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Isoflavones
Kinds of Isoflavones Terms modified by Isoflavones Selected AbstractsDifferentiation of sulfate and phosphate by H/D exchange mass spectrometry: application to isoflavoneJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 11 2004Akira Kanakubo Abstract Often phosphorylation or sulfation is an important step which occurs in the signal transduction and cascade of metabolic pathways. Some natural products and metabolites contain one or more sulfate or phosphate groups. Isoflavone sulfate has been identified from high-resolution mass spectrometry (HRMS) and enzymatic digestion by sulfatase. We previously reported the new water-soluble isoflavone analogs, daidzein 7- O -phosphate and genistein 7- O -phosphate, which were surprisingly hydrolyzed by sulfatase. In this previous study, we could not determine the phosphate from the results of HRMS and enzymatic digestion, that is, HRMS and enzymatic digestion did not provide clear evidence. In this case, we drew conclusions from NMR analysis. HRMS has been ineffective with a regular fast atom bombardment (FAB) mass spectrometer to distinguish between phosphate and sulfate since the mass difference is only 0.009 mass units. There was, however, no conventional method of microanalysis to distinguish phosphate from sulfate owing to the same nominal mass. It is still very difficult to determine by negative FABMS [OP(O)(OH)2] = 80 and [OS(O)2OH] = 80. In this paper, we report a method to distinguish between these groups by using a popular low-resolution mass instrument; thus, phosphate and sulfate were measured by H/D exchange mass spectrometry at the picomole level to differentiate [OP(O)(OD)2] = 82 and [OS(O)2OD] = 81, respectively. This method is applicable not only to the isoflavone, but also to other phospho and sulfo compounds. Copyright © 2004 John Wiley & Sons, Ltd. [source] Lack of Effect of Soy Isoflavone on Thyroid Hyperplasia in Rats Receiving an Iodine-deficient DietCANCER SCIENCE, Issue 2 2001Hwa-Young Son We have reported a dramatic synergism between soy intake and iodine deficiency regarding induction of thyroid hyperplasia in rats. Because isoflavones are active constituents of soybeans, in the present study, their possible contribution was examined. Female F344 rats were divided into 8 groups, exposed to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI+iodine deficiency (ID), 0.04% SI, 0.04% SI+ID, 20% defatted soybean (DS) alone, 20% DS+ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced by SI, but was increased by the ID and DS diets with a further significant increment in the DS+ID group (P<0.01). Compared to the control value, serum T4 was significantly (P<0.01) increased by 20% DS alone and decreased in all groups given the ID treatment (P<0.001). Serum thyroid stimulating hormone (TSH) level was increased by ID, and further enhanced by DS (P<0.01) but not SI. Histopathologically, diffuse hypertrophy and/or hyperplasia of thyroid follicles were observed in the ID-treated groups, the severity being enhanced by DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were elevated in the ID diet groups and again enhanced by DS, but not SI. These results thus suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency. [source] Genistein prevents thyroid hormone-dependent tail regression of Rana catesbeiana tadpoles by targetting protein kinase C and thyroid hormone receptor ,DEVELOPMENTAL DYNAMICS, Issue 3 2007L. Ji Abstract Thyroid hormone (TH)-regulated gene expression is mainly mediated by TH binding to nuclear thyroid hormone receptors (TRs). Despite extensive studies in mammalian cell lines that show that phosphorylation signaling pathways are important in TH action, little is known about their roles on TH signaling in vivo during development. Anuran metamorphosis is a postembryonic process that is absolutely dependent upon TH and tadpole tail resorption can be precociously induced by exogenous administration of 3,5,3,-triiodothyronine (T3). We demonstrate that genistein (a major isoflavone in soy products and tyrosine kinase inhibitor) and the PKC inhibitor (H7) prevent T3 -induced regression of the Rana catesbeiana tadpole tail. T3 -induced protein kinase C tyrosine phosphorylation and kinase activity are inhibited by genistein while T3 -induced up-regulation of TR, mRNA, but not TR, mRNA, is significantly attenuated, most likely through inhibition of T3 -dependent phosphorylation of the TR, protein. This phosphorylation may be modulated through PKC. These data demonstrate that T3 signaling in the context of normal cells in vivo includes phosphorylation as an important factor in establishing T3 -dependent tail regression during development. Developmental Dynamics 236:777,790, 2007. © 2007 Wiley-Liss, Inc. [source] Chemical Constituents from the Fruits of Madhuca