phytoestrogens and secoisolariciresinol

Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a >3-fold increase in 5-year risk, and baseline Ki-67 of ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG (50 mg/d) was given for 12 months, followed by repeat RPFNA. The primary end point was change in Ki-67. Secondary end points included change in cytomorphology, mammographic breast density, serum bioavailable estradiol and testosterone insulin-like growth factor-I and IGF-binding protein-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ∼9-fold, and total lignans increased 16-fold. Thirty-six (80%) of the 45 evaluable subjects showed a decrease in Ki-67, from a median of 4% (range, 2-16.8%) to 2% (range, 0-15.2%; P < 0.001, Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (P = 0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG versus placebo in premenopausal women.

Topics: Adult; Breast; Butylene Glycols; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Humans; Hyperplasia; Immunohistochemistry; Ki-67 Antigen; Lignans; Mammography; Middle Aged; Phytoestrogens; Pilot Projects; Premenopause; Progesterone; Risk Factors; Testosterone

Pea (Pisum sativum L.) is an important legume crop providing a good source of protein, vitamins, minerals and bioactive compounds with health benefits for humans. In this study, an improved method for simultaneous analysis of multiple phytoestrogens among 100 pea accessions was developed. Ipriflavone, (a synthetic isoflavone), was used as an internal standard for the semiquantitative analysis of 17 phytoestrogens including isoflavone aglycones and conjugates, allowing direct analysis of isoflavones in their naturally occurring forms. This comprehensive dataset demonstrated that the isoflavones varied greatly and some accessions tended to have high levels of multiple phytoestrogens among the 100 accessions analyzed. Isoliquiritigenin followed by glycitein were the predominant compounds detected in the accessions and showed the highest correlation with the total phytoestrogens content. Secoisolariciresinol content was consistently higher in yellow cotyledon peas than in green cotyledon peas, whereas the contents of coumestrol, genestein and secoisolariciresinol were significantly correlated with seed coat color. The total phenolics and saponins showed a wide range of variability among the accessions with higher concentrations of total phenolics observed in seeds with pigmented seed coat or yellow cotyledon seeds, suggesting the synthesis of saponins and phenolics are significantly affected by metabolic pathway genes controlling cotyledon color or seed coat color. This study profiled the variability of bioactive compounds of pea seed quality traits in diverse pea accessions and provides an immense resource for continued research, breeding and selection of genotypes for a wide range of applications.

Topics: Humans; Isoflavones; Lathyrus; Phytoestrogens; Pisum sativum; Plant Breeding

Phytoestrogens (PEs) are naturally estrogen-like chemicals, and increasing evidences have indicated their endocrine disruption effects on male reproductivity, but the conclusions from previous epidemiological studies were controversial.. To examine the associations between nine phytoestrogens in semen and semen quality in a Chinese population.. In this cross-sectional study, a total of 1319 reproductive-aged men were recruited from Shenzhen, China. Semen phytoestrogens were measured by ultra-performance liquid chromatography and tandem mass spectrometry. Semen quality was assessed by sperm concentration, sperm count, progressive motility, total motility, volume, and the sperm motion parameters. Both multivariate linear regression and logistic regression models were conducted to evaluate the associations between semen phytoestrogens and semen quality with adjustment for confounders.. In logistic regression models, we found significant associations between semen secoisolariciresinol (SEC) and lower sperm concentrations (odd ratios (OR): 2.38; 95% confidence interval, 95% CI: 1.47, 3.93), sperm counts (OR: 2.27; 95% CI: 1.34, 3.94), and total motility (OR: 1.55; 95% CI: 1.08, 2.24). Negative associations were also observed for semen genistein (GEN) with sperm counts (OR: 2.28; 95% CI: 1.29, 4.14; p for trend = 0.04) and sperm concentrations (OR: 1.98; 95% CI: 1.21, 3.03; p for trend = 0.07). Semen naringenin (NAR) were found to be positively associated with progressive motility (OR: 0.57; 95% CI: 0.38, 0.83) and total motility (OR: 0.57; 95% CI: 0.40, 0.81). Results from multivariate linear regression models were similar to those from logistic regression models for semen SEC, GEN, and NAR.. We suggested that semen levels of phytoestrogens may be associated with semen quality in men. Further investigations are warranted to confirm the findings in prospective studies and to explore the underlying mechanism.

