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PubMed2005

Synthesis of multiply 13C-labeled furofuran lignans using 13C-labeled cinnamyl alcohols as building blocks.

Plant lignans are currently being widely studied for their potential benefits for human health as their consumption has been correlated with lower risks for developing chronic diseases, such as breast cancer and coronary heart disease. However, studies of some classes of lignans, in particular the furofurans, are hampered by the lack of suitable standards to allow accurate analysis. Herein, we report the syntheses of two racemic (13)C-labeled furofuran lignans [7,8,9-(13)C(3)]medioresinol and [7,8,9-(13)C(3)]sesamin as internal standards for LC-MS analysis. The labeled furofuran lignans were constructed from triply labeled cinnamyl alcohols, using a radical cyclization method.

Carbon Isotopes↗

PubMed2005

Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR).

The pregnane X receptor (PXR) mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification. The receptor is expressed in liver and intestinal tissues and is activated by a wide range of compounds. The ability of a diverse range of dietary compounds to activate PXR-mediated transcription was assayed in HuH7 cells following transient transfection with human PXR (hPXR). The compounds investigated included phytochemicals such as lignans and phytoestrogens, organochlorine dietary contaminants such as polychlorinated biphenyls (PCBs) and triclosan and selected steroid, drug and herbal compounds. The hPXR activation at the top concentrations tested (10 microM) relative to the positive control 10 microM rifampicin ranged from 1.3% (trans-resveratrol) to 152% (ICI 182780). Hydroxylated compounds were marginally more potent than the parent compounds (tamoxifen activation was 74.6% whereas 4 hydroxytamoxifen activation was 84.2%) or significantly greater (vitamin D3 activation was 1.6%, while hydroxylated vitamin D3 activation was 55.6%). Enterolactone, the metabolite of common dietary lignans, was a medium activator of PXR (35.6%), compared to the lower activation of a parent lignan, secoisolariciresinol (20%). Two non-hydroxylated PCB congeners (PCB 118 and 153), which present a larger fraction of the PCB contamination of fatty foods, activated hPXR by 26.6% and 17%, respectively. The pesticide trans-nonachlor activation was 53.8%, while the widely used bacteriocide triclosan was a medium activator of hPXR at 46.2%. The responsiveness of PXR to activation by lignan metabolites suggests that dietary intake of these compounds may affect the metabolism of drugs that are CYP3A substrates. Additionally, the evidence that organochlorine chemicals, particularly the ubiquitous triclosan, activate hPXR suggests that these environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid hormone metabolism with potential adverse health effects in exposed individuals.

Alkaline Phosphatase↗

PubMed1982

Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer.

Dietary studies and assays of urinary lignans in postmenopausal women showed that lignan excretion is significantly lower in urine of women with breast cancer than in normal omnivorous and vegetarian women and confirmed that there is a significant correlation between fibre intake and lignan excretion. It is suggested that the precursors of the human lignans enterolactone and enterodiol formed by the intestinal microflora are to be found in fibre-rich foods such as grains, nuts, and legumes. Excretion of equol, which has antioestrogenic properties, was similar in all groups studied and did not correlate with fibre intake, but occasional high values were found in some subjects.

4-Butyrolactone↗

PubMed2007

Comparative analysis of sesame lignans (sesamin and sesamolin) in affecting hepatic fatty acid metabolism in rats.

Effects of sesamin and sesamolin (sesame lignans) on hepatic fatty acid metabolism were compared in rats. Rats were fed either a lignan-free diet, a diet containing 0.6 or 2 g/kg lignan (sesamin or sesamolin), or a diet containing both sesamin (1.4 g/kg) and sesamolin (0.6 g/kg) for 10 d. Sesamin and sesamolin dose-dependently increased the activity and mRNA abundance of various enzymes involved in hepatic fatty acid oxidation. The increase was much greater with sesamolin than with sesamin. These lignans increased parameters of hepatic fatty acid oxidation in an additive manner when added simultaneously to an experimental diet. In contrast, they decreased the activity and mRNA abundance of hepatic lipogenic enzymes despite dose-dependent effects not being necessarily obvious. Sesamin and sesamolin were equally effective in lowering parameters of lipogenesis. Sesamolin accumulated in serum at 33- and 46-fold the level of sesamin at dietary concentrations of 0.6 and 2 g/kg, respectively. The amount of sesamolin accumulated in liver was 10- and 7-fold that of sesamin at the respective dietary levels. Sesamolin rather than sesamin can account for the potent physiological effect of sesame seeds in increasing hepatic fatty acid oxidation observed previously. Differences in bioavailability may contribute to the divergent effects of sesamin and sesamolin on hepatic fatty acid oxidation. Sesamin compared to sesamolin was more effective in reducing serum and liver lipid levels despite sesamolin more strongly increasing hepatic fatty acid oxidation.

