The effect of microbial fermentation on the phenolic composition of soybeans 24 was studied. All the assayed microorganisms brought out variations in phenolics. An increase in 25 the concentration of phenolic acids was observed. Flavonoids were differently metabolized 26 depending on the microorganism used. In all samples the most important changes were produced 27 in the isoflavones content, observing an increase on the aglycones, glycitein, daidzein and 28 genistein. 29 30 Key words : soybean, fermentation, phenolic compounds, isoflavones 31 1 32 1.
    [Show full text]
  • Plant Phenolics: Bioavailability As a Key Determinant of Their Potential Health-Promoting Applications
    antioxidants Review Plant Phenolics: Bioavailability as a Key Determinant of Their Potential Health-Promoting Applications Patricia Cosme , Ana B. Rodríguez, Javier Espino * and María Garrido * Neuroimmunophysiology and Chrononutrition Research Group, Department of Physiology, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain; [email protected] (P.C.); [email protected] (A.B.R.) * Correspondence: [email protected] (J.E.); [email protected] (M.G.); Tel.: +34-92-428-9796 (J.E. & M.G.) Received: 22 October 2020; Accepted: 7 December 2020; Published: 12 December 2020 Abstract: Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic compounds has dramatically increased during the last decade due to their biological effects and promising therapeutic applications. In this review, we discuss the importance of phenolic compounds’ bioavailability to accomplish their physiological functions, and highlight main factors affecting such parameter throughout metabolism of phenolics, from absorption to excretion. Besides, we give an updated overview of the health benefits of phenolic compounds, which are mainly linked to both their direct (e.g., free-radical scavenging ability) and indirect (e.g., by stimulating activity of antioxidant enzymes) antioxidant properties. Such antioxidant actions reportedly help them to prevent chronic and oxidative stress-related disorders such as cancer, cardiovascular and neurodegenerative diseases, among others. Last, we comment on development of cutting-edge delivery systems intended to improve bioavailability and enhance stability of phenolic compounds in the human body. Keywords: antioxidant activity; bioavailability; flavonoids; health benefits; phenolic compounds 1. Introduction Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom with around 8000 different phenolic structures [1].
    [Show full text]
  • Antiproliferative Effects of Isoflavones on Human Cancer Cell Lines Established from the Gastrointestinal Tract 1
    [CANCER RESEARCH 53, 5815-5821, December 1, 1993] Antiproliferative Effects of Isoflavones on Human Cancer Cell Lines Established from the Gastrointestinal Tract 1 Kazuyoshi Yanagihara, 2 Akihiro Ito, Tetsuya Toge, and Michitaka Numoto Department of Pathology [K. Y, M. N.], Cancer Research [A. L], and Surgery iT. T.], Research Institute for Nuclear Medicine and Biology, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734, Japan ABSTRACT MATERIALS AND METHODS Seven isoflavones, biochanin A, daidzein, genistein, genistin, prunectin, Establishment of Cancer Cell Lines. Tumor tissues were trimmed of fat puerarin, and pseudobaptigenin were tested for cytostatic and cytotoxic and necrotic portions and minced with scalpels. The tissue pieces were trans- effects on 10 newly established cancer cell lines of the human gastrointes- ferred, together with medium, at 10 to 15 fragments/dish to 60-mm culture tinal origin. Proliferation of HSC-41E6, HSC-45M2, and SH101-P4 stom- dishes (Falcon, Lincoln Park, N J). The patient's ascitic tumor cells were ach cancer cell lines was strongly inhibited by biochanin A and genistein, harvested by centrifugation (1000 rpm for 10 min) and plated into 60-mm whereas other stomach, esophageal, and colon cancer lines were moder- dishes. Culture dishes initially selectively trypsinized [trypsin, 0.05% (w/v); ately suppressed by both compounds. Biochanin A and genistein were EDTA, 0.02% (w/v)], to remove overgrowing fibroblasts. In addition, we cytostatic at low concentrations (<20 pg/ml for biochanin A, <10/tg/ml for attempted to remove the fibroblasts mechanically and to transfer the tumor genistein) and were cytotoxic at higher concentrations (>40 pg/ml for cells selectively.
