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Tapio Hase - One of the best experts on this subject based on the ideXlab platform.
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synthesis of enterolactone and Enterodiol precursors as potential inhibitors of human estrogen synthetase aromatase
Steroids, 2000Co-Authors: Tapio Mäkelä, Kristina Wahala, Tapio HaseAbstract:A series of variably substituted derivatives of lignan lactones and diols were prepared using tandem conjugate addition reaction as a key step. These theoretical precursors of the mammalian lignans enterolactone 1 and Enterodiol 3 are moderate or weak inhibitors of human aromatase activity.
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isotope dilution gas chromatographic mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces with preliminary results in omnivorous and vegetarian women
Analytical Biochemistry, 1995Co-Authors: Herman Adlercreutz, Kristina Wahala, Theodore Fotsis, Mindy S Kurzer, Taru Makela, Tapio HaseAbstract:We describe an isotope dilution gas chromatographic-mass spectrometric (GC/MS) method for the identification and quantitative determination of the lignans enterolactone, Enterodiol, and matairesinol and the isoflavonoids daidzein, equol, O-desmethylangolensin, and genistein in feces. Following the addition of deuterated internal standards for all compounds, the feces samples are extracted and purified in several ion exchange chromatographic steps. Following formation of trimethylsilyl ethers, the samples are analyzed by combined capillary column GC/MS in the selective ion monitoring mode and corrected for all losses during the procedure using the deuterated internal standards. Results on the reliability of the method and values for nine Finnish omnivorous and nine vegetarian women are presented.
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quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography mass spectrometry
Scandinavian Journal of Clinical & Laboratory Investigation, 1993Co-Authors: Herma Adlercreutz, Kristina Wahala, Theodore Fotsis, Taru Makela, J Lampe, Gosta Unow, Tapio HaseAbstract:The first quantitative method for the determination of both lignans and isoflavonoid phytoestrogens in plasma is presented. Using ion-exchange chromatography the diphenols are separated into two fractions 1) the biologically "active" fraction containing the free compounds + mono- and disulfates and 2) the biologically "inactive" fraction containing the mono- and diglucuronides and the sulfoglucuronides. After hydrolysis the fractions are further purified by solid phase extraction and ion exchange chromatography. Losses during the complete procedure are corrected for using radioactive estrogen conjugates during the first steps and later by adding deuterated internal standards of all compounds measured (matairesinol, Enterodiol, enterolactone, daidzein, O-desmethylangolensin, equol, and genistein). The final determination is carried out by isotope dilution gas chromatography-mass spectrometry in the selected ion monitoring mode (GC/MS/SIM). The diphenols may be measured at concentrations as low as 0.2 to 1.0 nmol/l. Results of plasma analyses of all compounds in 27 pre- and postmenopausal omnivorous and vegetarian women are presented for the first time. The most important findings are that the free+sulfate fraction is low for genistein (3.8% of total), but as much as 21-25% of enterolactone and Enterodiol occurs in this fraction. A good correlation between plasma and urine values was found. Total concentrations of individual compounds vary greatly between the subjects (from pmol/l to mumol/l), the vegetarians having higher values, particularly one vegan subject. The highest total enterolactone concentration value exceeded 1 mumol/l. It is concluded that a highly specific method for the assay of 3 lignans and 4 isoflavonoids in plasma has been developed. This method will be useful in future studies of lignan and isoflavonoid metabolism.
