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Histology and Histopathology Oct 2011Daidzein is a potential natural alternative to estradiol during therapy of some malignancies in men. Besides weak inhibition of tyrosine kinase activity, daidzein has a...
Daidzein is a potential natural alternative to estradiol during therapy of some malignancies in men. Besides weak inhibition of tyrosine kinase activity, daidzein has a sizeable inhibitory effect on calcium channels. The aim of this study was to examine the effects of daidzein on the immunohistomorphometric features of pituitary adrenocorticotropes (ACTH cells) and circulating levels of ACTH and corticosterone, in comparison with estradiol, in an animal model of the andropause. Sixteen-month-old Wistar rats were divided into sham operated (SO), orchidectomized (Orx), estradiol treated orchidectomized (Orx+E) and daidzein treated orchidectomized (Orx+D) groups. Estradiol (0.625 mg/kg/day) and daidzein (30 mg/kg/day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. ACTH cells were identified by the peroxidase-antiperoxidase (PAP) immunohistochemical procedure. Peripheral circulating concentrations of ACTH and corticosterone were measured by immunoassay. Orchidectomy reduced (p<0.05) the cell volume and volume density of adrenocorticotropes by 11% and 16%, respectively, in comparison to SO rats. In Orx+E rats, the volume density of ACTH cells decreased (p<0.05) by 25%, but the circulating level of ACTH increased (p<0.05) by 29%, compared to Orx rats. Daidzein treatment significantly decreased (p<0.05): volume density of ACTH cells, circulating ACTH and corticosterone by 24%, 48% and 33%, respectively, compared to the Orx group. In conclusion, this study revealed that daidzein negatively modulated the immunohistomorphometric features of ACTH cells and, unlike estradiol, decreased ACTH and corticosterone secretion, in an animal model of the andropause.
Topics: Andropause; Animals; Corticosterone; Corticotrophs; Disease Models, Animal; Estradiol; Estrogens; Immunohistochemistry; Isoflavones; Male; Orchiectomy; Phytoestrogens; Rats; Rats, Wistar
PubMed: 21870329
DOI: 10.14670/HH-26.1257 -
Frontiers in Bioscience (Landmark... Jan 2009The amount of new bone formed in collagen matrix with daidzein was compared to that formed in collagen matrix alone. Eighteen bone defects, 5mm by 10mm were created in...
The amount of new bone formed in collagen matrix with daidzein was compared to that formed in collagen matrix alone. Eighteen bone defects, 5mm by 10mm were created in parietal bone of 9 New Zealand white rabbits. In the experimental group, 6 defects were grafted with collagen matrix with daidzein. In the control groups, 6 defects were grafted with collagen matrix alone (positive control) and 6 were left empty (negative control). Animals were killed on day 14 and the defects were dissected and prepared for histological assessment. Serial sections were cut across each defect. Quantitative analysis of new bone formation was made on 100 sections (50 sections for each group of daidzein and positive control) using image analysis. A total of 602% more new bone was present in defects grafted with daidzein in collagen matrix than those grafted with the collagen matrix alone. Very little new bone formed in the negative control group. In conclusion, daidzein in collagen matrix has the effect of increasing new bone formation locally and can be used for bone grafting.
Topics: Animals; Bone Development; Humans; Isoflavones; Rabbits
PubMed: 19273301
DOI: 10.2741/3479 -
Bioscience, Biotechnology, and... Apr 2021Analyses of metabolite secretions by field-grown plants remain scarce. We analyzed daidzein secretion by field-grown soybean. Daidzein secretion was higher during early...
Analyses of metabolite secretions by field-grown plants remain scarce. We analyzed daidzein secretion by field-grown soybean. Daidzein secretion was higher during early vegetative stages than reproductive stages, a trend that was also seen for hydroponically grown soybean. Daidzein secretion was up to 10 000-fold higher under field conditions than hydroponic conditions, leading to a more accurate simulation of rhizosphere daidzein content.
Topics: Genistein; Glucosides; Hydroponics; Isoflavones; Organ Specificity; Plant Leaves; Plant Roots; Rhizosphere; Glycine max
PubMed: 33784734
DOI: 10.1093/bbb/zbab017 -
Pharmaceutical Research Jun 2010Genistein, the major bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer (PCa) both in vitro and in vivo. However, pure genistein promoted...
