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Institute for Preventive Medicine, Nutrition, and Cancer, Folkhälsan Research Center, and Division of Clinical Chemistry, University of Helsinki, Helsinki, Finland; and * VTT Biotechnology, Espoo, Finland
2To whom correspondence should be addressed. E-mail: jose.penalvo{at}helsinki.fi.
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ABSTRACT |
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 TOP ABSTRACT SUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • enterodiol • enterolactone • lignans • sesame seed • sesamin
Enterolactone is the major end-product of dietary lignan fermentation by mammalian intestinal microflora (1–3). Laboratory and epidemiological data have shown that high plasma and urinary concentrations of enterolactone are inversely correlated with the risk for developing certain chronic diseases, such as cancer and coronary heart disease (4–8).
Sesamin, a furanofuran-type lignan, has been identified in several species of Piper genus (9) and from the stem and/or root bark of different tree species (10–13), although the highest concentrations are found in sesame (Sesamum indicum L.) seeds (14,15). Various biochemical actions, mainly related to lipid metabolism, have been attributed to sesamin; they include: specific inhibition of 
5-desaturation of (n-6) fatty acids (16,17) that interrupt the formation of proinflammatory 2-series prostaglandins (18); hypocholesterolemic activity via inhibition of cholesterol synthesis and absorption (19); antihypertensive effect (20–23); protection against ethanol and carbon tetrachloride-induced liver damage (24); synergy with 
-tocopherol (25); improvement of the bioavailability of 
-tocopherol (26); and a suppressive effect against induced carcinogenesis in animals (27). The mechanisms for some of these effects are unknown, but it has been suggested that sesamin may act as a proactive substance in the body (28) and that only its metabolites are responsible for the physiological effects observed.
We hypothesized that sesamin could metabolize to enterolactone, and we used 2 different approaches to test this. The in vivo formation of mammalian lignans after intake of a single dose of sesame seeds was studied by examining the plasma levels of lignans in 4 subjects. To compare these levels with the intake, the plant lignan content of the sesame seeds was characterized and quantified. Furthermore, in vitro metabolism of sesamin was studied by fermentating pure standard with human fecal microflora for 24 h.
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SUBJECTS, MATERIALS, AND METHODS |
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TOPABSTRACTSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The human study design (protocol 361/E5/03) was approved by the Ethics Committee for the Department of Medicine, Hospital District of Helsinki and Uusimaa. Four healthy volunteers (3 women and 1 man, S1 to S4) 43.5 ± 16.8 y old with BMI 22.6 ± 2.83 kg/m2 were selected among the staff members of the IPMNC (Folkhälsan Research Center). None of the subjects had undergone antibiotic treatment during 1 y preceding the sample collection.
Dietary intervention
Participants were requested to maintain a diet low in lignans for 1 wk prior to the sesame seed supplementation study. An informative sheet with the foods to be avoided (29–31) was provided for each subject. Whole grain products, seeds and nuts, legumes, berries, most vegetables and fruits, tea, beer, and wine were particularly avoided. After this food restriction period, subjects consumed a single dose of sesame seeds and continued the restricted diet for 24 h, after which the samples were collected. Whole, nonroasted sesame (S. indicum L.) seeds were purchased from a local store in Helsinki. The sample was kept at constant temperature and humidity until use, at which time 50 g of seeds was crushed (A11 Basic Homogenizer, Ika-Werke Gmbh) and given to the participants.
Collection and storage of plasma samples
Blood samples were collected from each participant at the beginning of the low-lignan diet period (initial) and before supplementation (0 h) to test the efficacy of the restricted diet. Following supplementation with sesame seeds, samples were collected at 0.5, 1, 2, 4, 8, 10, and 24 h via catheter from the brachial vein into evacuated tubes with heparin. Blood samples were cooled to room temperature and centrifuged (10 min, 2000 x g) to separate the plasma (15–20 mL), which was stored at –20°C until analysis.