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isotope dilution gas chromatographic mass spectrometric method for the determination of lignans and isoflavonoids in human urine including identification of genistein
Clinica Chimica Acta, 1991Co-Authors: Herman Adlercreutz, Kristina Wahala, Cyrill Bannwart, Gösta Brunow, Theodore Fotsis, Tapio HaseAbstract:Abstract We describe an isotope dilution gas chromatographic-mass spectrometric method for the quantitative determination of the lignans enterolactone, Enterodiol and matairesinol and the isoflavonoids daidzein, equol, O -desmethylangolensin and genistein in urine. Furthermore we present the gas chromatographic mass spectrometer identification of genistein. Urine samples were extracted on Sep-Pak cartridges, conjugated fractions were isolated by chromatography on the acetate form of DEAE-Sephadex and deuterated internal standards of all seven compounds were added to the samples before hydrolysis. The hydrolysate was extracted on a Sep-Pak cartridge and following chromatography on the acetate form of QAE-Sephadex two fractions were obtained: Fraction 1 contained equol, enterolactone, Enterodiol, matairesinol and all estrogens and fraction 2 contained O -desmethylangolensin, daidzein and genistein. The latter was ready for gas chromatography/mass spectrometry, but the first one was further purified to eliminate the estrogens by chromatography on the carbonate form of QAE-Sephadex. Following silylation, the samples were analyzed by combined capillary column gas chromatography/mass spectrometry in the selective ion monitoring mode. The within-assay imprecision varied from 0.8–15.2% (mean 8.7%) and the between-assay imprecision from 4.1–13.9% (mean 9.3%), depending on compound and concentration level. The mean recovery of authentic standards added to urine extracts before hydrolysis varied from 96.6 to 105.5%. Values obtained from 10 Finnish omnivorous men are presented. Individual values for matairesinol (excre-tion range 3.3–59.9 nmol/24 h) and genistein (range 21.8–1180 nmol/24 h) in human urine have never been published before.
Herman Adlercreutz - One of the best experts on this subject based on the ideXlab platform.
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effects of consumption of whole grain foods rich in lignans in healthy postmenopausal women with moderate serum cholesterol a pilot study
International Journal of Food Sciences and Nutrition, 2014Co-Authors: Alessandra Durazzo, Marina Carcea, Elena Azzini, Angela Polito, L. Olivieri, Carlo Meneghini, F. Maiani, Herman Adlercreutz, Maria Zaccaria, G. BausanoAbstract:This study aims at investigating the effect of an experimental period of intake of whole grain foods rich in lignans as part of an habitual diet on the plasma and urinary excretion of enterolignans, the biomarkers of lipid metabolism and the immunological and antioxidant status in a group of postmenopausal women with moderate serum cholesterol. A randomized double-blind crossover study was completed on 13 subjects in 12-weeks after protocol approval of an ethical committee. The subjects consumed whole grain foods high in lignans (30 g/d of breakfast cereals or biscuits, etc., 80 g/d of whole grain pasta) or refined grain foods for 4 weeks, separated by a 2-weeks wash-out period. A modest hypocholesterolemic effect (p < 0.05) of the whole grain diet was observed and the intake of whole grain products rich in lignans was also associated with an increase in urinary Enterodiol excretion (p < 0.05).
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in vitro metabolism of plant lignans new precursors of mammalian lignans enterolactone and Enterodiol
Journal of Agricultural and Food Chemistry, 2001Co-Authors: Satu-maarit Heinonen, Kristina Wahala, Kirsi Liukkonen, Takeshi Deyama, Sansei Nishibe, Tarja Nurmi, Herman AdlercreutzAbstract:The metabolism of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, syringaresinol, arctigenin, 7-hydroxymatairesinol, isolariciresinol, and lariciresinol by human fecal microflora was investigated to study their properties as mammalian lignan precursors. The quantitative analyses of lignan precursors and the mammalian lignans enterolactone and Enterodiol were performed by HPLC with coulometric electrode array detector. The metabolic products, including mammalian lignans, were characterized as trimethylsilyl derivatives by gas chromatography−mass spectrometry. Matairesinol, secoisolariciresinol, lariciresinol, and pinoresinol were converted to mammalian lignans only. Several metabolites were isolated and tentatively identified as for syringaresinol and arctigenin in addition to the mammalian lignans. Metabolites of 7-hydroxymatairesinol were characterized as enterolactone and 7-hydroxyenterolactone by comparison with authentic reference compounds. A metabolic scheme describing the convers...