PURPOSE
Genistein, the major bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer (PCa) both in vitro and in vivo. However, pure genistein promoted increased metastasis to lymph nodes. A mixture of soy isoflavones (genistein, daidzein, glycitein) did not cause increased metastasis, but potentiated radiotherapy. We tested whether daidzein could negate genistein-induced metastasis.
METHODS
Mice bearing PC-3 prostate tumors were treated with daidzein, genistein or both, and with tumor irradiation. Primary tumors and metastases were evaluated. The effects of each isoflavone and soy were compared in vitro using PC-3 (AR-) and C4-2B (AR+) androgen-independent PCa cell lines.
RESULTS
Daidzein did not increase metastasis to lymph nodes and acted as a radiosensitizer for prostate tumors. Daidzein inhibited cell growth and enhanced radiation in vitro but at doses higher than genistein or soy. Daidzein caused milder effects on inhibition of expression and/or activities of APE1/Ref-1, HIF-1alpha and NF-kappaB in PC-3 and C4-2B cells.
CONCLUSIONS
Daidzein could be the component of soy that protects against genistein-induced metastasis. Daidzein inhibited cell growth and synergized with radiation, affecting APE1/Ref-1, NF-kappaB and HIF-1alpha, but at lower levels than genistein and soy, in AR+ and AR- PCa cells, suggesting it is an AR-independent mechanism.
Topics: Androgens; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; DNA; DNA-(Apurinic or Apyrimidinic Site) Lyase; Gene Expression Regulation, Neoplastic; Genistein; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Isoflavones; Lymph Nodes; Male; Mice; NF-kappa B; Plant Extracts; Prostatic Neoplasms; Radiation-Sensitizing Agents; Glycine max
PubMed: 20309614
DOI: 10.1007/s11095-010-0107-9 -
Comparative Medicine Jun 2007Daidzein (4',7-dihydroxyisoflavone), a soy phytoestrogen, is a weakly estrogenic compound that may have potential health benefits. Biotransformation of daidzein by the...
Daidzein (4',7-dihydroxyisoflavone), a soy phytoestrogen, is a weakly estrogenic compound that may have potential health benefits. Biotransformation of daidzein by the human gut microflora after ingestion converts it to either the highly estrogenic metabolite equol or to nonestrogenic metabolites. We investigated the metabolism of daidzein by colonic microflora of rats. Fecal samples, obtained before and after rats were exposed to daidzein at 250 or 1000 parts per million, were incubated in brain-heart infusion (BHI) broth with daidzein under anaerobic conditions. Samples were removed from the cultures daily and analyzed by high-performance liquid chromatography (HPLC) and mass spectrometry. The fecal bacteria of all rats, regardless of prior daidzein exposure, metabolized the added daidzein to dihydrodaidzein. Both compounds disappeared rapidly from BHI cultures incubated for more than 24 h, but no other daidzein metabolites were detected. Only daidzein and dihydrodaidzein were found in a direct analysis of the feces of rats that had consumed daidzein in their diets. Unlike the fecal bacteria of humans and monkeys, the rat flora rapidly metabolized daidzein to aliphatic compounds that could not be detected by HPLC or mass spectral analysis.
Topics: Animals; Animals, Genetically Modified; Bacteria; Biotransformation; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Feces; Gastrointestinal Tract; Isoflavones; Phytoestrogens; Rats; Rats, Inbred F344; Spectrometry, Mass, Electrospray Ionization
PubMed: 17605343
DOI: No ID Found -
Phytomedicine : International Journal... Sep 2008We examined the mechanisms by which daidzein inhibits the growth of breast cancer cells. First, we investigated its antiproliferative effects in MCF-7 and MDA-MB-453...