Topics: Adult; Butylene Glycols; China; Cross-Sectional Studies; Genistein; Humans; Lignans; Male; Phytoestrogens; Semen; Sperm Count; Sperm Motility; Spermatozoa

Phytoestrogens are plant-derived polyphenols with structural and functional similarities to mammalian oestrogens. The aim of this work was to study the metabolism of phytoestrogens by children's intestinal microbiota and to compare it with previous results in adults. Faecal samples of 24 healthy children were subjected to phytoestrogen fermentation assay. Only one child produced equol, while O-desmethylangolensin was found in all. Urolithin production was detected in 14 children and enterolactone in 10. Further comparison with the metabolism of phytoestrogens by adult intestinal microbiota reflected that glycitein, dihydrogenistein, urolithins D and E, enterolactone, secoisolariciresinol and arctigenin were the most important metabolites differentiating between adult and child microbial gut metabolism. Although the child intestinal microbiota showed the ability to metabolise isoflavones, ellagitannins and lignans to a certain extent, it generally showed a reduced metabolism of phytoestrogens, with a lack of 5-hydroxy equol and enterodiol, and less urolithins and enterolactone producers.

Topics: 4-Butyrolactone; Adult; Butylene Glycols; Case-Control Studies; Child, Preschool; Coumarins; Equol; Feces; Female; Furans; Gastrointestinal Microbiome; Humans; Hydrolyzable Tannins; Infant; Isoflavones; Lignans; Male; Phytoestrogens; Polyphenols

The study is aimed at evaluating the chemosensitization and apoptotic effect of aglycone rich extracts of dietary phytoestrogens (derived from soybean and flaxseed) on estrogen receptor positive, MCF-7 and estrogen receptor negative, MDA-MB-231 cells. The extracts show potent activity on both the cell lines, hence, in silico studies have been carried out to find the possible reason for their activity.. MTT assay was carried to assess chemosensitization effect and activated caspase-3/7 activity was studied using flow-cytometry and western blotting. In silico studies were carried out using PharmMapper and the top hits were taken up for docking using the Schrödinger software. Top molecular targets were subjected to gene expression studies by qPCR and protein expression using Western blot analysis.. This study reports the apoptotic activity and chemosensitization effect of the phytoestrogens. Molecular docking studies predict AKR1B1 (aldose reductase), HRAS (Harvey rat sarcoma) and GSTP1 (glutathione s-transferase pi) as potential molecular targets for genistein, daidzein and secoisolariciresinol, respectively. Gene and protein expression studies show down-regulation of AKR1BI, HRAS and GSTP1 by the extracts.. The qPCR and western blot analysis results support the computational analyses, and hence genistein, daidzein and secoisolariciresinol may be considered as good candidates for future development into potent inhibitors of the respective protein targets through medicinal chemistry optimization.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Breast Neoplasms; Butylene Glycols; Caspase 3; Caspase 7; Cell Line, Tumor; Computer Simulation; Down-Regulation; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Genistein; Humans; Isoflavones; Lignans; MCF-7 Cells; Molecular Docking Simulation; Phytoestrogens