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reliability of serum measurements of lignans and isoflavonoid phytoestrogens over a two year period
Cancer Epidemiology Biomarkers & Prevention, 1998Co-Authors: Anne Zeleniuchjacquotte, Herman Adlercreutz, Arslan Akhmedkhanov, P TonioloAbstract:We examined the distribution and long-term reliability of serum measurements of the two main human lignans, enterolactone and Enterodiol, and the isoflavonoid phytoestrogens daidzein, genistein, equol, and O-Desmethylangolensin in the New York University Women's Health Study, a prospective cohort study of sex hormones and breast cancer. Serum samples collected at three yearly visits in 30 premenopausal and 30 postmenopausal women who had not been diagnosed with cancer or cardiovascular disease were included in the study. Assays were carried out by ion-exchange chromatography and capillary gas chromatography-mass spectrometry. Levels of isoflavonoid phytoestrogens were low, often at or below the sensitivity level of the assay. The reliability coefficients for these compounds were also low (< or =0.30). The median levels of Enterodiol and enterolactone were 1.52 nmol/liter and 20.2 nmol/liter, respectively, and were comparable with the levels observed in omnivorous Finnish women living in the Helsinki area. A substantial number of women, though, had fairly high levels: for instance, 15% of the assays showed levels of enterolactone greater than the mean level observed in vegetarian Finnish women, i.e., 89.1 nmol/liter (H. Adlercreutz et al., Cancer Detec. Prev., 18: 259-271, 1994). The reliability coefficient of a single measurement of enterolactone was moderately high (0.55), suggesting that serum measurements of this compound could be a useful tool in prospective epidemiological studies with access to repeated blood or serum specimens. For instance, the reliability coefficient of the average of three measurements of enterolactone would be 0.79, a level considered acceptable in light of the other sources of error that are present in epidemiological studies (W. Willett, Stat. Med., 8: 1031-1040, 1989).
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isotope dilution gas chromatographic mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces with preliminary results in omnivorous and vegetarian women
Analytical Biochemistry, 1995Co-Authors: Herman Adlercreutz, Kristina Wahala, Theodore Fotsis, Mindy S Kurzer, Taru Makela, Tapio HaseAbstract:We describe an isotope dilution gas chromatographic-mass spectrometric (GC/MS) method for the identification and quantitative determination of the lignans enterolactone, Enterodiol, and matairesinol and the isoflavonoids daidzein, equol, O-desmethylangolensin, and genistein in feces. Following the addition of deuterated internal standards for all compounds, the feces samples are extracted and purified in several ion exchange chromatographic steps. Following formation of trimethylsilyl ethers, the samples are analyzed by combined capillary column GC/MS in the selective ion monitoring mode and corrected for all losses during the procedure using the deuterated internal standards. Results on the reliability of the method and values for nine Finnish omnivorous and nine vegetarian women are presented.
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urinary lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder
The American Journal of Clinical Nutrition, 1994Co-Authors: Johanna W Lampe, Margaret C Martini, Herman Adlercreutz, Mindy S Kurzer, Joanne L SlavinAbstract:Lignans and isoflavonoid phytoestrogens, produced from plant precursors by colonic bacteria, may protect against certain cancers. We examined the effects of flaxseed consumption on urinary lignans and isoflavonoids. Eighteen women consumed their usual omnivorous diets for three menstrual cycles and their usual diets supplemented with flaxseed powder (10 g/d) for three cycles in a randomized crossover design. Three-day urine samples from follicular and luteal phases were analyzed for lignans and isoflavonoids by isotope-dilution gas chromatography--mass spectrometry. Excretion of the lignans Enterodiol and enterolactone increased with flaxseed from 1.09 +/- 1.08 and 3.16 +/- 1.47 to 19.48 +/- 1.10 and 27.79 +/- 1.50 mumol/d, respectively (P < 0.0002). Enterodiol and enterolactone excretion varied among subjects in response to flaxseed (3- to 285-fold increase). There were no differences in excretion of isoflavonoids (daidzein, genistein, equol, and O-desmethylangolensin) or the lignan matairesinol with flaxseed. Excretion was not altered by phase of menstrual cycle or duration of flaxseed consumption.