    [Show full text]
  • Phenolics in Human Health
    International Journal of Chemical Engineering and Applications, Vol. 5, No. 5, October 2014 Phenolics in Human Health T. Ozcan, A. Akpinar-Bayizit, L. Yilmaz-Ersan, and B. Delikanli with proteins. The high antioxidant capacity makes Abstract—Recent research focuses on health benefits of polyphenols as an important key factor which is involved in phytochemicals, especially antioxidant and antimicrobial the chemical defense of plants against pathogens and properties of phenolic compounds, which is known to exert predators and in plant-plant interferences [9]. preventive activity against infectious and degenerative diseases, inflammation and allergies via antioxidant, antimicrobial and proteins/enzymes neutralization/modulation mechanisms. Phenolic compounds are reactive metabolites in a wide range of plant-derived foods and mainly divided in four groups: phenolic acids, flavonoids, stilbenes and tannins. They work as terminators of free radicals and chelators of metal ions that are capable of catalyzing lipid oxidation. Therefore, this review examines the functional properties of phenolics. Index Terms—Health, functional, phenolic compounds. I. INTRODUCTION In recent years, fruits and vegetables receive considerable interest depending on type, number, and mode of action of the different components, so called as “phytochemicals”, for their presumed role in the prevention of various chronic diseases including cancers and cardiovascular diseases. Plants are rich sources of functional dietary micronutrients, fibers and phytochemicals, such
    [Show full text]
  • The Importance of Isoflavone Dose and Estrogen Receptor
    Journal of Personalized Medicine Article From Proteomics to Personalized Medicine: The Importance of Isoflavone Dose and Estrogen Receptor Status in Breast Cancer Cells 1 2, 1,3 4 Maria Ilies, , Alina Uifălean * , Sergiu Pas, ca , Vishnu Mukund Dhople , Michael Lalk 5 , Cristina Adela Iuga 1,2 and Elke Hammer 4,6 1 MedFuture Research Center for Advanced Medicine, Department of Proteomics and Metabolomics, “Iuliu Hat, ieganu” University of Medicine and Pharmacy, no. 4–6 Louis Pasteur st., 400349 Cluj-Napoca, Romania; [email protected] (M.I.); [email protected] (S.P.); [email protected] (C.A.I.) 2 Department of Pharmaceutical Analysis, Faculty of Pharmacy, “Iuliu Hat, ieganu” University of Medicine and Pharmacy, Louis Pasteur Street 6, 400349 Cluj-Napoca, Romania 3 Department of Hematology, “Iuliu Hat, ieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania 4 Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Straße 8, 17475 Greifswald, Germany; [email protected] (V.M.D.); [email protected] (E.H.) 5 Institute of Biochemistry, University of Greifswald, Felix-Hausdorff-Straße 4, 17489 Greifswald, Germany; [email protected] 6 DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany * Correspondence: [email protected] Received: 12 November 2020; Accepted: 17 December 2020; Published: 19 December 2020 Abstract: Continuing efforts are directed towards finding alternative breast cancer chemotherapeutics, with improved safety and efficacy profiles. Soy isoflavones represent promising agents but, despite extensive research, limited information exists regarding their impact on the breast cancer cell proteome. The purpose of this study was to compare the proteomic profiles of MCF-7 (estrogen responsive) and MDA-MB-231 (estrogen non-responsive) breast cancer cells exposed to different concentrations of genistein, daidzein, and a soy seed extract, using a high throughput LC–UDMSE protein profiling approach.
    [Show full text]
  • Transcriptome Analysis of Pueraria Candollei Var
    Suntichaikamolkul et al. BMC Plant Biology (2019) 19:581 https://doi.org/10.1186/s12870-019-2205-0 RESEARCH ARTICLE Open Access Transcriptome analysis of Pueraria candollei var. mirifica for gene discovery in the biosyntheses of isoflavones and miroestrol Nithiwat Suntichaikamolkul1, Kittitya Tantisuwanichkul1, Pinidphon Prombutara2, Khwanlada Kobtrakul3, Julie Zumsteg4, Siriporn Wannachart5, Hubert Schaller4, Mami Yamazaki6, Kazuki Saito6, Wanchai De-eknamkul7, Sornkanok Vimolmangkang7 and Supaart Sirikantaramas1,2* Abstract Background: Pueraria candollei var. mirifica, a Thai medicinal plant used traditionally as a rejuvenating herb, is known as a rich source of phytoestrogens, including isoflavonoids and the highly estrogenic miroestrol and deoxymiroestrol. Although these active constituents in P. candollei var. mirifica have been known for some time, actual knowledge regarding their biosynthetic genes remains unknown. Results: Miroestrol biosynthesis was reconsidered and the most plausible mechanism starting from the isoflavonoid daidzein was proposed. A de novo transcriptome analysis was conducted using combined P. candollei var. mirifica tissues of young leaves, mature leaves, tuberous cortices, and cortex-excised tubers. A total of 166,923 contigs was assembled for functional annotation using protein databases and as a library for identification of genes that are potentially involved in the biosynthesis of isoflavonoids and miroestrol. Twenty-one differentially expressed genes from four separate libraries were identified as candidates involved in these biosynthetic pathways, and their respective expressions were validated by quantitative real-time reverse transcription polymerase chain reaction. Notably, isoflavonoid and miroestrol profiling generated by LC-MS/MS was positively correlated with expression levels of isoflavonoid biosynthetic genes across the four types of tissues. Moreover, we identified R2R3 MYB transcription factors that may be involved in the regulation of isoflavonoid biosynthesis in P.