Flaxseed is a rich source of α-linolenic acid and phytoestrogens, mainly lignans, whose metabolites (enterodiol and enterolactone) can affect estrogen functions. The present study evaluated the influence of dietary flaxseed supplementation on reproductive performance and egg characteristics (fatty acids, cholesterol, lignans and isoflavones) of 40 Hy-Line hens (20/group) fed for 23 weeks a control diet or the same diet supplemented with 10% of extruded flaxseed. The flaxseed diet had approximately three times the content of lignans (2608.54 ng/g) as the control diet, mainly secoisolariciresinol diglucoside (1534.24 v. 494.72 ng/g). When compared with the control group, hens fed flaxseed showed a similar deposition rate (72.0% v. 73.9%) and egg yield. Furthermore, there was no effect of flaxseed on the main chemical composition of the egg and on its cholesterol content. Estradiol was higher in the plasma of the control group (1419.00 v. 1077.01 pg/ml) probably due to the effect of flaxseed on phytoestrogen metabolites. The plasma lignans were higher in hens fed flaxseed, whereas isoflavones were lower, mainly due to the lower equol value (50.52 v. 71.01 ng/ml). A similar trend was shown in eggs: the flaxseed group had higher level of enterodiol and enterolactone, whereas the equol was lower (198.31 v. 142.02 ng/g yolk). Secoisolariciresinol was the main lignan in eggs of the flaxseed group and its concentration was three times higher then control eggs. Flaxseed also improved the n-3 long-chain polyunsaturated fatty acids of eggs (3.25 v. 0.92 mg/g egg), mainly DHA, however, its oxidative status (thiobarbituric reactive substances) was negatively affected. In conclusion, 10% dietary flaxseed did not affect the productive performance of hens or the yolk cholesterol concentration, whereas the lignans and n-3 polyunsaturated fatty acid content of eggs improved. Further details on the competition between the different dietary phytoestrogens and their metabolites (estrogen, equol, enterodiol and enterolactone) should be investigated.

Topics: 4-Butyrolactone; alpha-Linolenic Acid; Animal Feed; Animals; Butylene Glycols; Chickens; Cholesterol; Diet; Dietary Supplements; Eggs; Fatty Acids; Fatty Acids, Omega-3; Female; Flax; Isoflavones; Lignans; Phytoestrogens; Seeds

Postmenopausal women often develop hemorheological disorders which may affect the systemic blood circulation and present a cardiovascular risk factor.. We evaluated effects of secoisolariciresinol (SECO), a phytoestrogen, on hemorheological parameters and lipid peroxidation in a model of the age-related and/or surgical menopause induced by ovariectomy in rats.. Arterial blood was sampled from sham-operated female rats, ovariectomized rats (OVX), and OVX treated with SECO (OVXSECO) (20 mg/kg/day intragastrically for two weeks). Plasma estrogen concentration and the following hemorheological parameters were measured: RBC aggregation (half-time of aggregation, T1/2; amplitude of aggregation, AMP; aggregation index, AI), RBC deformability (elongation index, EI), whole blood viscosity at the shear rate of 3-300 s-1, plasma viscosity, hematocrit, plasma fibrinogen. Lipid peroxidation was evaluated by measuring conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in plasma.. Ovariectomy in rats caused a 60% decrease in plasma estrogen level and triggered the development of macro- and microhemorheological abnormalities. Blood viscosity increased by 12-31%, RBC elongation index reduced by 16-28%, and T1/2 and AI increased by 35% and 29% respectively. The increase in blood viscosity correlated predominantly with reduced RBC deformability. Plasma CD and TBARS were elevated by 47% and 104% respectively. SECO therapy for OVX rats reduced blood viscosity by 9-18% and T1/2 by 32%, and increased EI by 4-17%. SECO therapy disrupted the correlation between blood viscosity and RBC deformability. Lipid peroxidation was significantly inhibited, as shown by the reduction in CD and TBARS plasma concentrations by 89% and 70% respectively. SECO did not affect plasma viscosity, estrogen or fibrinogen levels.. SECO treatment for OVX rats improves blood macro- and microrheological parameters, possibly through antioxidant protection of RBC.

Topics: Animals; Blood Viscosity; Butylene Glycols; Erythrocyte Aggregation; Erythrocyte Deformability; Estradiol; Female; Hematocrit; Hemorheology; Lignans; Lipid Peroxidation; Ovariectomy; Ovary; Phytoestrogens; Rats; Rats, Wistar

Dioxins and dioxin-like compounds (DLCs) enter the body mainly through diet and cause various toxicological effects through activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. Some plant extracts and phytochemicals are reported to suppress this transformation. However, most of these reports have been from in vitro experiments and few reports have been from in vivo experiments. In addition, there has been no report of foodstuffs that effectively prevent AhR-associated morphological abnormalities such as deformities caused by dioxins and DLCs in vivo. In this study, we show that secoisolariciresinol (SECO), a natural lignan-type polyphenolic phytochemical found mainly in flaxseed, has a rescuing effect, actually suppressing morphological abnormalities (pericardial edema) in zebrafish embryos exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126), a dioxin-like PCB congener. Importantly, the rescuing effect of SECO was still evident when it was applied 16 h after the beginning of exposure to PCB126. This study suggests that SECO may be useful as a natural suppressive agent for morphological abnormalities caused by dioxins and DLCs.