Kristina Wahala - One of the best experts on this subject based on the ideXlab platform.
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in vitro metabolism of plant lignans new precursors of mammalian lignans enterolactone and Enterodiol
Journal of Agricultural and Food Chemistry, 2001Co-Authors: Satu-maarit Heinonen, Kristina Wahala, Kirsi Liukkonen, Takeshi Deyama, Sansei Nishibe, Tarja Nurmi, Herman AdlercreutzAbstract:The metabolism of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, syringaresinol, arctigenin, 7-hydroxymatairesinol, isolariciresinol, and lariciresinol by human fecal microflora was investigated to study their properties as mammalian lignan precursors. The quantitative analyses of lignan precursors and the mammalian lignans enterolactone and Enterodiol were performed by HPLC with coulometric electrode array detector. The metabolic products, including mammalian lignans, were characterized as trimethylsilyl derivatives by gas chromatography−mass spectrometry. Matairesinol, secoisolariciresinol, lariciresinol, and pinoresinol were converted to mammalian lignans only. Several metabolites were isolated and tentatively identified as for syringaresinol and arctigenin in addition to the mammalian lignans. Metabolites of 7-hydroxymatairesinol were characterized as enterolactone and 7-hydroxyenterolactone by comparison with authentic reference compounds. A metabolic scheme describing the convers...
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in vitro metabolism of plant lignans new precursors of mammalian lignans enterolactone and Enterodiol
Journal of Agricultural and Food Chemistry, 2001Co-Authors: Satu Heinone, Kristina Wahala, Takeshi Deyama, Sansei Nishibe, Tarja Nurmi, Kirsi Liukkone, Kaisa Poutane, Herma AdlercreutzAbstract:The metabolism of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, syringaresinol, arctigenin, 7-hydroxymatairesinol, isolariciresinol, and lariciresinol by human fecal microflora was investigated to study their properties as mammalian lignan precursors. The quantitative analyses of lignan precursors and the mammalian lignans enterolactone and Enterodiol were performed by HPLC with coulometric electrode array detector. The metabolic products, including mammalian lignans, were characterized as trimethylsilyl derivatives by gas chromatography-mass spectrometry. Matairesinol, secoisolariciresinol, lariciresinol, and pinoresinol were converted to mammalian lignans only. Several metabolites were isolated and tentatively identified as for syringaresinol and arctigenin in addition to the mammalian lignans. Metabolites of 7-hydroxymatairesinol were characterized as enterolactone and 7-hydroxyenterolactone by comparison with authentic reference compounds. A metabolic scheme describing the conversion of the most abundant new mammalian lignan precursors, pinoresinol and lariciresinol, is presented.
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synthesis of enterolactone and Enterodiol precursors as potential inhibitors of human estrogen synthetase aromatase
Steroids, 2000Co-Authors: Tapio Mäkelä, Kristina Wahala, Tapio HaseAbstract:A series of variably substituted derivatives of lignan lactones and diols were prepared using tandem conjugate addition reaction as a key step. These theoretical precursors of the mammalian lignans enterolactone 1 and Enterodiol 3 are moderate or weak inhibitors of human aromatase activity.