    [Show full text]
  • Soy Isoflavone: the Multipurpose Phytochemical (Review)
    BIOMEDICAL REPORTS 1: 697-701, 2013 Soy isoflavone: The multipurpose phytochemical (Review) QINGLU WANG1, XIAOYUE GE1, XUEWEN TIAN2, YUJUN ZHANG1, JIE ZHANG1 and PINGPING ZHANG1 1Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Shandong Wanjie Medical College, Zibo, Shandong 255213; 2Shandong Research Center of Sports Science, Jinan, Shandong 250102, P.R. China Received April 10, 2013; Accepted May 21, 2013 DOI: 10.3892/br.2013.129 Abstract. Soy isoflavones are compounds found in soybean specifically Seventh-day Adventists and vegetarians, have used and soybean products. They have been reported to possess soyfoods for ~100 years, although the quintessential soyfood numerous physiological properties, such as antitumor, anti- tofu was first introduced on a large scale to the general US menopausal (female) osteoporosis and anti-aging. They have population in the early 1970s. Health-conscious and ecologi- also been reported to improve learning and memory skills in cally-minded consumers were particularly attracted to soy at menopausal women and aid in the prevention and treatment that time since it was perceived as a source of high quality of heart disease, diabetes and Kawasaki disease (KD). In this protein, low in saturated fat, that was more efficiently produced review, the effects of soy isoflavones on various diseases were compared to animal sources of protein. A significant increase analyzed. Based on the analysis, it was hypothesized that the in soyfood consumption occurred during the last decade of the function of soybean isoflavones in the prevention and treat- 20th century, mainly due to the belief among many consumers ment of various diseases results from their phytoestrogen and that soyfoods may offer health benefits, independent of their antioxidant properties.
    [Show full text]
  • Isoflavone Supplements for Menopausal Women
    nutrients Review Isoflavone Supplements for Menopausal Women: A Systematic Review 1,2, 1, 3,4, Li-Ru Chen y, Nai-Yu Ko y and Kuo-Hu Chen * 1 Department of Physical Medicine and Rehabilitation, Mackay Memorial Hospital, Taipei 10449, Taiwan; [email protected] (L.-R.C.); [email protected] (N.-Y.K.) 2 Department of Mechanical Engineering, National Chiao-Tung University, Hsinchu 300, Taiwan 3 Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, Taipei 23142, Taiwan 4 School of Medicine, Tzu-Chi University, Hualien 970, Taiwan * Correspondence: [email protected]; Tel.: +886-2-6628-9779 These authors contributed equally to this work. y Received: 17 September 2019; Accepted: 29 October 2019; Published: 4 November 2019 Abstract: Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms “isoflavone” and “menopause”, which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition.
    [Show full text]
  • Physiologically Active Molecules and Functional Properties of Soybeans in Human Health—A Current Perspective
    International Journal of Molecular Sciences Review Physiologically Active Molecules and Functional Properties of Soybeans in Human Health—A Current Perspective Il-Sup Kim 1 , Cheorl-Ho Kim 2,3,* and Woong-Suk Yang 4,* 1 Advanced Bio-resource Research Center, Kyungpook National University, Daegu 41566, Korea; [email protected] 2 Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Gyunggi-Do 16419, Korea 3 Samsung Advanced Institute of Health Science and Technology, Gyunggi-Do 16419, Korea 4 Nodaji Co., Ltd., Pohang, Gyeongsangbuk-Do 37927, Korea * Correspondence: [email protected] (C.-H.K.); [email protected] (W.-S.Y.) Abstract: In addition to providing nutrients, food can help prevent and treat certain diseases. In particular, research on soy products has increased dramatically following their emergence as functional foods capable of improving blood circulation and intestinal regulation. In addition to their nutritional value, soybeans contain specific phytochemical substances that promote health and are a source of dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, and phytic acid, while serving as a trypsin inhibitor. These individual substances have demonstrated effectiveness in preventing chronic diseases, such as arteriosclerosis, cardiac diseases, diabetes, and senile dementia, as well as in treating cancer and suppressing osteoporosis. Furthermore, soybean can affect fibrinolytic activity, control blood pressure, and improve lipid metabolism, while eliciting antimutagenic, anticarcinogenic, and antibacterial effects. In this review, Citation: Kim, I.-S.; Kim, C.-H.; rather than to improve on the established studies on the reported nutritional qualities of soybeans, Yang, W.-S. Physiologically Active Molecules and Functional Properties we intend to examine the physiological activities of soybeans that have recently been studied and of Soybeans in Human Health—A confirm their potential as a high-functional, well-being food.