Fecal fermentation
The incubation method of Aura et al. (32) was modified as follows: a carbonate-phosphate buffer solution with trace elements was maintained in an anaerobic chamber for 2 d prior to fermentation. A quantity of 1.89 mg of sesamin was dissolved in 1 mL of methanol, from which 100 µL (corresponding to 0.5 µmol) was placed into 50-mL glass vials. After evaporation of the methanol, bottles were transferred to the anaerobic chamber where 5 mL of fecal suspension was added. Feces were collected from 3 healthy human volunteers, who consumed a Western diet, presented no digestive diseases, and had not received antibiotics for at least 3 mo prior to the study. Freshly passed feces were immediately taken in an anaerobic chamber, pooled, and homogenized at the same time with an equal weight of culture medium using a Waring blender. The slurry was diluted to 5.0% (w:w) with culture medium, filtered through a 1-mm sieve, and used immediately as inoculum. Bottles were closed tightly to ensure anaerobic conditions. Duplicate samples and blanks (only fecal suspension) were incubated with magnetic stirring for 24 h at 37°C. The fermentation was terminated by immersion of the vials in liquid nitrogen, and subsequently samples were freeze-dried and stored at constant temperature and humidity.
Analytical methods
Reference compounds. Plant-isolated standards of sesamin (Ses),3 and lariciresinol (Lar) were provided by Prof. Nishibe (Department of Pharmacognosy, University of Hokkaido) and Dr. Deyama (Yomeishu Seizo). Pinoresinol (Pin) and syringaresinol (Syr) were synthesized by Dr. Botting’s group (School of Chemistry, University of St. Andrews). Synthetic standards of isolariciresinol (IsoL, or cyclolariciresinol), matairesinol (Mat), secoisolariciresinol (Seco), anhydrosecoisolariciresinol (Anse, or shonanin), enterolactone (Enl), and enterodiol (End) as well as the deuterated standards 2H6-matairesinol, 2H6-secoisolariciresinol, and 2H6-anhydrosecoisolariciresinol were provided by Prof. Wähälä (Laboratory of Organic Chemistry, University of Helsinki). 7'-hydroxymatairesinol (Hmr) was a gift from Hormos Medical (Fig. 1). All standards for quantitative analysis were dissolved in methanol.
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Lignans in plasma and fecal fermentation samples. Determination of plant and mammalian lignans in human plasma was carried out by HPLC with coulometric electrode array detector following a previously published method (36). For the quantification of Ses in plasma, 500 µL of sample was extracted twice with 3 mL of diethyl ether in Vortex. Organic phases were pooled, evaporated under N2 flow, and redissolved in 100 µL methanol. Extracts were purified in C18-cartridges (Waters) with 6 mL methanol elution, evaporated to dryness, and redissolved in 100 µL QSM to be injected into the GC-MS under the same conditions described above except for the oven temperature program, which was 170°C (for 1 min), increased 50°C/min to 230°C, increased 1°C/min to 247°C, and finally increased 20°C/min to 280°C and kept for 5 min. Injection volume was 2 µL. Identification of the metabolites formed during the in vitro fecal fermentation of sesamin was performed by GC-MS as described earlier (2).
Data analysis
Noncompartmental pharmacokinetic analysis of the data was conducted with PK Solutions 2.0 (Summit Research Services). A best-fit line was calculated after assessment of the residuals and visual inspection of the line. Values are means ± SEM, n = 3. Comparison of the means was carried out using ANOVA and Tukey’s HSD test at = 0.05 with SPSS for Windows 11.0.