Topics: Abnormalities, Drug-Induced; Animals; Butylene Glycols; Dioxins; Edema; Embryo, Nonmammalian; Lignans; Pericardial Effusion; Phytoestrogens; Zebrafish

Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG < SECO < ED; volume of distribution, SDG < SECO < ED; half-life, SDG < ED < SECO. The percentage of oral bioavailability was 0, 25 and < 1 % for SDG, SECO and ED, respectively.

Topics: 4-Butyrolactone; Administration, Oral; Animals; Biological Availability; Butylene Glycols; Dietary Supplements; Dose-Response Relationship, Drug; Estrogens; Flax; Glucosides; Half-Life; Injections, Intravenous; Intestinal Absorption; Kinetics; Lignans; Male; Metabolic Clearance Rate; Phytoestrogens; Random Allocation; Rats, Wistar; Seeds

Phytoestrogens are plant-derived compounds that may interact with estrogen receptors and mimic estrogenic effects. It remains unclear whether the individual variability in metabolizing phytoestrogens contributes to phytoestrogens-induced beneficial or detrimental effects. Our aim was to determine whether there is any interaction between metabolic rates (MR) of phytoestrogens and genetic polymorphisms in related xenobiotic metabolizing enzyme genes. MR was used to assess phytoestrogen exposure and individual metabolic ability. The amount of phytoestrogens in urine was measured by ultra-high performance liquid chromatography-tandem mass spectrometry in 600 idiopathic infertile male patients and 401 controls. Polymorphisms were genotyped using the SNPstream platform combined with the Taqman method. Prototypes and metabolites of secoisolariciresinol (SEC) have inverse effects on male reproduction. It was found that low MR of SEC increased the risk of male infertility (OR 2.49, 95 % CI 1.78, 3.48, P trend = 8.00 × 10(-8)). Novel interactions were also observed between the MR of SEC and rs1042389 in CYP2B6, rs1048943 in CYP1A1, and rs1799931 in NAT2 on male infertility (P inter = 1.06 × 10(-4), 1.14 × 10(-3), 3.55 × 10(-3), respectively). By analyzing the relationships between urinary phytoestrogen concentrations, their metabolites and male infertility, we found that individual variability in metabolizing SEC contributed to the interpersonal differences in SEC's effects on male reproduction.

Topics: Adult; Arylamine N-Acetyltransferase; Asian People; Biotransformation; Butylene Glycols; Case-Control Studies; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2B6; Humans; Infertility, Male; Lignans; Male; Phytoestrogens; Polymorphism, Single Nucleotide; Young Adult

Experimental data indicate that gestational exposures to estrogenic compounds impact risk of hypospadias. We examined whether risk of hypospadias (i.e., a congenital malformation in which the opening of the penile urethra occurs on the ventral side of the penis) was associated with maternal intake of phytoestrogens, given their potential impact on estrogen metabolism. The analysis included data on mothers of 1,250 hypospadias cases and 3,118 controls who delivered their infants from 1997 to 2005 and participated in the National Birth Defects Prevention Study, a multistate, population-based, case-control study. After adjustment for several covariates, high intakes of daidzein, genistein, glycetin, secoisolariciresinol, total isoflavones, total lignans, and total phytoestrogens were associated with reduced risks; odds ratios comparing intakes ≥90th percentile with intakes between the 11th and 89th percentiles ranged from 0.6 to 0.8. For example, the odds ratio for total phytoestrogen intake was 0.7 (95% confidence interval: 0.5, 1.0). This study represents the first large-scale analysis of phytoestrogen intake and hypospadias. The observed associations merit investigation in additional populations before firm conclusions can be reached.