latifoliaHELVETICA CHIMICA ACTA, Issue 5 2004From the fruit coats of the medicinal plant Madhuca latifolia were isolated three new compounds, the triterpenoid madhucic acid (=3,- (octanoyloxy)-11-oxoolean-12-en-28-oic acid; 1), the untypical isoflavone madhushazone (=9-methoxy-7-(2,3,6-trimethoxyphenyl)-[1,3]dioxolo[4,5- g][1]benzopyran-8(8H)-one; 2), and a bis(isoflavone) named madhusalmone (=5,14-dimethoxy-3,12-bis(3,4,5-trimethoxyphenyl)-1,6,8,10,15,17-hexaoxanaphtho[2,,3,:,6,7]cyclodeca[1,2- b]naphthalene-4,13(4H,13H)-dione; 3), as well as eight known constituents, and their structures were elucidated by spectral analysis, including 2D-NMR techniques. [source] Genistein selectively potentiates arsenic trioxide-induced apoptosis in human leukemia cells via reactive oxygen species generation and activation of reactive oxygen species-inducible protein kinases (p38-MAPK, AMPK)INTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Yolanda Sánchez Abstract The observation that genistein may behave as a pro-oxidant agent lead us to examine the capacity of this isoflavone to modulate the toxicity of the oxidation-sensitive anti-leukemic agent arsenic trioxide (ATO), and for comparison other anti-tumor drugs. Co-treatment with genistein increased ATO-provoked apoptosis and activated apoptosis regulatory events (Bcl-XL down-regulation, cytochrome c and Omi/HtrA2 release from mitochondria, XIAP decrease and caspase-8/Bid and caspase-3 activation) in U937 promonocytes and other human leukemia cell lines (HL60, THP-1, Jurkat, RPMI-8866), but not in phytohemagglutinin-stimulated non-tumor peripheral blood lymphocytes (PBLs). Genistein, alone and with ATO, stimulated reactive oxygen species generation, and apoptosis was attenuated by N -acetyl- L -cysteine and butylated hydroxyanisole. Addition of low H2O2 concentrations mimicked the capacity of genistein to increase ATO-provoked apoptosis in leukemia cells, but not in PBLs. By contrast, co-treatment with genistein or H2O2 failed to potentiate the toxicity of DNA-targeting agent cisplatin, the proteasome inhibitor MG-132 and the histone deacetylase inhibitor MS-275. Within the here used time-period (14 hr) genistein, alone or with ATO, did not significantly affect Akt phosphorylation and NF-,B binding activity, nor decreased intracellular GSH content. However, it elicited N -acetyl- L -cysteine-inhibitable phosphorylation of p38-MAPK and AMPK, and apoptosis was attenuated by pharmacologic inhibitors against these kinases. The pro-oxidant capacity of genistein might be exploited to improve the efficacy of ATO as anti-leukemic agent, and perhaps the efficacy of other oxidation-based therapeutic approaches. © 2008 Wiley-Liss, Inc. [source] Chemical components of Aspergillus -type Douchi, a Chinese traditional fermented soybean product, change during the fermentation processINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 3 2007Jian-Hua Zhang Summary Douchi, a traditional fermented soybean product that originated in China, has been consumed since ancient times as a food seasoning. The influence of fermentation on the chemical components of naturally fermented douchi and Aspergillus egypticus pure-cultured douchi was investigated. Changes in per cent and/or concentration of amino-type nitrogen, total acid, reducing sugar, organic acid, amino acids (AA) and isoflavone, along with the neutral protease and , -glucosidase activities during the fermentation, were analysed. The results indicated that fermentation had a significant effect on the concentration of chemical components. The concentration of all free amino acids (FAA) increased gradually during fermentation, to a maximum of 109.54 mg g,1 in 15-day fermented products. The main organic acids in douchi are 7.788 and 17.778 mg g,1, respectively. During fermentation, the contents of daidzin and genistin decreased from 160.7 and 207.9 to 7.54 and 24.12 ,g g,1 respectively. Daidzein and genistein increased from 18.2 and 16.9 to 63.4 and 84.6 ,g g,1, respectively. [source] Production of ,-Glucosidase and Hydrolysis of Isoflavone Phytoestrogens by Lactobacillus acidophilus, Bifidobacterium lactis, and Lactobacillus casei in SoymilkJOURNAL OF FOOD SCIENCE, Issue 1 2008O.N. Donkor ABSTRACT:, The study determined ,-glucosidase activity of commercial probiotic organisms for hydrolysis of isoflavone to aglycones in fermenting soymilk. Soymilk made with soy protein isolate (SPI) was fermented with Lactobacillus acidophilus LAFTI® L10, Bifidobacterium lactis LAFTI® B94, and Lactobacillus casei LAFTI® L26 at 37 °C for 48 h and the fermented soymilk was stored for 28 d at 4 °C. ,-Glucosidase activity of organisms was determined using ,-nitrophenyl ,-D-glucopyranoside as a substrate and the hydrolysis of isoflavone glycosides to aglycones by these organisms was carried out. The highest level of growth occurred at 12 h for L. casei