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RESULTS |
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TOPABSTRACTSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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373 mg/100 g (10.8 µmol/g) and was characterized by a high content of nonconjugated lignans. In addition to sesamin, whose chemical structure does not permit conjugation, almost 35% of the lignans appeared in a free form, being liberated from the matrix after the first organic (acetone/water) extraction. Ses and Hmr were found only in free form, Lar was mainly found in free form, and Pin, Mat, and Syr appeared mostly after the hydrolysis of the residue and therefore they probably were conjugated in sesame seeds (Table 1). During the sample pretreatment Seco was converted to Anse (33), and Lar was converted to IsoL due to the acidic conditions during the process. The extent of these conversions cannot be defined because it varied depending on the matrix and therefore the results were expressed as the sum of the correspondent plant lignan forms (Table 1). Two isomers of sesaminol (Fig. 1), appearing in considerable amounts in the hydrolyzed residue, were tentatively identified (M+ 442, base peak m/z 149, retention times 19.8 and 20.4 min), although their quantification was not possible due to the lack of a standard.
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DISCUSSION |
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TOPABSTRACTSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The total plant lignan content of the sesame seeds used in the study was similar to that reported for flaxseed (43). In flaxseed the main lignan is Seco (95%), and in sesame seeds it is Ses (90%), although the amount of sesaminol was not quantified. Flaxseed is the richest known source of mammalian lignan precursors (31), but our study shows that sesame seeds may contain comparable or even higher amounts of plant lignans, mainly Ses, but also Pin, Lar, and Hmr, which are converted to enterolactone. This can be important when the worldwide use of sesame seeds as a food and as an oilseed is considered. Ses is a lipophilic lignan and it is extracted together with the oil in the unsaponifiable fraction (44), resulting in sesame oil very rich in lignans. Seco appears in flaxseed as a diglucoside, being part of the complex phenolic polymers that are insoluble in oil matrices, and therefore flaxseed oil may contain negligible amounts of lignans compared to sesame oil.
Plant lignans undergo extensive metabolism in the intestine that depends on the individual characteristics of the intestinal microflora. Although some pathways of lignan metabolism in the gut have been elucidated (2,3), the extent and rate of in vivo conversion have not yet been defined and very little is know of the absorption process. Individual characteristics of the intestinal microflora can explain the high intersubject variation in plasma plant lignans. We found high plasma concentrations of Pin, in agreement with its predominance in sesame seeds. It seems that no Pin precursor exists in sesame seeds because the intersubject variability is much lower compared to that of the other lignans (Table 2). For other lignans it is not possible to deduce whether their plasma concentrations are attributable to their presence in sesame seeds or to metabolic conversions in the gut. Plasma Seco concentrations vary greatly because its amount in plasma depends on the rate of precursor conversion by individual intestinal microflora. It was not possible to calculate the elimination rate and AUC for Seco due to the appearance of a second absorption phase in most of the subjects. No conversions of Seco to Anse or Lar to IsoL during the plasma sample pretreatment were reported (36) and the quantified levels should reflect the actual plasma concentrations. However, we decided to express the values of Seco and Lar as the sum of the correspondent forms in order to simplify the data treatment. Anse and IsoL could have been formed by the action of intestinal microflora and subsequently absorbed. This should be taken into consideration when studying samples containing larger concentrations of Seco and Lar. Considerable amounts of plant lignans exist in plasma after sesame seed intake, suggesting a possible physiological role of these compounds in vivo.
This study aimed to determine how a challenge with sesame seeds modifies the levels of lignans in humans consuming their normal diets. The time points selected in this trial were appropriate for the rapidly absorbed plant lignans but not sufficient for the mammalian lignans. During the interval from 10 to 24 h, mammalian lignan concentrations could have reached their maximum, and our 24-h data could represent the plateau or even the elimination phase. Further studies are required to cover this interval, as well as to show continued elimination. Nevertheless, it can be seen that mammalian lignans did not appear in plasma before 8 h after the intake of sesame seeds. When mean levels of Enl and End are compared, the high interindividual variation is evident (Table 4). However, this variation is much smaller considering total mammalian lignan concentration (1073–1547 nmol/L; median 1223 nmol/L). The production of enterolactone in humans intrinsically depends on intestinal microflora characteristics, but the extent of conversion at 24 h seems to be the same when both mammalian lignans are considered.