Animals↗

PubMed2000

Oxidative metabolites of the mammalian lignans enterodiol and enterolactone in rat bile and urine.

Recent studies have shown that the mammalian lignans enterodiol (END) and enterolactone (ENL) are biotransformed in vitro by hepatic microsomes from rats and humans to various metabolites carrying one additional hydroxy group either at the aromatic or at the aliphatic moiety. To clarify whether these metabolites are also formed in vivo, each lignan was administered intraduodenally at a dose of 10 mg/kg of bw to bile duct-catheterized female Wistar rats and the 6 h bile analyzed by HPLC and GC-MS. With END-dosed rats, three products of aromatic and two of aliphatic monohydroxylation were found, whereas six aromatic and five aliphatic monohydroxylated biliary metabolites were detected after administration of ENL. The metabolites hydroxylated at the aromatic rings were unequivocally identified by comparison with synthetic reference compounds. The structures of the in vivo metabolites arising from aliphatic hydroxylation could not be completely elucidated; they were identical with some of the formerly reported microsomal products according to GC retention times and mass spectra. Significant amounts of most of the metabolites of the mammalian lignans identified in bile were also found in the urine of female rats after oral administration of 10 mg/kg of bw END or ENL and in the urine of female and male Wistar rats after they had been fed a diet containing 5% flaxseed. Thus, the mammalian lignans END and ENL give rise to several hydroxylated metabolites in vivo, which may contribute to the biological effects of these important food constituents.

4-Butyrolactone↗

PubMed2004

Plant lignans in soy-based health supplements.

The presence of plant lignans in 14 different soy-based health supplements is reported here for the first time together with the analysis of the isoflavone content, for which these products are commercialized. Six plant lignans, i.e., secoisolariciresinol, matairesinol, syringaresinol, lariciresinol, isolariciresinol, and pinoresinol, have been identified and quantified by gas chromatography-mass spectrometry, and a positive correlation has been found between the levels of plant lignans and the levels of isoflavones in the different products. Additional quantification of plant lignans and isoflavones in soybeans has been carried out, and results are provided to allow the comparison of the average levels in soybeans and soy-based supplements.

Dietary Supplements↗

PubMed2005

Effect of benzylic oxygen on the antioxidant activity of phenolic lignans.

It has been clarified in the present investigation that a high degree of oxidation at the benzylic position of phenolic lignans bearing a 4-hydroxy-3-methoxybenzyl group reduces their antioxidant activity and that the antioxidant activity of the bis(4-hydroxy-3-methoxybenzyl)tetrahydrofuran lignan 2 is higher than that of the corresponding gamma-butyrolactone lignan 1. This was demonstrated by comparing the antioxidant activities of compounds 1 and 2 with those of the (benzyl)(hydroxybenzyl)tetrahydrofurans 3 and 4, the bis(hydroxybenzyl)tetrahydrofurans 7 and 8, the (benzoyl)(benzyl)tetrahydrofuran 6, and the dibenzoyltetrahydrofuran 9. The activity level of compound 2 was approximately the same potency as that of the tetrahydronaphthalene-tetrahydrofuran 5. These compounds possess either a 4-hydroxy-3-methoxybenzyl group or a 4-hydroxy-3-methoxybenzoyl group as the benzyl or benzoyl group. An examination of radical scavenging activity showed differences of activity between diastereomers. To make this comparison possible, compounds 1-9 were synthesized using new synthetic routes for several of these lignans. In this investigation, stereoisomers of the (benzyl)(hydroxybenzyl)tetrahydrofurans 3 and 4 and liovils 7 and 8 were synthesized for the first time.

Antioxidants↗

PubMed2004

Sesame lignans enhance antioxidant activity of vitamin E in lipid peroxidation systems.