    [Show full text]
  • Daidzein and Breast Cancer Risk in Later Years FACT SHEET on the PHYTOESTROGEN DAIDZEIN
    BREAST CANCER & THE ENVIRONMENT RESEARCH CENTERS Early Life Exposure to the Phytoestrogen Daidzein and Breast Cancer Risk in Later Years FACT SHEET on the PHYTOESTROGEN DAIDZEIN Abstract Daidzein is a phytoestrogen (estrogen-like chemical compound present in plants) that binds to estrogen receptors and has both weak estrogenic and weak anti-estrogenic effects. There are three major classes of phytoestrogens that have estrogen-like actions in the human body. They are lignans, isoflavones, and coumestans. Daidzein is an isoflavone. Exposure to daidzein occurs principally through foods made with soybeans and soy protein. In a proportion of the population, daidzein is metabolized by intestinal bacteria to produce equol and O-DMA, metabolites that are more estrogenic than daidzein. Daidzein can cross the placenta and has been found in breast milk. It is unknown whether daidzein influences early onset of puberty in girls. Exposure to daidzein can be measured using a blood or urine test; however levels vary widely in each person due to considerable variability in the metabolism of daidzein. In vitro and in vivo studies have found that daidzein stimulates the growth of estrogen-sensitive breast cancer cells. Epidemiologic studies have found conflicting evidence; some studies have found an association between soy exposure and decreased breast cancer risk while others have found no association. Some epidemiological evidence indicates that soy intake may be more protective when the exposure occurs prior to puberty. More research needs to be conducted on the association between breast cancer risk and daidzein specifically before conclusions can be drawn. The International Agency for Research on Cancer (IARC) has not determined whether phytoestrogens are carcinogenic to humans.
    [Show full text]
  • Effect of Soy Isoflavone Protein and Soy Lecithin on Endothelial Function in Healthy Postmenopausal Women Mary Pearson
    Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine 11-15-2006 Effect of Soy Isoflavone Protein and Soy Lecithin on Endothelial Function in Healthy Postmenopausal Women Mary Pearson Follow this and additional works at: http://elischolar.library.yale.edu/ymtdl Recommended Citation Pearson, Mary, "Effect of Soy Isoflavone Protein and Soy Lecithin on Endothelial Function in Healthy Postmenopausal Women" (2006). Yale Medicine Thesis Digital Library. 279. http://elischolar.library.yale.edu/ymtdl/279 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. Effect of Soy Isoflavone Protein and Soy Lecithin on Endothelial Function in Healthy Postmenopausal Women A Thesis Submitted to the Yale University School of Medicine in Partial Fulfillment of the Requirements for the Degree of Doctor of Medicine by Mary Margaret Pearson 2006 ABSTRACT EFFECT OF SOY ISOFLAVONE AND SOY LECITHIN ON ENDOTHELIAL FUNCTION IN HEALTHY POSTMENOPAUSAL WOMEN Meg Pearson, Valentine Njike, Marian Evans, Martha Huxley, and David L. Katz. Department of Epidemiology and Public Health, Yale University, School of Medicine, New Haven, CT. The purpose of this study was to assess the effects of soy isoflavone protein concentrate and soy lecithin on endothelial function measured as flow mediated dilation (FMD) of the brachial artery in healthy postmenopausal women.
    [Show full text]
  • A Randomized Controlled Trial of Phytoestrogen Supplementation, Growth and Bone Turnover in Adolescent Males
    European Journal of Clinical Nutrition (2003) 57, 324–327 ß 2003 Nature Publishing Group All rights reserved 0954–3007/03 $25.00 www.nature.com/ejcn ORIGINAL COMMUNICATION A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males G Jones1*, T Dwyer1, K Hynes1, FS Dalais2, V Parameswaran3 and TM Greenaway3 1Menzies Centre for Population Health Research, Hobart, Tasmania, Australia; 2Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Hospital, Prahran, Victoria, Australia; and 3Diabetes and Endocrine Services, Royal Hobart Hospital, Hobart, Tasmania Objective: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. Design: Randomized double-blind placebo-controlled trial. Setting: Single school in northwest Tasmania. Participants: Adolescent boys (treatment n ¼ 69, placebo n ¼ 59, mean age 16.8 y). Interventions: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. Results: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P < 0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. Conclusions: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.
    [Show full text]