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Plant synthesis of sesame seed lignans was recently studied (50), and Pin was identified as a precursor of Ses. Pin could be an intermediate of Ses breakdown in humans, but the maximum plasma concentrations of the plant lignans, including Pin, in the present study do not support this idea. Ses seems to be metabolized by an alternative pathway that does not involve the plant lignans studied in this trial. In vitro metabolites M1, M2, and M3 found together with End and Enl support the idea of a different pathway; the structures of the metabolites M2 and M3 are identical to the metabolites identified in vitro by Nakai and co-workers (28), who postulated that Ses is absorbed in the intestine and selectively captured in the liver due to its hydrophobicity and metabolized to M2 and M3. In our study the same metabolites were found after fermentation with human microflora, suggesting that oxidative demethylenation to afford catechol groups is not an exclusive process of the dependent mixed function oxidases. Additionally, Ses bioavailability was limited, with only moderate concentrations found in plasma after sesame seed intake. These findings suggest that Ses is not completely absorbed as such but is metabolized by the intestinal microflora to a series of demethylenated intermediates (M2 and M3) that might be absorbed as such or transformed in situ to mammalian lignans, which will be subsequently absorbed. The Ses fraction absorbed might undergo metabolism in the liver, explaining previous results (28). These findings are in contrast with previously reported studies in which Ses was present in high amounts in plasma of rats fed pure compounds (51) and recently in serums of mice and rats (52). In the report of Hirose and co-workers (53), Ses was not found in the serum of male rats after the intake of sesamin-supplemented diets and a very limited absorption of Ses to the lymph and fecal excretion of 15–34% has been reported, supporting our idea of the transformation of Ses by the intestinal microflora. A selective absorption of sesamin through the portal vein and metabolism in the liver to compounds M2 and M3 (28) that could go under enterohepatic circulation and be deconjugated, demethylenated, and transformed to mammalian lignans is also possible, and human metabolism of Ses might be a combination of the 2 mechanisms described. Further experiments should be carried out in order to completely understand the pathway. However, Enl, independent of the intermediates, is the final product of this process and this should be taken into account when physiological actions of Ses are considered.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: Anse, anhydrosecoisolariciresinol; End, enterodiol; Enl, enterolactone; Hmr, 7'-hydroxymatairesinol; IsoL, isolariciresinol; Lar, lariciresinol; Mat, matairesinol; Pin, pinoresinol; QSM, quick silylation mixture; Seco, secoisolariciresinol; Ses, sesamin; Syr, syringaresinol.
Manuscript received 21 October 2004. Initial review completed 13 December 2004. Revision accepted 25 January 2005.
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LITERATURE CITED |
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TOPABSTRACTSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Borriello, S. P., Setchell, K.D.R., Axelson, M. & Lawson, A. M. (1985) Production and metabolism of lignans by the human faecal flora. J. Appl. Bacteriol. 58:37-43.[Medline]
2. Heinonen, S., Nurmi, T., Liukkonen, K., Poutanen, K., Wähälä, K., Deyama, T., Nishibe, S. & Adlercreutz, H. (2001) In vitro metabolism of plant lignans: New precursors of mammalian lignans enterolactone and enterodiol. J. Agric. Food Chem. 49:3178-3186.[Medline]
3. Saarinen, N. M., Wärri, A., Mäkelä, S. I., Eckerman, C., Reunanen, M., Ahotupa, M., Salmi, S. M., Franke, A. A., Kangas, L. & Santti, R. (2000) Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies). Nutr. Cancer 36:207-216.[Medline]
4. Adlercreutz, H., Fotsis, T., Heikkinen, R., Dwyer, J. T., Woods, M., Goldin, B. R. & Gorbach, S. L. (1982) Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian women and in women with breast cancer. Lancet 2:1295-1299.[Medline]
5. Ingram, D., Sanders, K., Kolybaba, M. & Lopez, D. (1997) Case-control study of phyto-oestrogens and breast cancer. Lancet 350:990-994.[Medline]
6. Vanharanta, M., Voutilainen, S., Lakka, T. A., van der Lee, M., Adlercreutz, H. & Salonen, J. T. (1999) Risk of acute coronary events according to serum concentrations of enterolactone: a prospective population-based case-control study. Lancet 354:2112-2115.[Medline]
7. Pietinen, P., Stumpf, K., Mannisto, S., Kataja, V., Uusitupa, M. & Adlercreutz, H. (2001) Serum enterolactone and risk of breast cancer: a case-control study in Eastern Finland. Cancer Epidemiol. Biomark. Prev. 10:339-344.