Topics: Adult; Butylene Glycols; Case-Control Studies; Diet, Vegetarian; Female; Genistein; Humans; Hypospadias; Infant, Newborn; Isoflavones; Lignans; Male; Odds Ratio; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Risk Assessment; Risk Factors; Surveys and Questionnaires

Phytoestrogens (PEs) are naturally occurring chemical constituents of certain plants. The internal PE exposures, mainly from diet, vary among different populations and in different regions due to various eating habits. To investigate the potential relationship between urinary PE levels and idiopathic male infertility and semen quality in Chinese adult males, 608 idiopathic infertile men and 469 fertile controls were recruited by eligibility screening procedures. Individual exposure to PEs was measured using UPLC-MS/MS as spot urinary concentrations of 6 PEs (daidzein, DAI; equol, EQU; genistein, GEN; naringenin, NAR; coumestrol, COU; and secoisolariciresinol, SEC), which were adjusted with urinary creatinine (CR). Semen quality was assessed by sperm concentration, number per ejaculum and motility. We found that exposures to DAI, GEN and SEC were significantly associated with idiopathic male infertility (P-value for trend=0.036; 0.002; and 0.0001, respectively), while these exposures had stronger association with infertile subjects with at least one abnormal semen parameter than those with all normal semen parameters. Exposures to DAI, GEN and SEC were also related to idiopathic male infertility with abnormal sperm concentration, number per ejaculum and motility (P-value for trend<0.05), while these exposures had stronger association with the infertile men with abnormal sperm number per ejaculum. These findings provide the evidence that PE exposures are related to male reproductive function and raise a public health concern because that exposure to PEs is ubiquitous in China.

Topics: Adult; Butylene Glycols; China; Diet; Feeding Behavior; Genistein; Humans; Infertility, Male; Isoflavones; Lignans; Male; Phytoestrogens; Semen; Semen Analysis; Sperm Count; Tandem Mass Spectrometry

Secoisolariciresinol (SECO) is a natural lignan-type phytoestrogen constituent mainly found in flaxseed. It can be metabolized in vivo to mammalian lignans of enterodiol and enterolactone, which have been proven to be effective in relieving menopausal syndrome. Depression is one of the most common symptoms of menopausal syndrome, and is currently treated with estrogen replacement and antidepressant therapy. However, due to the serious side-effects of such agents, there are urgent needs for safer and more tolerable treatments. In this paper, using two classical depression models, the forced swimming test and the tail suspension test, we report the antidepressant effect of SECO on ovariectomized (OVX) mice by intragastric administration for 14 consecutive days at doses of 5, 10 and 20 mg/kg. The results showed that SECO (10 mg/kg) treatment could significantly reduce the duration of immobility of OVX mice in these two models compared with the control group (OVX mice + vehicle), which was similar to the positive control imipramine. In addition, SECO treatment could substantially increase brain monoamine (norepinephrine and dopamine) levels in OVX mice. The present studies showed that SECO can reverse depressive-like behavior and exhibit monoamine-enhancing effects.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Butylene Glycols; Depression; Female; Flax; Lignans; Mice; Ovariectomy; Phytoestrogens

Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40-75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169-5759) μg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).

Topics: Adult; Aged; Bread; Butylene Glycols; Cardiovascular Diseases; Diet; Feeding Behavior; Female; Flax; Furans; Humans; Latvia; Lignans; Male; Middle Aged; Neoplasms; Phenols; Phytoestrogens; Plant Extracts; Sex Factors

Phytoestrogens are plant-derived, non-steroidal phytochemicals with anticarcinogenic potential. The major structural classes are the isoflavones and lignans. The aim of this study was to compare the effect of the plant-derived lignans secoisolariciresinol and matairesinol with the human lignans enterodiol and enterolactone as well as with 17β estradiol and tamoxifen on cell proliferation of breast carcinoma cell lines.. The influence of the lignans, 17β estradiol and tamoxifen on cell proliferation was determined using the BrdU test in MCF 7 and BT 20 cell lines.. Enterodiol and enterolactone induced a stronger inhibition of cell growth in MCF 7 and BT 20 cells than secoisolariciresinol and matairesinol. The inhibition effects were less expressed in the BT 20 than in the MCF 7 cells.. The human lignans enterodiol and enterolactone are more biologically active than their precursors secoisolariciresinol and matairesinol, and may be defined as the real drugs in cancer prevention.