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isotope dilution gas chromatographic mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces with preliminary results in omnivorous and vegetarian women
Analytical Biochemistry, 1995Co-Authors: Herman Adlercreutz, Kristina Wahala, Theodore Fotsis, Mindy S Kurzer, Taru Makela, Tapio HaseAbstract:We describe an isotope dilution gas chromatographic-mass spectrometric (GC/MS) method for the identification and quantitative determination of the lignans enterolactone, Enterodiol, and matairesinol and the isoflavonoids daidzein, equol, O-desmethylangolensin, and genistein in feces. Following the addition of deuterated internal standards for all compounds, the feces samples are extracted and purified in several ion exchange chromatographic steps. Following formation of trimethylsilyl ethers, the samples are analyzed by combined capillary column GC/MS in the selective ion monitoring mode and corrected for all losses during the procedure using the deuterated internal standards. Results on the reliability of the method and values for nine Finnish omnivorous and nine vegetarian women are presented.
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quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography mass spectrometry
Scandinavian Journal of Clinical & Laboratory Investigation, 1993Co-Authors: Herma Adlercreutz, Kristina Wahala, Theodore Fotsis, Taru Makela, J Lampe, Gosta Unow, Tapio HaseAbstract:The first quantitative method for the determination of both lignans and isoflavonoid phytoestrogens in plasma is presented. Using ion-exchange chromatography the diphenols are separated into two fractions 1) the biologically "active" fraction containing the free compounds + mono- and disulfates and 2) the biologically "inactive" fraction containing the mono- and diglucuronides and the sulfoglucuronides. After hydrolysis the fractions are further purified by solid phase extraction and ion exchange chromatography. Losses during the complete procedure are corrected for using radioactive estrogen conjugates during the first steps and later by adding deuterated internal standards of all compounds measured (matairesinol, Enterodiol, enterolactone, daidzein, O-desmethylangolensin, equol, and genistein). The final determination is carried out by isotope dilution gas chromatography-mass spectrometry in the selected ion monitoring mode (GC/MS/SIM). The diphenols may be measured at concentrations as low as 0.2 to 1.0 nmol/l. Results of plasma analyses of all compounds in 27 pre- and postmenopausal omnivorous and vegetarian women are presented for the first time. The most important findings are that the free+sulfate fraction is low for genistein (3.8% of total), but as much as 21-25% of enterolactone and Enterodiol occurs in this fraction. A good correlation between plasma and urine values was found. Total concentrations of individual compounds vary greatly between the subjects (from pmol/l to mumol/l), the vegetarians having higher values, particularly one vegan subject. The highest total enterolactone concentration value exceeded 1 mumol/l. It is concluded that a highly specific method for the assay of 3 lignans and 4 isoflavonoids in plasma has been developed. This method will be useful in future studies of lignan and isoflavonoid metabolism.
Theodore Fotsis - One of the best experts on this subject based on the ideXlab platform.
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isotope dilution gas chromatographic mass spectrometric method for the determination of unconjugated lignans and isoflavonoids in human feces with preliminary results in omnivorous and vegetarian women
Analytical Biochemistry, 1995Co-Authors: Herman Adlercreutz, Kristina Wahala, Theodore Fotsis, Mindy S Kurzer, Taru Makela, Tapio HaseAbstract:We describe an isotope dilution gas chromatographic-mass spectrometric (GC/MS) method for the identification and quantitative determination of the lignans enterolactone, Enterodiol, and matairesinol and the isoflavonoids daidzein, equol, O-desmethylangolensin, and genistein in feces. Following the addition of deuterated internal standards for all compounds, the feces samples are extracted and purified in several ion exchange chromatographic steps. Following formation of trimethylsilyl ethers, the samples are analyzed by combined capillary column GC/MS in the selective ion monitoring mode and corrected for all losses during the procedure using the deuterated internal standards. Results on the reliability of the method and values for nine Finnish omnivorous and nine vegetarian women are presented.