8. Vanharanta, M., Voutilainen, S., Rissanen, T. H., Adlercreutz, H. & Salonen, J. T. (2003) Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study. Arch. Int. Med. 163:1099-1104.
9. Parmar, V. S., Jain, S. C., Bisht, K. S., Jain, R., Taneja, P., Jha, A., Tyagi, O. D., Prasad, A. K., Wengel, J., Olsen, C. E. & Boll, P. M. (1997) Phytochemistry of the genus Piper. Phytochemistry 46:597-673.
10. Chen, C., Chen, H., Shiao, M., Lin, Y., Kuo, Y. & Ou, J. (1999) Inhibition of low density lipoprotein oxidation by tetrahydrofurofuran lignans from Forsythia suspensa and Magnolia coco. Planta Med. 65:709-711.[Medline]
11. Ju, Y., Still, C. C., Sacalis, J. N., Li, J. & Ho, C.-T. (2001) Cytotoxic coumarins and lignans from extracts of the northern prickly ash (Zanthoxylum americanum). Phytother. Res. 15:441-443.[Medline]
12. Meselhy, M. R. (2003) Constituents from Moghat, the roots of Glossostemon bruguieri (desf.). Molecules 8:614-621.
13. Wang, C.-C., Chen, S. & Wu, T.-S. (2003) The facile reversed-phase HPLC resolution of tetrahydrofurofuran nucleus lignans in traditional Chinese medicine: Quantitative analysis of asarinin and sesamin in Asari radix. J. Chin. Chem. Soc. 50:261-266.
14. Jiao, Y., Davin, L. B. & Lewis, N. G. (1998) Furanofuran lignan metabolism as a function of seed maturation in Sesamum indicum: Methylenedioxy bridge formation: In honour of Professor G. H. Neil Towers’ 75th birthday. Phytochemistry 49:387-394.
15. Shyu, Y.-S. & Hwang, L. S. (2002) Antioxidative activity of the crude extract of lignan glycosides from unroasted Burma black sesame meal. Food Res. Int. 35:357-365.
16. Shimizu, S., Akimoto, K., Shinmen, Y., Sugano, M. & Yamada, H. (1991) Sesamin is a potent and specific inhibitor of D5 desaturase in polyunsaturated fatty acid biosynthesis. Lipids 26:512-516.[Medline]
17. Chatrattanakunchai, S., Fraser, T. & Stobart, K. (2000) Sesamin inhibits lysophosphatidylcholine acyltransferase in Mortierella alpina. Biochem. Soc. Trans. 28:718-721.[Medline]
18. Utsunomiya, T., Chavali, S. R., Zhong, W. W. & Forse, R. A. (2000) Effects of sesamin-supplemented dietary fat emulsions on the ex vivo production of lipopolysaccharide-induced prostanoids and tumor necrosis factor {alpha} in rats. Am. J. Clin. Nutr. 72:804-808.