The antioxidant properties of sesame lignans (sesamol, sesamin and sesamolin) were evaluated in comparison to tocols (alpha- and gamma-tocopherols and alpha-tocotrienol) and butylated hydroxytoluene (BHT) using the following in vitro lipid peroxidation systems: (i) rat liver microsomes and cumene hydroperoxide (CumOOH)/Fe2+-ADP-NADPH (enzymatic) or (ii) rat liver mitochondria and Fe2+-ascorbate (nonenzymatic) systems. Sesamol containing a free phenolic group inhibited lipid peroxidation in both the systems whereas sesamin and sesamolin having methylenedioxy groups were effective only in the microsomal system. Since detoxifying enzymes are localized in microsomes, the inhibitory effects of sesamin and sesamolin observed in the microsomal system may be attributed to their metabolites. However, the inhibitory effects of lignans were lower than tocols and BHT. Combination of individual lignans and tocopherols (alpha, gamma) or alpha-tocotrienol showed higher inhibitory effects than the sum of individual inhibitions in CumOOH and Fe2+-ascorbate systems suggesting synergistic interactions. The time course of CumOOH-mediated lipid peroxidation showed a lag period and a decreased rate of thiobarbituric acid reactive product formation in the presence of individual lignans in combination with alpha-tocopherol suggesting recycling of alpha-tocopherol.

Animals↗

PubMed2000

Tetrahydrofuran lignans from Illicium floridanum and their activity in a luminol enhanced chemiluminescence assay.

Two lignans of the tetrahydrofuran type, di-O-methyltetrahydrofuroguaiacin B (1) and (+)-veraguensin (2) were isolated from fruits and leaves of Illicium floridanum Ellis (Illiciaceae). These compounds are the first genuine lignans isolated from the genus Illicium. We investigated their radical scavenging potency towards 1,1-diphenyl-2-picrylhydrazyl radical reagent and their influence on luminol enhanced chemiluminescence (CHL) induced by different stimuli in human polymorphonuclear neutrophils (PMN). Both compounds were inactive in the TLC assay for chemical radical scavenge. In the PMN assay, the symmetric lignan 1 at concentrations below 1.0 microM displayed a strong inhibition of CHL induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). At concentrations above 5 microM, 1 led to a pronounced increase of fMLP induced CHL. When CHL was stimulated with opsonized zymosan, both compounds were completely inactive. Thus, 1 must interfere selectively with a step in the signal cascade evoked by fMLP. In addition to their known PAF-receptor antagonism tetrahydrofuran lignans may thus also interfere with inflammatory responses by inhibition of free radical formation.

Cell Line↗

PubMed2006

The cytotoxic effect and the multidrug resistance reversing action of lignans from Phyllanthus amarus.

Multidrug resistance (MDR) constitutes the major obstacle to the successful treatment of cancer. In several cancer cells, MDR is thought to be mediated by the super-expression of P-glycoprotein (Pgp). Pgp extrudes drugs from the cells, therefore reducing their cytotoxicity, and its activity inhibition may reverse the MDR phenotype. The present study evaluated the possible cytotoxic effect and MDR reversing properties of the extract and compounds isolated from Phyllanthus amarus. To this purpose, two human leukaemia cell lines were employed: K-562 and its vincristine-resistant counterpart Lucena-1, a Pgp-overexpressing subline. We report here that Lucena-1 was significantly more resistant to the cytotoxicity of P. amarus derivatives: the hexane extract (HE, 100 microg/mL), the lignans-rich fraction (LRF, 100 microg/mL) and the lignans nirtetralin (NIRT, 43.2 microg/mL), niranthin (NIRA, 43 microg/mL) or phyllanthin (PHYLLA, 43 microg/mL) exerted cytotoxic effects on K-562 cells with 40.3, 66.0, 62.0, 61.0 or 24.1% of cell death, respectively. The cellular toxicity observed on Lucena-1 was 16.3, 40.4, 29.4, 30.2, or 24.8%, respectively. However, cell treatment with the lignan phyltetralin (PHYLT) up to 41.6 microg/mL had no cytotoxic action on either of the cell lines. P. amarus derivatives were also found to be effective in inhibiting Pgp activity as assessed by rhodamine accumulation in Lucena-1 cells, as were the classical Pgp inhibitors, cyclosporine A (160 nM), PSC-833 (2 microM) and verapamil (5 microM). The lignan NIRT produced the most potent inhibition (EC (50) = 29.4 microg/mL) followed by NIRA (44.3 microg/mL), LRF (49.1 microg/mL), PHYLT (99.4 microg/mL), PHYLLA and HE (> 100 microg/mL). Lucena-1 cells were more resistant to daunorubicin-induced cell death (LC (50) = 50 microM) than K562 cells (LC (50) = 4.95 microM). Of note, the P. amarus derivatives significantly potentiated 5 microM daunorubicin-induced cell death in Lucena-1 cells (P < 0.01) but not in K562 cells. After treatment only with P. amarus derivatives (100 microg/mL HE, 30 microg/mL LRF, 12.9 microg/mL NIRA, 43.2 microg/mL NIRT, 43 microg/mL PHYLLA or 41.6 microg/mL PHYLT), the Lucena-1 cellular viability was 83.7, 85.3, 101, 69.7, 75.6 or 88.7%, respectively, whereas the in the presence of daunorubincin, which was not cytotoxic PER SE, the cell viability decreased to 42.9, 42.2, 64.2, 35.4, 30.4 or 52.6%, respectively. Together, these results suggest a potential action of P. amarus derivatives as MDR reversing agents, mainly due to their ability to synergize with the action of conventional chemotherapeutics.