L26, 24 h for B. lactis B94, and 36 h for L. acidophilus L10 during fermentation in soymilk. Survival after storage at 4 °C for 28 d was 20%, 15%, and 11% greater (P < 0.05) than initial cell counts, respectively. All the bacteria produced ,-glucosidase, which hydrolyzed isoflavone ,-glycosides to isoflavone aglycones. The decrease in the concentration of ,-glycosides and the increase in the concentration of aglycones were significant (P < 0.05) in the fermented soymilk. Increased isoflavone aglycone content in fermented soymilk is likely to improve the biological functionality of soymilk. [source] Bitterness of Soy Extracts Containing Isoflavones and SaponinsJOURNAL OF FOOD SCIENCE, Issue 3 2006Erica Aldin ABSTRACT: Chemical profiles of isoflavones and saponins in defatted soy flakes, soy protein isolate, and soy germ extracts were determined. The isoflavone and saponin concentration and distribution in the soy extracts were different. Recognition thresholds for bitterness were lower for extracts of defatted soy flake and soy protein isolate than for soy germ extract in water. Bitterness thresholds were higher in milk; bitterness was detected in the soy flake extract at lower concentrations of isoflavone and saponins than in isolate or germ extracts. Soy protein isolate extracts were less astringent and had less off-flavor than the soy flake and soy germ extracts in water at same total isoflavone concentration. The distribution of isoflavone and saponin forms compared with threshold and descriptive analysis suggested that the ,-malonyl-glucoside isoflavone and the 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) -saponins may be the components responsible for flavor differences in soy matrices. [source] Differentiation of sulfate and phosphate by H/D exchange mass spectrometry: application to isoflavoneJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 11 2004Akira Kanakubo Abstract Often phosphorylation or sulfation is an important step which occurs in the signal transduction and cascade of metabolic pathways. Some natural products and metabolites contain one or more sulfate or phosphate groups. Isoflavone sulfate has been identified from high-resolution mass spectrometry (HRMS) and enzymatic digestion by sulfatase. We previously reported the new water-soluble isoflavone analogs, daidzein 7- O -phosphate and genistein 7- O -phosphate, which were surprisingly hydrolyzed by sulfatase. In this previous study, we could not determine the phosphate from the results of HRMS and enzymatic digestion, that is, HRMS and enzymatic digestion did not provide clear evidence. In this case, we drew conclusions from NMR analysis. HRMS has been ineffective with a regular fast atom bombardment (FAB) mass spectrometer to distinguish between phosphate and sulfate since the mass difference is only 0.009 mass units. There was, however, no conventional method of microanalysis to distinguish phosphate from sulfate owing to the same nominal mass. It is still very difficult to determine by negative FABMS [OP(O)(OH)2] = 80 and [OS(O)2OH] = 80. In this paper, we report a method to distinguish between these groups by using a popular low-resolution mass instrument; thus, phosphate and sulfate were measured by H/D exchange mass spectrometry at the picomole level to differentiate [OP(O)(OD)2] = 82 and [OS(O)2OD] = 81, respectively. This method is applicable not only to the isoflavone, but also to other phospho and sulfo compounds. Copyright © 2004 John Wiley & Sons, Ltd. [source] CJY, an isoflavone, reverses P-glycoprotein-mediated multidrug-resistance in doxorubicin-resistant human myelogenous leukaemia (K562/DOX) cellsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2007Bian-Sheng Ji In an effort to develop safe and effective multidrug-resistance (MDR) reversing agents, the effect of CJY, an isoflavone, on the P-glycoprotein (P-gp) function and P-gp-mediated MDR was evaluated in doxorubicin-resistant human myelogenous leukaemia (K562/DOX) cells. The results showed that CJY caused a marked increase in accumulation and a notable decrease in efflux of rhodamine 123 (Rh123). The inhibitory effect of the agent on P-gp function persisted for at least 120 min after removal of 2.5 ,M CJY from the incubation medium. The doxorubicin-induced cytotoxicity, apoptosis and cell cycle perturbations were significantly potentiated by CJY. The intracellular accumulation of doxorubicin was also enhanced. The compound exhibited potent effects in-vitro on the reversal of P-gp-mediated MDR, suggesting that it could become a candidate as an effective MDR reversing agent in cancer chemotherapy. [source] Characterization of fermented black soybean natto inoculated with Bacillus natto during fermentationJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 7 2010Yongjin Hu Abstract BACKGROUND: To make nutrients more accessible and further