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quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography mass spectrometry
Scandinavian Journal of Clinical & Laboratory Investigation, 1993Co-Authors: Herma Adlercreutz, Kristina Wahala, Theodore Fotsis, Taru Makela, J Lampe, Gosta Unow, Tapio HaseAbstract:The first quantitative method for the determination of both lignans and isoflavonoid phytoestrogens in plasma is presented. Using ion-exchange chromatography the diphenols are separated into two fractions 1) the biologically "active" fraction containing the free compounds + mono- and disulfates and 2) the biologically "inactive" fraction containing the mono- and diglucuronides and the sulfoglucuronides. After hydrolysis the fractions are further purified by solid phase extraction and ion exchange chromatography. Losses during the complete procedure are corrected for using radioactive estrogen conjugates during the first steps and later by adding deuterated internal standards of all compounds measured (matairesinol, Enterodiol, enterolactone, daidzein, O-desmethylangolensin, equol, and genistein). The final determination is carried out by isotope dilution gas chromatography-mass spectrometry in the selected ion monitoring mode (GC/MS/SIM). The diphenols may be measured at concentrations as low as 0.2 to 1.0 nmol/l. Results of plasma analyses of all compounds in 27 pre- and postmenopausal omnivorous and vegetarian women are presented for the first time. The most important findings are that the free+sulfate fraction is low for genistein (3.8% of total), but as much as 21-25% of enterolactone and Enterodiol occurs in this fraction. A good correlation between plasma and urine values was found. Total concentrations of individual compounds vary greatly between the subjects (from pmol/l to mumol/l), the vegetarians having higher values, particularly one vegan subject. The highest total enterolactone concentration value exceeded 1 mumol/l. It is concluded that a highly specific method for the assay of 3 lignans and 4 isoflavonoids in plasma has been developed. This method will be useful in future studies of lignan and isoflavonoid metabolism.
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isotope dilution gas chromatographic mass spectrometric method for the determination of lignans and isoflavonoids in human urine including identification of genistein
Clinica Chimica Acta, 1991Co-Authors: Herman Adlercreutz, Kristina Wahala, Cyrill Bannwart, Gösta Brunow, Theodore Fotsis, Tapio HaseAbstract:Abstract We describe an isotope dilution gas chromatographic-mass spectrometric method for the quantitative determination of the lignans enterolactone, Enterodiol and matairesinol and the isoflavonoids daidzein, equol, O -desmethylangolensin and genistein in urine. Furthermore we present the gas chromatographic mass spectrometer identification of genistein. Urine samples were extracted on Sep-Pak cartridges, conjugated fractions were isolated by chromatography on the acetate form of DEAE-Sephadex and deuterated internal standards of all seven compounds were added to the samples before hydrolysis. The hydrolysate was extracted on a Sep-Pak cartridge and following chromatography on the acetate form of QAE-Sephadex two fractions were obtained: Fraction 1 contained equol, enterolactone, Enterodiol, matairesinol and all estrogens and fraction 2 contained O -desmethylangolensin, daidzein and genistein. The latter was ready for gas chromatography/mass spectrometry, but the first one was further purified to eliminate the estrogens by chromatography on the carbonate form of QAE-Sephadex. Following silylation, the samples were analyzed by combined capillary column gas chromatography/mass spectrometry in the selective ion monitoring mode. The within-assay imprecision varied from 0.8–15.2% (mean 8.7%) and the between-assay imprecision from 4.1–13.9% (mean 9.3%), depending on compound and concentration level. The mean recovery of authentic standards added to urine extracts before hydrolysis varied from 96.6 to 105.5%. Values obtained from 10 Finnish omnivorous men are presented. Individual values for matairesinol (excre-tion range 3.3–59.9 nmol/24 h) and genistein (range 21.8–1180 nmol/24 h) in human urine have never been published before.
Peter C H Hollman - One of the best experts on this subject based on the ideXlab platform.
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Plasma enterolignans are not associated with nonfatal myocardial infarction risk.