Topics: 4-Butyrolactone; Anticarcinogenic Agents; Breast Neoplasms; Butylene Glycols; Cell Line, Tumor; Cell Proliferation; Estradiol; Estrogens; Female; Furans; Humans; Lignans; Phytoestrogens; Selective Estrogen Receptor Modulators; Tamoxifen

Phytooestrogens are known to cause anti-cancer effects on mamma carcinoma cells. In this study, the effects of the lignan secoisolariciresinol and the isoflavone glycosides and aglycones genistein, genistin, daidzein and daidzin were tested on MCF-7 and BT20 cells in vitro.. First, the cellular expression of hormone receptors was examined by immunohistochemical procedures. The effects of the phytooestrogens on the cells were detected by using three different assays measuring cell letality, viability and proliferation. The phytooestrogens were tested in concentrations of 1, 5, 10 and 50 μg/mL, respectively. 17β-oestradiol and tamoxifen were used as controls, respectively, in the same concentrations as the phytooestrogens.. The immunohistochemistry showed evidence of oestrogen- and progesterone receptors at the MCF-7 cell line, whereas no expression could be seen at the BT20 cells. Among the phytooestrogens, genistein and secoisolariciresinol showed various anti-cancerogenic effects on both cell lines, respectively, but only in the highest concentration. Regarding the controls, tamoxifen showed a stronger antivital and anti-proliferative effect on BT20 than on MCF-7. Oestradiol caused sporadic anti-cancer effects on both cell lines, respectively, at its highest concentration.. Genistein and Secoisolariciresinol have anti-cancer properties on MCF-7 and BT20 in vitro. There are differences in the effects of isoflavones depending on the glycolysation status. The role of the oestrogen receptors in the mechanisms of action of both the phytooestrogens and controls is of less importance. Further investigations have to be carried out, especially concerning the mechanisms of action. Phytooestrogens may be potential substances in the therapy of mamma carcinomas.

Topics: Breast Neoplasms; Butylene Glycols; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Female; Genistein; Humans; Immunohistochemistry; Isoflavones; L-Lactate Dehydrogenase; Lignans; Phytoestrogens; Receptors, Estrogen; Receptors, Progesterone

Flaxseed, rich in the phytoestrogen lignan secoisolariciresinol diglycoside (SDG), provides protection against bone loss at the lumbar vertebrae primarily when combined with low-dose estrogen therapy in the ovariectomized rat model of postmenopausal osteoporosis. Whether SDG metabolites are accessible to skeletal tissue, and thus have the potential to interact with low-dose estrogen therapy to exert direct local action on bone metabolism, is unknown. The objective of this study was to determine whether metabolites of SDG are accessible to the skeleton of ovariectomized rats and to compare the distribution of SDG metabolites in skeletal tissue with that in other tissues. Rats were fed a 10% flaxseed diet and gavaged daily with tritium-labeled SDG (7.4 kBq/g of body weight) in deionized water (500 μL) (n=3) or deionized water alone (n=3) for 7 days, after which tissues were collected for liquid scintillation counting. Radioactivity was detected in similar concentrations in the lumbar vertebrae, femurs, and tibias. Compared with non-skeletal tissues, total radioactivity in the skeleton was significantly lower than in the liver, heart, kidney, thymus, and brain (P < .001). There were no significant differences in levels of radioactivity between skeletal tissue versus the spleen, lung, bladder, uterus, vagina, and mammary gland. In conclusion, SDG metabolites are accessible to skeletal tissue of ovariectomized rats. Thus, it is biologically plausible that SDG metabolites may play a direct role in the protective effects of flaxseed combined with low-dose estrogen therapy against the loss of bone mass and bone strength in the ovariectomized rat model of postmenopausal osteoporosis.