increase biological activity, cooked black soybeans were inoculatedwith Bacillus natto and fermented at 37 °C for 48 h. The changes in physiochemical properties of fermented black soybean natto were investigated. RESULTS: The inoculation procedure significantly increased moisture, viscosity, color, polyphenol compounds and anthocyanin, and significantly decreased hardness after 48 h fermentation. Fibrinolytic and caseinolytic protease, ,-glucosidase activities, TCA-soluble nitrogen, and ammonia nitrogen contents in the inoculated samples significantly increased as fermentation time increased. Genistin and daidzin concentrations gradually decreased with increased fermentation time. However, genistein and daidzein increased with fermentation time, which reached 316.8 and 305.2 µg g,1 during 48 h fermentation, respectively. DPPH radical scavenging activities of the fermented black soybeans increased linearly with fermentation time and concentration. Compared with the soaked black soybeans and cooked black soybeans, the fermented black soybeans with B. natto resulted in higher scavenging activity towards DPPH radicals, which correlated well with the content of total phenols (r = 0.9254, P < 0.05) and aglycone isoflavone (r = 0.9861, P < 0.05). CONCLUSION: Black soybean natto fermented by B. natto has the potential to become a functional food because of its high antioxidant activity. Copyright © 2010 Society of Chemical Industry [source] Effect of thermal processing on genistein, daidzein and glycitein content in soymilkJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 7 2006Huihua Huang Abstract Soymilk was subjected to various heat treatments at 95, 121 and 140 °C for various lengths of time. The contents of the aglycones of isoflavone (daidzein, glycitein and genistein) of the soymilk were determined using C18 reversed-phase high-performance liquid chromatography. Genistein showed greater stability to heat treatment than daidzein and glycitein. Both the daidzein and glycitein contents decreased rapidly during the early stage of heating, but on continued heating the rates of decrease were much slower. Heating may cause an increase or decrease in the genistein content of soymilk depending on the temperature and time used. Upon heating at 95 and 121 °C, there was an increase in the genistein content in the early stage of heating, possibly due the conversion of genistin to genistein. Heating at 140 °C for more than 15 s and prolonged heating at 95 and 121 °C, however, caused a slow decline in the genistein content. Copyright © 2006 Society of Chemical Industry [source] Different antibacterial actions of isoflavones isolated from Erythrina poeppigiana against methicillin-resistant Staphylococcus aureusLETTERS IN APPLIED MICROBIOLOGY, Issue 3 2006M. Sato Abstract Aims:, To screen six isoflavones isolated from Erythrina poeppigiana (Leguminosae) for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Methods and Results:, Stem bark of E. poeppigiana was macerated with acetone and the methylene chloride-soluble fraction of the residue was applied to repeated silica gel column chromatography and eluted. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by a broth dilution method. Inactive compounds that failed inhibiting bacterial growth at 25 ,g ml,1 were further investigated for their combination effects with methicillin and oxacillin. Of the isolated isoflavones, 5,7,4,-trihydroxy-8,3,-di(,,, -dimethylallyl)isoflavone (isolupalbigenin) exhibited the highest anti-MRSA activity (MICs: 1·56,3·13 ,g ml,1; MBCs: 6·25,12·5 ,g ml,1), followed by 5,7,4,-trihydroxy-6- ,,, -dimethylallylisoflavone (erythrinin B). Inactive compounds were combined with methicillin or oxacillin, 5,4,-dihydroxy-(3,,,4,,-dihydro-3,,-hydroxy)-2,,,2,,-dimethylpyrano[5,,,6,,:6,7]isoflavone (M-Wi-2) intensifying the susceptibility of MRSA strains to these antibiotics. In all but one strain, the MIC values of methicillin were reduced from ,100 to 6·25,12·5 ,g ml,1 in the presence of M-Wi-2 (25 ,g ml,1). Conclusions:, Isoflavones from E. poeppigiana showed two different antibacterial activities against MRSA: direct growth inhibition and intensification of methicillin sensitivity. Significance and Impact of the Study:, Isolupalbigenin and M-Wi-2 could lead to the development of compounds for new approaches against MRSA infection. [source] Emerging Evidence on the Role of Soy in Reducing Prostate Cancer RiskNUTRITION REVIEWS, Issue 4 2003Mark J. Messina PhD Soyfoods are a unique dietary source of isoflavones, which have both hormonal and non-hormonal effects relevant to prostate cancer prevention. In vitro, the main soybean isoflavone, genistein, inhibits prostate cancer cell growth; in animals, most but not all studies show isoflavone-rich soy protein and isolated isoflavones inhibit prostate tumor development. Currently, although only limited