19. Hirata, F., Fujita, K., Ishikura, Y., Hosoda, K., Ishikawa, T. & Nakamura, H. (1996) Hypocholesterolemic effect of sesame lignan in humans. Atherosclerosis 122:135-136.[Medline]
20. Kita, S., Matsumura, Y., Morimoto, S., Akimoto, K., Furuya, M., Oka, N. & Tanaka, T. (1995) Antihypertensive effect of sesamin. II. Protection against two-kidney, one-clip renal hypertension and cardiovascular hypertrophy. Biol. Pharm. Bull. 18:1283-1285.[Medline]
21. Nakano, D., Itoh, C., Takaoka, M., Kiso, Y., Tanaka, T. & Matsumura, Y. (2002) Antihypertensive effect of sesamin. IV. Inhibition of vascular superoxide production by sesamin. Biol. Pharm. Bull. 25:1247-1249.[Medline]
22. Matsumura, Y., Kita, S., Morimoto, S., Akimoto, K., Furuya, M., Oka, N. & Tanaka, T. (1995) Antihypertensive eddect of sesamin. I. Protection against deoxycorticosterone acetate salt-induced hypertension and cardiovascular hypertrophy. Biol. Pharm. Bull. 18:1016-1019.[Medline]
23. Matsumura, Y., Kita, S., Tanida, Y., Taguchi, Y., Morimoto, S., Akimoto, K. & Tanaka, T. (1998) Antihypertensive effect of sesamin. III. Protection against development and maintenance of hypertension in stroke-prone spontaneously hypertensive rats. Biol. Pharm. Bull. 21:469-473.[Medline]
24. Akimoto, K., Kitagawa, Y., Akamatsu, T., Hirose, N., Sugano, M., Shimizu, S. & Yamada, H. (1993) Protective effects of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents. Ann. Nutr. Metab. 37:218-224.[Medline]
25. Yamashita, K., Kagaya, M., Higuti, N. & Kiso, Y. (2000) Sesamin and -tocopherol synergistically suppress lipid-peroxide in rats fed with a high docosahexaenoic acid diet. Biofactors 11:11-13.[Medline]
26. Kamal-Eldin, A., Pettersson, D. & Appelqvist, L. A. (1995) Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids 30:499-505.[Medline]
27. Hirose, N., Doi, F., Ueki, T., Akazawa, K., Chijiiwa, K., Sugano, M., Akimoto, K., Shimizu, S. & Yamada, H. (1992) Suppressive effect of sesamin against 7,12-dimethylbenz[a]-anthracene induced rat mammary carcinogenesis. Anticancer Res. 12:1259-1265.[Medline]
28. Nakai, M., Harada, M., Nakahara, K., Akimoto, K., Shibata, H., Miki, W. & Kiso, Y. (2003) Novel antioxidative metabolites in rat liver with ingested sesamin. J. Agric. Food Chem. 51:1666-1670.[Medline]
29. Mazur, W. M., Duke, J. A., Wähälä, K., Rasku, S. & Adlercreutz, H. (1998) Isoflavonoids and lignans in legumes: Nutritional and health aspects in humans. Nutr. Biochem. 9:193-200.
30. Mazur, W. M. & Adlercreutz, H. (1998) Naturally occurring oestrogens in food. Pure Appl. Chem. 70:1759-1776.
31. Thompson, L. U., Robb, P., Serraino, M. & Cheung, F. (1991) Mammalian lignan production from various foods. Nutr. Cancer 16:43-52.[Medline]
32. Aura, A.-M., O’Leary, K. A., Williamson, G., Ojala, M., Bailley, M., Puuponen-Pimïa, R., Nuutila, A. M., Oksman-Caldentey, K.-M. & Poutanen, K. (2002) Quercetin derivatives are deconjugated and converted to hydroxyphenilacetic acids but not methylated by human fecal flora in vitro. J. Agric. Food Chem. 50:1725-1730.[Medline]
33. Mazur, W., Fotsis, T., Wähälä, K., Ojala, S. & Salakka, A. (1996) Isotope dilution gas chromatographic—Mass spectrometric method for the determination of isoflavonoids, coumesterol, and lignans in food samples. Anal. Biochem. 233:169-180.[Medline]
34. Begum, A. N., Nicolle, C., Mila, I., Lapierre, C., Nagano, K., Fukushima, K., Heinonen, S.-M., Adlercreutz, H., Remesy, C. & Scalbert, A. (2004) Dietary lignins are precursors of mammalian lignans in rats. J. Nutr. 134:120-127.