Topics: Animals; Butylene Glycols; Disease Models, Animal; Female; Femur; Flax; Lignans; Lumbar Vertebrae; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Tibia

It has been suggested that lignan intake may decrease the risk for cardiovascular disease (CVD) by modifying traditional risk factors as well as aortic stiffness. However, the role of dietary lignans on the vascular system is largely unknown. The objective was to investigate whether dietary intake of plant lignans in a free-living population was associated with markers of vascular inflammation and function.. We performed a cross-sectional study in 242 (151 males) men and post-menopausal women. Anthropometric characteristics and lignan intake were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), insulin, high-sensitive C-reactive protein, glucose, total cholesterol, HDL-cholesterol and triacylglycerols were measured in fasting blood samples. Brachial flow-mediated dilation (FMD) measurements were available for 101 subjects (56 males). Median (interquartile range) daily intake of matairesinol (MAT), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol (LARI), and total lignans was 20.9 microg (17.4), 335.3 microg (289.1), 96.7 microg (91.1), 175.7 microg (135.8), and 665.5 microg (413.7), respectively, as assessed by 3-day weighed food record. Plasma concentrations of sICAM-1 (whole sample) significantly decreased (mean (95%CI) = 358 microg/L (320-401), 276 microg/L (252-303), 298 microg/L (271-326), and 269 microg/L (239-303), P per trend 0.013) and FMD values (FMD sub-group) significantly increased (4.1% (2.2-6.0), 5.7% (4.3-7.2), 6.4% (4.9-7.8), and 8.1% (6.3-10.0), P per trend 0.016) across quartiles of energy-adjusted MAT intake, even after adjustment for relevant clinical and dietary variables. Intake of SECO was also inversely related to plasma sICAM-1 (P per trend 0.018), but not to FMD values. No relationship between intake of PINO, LARI or total lignans and either sICAM-1 or FMD values was observed.. Higher MAT intakes in the context of a typical Northern Italian diet are associated to lower vascular inflammation and endothelial dysfunction, which could have some implications in CVD prevention.

Topics: Aged; Biomarkers; Butylene Glycols; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Diet Records; Diet, Mediterranean; Endothelium, Vascular; Female; Furans; Hemodynamics; Humans; Inflammation; Italy; Lignans; Male; Middle Aged; Phytoestrogens; Surveys and Questionnaires; Vascular Diseases

To evaluate the estrogenic potential of secoisolariciresinol diglycoside (SDG) found in linseed meal (LSM) on visceral organ mass, IGF-I, and thyroid hormone (T(3) and T(4)) concentrations, 48 multiparous, ovariectomized ewes (54.6 +/- 1.1 kg) were used in a 3 x 4 factorial arrangement. Main effects were length of LSM feeding (0, 1, 7, or 14 d) and length of exposure to estradiol-17beta (E(2)) implant (0, 6, or 24 h prior to tissue collection). Implanting ewes with E(2) for 24h increased liver mass relative to empty body weight (EBW; g/kg EBW) compared with ewes implanted for 0 or 6 h (P or= 0.12) CYP2C or CYP3A mRNA expression or cellularity of the liver. Exogenous E(2) influenced circulating concentrations of IGF-I, T(3), and T(4). The estrogenic or anti-estrogenic potential of LSM is dependent upon the tissue, exposure to E(2), and the duration of LSM feeding. Feeding LSM during gestation, lactation, or during the grow-finish phase warrants further investigation.

Topics: Animals; Butylene Glycols; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Estradiol; Female; Flax; Food-Drug Interactions; Gastric Mucosa; Insulin-Like Growth Factor I; Intestine, Small; Lignans; Liver; Organ Size; Ovariectomy; Phytoestrogens; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; RNA; Sheep; Stomach; Thyroxine; Triiodothyronine