epidemiologic data indicate soy intake reduces prostate cancer risk, results from a pilot intervention trial suggest isoflavones may be beneficial to prostate cancer patients. For several reasons, men concerned about their prostate health may consider incorporating soy into their diet. [source] Different amounts of isoflavones in various commercially available soy extracts in the light of gene expression-targeted isoflavone therapyPHYTOTHERAPY RESEARCH, Issue S1 2010Ewa Piotrowska Abstract Isoflavones are plant-derived, biologically active compounds that are commonly used as natural drugs or diet supplements in the treatment of menopausal symptoms and as antioxidants. Recently, it was proposed that genistein (4,,5,7-trihydroxyisoflavone) may be used in the treatment of patients suffering from Sanfilippo disease (mucopolysaccharidosis type III), a severe genetic disorder for which no therapy is available. A pilot clinical study with this novel therapy, called ,gene expression-targeted isoflavone therapy' (GET IT), indicated that a standardized, genistin-rich soy isoflavone extract is effective in the treatment of such patients. Since various isoflavone-containing products are commercially available, the content of the main isoflavones were measured in such products. Extremely different amounts of isoflavones were determined in various products, from 0.13 to 39 mg per tablet. Only some of these products were found to be effective in inhibition of the synthesis of glycosaminoglycans (compounds whose degradation is severely impaired in mucopolysaccharidoses, including Sanfilippo disease) in cultured fibroblasts. Since in GET IT the dose of genistein is calculated per patient's body weight, the amount of this isoflavone in a tablet is crucial for this therapy. Therefore, the results presented in this report indicate that a careful choice of a proper isoflavone extract is necessary for GET IT. Copyright © 2009 John Wiley & Sons, Ltd. [source] Enhanced pro-apoptotic and anti-adipogenic effects of genistein plus guggulsterone in 3T3-L1 adipocytesBIOFACTORS, Issue 3 2007Jeong-Yeh Yang Abstract Genistein (G), an isoflavone, and guggulsterone (GS), the active substance in guggulipid, have been reported to possess therapeutic effects for obesity. In the present study, we investigated the effects of combinations of G plus GS on apoptosis and adipogenesis in 3T3-L1 cells. In mature adipocytes, G and GS individually caused apoptosis, but combination of G plus GS significantly increased apoptosis, more than either compound alone. Furthermore, G plus GS caused a greater increase in procaspase-3 cleavage, Bax expression, cytochrome c release, and proteolytic cleavage of PARP than either compound alone. In maturing preadipocytes G and GS each suppressed lipid accumulation, but the combination potentiated the inhibition of lipid accumulation. These results suggest that combination of genistein and guggulsterone may exert anti-obesity effects by inhibiting adipogenesis and inducing apoptosis in adipocytes. [source] Novel physiological function of fructooligosaccharidesBIOFACTORS, Issue 1-4 2004Takahisa Tokunaga Abstract Two key properties of short chain fructooligosaccharides (sc-FOS) which lead to physiological functions are indigestibility in the small intestine and fermentability in the colon. Sc-FOS is converted into short chain fatty acids (SCFAs) by intestinal bacteria in the colon and absorbed. Through the metabolic pathway, sc-FOS improves gastrointestinal (GI) condition such as relief from constipation, formation of preferable intestinal microflora and intestinal immunomodulation those are known as prebiotics' function. Besides improvement of GI condition, dietary sc-FOS influences on calcium and magnesium absorption in the colon. A major mineral absorption site is the small intestine, but the colon also works as a Ca and Mg absorption site with an aid of SCFAs made from sc-FOS. Furthermore dietary sc-FOS influences on bioavailability of soy-isoflavones. Plasma and urinal concentration of Genistein and Daidzein, aglycones of Daidzin and Genistin, are higher in the rat fed with sc-FOS than the control rat. An additive effect of dietary isoflavone and sc-FOS was observed on the bone mineral density in OVX mice and moreover sc-FOS increased ceacal ,-glycosidase activity and equol production. These results suggest that FOS increase the bioavailability of isoflavones. [source] Transcellular transport of genistein, a soybean-derived isoflavone, across human colon carcinoma cell line (Caco-2)BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2001Masataka Oitate Abstract Genistein, a soybean-derived isoflavone, is thought to have an anticarcinogenic action, but little is known about the cellular mechanisms of its intestinal absorption. This study was designed to investigate the absorption mechanisms of genistein using