35. Peñalvo, J. L., Heinonen, S.-M., Nurmi, T., Deyama, T., Nishibe, S. & Adlercreutz, H. (2004) Plant lignans in soy-based health supplements. J. Agric. Food Chem. 52:4133-4138.[Medline]
36. Peñalvo, J. L., Nurmi, T., Haajanen, K., Al-Maharik, N., Botting, N. P. & H, A. (2004) Determination of lignans in human plasma by liquid chromatography with coulometric electrode array detection. Anal. Biochem. 332:384-393.[Medline]
37. Namiki, M. (1995) The chemistry and physiological functions of sesame. Food Rev. Int. 11:282-329.
38. Fukuda, Y., Isobe, M., Nagata, M., Osawa, T. & Namiki, M. (1986) Acidic transformation of sesamolin, the sesame-oil constituent, into an antioxidant bisepoxylignan, sesaminol. Heterocycles 24:923-926.
39. Liggins, J., Grimwood, R. & Bingham, S. A. (2000) Extraction and quantification of lignan phytoestrogens in food and human samples. Anal. Biochem. 287:102-109.[Medline]
40. Milder, I. E., Arts, I. C., Venema, D. P., Lasaroms, J. J., Wahala, K. & Hollman, P. C. (2004) Optimization of a liquid chromatography-tandem mass spectrometry method for quantification of the plant lignans secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol in foods. J. Agric. Food Chem. 52:4643-4651.[Medline]
41. Saarinen, N. M., Huovinen, R., Warri, A., Makela, S. I., Valentin-Blasini, L., Sjoholm, R., Ammala, J., Lehtila, R., Eckerman, C., Collan, Y. U. & Santti, R. S. (2002) Enterolactone inhibits the growth of 7,12-dimethylbenz(a) anthracene-induced mammary carcinomas in the rat. Mol. Cancer Ther. 1:869-876.
42. Katsuda, S.-I., Yoshida, M., Saarinen, N., Smeds, A., Nakae, D., Santti, R. & Maekawa, A. (2004) Chemopreventive effects of hydroxymatairesinol on uterine carcinogenesis in donryu rats. Exp. Biol. Med. 229:417-424.
43. Eliasson, C., Kamal-Eldin, A., Andersson, R. & Aman, P. (2003) High-performance liquid chromatographic analysis of secoisolariciresinol diglucoside and hydroxycinnamic acid glucosides in flaxseed by alkaline extraction. J. Chromatogr. A 1012:151-159.[Medline]
44. Mohamed, H.M.A. & Awatif, I. I. (1998) The use of sesame oil unsaponifiable matter as a natural antioxidant. Food Chem. 62:269-276.
45. Atkinson, D. A., Hill, H. H. & Shultz, T. D. (1993) Quantification of mammalian lignans in biological fluids using gas chromatography with ion mobility detection. J. Chromatogr. B 617:173-179.
46. Morton, M. S., Wilcox, G., Wahlqvist, M. L. & Griffiths, K. (1994) Determination of lignans and isoflavonoids in human female plasma following dietary supplementation. J. Endocrinol. 142:251-259.[Abstract]
47. Adlercreutz, H., Fotsis, T., Watanabe, S., Lampe, J., Wähälä, K., Mäkelä, T. & Hase, T. (1994) Determination of lignans and isoflavonoids in plasma by isotope dilution gas chromatography-mass spectrometry. Cancer Detect. Prev. 18:259-271.[Medline]
48. Adlercreutz, H., Fotsis, T., Lampe, J., Wahala, K., Makela, T., Brunow, G. & Hase, T. (1993) Quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography-mass spectrometry. Scand. J. Clin. Lab. Invest. 215(suppl.):5-18.