Lariciresinol is a dietary lignan that accounts for a significant portion of the total phytoestrogen intake from Western foods. Recent epidemiological studies suggest that high dietary intake of lignans and lariciresinol is associated with reduced breast cancer risk. However, no causal relationship between lariciresinol intake and breast cancer development has been established. In this study, we investigated for the first time the effects and possible mechanisms of action of lariciresinol on hormone responsive mammary cancer in vivo in dimethylbenz[a]anthracene induced mammary cancer in rats, and in human MCF-7 breast cancer xenografts in athymic mice. For tumor bearing rats, lariciresinol (3 or 15 mg/kg of body weight) or vehicle was administered p.o. daily for 9 weeks. For E2-maintained ovariectomized athymic mice bearing orthotopic MCF-7 tumors, control diet (AIN-93G) or lariciresinol containing diet (AIN-93G supplemented with 20 or 100 mg of lariciresinol/kg of diet) was administered for 5 weeks. In both models, lariciresinol administration inhibited the tumor growth and tumor angiogenesis. In MCF-7 cells, enterolactone significantly inhibited the E2-stimulated VEGF secretion. Moreover, in MCF-7 xenografts, lariciresinol administration enhanced tumor cell apoptosis and increased estrogen receptor beta expression. Lariciresinol and its further metabolites secoisolariciresinol, enterodiol and enterolactone were found in serum of both rats and athymic mice confirming a similar lignan metabolism pattern as in humans. These findings indicate conceivable importance of dietary lignan lariciresinol in inhibition of breast cancer development.

Topics: 4-Butyrolactone; 9,10-Dimethyl-1,2-benzanthracene; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Apoptosis; Butylene Glycols; Carcinogens; Cell Proliferation; Dietary Supplements; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Furans; Gene Expression Regulation, Neoplastic; Humans; Lignans; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Ovariectomy; Phytoestrogens; Rats; Receptors, Progesterone; Transplantation, Heterologous

Dietary phytoestrogens have a number of biological effects, including endocrine disruption, antioxidant potential, and protein tyrosine kinase inhibition. Secoisolariciresinol, matairesinol, and shonanin are lignan phytoestrogens found in foodstuffs, especially flaxseed. Normally they are glycosidically linked to carbohydrates and in the large intestine are deconjugated from the carbohydrate portion by bacteria. The aglycone lignans can be further modified to form the mammalian phytoestrogens enterodiol, enterolactone, and enterofuran, which are absorbed into the body and excreted in urine. To assess the health implications of phytoestrogens in general populations, knowledge of the quantity in the foods eaten is necessary. This article describes a simple preparative procedure for the assay of secoisolariciresinol, matairesinol, and shonanin in foodstuffs after hydrolytic removal of any conjugated carbohydrate. The difficulties in the practical application of the assay procedure are illustrated and discussed. Analytical results indicating the concentration of secoisolariciresinol, matairesinol, and shonanin in a number of foodstuffs are presented. Also, the mass spectral data of a putative mammalian phytoestrogen, called enterofuran, identified in urine are presented.

Topics: Butylene Glycols; Estrogens, Non-Steroidal; Flax; Food Analysis; Furans; Humans; Isoflavones; Lignans; Mass Spectrometry; Phytoestrogens; Plant Preparations; Reference Standards; Triticum

High-performance liquid chromatographic (HPLC) and mass spectrometric (MS) procedures were developed to determine lignans in flaxseed (Linum usitatissimum) and chaparral (Larrea tridentata). Flaxseed contains high levels of phytoestrogens. Chaparral has been associated with acute nonviral toxic hepatitis and contains lignans that are structurally similar to known estrogenic compounds. Both flaxseed and chaparral products have been marketed as dietary supplements. A mild enzyme hydrolysis procedure to prevent the formation of artifacts in the isolation step was used in the determination of secoisolariciresinol in flaxseed products. HPLC with ultraviolet spectral (UV) or MS detection was used as the determinative steps. HPLC procedures with UV detection and mass spectrometry were developed to characterize the phenolic components, including lignans and flavonoids, of chaparral and to direct fractionation studies for the bioassays.

Topics: Butylene Glycols; Chromatography, High Pressure Liquid; Estrogens, Non-Steroidal; Food, Fortified; Isoflavones; Lignans; Lignin; Mass Spectrometry; Phytoestrogens; Plant Preparations; Plants