Antineoplastic Agents, Phytogenic↗

PubMed1991

Suppression of mitogen-induced proliferation of human peripheral blood lymphocytes by plant lignans.

The effects of seven lignans and two neolignans derived from plants and herbs on the concanavalin A-induced proliferation of human peripheral blood lymphocytes in vitro were studied. All compounds showed inhibitory activity with an IC50, ranging from 0.02 to 4.30 micrograms/ml (1.6 x 10(-8) to 1.6 x 10(-5) M). Machilin A (2,3-dimethyl-1,4-dipiperonylbutane), a Lauraceae lignan, was the strongest inhibitor and was quite effective as the synthetic immunosuppressive glucocorticoid prednisolone. The viability of lymphocytes before and after treatment, as assessed by a dye exclusion test, indicated no change, and thus the lignans are not lymphocytotoxic but may inhibit DNA synthesis. The results suggest the value of further assessment of plant lignans as immunosuppressive agents.

Cell Division↗

PubMed2003

The effect of flax seed cultivars with differing content of alpha-linolenic acid and lignans on responses to mental stress.

BACKGROUND: Phytoestrogens offer a possible alternative to hormone replacement therapy. Flax seed contains large quantities of a phytoestrogen precursor, secoisolariciresinol diglucoside (SDG), as well as large quantities of alpha-linolenic acid; these factors may be protective against vascular disease. We have previously shown that the rise in blood pressure during mental stress is a strong predictor of atherosclerosis progression. METHODS: 35 postmenopausal women with vascular disease, 62 +/- 8 years of age, were treated in a random-sequence double-blind Latin square crossover study comparing three strains of flax seed: Flanders (low in lignan and high in alpha-linolenic acid), Linola 989 (high in lignan and low in alpha-linolenic acid) and AC Linora (intermediate in both lignan and alpha-linolenic acid). RESULTS: Compared to the pre-treatment baseline diet, all three strains of flax significantly reduced blood pressure during mental stress induced by a frustrating cognitive task (Stroop color-word interference task) (p = 0.004). Linola 989, the strain highest in lignan and lowest in alpha-linolenic acid, was associated with the least increase in peripheral resistance during stress, the greatest reduction in plasma cortisol during stress and the smallest increase in plasma fibrinogen during mental stress. CONCLUSION: Flax phytoestrogens ameliorate certain responses to stress and thus may afford protection against atherosclerosis; this hypothesis should be tested in clinical trials.

Aged↗

PubMed1996

The influence of flaxseed and lignans on colon carcinogenesis and beta-glucuronidase activity.

Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk. This study determined whether over the long term flaxseed still exerts a colon cancer protective effect, whether its effect may, in part, be due to its high content of SD and whether any change in beta-glucuronidase activity plays a role in the protective effect. Six groups of male Sprague-Dawley rats were fed for 100 days either a basal high fat (20%) diet (BD), BD supplemented with 2.5 or 5% flaxseed or 2.5 or 5% defatted flaxseed (equivalent to the respective flaxseed diets) or BD with a daily gavage of 1.5 mg SD. All rats were injected with a single dose of azoxymethane (15 mg/kg body wt) 1 week prior to commencing the dietary treatments. Urinary lignan excretion, which is an indicator of mammalian lignan production, was significantly increased in the flaxseed and defatted flaxseed groups. The total activity of cecal beta-glucuronidase was significantly increased in a dose-dependent manner by the flaxseed and defatted flaxseed diet groups. Compared with the control the number of aberrant crypts per focus was significantly reduced in the distal colon of the treated rats. Four microadenomas and two polyps were observed in the control group, but not in the treated groups. The total activity of beta-glucuronidase was positively correlated with total urinary lignan excretion and negatively with the total number of aberrant crypts and the total number of aberrant crypt foci in the distal colon. There were no significant differences between the flaxseed and the corresponding defatted flaxseed groups. It is concluded that flaxseed has a colon cancer protective effect, that it is due, in part, to SD and that the protective effect of flaxseed is associated with increased beta-glucuronidase activity.