We examined the mechanisms by which daidzein inhibits the growth of breast cancer cells. First, we investigated its antiproliferative effects in MCF-7 and MDA-MB-453 cells exposed to 1-100 microM daidzein for 24, 48, or 72 h. Daidzein significantly inhibited cell proliferation in a dose- and time-dependent manner (p<0.05) and resulted in significant cell cycle arrest in the G1 and G2/M phases after 72 h of treatment at concentrations over 5 and 10 microM in MCF-7 and MDA-MB-453 cells, respectively (p<0.05). In addition, daidzein caused the accumulation of cells in sub-G0 phase in a dose-dependent manner in MDA-MB-453 (p<0.05), but not MCF-7, cells. As another biomarker of apoptosis induction, caspase-9 activity was significantly increased by daidzein in both cells. To investigate the effects of daidzein on the proteins regulating cell cycle arrest, cells were treated with 100 microM daidzein for 72 h. Similar changes in the expression of regulatory proteins were detected in both cells. Daidzein treatment resulted in decreases in cyclin D, CDK2, and CDK4, whereas the expression of CDK6 and cyclin E was unchanged. The protein expression of CDK1 related to the G2/M phase decreased markedly with daidzein treatment, whereas slight expression of cyclins A and B occurred. Daidzein treatment increased the expression of the CDK inhibitors p21(Cip1) and p57(Kip2), but not that of p27(Kip1). Thus, daidzein exerts its anticancer effects in human breast cancer cells via cell cycle arrest at the G1 and G2/M phases.
Topics: Apoptosis; Blotting, Western; Breast Neoplasms; Cell Division; Cell Line, Tumor; Cell Proliferation; G1 Phase; G2 Phase; Humans; Isoflavones
PubMed: 18541420
DOI: 10.1016/j.phymed.2008.04.006 -
Bone Aug 2004As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as...
As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as soy isoflavones to help prevent postmenopausal osteoporosis. Daidzein is one of the most abundant isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The objective of this study was to determine the effects of purified daidzein in combination with high calcium (Ca) on preserving femur and lumbar vertebrae (LV1-LV4) bone mineral density (BMD) and biomechanical bone strength at three different sites (femur midpoint, femur neck and LV3) in ovariectomized mice. Sham (SH) mice (n = 12) received control diet (AIN93G) containing 2 g Ca/kg diet and ovariectomized mice were randomized to 1 of 6 groups (n = 12/group): OVX (2 g Ca/kg diet), HCa (25 g Ca/kg diet), HD (2 g Ca + 200 mg daidzein/kg diet), HDCa (25 g Ca + 200 mg daidzein/kg diet), LD (2 g Ca + 100 mg daidzein/kg diet) or LDCa (25 g Ca + 100 mg daidzein/kg diet) for 12 weeks. HDCa preserved femur and vertebrae BMD and biomechanical bone strength (at all three sites) compared to the OVX group, however, only femur yield load (at midpoint) was preserved to a level that was greater (P < 0.05) than HCa alone. Mice fed HD diet had greater (P < 0.05) femur BMD than OVX group, however, daidzein alone (HD) did not appear to preserve trabecular bone (i.e., vertebrae BMD and vertebra peak load). All mice fed daidzein produced equol and there were no uterotrophic effects of daidzein at either dose. Both daidzein and Ca attenuated the increase in serum IL-1beta observed in the OVX group. The results from this study suggest that the combination of daidzein and high Ca favorably affect cortical and trabecular bone as indicated by femur and lumbar vertebrae BMD and biomechanical strength but much of this effect is mediated by the high Ca diet. Further investigation is required to determine optimal dietary levels of daidzein and Ca with the long-term goal of developing a dietary strategy to prevent postmenopausal osteoporosis and related fragility fractures.
Topics: Animals; Biomechanical Phenomena; Body Weight; Bone Density; Bone and Bones; Calcium; Female; Isoflavones; Mice; Organ Size; Ovariectomy
PubMed: 15268901
DOI: 10.1016/j.bone.2004.03.031 -
Biochemical Pharmacology Mar 2003Daidzein, a natural isoflavonoid found in Leguminosae, has received increasing attention because of its possible role in the prevention of osteoporosis. In the present...
Daidzein, a natural isoflavonoid found in Leguminosae, has received increasing attention because of its possible role in the prevention of osteoporosis. In the present investigation, primary osteoblastic cells isolated from newborn Wistar rats were used to investigate the effect of this isoflavonoid on osteoblasts. Daidzein (2-50 microM) increased the viability (P<0.05) of osteoblasts by about 1.4-fold. In addition, daidzein (2-100 microM) increased the alkaline phosphatase activity and osteocalcin synthesis (P<0.05) of osteoblasts by about 1.4- and 2.0-fold, respectively. Alkaline phosphatase and osteocalcin are phenotypic markers for early-stage differentiated osteoblasts and terminally differentiated osteoblasts, respectively. Our results indicated that daidzein stimulated osteoblast differentiation at various stages (from osteoprogenitors to terminally differentiated osteoblasts). We also investigated the effect of daidzein on bone morphogenetic protein (BMP) production in osteoblasts that display the mature osteoblast phenotype. The results indicated that BMP2 synthesis was elevated significantly in response to daidzein (the mRNA increased 5.0-fold, and the protein increased 7.0-fold), suggesting that some of the effects of daidzein on the cell may be mediated by the increased production of BMPs by the osteoblasts. In conclusion, daidzein has a direct stimulatory effect on bone formation in cultured osteoblastic cells in vitro, which may be mediated by increased production of BMPs in osteoblasts.