49. Nesbitt, P. D., Lam, Y. & Thompson, L. U. (1999) Human metabolism of mammalian lignan precursors in raw and processed flaxseed. Am. J. Clin. Nutr. 69:549-555.
50. Kato, M. J., Chu, A., Davin, L. B. & Lewis, N. G. (1998) Biosynthesis of antioxidant lignans in Sesamum indicum seeds. Phytochemistry 47:583-591.
51. Umeda-Sawada, R., Ogawa, M. & Igarashi, O. (1999) The metabolism and distribution of sesame lignans (sesamin and episesamin) in rats. Lipids 34:633-637.[Medline]
52. Kushiro, M., Takahashi, K. & Ide, T. (2004) Species differences in the physiological activity of dietary lignan (sesamin and episesamin) in affecting hepatic fatty acid metabolism. Br. J. Nutr. 91:377-386.[Medline]
53. Hirose, N., Inoue, T., Nishihara, K., Sugano, M., Akimoto, K., Shimizu, S. & Yamada, H. (1991) Inhibition of cholesterol absorption and synthesis in rats by sesamin. J. Lipid. Res. 32:629-638.[Abstract]
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 A.-M. Linko-Parvinen, R. Landberg, M. J. Tikkanen, H. Adlercreutz, and J. L. Penalvo Alkylresorcinols from Whole-Grain Wheat and Rye Are Transported in Human Plasma Lipoproteins J. Nutr., May 1, 2007; 137(5): 1137 - 1142. [Abstract] [Full Text] [PDF]
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I. E. J. Milder, A. Kuijsten, I. C. W. Arts, E. J. M. Feskens, E. Kampman, P. C. H. Hollman, and P. Van 't Veer Relation between Plasma Enterodiol and Enterolactone and Dietary Intake of Lignans in a Dutch Endoscopy-Based Population J. Nutr., May 1, 2007; 137(5): 1266 - 1271. [Abstract] [Full Text] [PDF]
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A. A. Moazzami, R. E. Andersson, and A. Kamal-Eldin Quantitative NMR Analysis of a Sesamin Catechol Metabolite in Human Urine J. Nutr., April 1, 2007; 137(4): 940 - 944. [Abstract] [Full Text] [PDF]
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J. Hallund, I. Tetens, S. Bugel, T. Tholstrup, M. Ferrari, T. Teerlink, A. Kjaer, and N. Wiinberg Daily Consumption for Six Weeks of a Lignan Complex Isolated from Flaxseed Does Not Affect Endothelial Function in Healthy Postmenopausal Women J. Nutr., September 1, 2006; 136(9): 2314 - 2318. [Abstract] [Full Text] [PDF]
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 I. E. Milder, E. J. Feskens, I. C. Arts, H B. Bueno-de-Mesquita, P. C. Hollman, and D. Kromhout Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the Zutphen Elderly Study. Am. J. Clinical Nutrition, August 1, 2006; 84(2): 400 - 405. [Abstract] [Full Text] [PDF]
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W.-H. Wu, Y.-P. Kang, N.-H. Wang, H.-J. Jou, and T.-A. Wang Sesame Ingestion Affects Sex Hormones, Antioxidant Status, and Blood Lipids in Postmenopausal Women J. Nutr., May 1, 2006; 136(5): 1270 - 1275. [Abstract] [Full Text] [PDF]
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Z. Liu, N. M. Saarinen, and L. U. Thompson Sesamin Is One of the Major Precursors of Mammalian Lignans in Sesame Seed (Sesamum indicum) as Observed In Vitro and in Rats J. Nutr., April 1, 2006; 136(4): 906 - 912. [Abstract] [Full Text] [PDF]
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