Atherosclerosis, 2008Co-Authors: Anneleen Kuijsten, Ilja C W Arts, H. Bas Bueno-de-mesquita, Jolanda M. A. Boer, Frans J. Kok, Pieter Van 't Veer, Peter C H HollmanAbstract:Plant lignans present in foods such as whole grains, seeds and nuts, fruits and vegetables, and beverages. Plant lignans are converted by intestinal bacteria into the enterolignans Enterodiol and enterolactone. Up to now, epidemiological evidence for a protective role of enterolignans on cardiovascular diseases is limited and inconsistent. We investigated the association between plasma Enterodiol and enterolactone and nonfatal myocardial infarction risk in a prospective study. During follow-up (1987-1998) of 15,107 subjects, aged 20-59 years, 236 incident nonfatal myocardial infarction cases were diagnosed. Controls (n=283) were frequency matched to the cases on age, sex, and study center. No statistically significant associations between plasma Enterodiol and enterolactone and risk of nonfatal myocardial infarction were detected. The odds ratio for the highest versus the lowest quartile of Enterodiol was 1.21 (95% confidence interval (CI): 0.70, 2.12; p for trend=0.74), and that of enterolactone 1.51 (95% CI: 0.87, 2.61; p for trend=0.12) after adjustment for known dietary risk factors for coronary heart disease. No effect modification was observed for sex, menopausal status, or smoking status. Our results do not support the hypothesis that high plasma Enterodiol or enterolactone concentrations are associated with a reduced risk of nonfatal myocardial infarction.
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A validated method for the quantification of Enterodiol and enterolactone in plasma using isotope dilution liquid chromatography with tandem mass spectrometry.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2005Co-Authors: Anneleen Kuijsten, Michel N C P Buijsman, Ilja C W Arts, Patrick P.j. Mulder, Peter C H HollmanAbstract:Enterolactone and Enterodiol are phytoestrogens with structural similarity to endogenous estrogens. Because of their biological activities, they may affect the development of several diseases. To quantify Enterodiol and enterolactone in plasma, we developed and validated a liquid chromatography-tandem mass spectrometry method with electrospray ionization using 13C3 labeled isotopes. The method consists of a simple enzymatic hydrolysis and ether extraction followed by a rapid LC separation (run-time of 11 min). Detection limits as low as 0.15 nM for Enterodiol and 0.55 nM for enterolactone were achieved. The within-run R.S.D. ranges from 3 to 6% and the between-run R.S.D. ranges from 10 to 14% for both enterolignans. This method allows simple, rapid, and sensitive quantification, and is suitable for measuring large numbers of samples.
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pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside
Journal of Nutrition, 2005Co-Authors: Anneleen Kuijsten, Ilja C W Arts, Tom B. Vree, Peter C H HollmanAbstract:High concentrations of enterolignans in plasma are associated with a lower risk of acute coronary events. However, little is known about the absorption and excretion of enterolignans. The pharmacokinetic parameters and urinary excretion of Enterodiol and enterolactone were evaluated after consumption of their purified plant precursor, secoisolariciresinol diglucoside (SDG). Twelve healthy volunteers ingested a single dose of purified SDG (1.31 ?mol/kg body wt). Enterolignans appeared in plasma 8-10 h after ingestion of the purified SDG. Enterodiol reached its maximum plasma concentration 14.8 ± 5.1 h (mean ± SD) after ingestion of SDG, whereas enterolactone reached its maximum 19.7 ± 6.2 h after ingestion. The mean elimination half-life of Enterodiol (4.4 ± 1.3 h) was shorter than that of enterolactone (12.6 ± 5.6 h). The mean area under the curve of enterolactone (1762 ± 1117 nmol/L·h) was twice as large as that of Enterodiol (966 ± 639 nmol/L·h). The mean residence time for Enterodiol was 20.6 ± 5.9 h and that for enterolactone was 35.8 ± 10.6 h. Within 3 d, up to 40% of the ingested SDG was excreted as enterolignans via urine, with the majority (58%) as enterolactone. In conclusion, a substantial part of enterolignans becomes available in the blood circulation and is subsequently excreted. The measured mean residence times and elimination half-lives indicate that enterolignans accumulate in plasma when consumed 2-3 times a day and reach steady state. Therefore, plasma enterolignan concentrations are expected to be good biomarkers of dietary lignan exposure and can be used to evaluate the effects of lignans