Animals↗

PubMed1998

Flaxseed and its lignan precursor, secoisolariciresinol diglycoside, affect pregnancy outcome and reproductive development in rats.

Flaxseed is the richest source of the mammalian lignan precursor secoisolariciresinol diglycoside (SDG). Because lignans have estrogen agonist or antagonist properties, the objective of this study was to determine whether feeding flaxseed to rats during a hormone-sensitive period has reproductive effects. Rat dams were fed a basal diet or the basal diet supplemented with 10% flaxseed, 5% flaxseed or SDG at the level in 5% flaxseed during pregnancy and lactation. At weaning, the offspring were fed the basal diet. Flaxseed had no effect on pregnancy outcome except that the 10% flaxseed diet lowered birth weight (P < 0.05), compared with other treatments, and produced hormonal effects. The female offspring had shortened anogenital distance, greater uterine and ovarian relative weights, earlier age and lighter body weight at puberty, lengthened estrous cycle and persistent estrus (P < 0.05), whereas the males had reduced postnatal weight gain and, at postnatal d 132, greater sex gland and prostate relative weights (P < 0.05), suggesting estrogenic effects. In contrast, compared with the basal diet, 5% flaxseed reduced immature ovarian relative weight by 29% (P < 0.05), delayed puberty by approximately 5 d (P < 0.05) and tended to lengthen diestrus, indicating an antiestrogenic effect. The SDG produced results similar to those of 5% flaxseed, suggesting that lignans were responsible for the observed effects. Lignans were transferred to the offspring via rat dam's milk as indicated by the recovery of radioactivity in the offspring of lactating dams given 3H-SDG. Because flaxseed affects the reproductive development of offspring, caution is suggested when consuming flaxseed during pregnancy and lactation.

Anal Canal↗

PubMed1998

Chronic exposure to secoisolariciresinol diglycoside alters lignan disposition in rats.

Mammalian lignans from colonic bacterial action on secoisolariciresinol diglycoside (SDG) may mediate the anticarcinogenic effect of prolonged SDG feeding in rats. To elucidate lignan bioactivity, our objective was to determine 3H-SDG disposition in rats with acute or chronic SDG treatment over 48 h. After food deprivation overnight, female Sprague-Dawley rats (70-72 d old) were given a single gavage of 3H-SDG (3.7 kBq/g body weight) either immediately (acute, n = 12) or after 10 d of gavage with 1.5 mg unlabeled SDG/d (chronic, n = 12). Rats were killed at 12, 24, 36 and 48 h after gavage, and samples collected and analyzed for radioactivity by liquid scintillation counting. Radioactivity was 1- to 16-fold higher at 12 vs. 48 h for tissues, blood and gastrointestinal contents (P < 0.05). By 48 h, >80% of the recovered dose was excreted in both groups (feces > 50%, urine = 28-32%). Tissue radioactivity was highest (by 0.5- to 176-fold) in the cecum (P < 0.05). Levels in the liver, kidney and uterus (12 h) were 0.2- to 7.5-fold higher than in other nongastrointestinal tissues. At 12 h, fecal radioactivity was negligible, and cecal content, liver and adipose radioactivity were one- to threefold greater in rats with chronic SDG exposure than in those acutely exposed (P < 0.05). Blood radioactivity, present mostly in the plasma fraction (0.4% of dose), suggested that lignan concentrations could be 3000 times higher than peak estrogen levels in rats. Thus, SDG metabolites accumulated in the liver, kidney, intestinal tissues and uterus. Chronic SDG exposure delayed fecal excretion while increasing liver and adipose lignan levels.

Animals↗

PubMed2002

Dietary sesame seed and its lignans inhibit 2,7,8-trimethyl- 2(2'-carboxyethyl)-6-hydroxychroman excretion into urine of rats fed gamma-tocopherol.