human colon carcinoma cell line, Caco-2 cells. The apical-to-basolateral transcellular transport of genistein across a Caco-2 cell monolayer was significantly greater than that in the opposite direction. An uptake experiment revealed that cellular uptake of genistein by Caco-2 cells was concentrative. The transcellular transport of genistein was saturable and temperature-dependent, and was inhibited by other flavonoids such as rutin, quercetin, (+)-catechin and (,)-epicatechin. These results suggest that genistein is transported across Caco-2 cells by a carrier-mediated system, located on the apical membrane. Copyright © 2001 John Wiley & Sons, Ltd. [source] Genistein potentiates activity of the cation channel TRPC5 independently of tyrosine kinasesBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2010Ching-On Wong 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 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. [source] Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type IIBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2010A Friso Background and purpose:, Mucopolysaccharidoses (MPS) are lysosomal storage disorders resulting from a deficit of specific lysosomal enzymes catalysing glycosaminoglycan (GAG) degradation. The typical pathology involves most of the organ systems, including the brain, in its severe forms. The soy isoflavone genistein has recently attracted considerable attention as it can reduce GAG synthesis in vitro. Furthermore, genistein is able to cross the blood,brain barrier in the rat. The present study was undertaken to assess the ability of genistein to reduce urinary and tissue GAG levels in vivo. Experimental approach:, We used mice with genetic deletion of iduronate-2-sulphatase (one of the GAG catabolizing enzymes) which provide a model of MPS type II. Two doses of genistein, 5 or 25 mg·kg,1·day,1, were given, in the diet for 10 or 20 weeks. Urinary and tissue GAG content was evaluated by biochemical and histochemical procedures. Key results:, Urinary GAG levels were reduced after 10 weeks' treatment with genistein at either 5 or 25 mg·kg,1·day,1. In tissue samples from liver, spleen, kidney and heart, a reduction in GAG content was observed with both dosages, after 10 weeks' treatment. Decreased GAG deposits in brain were observed after genistein treatment in some animals. Conclusions and implications:, There was decreased GAG storage in the MPSII mouse model following genistein administration. Our results would support the use of this plant-derived isoflavone in a combined therapeutic protocol for treatment of MPS. [source] EFFECT OF A SOYBEAN PRODUCT ON SERUM LIPID LEVELS IN FEMALE UNIVERSITY STUDENTSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2004Kyoko Takahashi SUMMARY 1.,A dietary intervention study targeting female students by using cake containing soybean protein and isoflavone was conducted. Female students (n = 120) were divided into three Groups (A, 6.26 g of soybean protein and isoflavone at 50 mg/day; B, 1.36 g soybean protein and isoflavone 50 mg; and C, a wheat puff as placebo). Intervention period was 4 weeks. The ratio of hypercholesterol in each group indicated a high value; A: 25%, B: 17.9% and C: 24.4%. 2.,Total cholesterol as well as the rate of hypercholesterolemia decreased in Group A. The average total cholesterol significantly reduced (P < 0.001) from 242 ± 17 to 220 ± 25 mg/dL in Group A. 3.,Dietary intake of soy protein for 4 weeks could be effective in reducing CHD risk among Japanese female students with a high plasma cholesterol level. [source] Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2005Tao Chen Abstract A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats. Environ. Mol. Mutagen., 2005. Published 2005 Wiley-Liss, Inc. [source] Dietary phytoestrogens improve stroke outcome after transient focal cerebral ischemia in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006María C. Burguete Abstract As phytoestrogens are postulated as being neuroprotectants, we assessed the hypothesis that dietary isoflavone-type phytoestrogens are neuroprotective against ischemic stroke. Transient focal cerebral ischemia (90 min) was induced by middle cerebral artery occlusion (MCAO) following the intraluminal thread technique, both in rats fed with soy-based diet and in rats fed with isoflavone-free diet. Cerebro-cortical laser-Doppler flow (cortical perfusion, CP), arterial blood pressure, core temperature, PaO2, PaCO2, pH and glycemia were measured before, during and after MCAO. Neurological examination and infarct volume measurements were carried out 3 days after the ischemic insult. Dietary isoflavones (both glycosides and aglycones) were measured by high-performance liquide chromatography. Neither pre-ischemic, intra-ischemic nor post-ischemic CP values were significantly different between the soy-based diet and the