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uptake and metabolism of enterolactone and Enterodiol by human colon epithelial cells
Archives of Biochemistry and Biophysics, 2005Co-Authors: Guus H E Jansen, Peter C H Hollman, Michel W F Nielen, Ilja C W Arts, Michael Müller, Jaap KeijerAbstract:Abstract The enterolignans enterolactone and Enterodiol are phytoestrogens that are formed from plant lignans by microorganisms in the human colon. Enterolignans circulate in plasma as conjugates. We hypothesized that conjugation of enterolignans takes place in colon epithelial cells, and studied the time course of uptake and metabolism of enterolactone and Enterodiol in three human colon epithelial cell lines. In addition, the conjugates were identified by mass spectrometry with accurate mass measurement (LC/QTOFMS/MS). Intracellular levels of conjugated enterolactone and Enterodiol in HT29 cells rose immediately after starting the exposure. This was accompanied by a rapid decrease in free enterolactone and Enterodiol in the exposure medium of HT29 and (un)differentiated CaCo-2 but not of CCD841CoTr cells. Conjugation and excretion of enterolactone and Enterodiol was complete within 8 h, except for Enterodiol in CaCo-2 cells (∼48 h). Enterolactone appears to be more rapidly metabolized and/or excreted than Enterodiol, and also the appearance of conjugated enterolactone in medium is less affected by the presence of Enterodiol than vice versa. Total (free plus conjugated) enterolignan concentrations remained constant throughout the experiments. Three conjugates were identified in exposure medium of HT29 cells: enterolactone-sulfate, enterolactone-glucuronide, and Enterodiol-glucuronide.Taken together, our data suggest that phase II metabolism of enterolactone and Enterodiol already may take place during uptake in the colon and that colon epithelial cells may be responsible for this metabolism.
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uptake and metabolism of enterolactone and Enterodiol by human colon epithelial cells
Archives of Biochemistry and Biophysics, 2005Co-Authors: Guus H E Jansen, Peter C H Hollman, Michel W F Nielen, Ilja C W Arts, Michael Müller, Jaap KeijerAbstract:The enterolignans enterolactone and Enterodiol are phytoestrogens that are formed from plant lignans by microorganisms in the human colon. Enterolignans circulate in plasma as conjugates. We hypothesized that conjugation of enterolignans takes place in colon epithelial cells, and studied the time course of uptake and metabolism of enterolactone and Enterodiol in three human colon epithelial cell lines. In addition, the conjugates were identified by mass spectrometry with accurate mass measurement (LC/QTOFMS/MS). Intracellular levels of conjugated enterolactone and Enterodiol in HT29 cells rose immediately after starting the exposure. This was accompanied by a rapid decrease in free enterolactone and Enterodiol in the exposure medium of HT29 and (un)differentiated CaCo-2 but not of CCD841CoTr cells. Conjugation and excretion of enterolactone and Enterodiol was complete within 8 h, except for Enterodiol in CaCo-2 cells ( approximately 48 h). Enterolactone appears to be more rapidly metabolized and/or excreted than Enterodiol, and also the appearance of conjugated enterolactone in medium is less affected by the presence of Enterodiol than vice versa. Total (free plus conjugated) enterolignan concentrations remained constant throughout the experiments. Three conjugates were identified in exposure medium of HT29 cells: enterolactone-sulfate, enterolactone-glucuronide, and Enterodiol-glucuronide. Taken together, our data suggest that phase II metabolism of enterolactone and Enterodiol already may take place during uptake in the colon and that colon epithelial cells may be responsible for this metabolism.