We showed previously that dietary sesame seed and its lignans elevate the tocopherol concentration in rats. To clarify their effect on tocopherol metabolism, we determined in this study the urinary excretion of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a gamma-tocopherol metabolite, in rats fed sesame seed or its lignans. Rats were fed diets with or without sesame seed for 28 d in Experiment 1, and for 1, 3 and 7 d in Experiment 2. On d 28, dietary sesame seed elevated (P < 0.05) gamma-tocopherol concentrations in liver, kidney, brain and serum, and decreased (P < 0.05) urinary excretion of gamma-CEHC. The excretion was completely inhibited by feeding sesame seed on d 1 and 3. In Experiment 3, the effects of dietary sesamin and sesaminol (major lignans in sesame seed) or ketoconazole (a selective inhibitor of cytochrome P(450) (CYP)3A on urinary excretion of gamma-CEHC in rats fed gamma-tocopherol were examined. The urinary gamma-CEHC in rats fed sesamin or sesaminol was markedly lower than in rats fed gamma-tocopherol alone (P < 0.05). Dietary ketoconazole also inhibited (P < 0.05) urinary excretion of gamma-CEHC, and elevated (P < 0.05) gamma-tocopherol concentrations in tissues and serum of rats fed gamma-tocopherol. These data suggest that sesame seed and its lignans elevate gamma-tocopherol concentration due to the inhibition of CYP3A-dependent metabolism of gamma-tocopherol.

Animals↗

PubMed1985

Production and metabolism of lignans by the human faecal flora.

Lignans have, until recently, been found only in plants. Enterolactone and enterodiol are the major lignans present in the urine of humans and have a potential physiological protective role against cancer. It has been shown that these compounds can be formed in vitro by human faecal flora and that enterodiol is oxidized to enterolactone by bacteria that are present in stools at a concentration of up to 10(3)/g. It was also possible to produce both of these lignans in vitro from linseeds and from secoisolariciresinol, a precursor present in linseed, by bacteria present in stools, at a concentration of between 10(3) and 10(4)/g. Enterolactone was produced from matairesinol, a more abundant plant lignan than secoisolariciresinol, after incubation with a mixed faecal flora under both aerobic and anaerobic conditions. In each case conversion was dependent on the presence of viable bacteria. These findings indicate that a number of different pathways operate to produce enterolactone and enterodiol depending on the ingested dietary precursor.

4-Butyrolactone↗

PubMed2003

Exposure to flaxseed or its purified lignan during suckling inhibits chemically induced rat mammary tumorigenesis.

Previous studies have shown that feeding flaxseed (FS) or its lignan secoisolariciresinol diglucoside (SDG) to rat dams during lactation enhances the differentiation of rat mammary gland in the female offspring. This study determined whether exposure to a diet with 10% FS or SDG (equivalent to the amount in 10% FS) during suckling could protect against 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced rat mammary tumorigenesis later in life. Dams were fed the AIN-93G basal diet (BD) throughout pregnancy. After delivery, dams were randomized to continue on BD or were fed BD supplemented with 10% FS or SDG during lactation. Three-day urine of dams was analyzed for mammalian lignans. After weaning, all offspring were fed BD. At postnatal Days 49 to 51, during proestrus phase, offspring were gavaged with 5 mg of DMBA. At Week 21 post-DMBA administration, compared with the BD group, the FS and SDG groups had significantly lower (P < 0.05) tumor incidence (31.3% and 42.0% lower, respectively), total tumor load (50.8% and 62.5% lower, respectively), mean tumor size (43.9% and 67.7% lower, respectively), and tumor number (46.9% and 44.8% lower, respectively) per rat. There was a significant decreasing trend (P < 0.05) in final tumor weights in rats fed FS or SDG. The high urinary lignan excretion in dams fed with FS or SDG corresponded with the reduced tumor development. The FS and SDG groups did not differ significantly in tumor indices, indicating that the effect of FS is primarily due to its SDG. There were no significant changes in selective reproductive indices measured among dams and offspring. In conclusion, exposure to FS or SDG during suckling suppressed DMBA-induced rat mammary tumorigenesis, suggesting that exposure to lignans at this early stage of mammary gland development reduces susceptibility to mammary carcinogenesis later in life without adverse effects on selective reproductive indices in dams or offspring.

9,10-Dimethyl-1,2-benzanthracene↗