isoflavone-free diet groups. Animals fed with the soy-based diet showed an infarct volume of 122 ± 20.2 mm3 (19 ± 3.3% of the whole ipsilateral hemisphere volume). In animals fed with the isoflavone-free diet the mean infarct volume was significantly higher, 191 ± 26.7 mm3 (28 ± 4.1%, P < 0.05). Neurological examination revealed significantly higher impairment in the isoflavone-free diet group compared with the soy-based diet group (3.3 ± 0.5 vs. 1.9 ± 0.5, P < 0.05). These results demonstrate that dietary isoflavones improve stroke outcome after transient focal cerebral ischemia in such a way that a higher dietary isoflavone content results in a lower infarct volume and a better neurological status. [source] A fluorescence quenching test for the detection of flavonoid transformationFEMS MICROBIOLOGY LETTERS, Issue 2 2001Lilian Schoefer Abstract A novel fluorescence quenching test for the detection of flavonoid degradation by microorganisms was developed. The test is based on the ability of the flavonoids to quench the fluorescence of 1,6-diphenyl-1,3,5-hexatriene (DPH). Several members of the anthocyanidins, flavones, isoflavones, flavonols, flavanones, dihydroflavanones, chalcones, dihydrochalcones and catechins were tested with regard to their quenching properties. The anthocyanidins were the most potent quenchers of DPH fluorescence, while the flavanones, dihydroflavanones and dihydrochalcones, quenched the fluorescence only weakly. The catechins had no visible impact on DPH fluorescence. The developed test allows a quick and easy differentiation between flavonoid-degrading and flavonoid-non-degrading bacteria. The investigation of individual reactions of flavonoid transformation with the developed test system is also possible. [source] Randomised clinical trial of isoflavones in reducing prostate cancer riskFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 4 2003NB Kumar [source] The role of red clover (Trifolium pratense) isoflavones in women's reproductive health: a systematic review and meta-analysis of randomised clinical trialsFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 4 2003JS Thompson Coon [source] New Beverage for Cardiovascular Health, Proposal Based on Oriental and Occidental Food Culture from a World-Wide Epidemiological StudyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2008Emilio Hideyuki Moriguchi Objectives: To investigate whether combined isoflavones and antioxidants in oriental and occidental drinks reduce the risk of cardiovascular disease (CVD) in high-risk Japanese immigrants living in Brazil. Materials and methods: From among over 100 Japanese immigrants thirty-seven females aged 45,60 years in Porto Alegre, Brazil, were randomized after informed consent into two groups to drink 200 ml of whole soy cell juice (S) containing 7.5 g soy protein and 10 mg of isoflavones (aglycone) in peach juice or placebo peach juice (P) with 80 Kcal for 12 weeks. Health survey including 24-hour urine (24 U) examination were carried out before the randomization and after the double blind placebo controlled intervention study. Results: Both weight and body mass index (BMI) were significantly (p < 0.05, 0.01) decreased from the baseline only in the S group. Systolic blood pressure (SBP) was decreased significantly (p < 0.05) from the baseline in the S group with elevated 24 U isoflavone excretion (>10 µmol), and there was a significant (p < 0.05) inter-group difference between the S and P groups after intervention. Total and low density lipoprotein (LDL)-cholesterol (C) decreased significantly (p < 0.05) in the S group from the baseline and there was a significant difference (p < 0.05) between the S and P groups after intervention. HbA1c and atherogenic index (non-high density lipoprotein (HDL)-C/HDL-C) were significantly (p < 0.05) decreased in both groups. Conclusions: Soy isoflavones combined with fruit antioxidants, the combination of which might potentiate local nitric oxide (NO) affect, decreased SBP, total cholesterol and LDL-C. Peach juice itself improved blood glucose levels and the atherogenic index of the high-risk Japanese population in Brazil. [source] Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patientsINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Srilatha Swami Abstract Soy and its constituent isoflavone genistein inhibit the development and progression of prostate cancer (PCa). Our study in both cultured cells and PCa patients reveals a novel pathway for the actions of genistein, namely the inhibition of the synthesis and biological actions of prostaglandins (PGs), known stimulators of PCa growth. In the cell culture experiments, genistein decreased cyclooxygenase-2 (COX-2) mRNA and protein expression in both human PCa cell lines (LNCaP and PC-3) and primary prostate epithelial cells and increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA levels in primary prostate cells. As a result genistein significantly reduced the secretion of PGE2 by these cells. EP4 and FP PG receptor mRNA were also reduced by genistein, providing an additional mechanism for the suppression of PG biological effects. Further, the growth stimulatory effects of both exogenous PGs and endogenous PGs derived from precursor arachidonic acid were attenuated by genistein. We also performed a pilot randomised double blind clinical study in which placebo or soy isoflavone supplements were given to PCa patients in the neo-adjuvant setting for 2 weeks before prostatectomy. Gene expression changes were measured in the prostatectomy specimens. In PCa patients ingesting isoflavones, we observed significant decreases in prostate COX-2 mRNA and increases in p21 mRNA. There were significant correlations between COX-2 mRNA suppression, p21 mRNA stimulation and serum isoflavone levels. We propose that the inhibition of the PG pathway contributes to the beneficial effect of soy isoflavones in PCa chemoprevention and/or treatment. © 2008 Wiley-Liss, Inc. [source] Radiation-induced HIF-1, cell survival pathway is inhibited by soy isoflavones in prostate cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 7 2009Vinita Singh-Gupta Abstract We previously showed that treatment of prostate cancer cells with soy isoflavones and radiation resulted in greater cell killing in vitro, and caused downregulation of NF-,B and APE1/Ref-1. APE1/Ref-1 functions as a redox activator of transcription factors, including NF-,B and HIF-1,. These molecules are upregulated by radiation and implicated in radioresistance of cancer cells. We extended our studies to investigate the role of HIF-1, survival pathway and its upstream Src and STAT3 molecules in isoflavones and radiation interaction. Radiation induced phosphorylation of Src and STAT3 leading to induction of HIF-1,. Genistein, daidzein or a mixture of soy isoflavones did not activate this pathway. These data were observed both in PC-3 (AR-) and C4-2B (AR+) androgen-independent cell lines. Pretreatment with isoflavones inhibited Src/STAT3/HIF-1, activation by radiation and nuclear translocation of HIF-1,. These findings correlated with decreased expression of APE1/Ref-1 and DNA binding activity of HIF-1, and NF-,B. In APE1/Ref-1 cDNA transfected cells, radiation caused a greater increase in HIF-1, and NF-,B activities but this effect was inhibited by pretreatment with soy prior to radiation. Transfection experiments indicate that APE1/Ref-1 inhibition by isoflavones impairs the radiation-induced transcription activity of NF-,B and HIF-1,. This mechanism could result in the inhibition of genes essential for tumor growth and angiogenesis, as demonstrated by inhibition of VEGF production and HUVECs tube formation. Our novel findings suggest that the increased responsiveness to radiation mediated by soy isoflavones could be due to pleiotropic effects of isoflavones blocking cell survival pathways induced by radiation including Src/STAT3/HIF-1,, APE1/Ref-1 and NF-,B. © 2008 Wiley-Liss, Inc. [source] Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Niina M. Saarinen Abstract In several epidemiological studies, a phytoestrogen-rich diet containing lignans and isoflavones is associated with reduced breast cancer risk, but experimental findings are controversial. In postmenopausal mammary cancer xenograft model, flaxseed (FS), a rich source of plant lignans, reduced breast cancer growth, while soy protein (SP), a rich source of isoflavones, enhanced it. The intake of phytoestrogens is increasing particularly among postmenopausal women, emphasizing the importance of elucidating their interactive effects on breast cancer. Our study determined the effect of FS and SP diets, alone and in combination, on the established human breast cancer MCF-7 tumor growth in ovariectomized athymic nude mice. Tumor bearing mice were divided into 4 groups and fed for 25 weeks either the basal diet (BD), or BD supplemented with 10% FS, 20% SP or 10% FS and 20% SP. After estrogen deprivation, FS regressed the tumor size similar to that of control. SP initially regressed the tumors but starting at week 13, the tumors regressed significantly less than in control and 43% of the tumors were regrowing until the end of the experiment and were significantly larger in size than in control. The combination of SP with FS reduced the tumor growth similar to that of control, as suggested also by the reduced tumor cell proliferation index. In conclusion, dietary FS did not stimulate the growth of estrogen responsive MCF-7 cancers in ovariectomized mice, while long-term consumption of SP did. Furthermore, FS reduced the tumor growth stimulating effect of SP to the same level as control, suggesting tumor growth attenuating effect of FS. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||