Topics: Alkaline Phosphatase; Animals; Blotting, Western; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cell Survival; Cells, Cultured; Drug Interactions; Estrogens, Non-Steroidal; Isoflavones; Osteoblasts; RNA, Messenger; Rats; Recombinant Proteins; Transforming Growth Factor beta
PubMed: 12628484
DOI: 10.1016/s0006-2952(02)01585-x -
Life Sciences Feb 2009We tested the hypothesis that daidzein may reduce myocardial damage by both inhibiting the release of cytokines and limiting the nuclear translocation of NF-kappaB.
AIMS
We tested the hypothesis that daidzein may reduce myocardial damage by both inhibiting the release of cytokines and limiting the nuclear translocation of NF-kappaB.
MAIN METHODS
Male Sprague-Dawley rats were anesthetized, and the left anterior descending coronary artery (LAD) was ligated for 25 min. Twenty-four hours after reperfusion was established, the hemodynamics and infarct size were examined.
KEY FINDINGS
Treatment with daidzein (10 mg/kg, i.p.) 1 h prior to the ischemia/reperfusion procedure (I/R) reduced the infarct size by 52.8% (P<0.05). Daidzein also significantly improved I/R-induced myocardial contractile dysfunction by improving the left ventricular diastolic pressure and the positive and negative maximal values of the first derivative of the left ventricular pressure. In addition, daidzein reduced the plasma levels of TNF-alpha and IL-6 in I/R rats and decreased malondialdehyde levels, myeloperoxidase activity, catalase activity and neutrophil infiltration in I/R rat myocardium. Interestingly, daidzein inhibited I/R-induced myocardial apoptosis by decreasing DNA strand breaks and cleaved caspase-3 activity. Furthermore, daidzein inhibited both the nuclear translocation of NF-kappaB in I/R rat hearts and the H(2)O(2)-induced activation of NF-kappaB-luciferase activity in human umbilical vein endothelial cells.
SIGNIFICANCE
This study reveals that the administration of daidzein in vivo attenuates I/R-induced myocardial damage via inhibition of NF-kappaB activation, which in turn may suppress inflammatory cytokine expression.
Topics: Animals; Hemodynamics; Humans; Interleukin-6; Isoflavones; Male; Myocardial Infarction; Myocardial Reperfusion Injury; NF-kappa B; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha
PubMed: 19109981
DOI: 10.1016/j.lfs.2008.12.005 -
Bioscience, Biotechnology, and... Sep 2017We compared the effects of two major isoflavones, daidzein and genistein, on lipid metabolism in rats. Daidzein (150 mg/kg diet), genistein (150 mg/kg diet), daidzein...
We compared the effects of two major isoflavones, daidzein and genistein, on lipid metabolism in rats. Daidzein (150 mg/kg diet), genistein (150 mg/kg diet), daidzein and genistein (1:1, 300 mg/kg diet), or control diets were fed to 4 groups of 6-week-old ovariectomized (Ovx) and non-Ovx Sprague Dawley rats for 4 weeks. Dietary daidzein, but not genistein, reduced serum and hepatic total cholesterol levels significantly relative to that by the control group, regardless of whether the rats had undergone ovariectomy. Genistein did not exhibit any physiological effects on lipid levels, but did affect genes involved in cholesterol metabolism. These results indicate that daidzein and genistein may influence lipid regulation via differing modes of action.
Topics: Adipose Tissue; Animals; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Diet; Feces; Female; Genistein; Intestine, Small; Isoflavones; Liver; Organ Size; Ovariectomy; Rats; Rats, Sprague-Dawley
PubMed: 28715285
DOI: 10.1080/09168451.2017.1350562