Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERα transcriptional activation in human breast cancer cells

Carreau, Charlotte; Flouriot, Gilles; Bennetau-Pelissero, Catherine; Potier, M.

doi:10.1016/j.jsbmb.2008.03.032

Cited by 83 publications

(63 citation statements)

References 43 publications

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“…), and most of their health-related effects have been attributed to their activity as antioxidants [29,30]. A certain amount of data are now becoming available on the activity of these compounds at doses lower than those required to exert antioxidant activities, but sufficient to activate fundamental cell pathway-regulating metabolic functions [18,19,22,65,66].…”

Section: Discussionmentioning

confidence: 99%

“…The identified variables were as follows: the source of the lignans and other factors in the food, the doses of compounds in different preparations (extracts or whole grains), the time of intake, the targeted cohorts, the analyzed end-points and the methods of analysis [28]. Some mechanistic studies have also been performed identifying the lignans mainly as efficient antioxidants and phytoestrogenic compounds [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

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Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

et al. 2014

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Purpose and background The focus was directed to the study of two of the most lignan-rich food sources: sesame and flaxseeds. Recent epidemiological and experimental evidences suggesting that these foods may improve metabolic functions underlying metabolic syndrome (MetS). Methods To characterize the effect of these oilseeds on metabolic functions, we conducted an experimental study aimed at preventing adiposity and metabolic imbalance in a mouse model of high-fat diet (HFD)-induced MetS. Statistical analysis was performed by two-way analysis of variance test followed by post hoc Bonferroni analysis. Results We studied the effect of the oilseeds sesame and flaxseed on metabolic parameters in mice on a HFD. When the HFD was integrated with 20 % of sesame or flaxseed flours, the mice showed a decrease in body fat, already at day 15, from time 0. The size of the adipocytes was smaller in epididymal fat, liver steatosis was inhibited, and insulin sensitivity was higher in mice on the supplemented diets. The supplemented diets also resulted in a significant increase in the serum levels of the lignan metabolites enterodiol and enterolactone compared with the controls. The expression of genes associated with the inflammatory response, glucose metabolism, adipose metabolism and nuclear receptor were altered by the oilseed-supplemented diets. Some of the most abundant lignans in these oilseeds were studied in 3T3-L1 preadipocyte cells and were effective in inhibiting adipocyte differentiation at the minimal dose of 1 nM. Conclusions The consumption of sesame and flaxseed may be beneficial to decrease metabolic parameters that are generally altered in MetS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

et al. 2014

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“…Binding of these lignans to estrogen receptors can exert weak estrogenic or anti-estrogenic effects (Carreau et al, 2008;Penttinen-Damdimopoulou et al, 2009;Penttinen et al, 2007), and such activity is believed to decrease the risk of hormone-sensitive cancers (Buck et al, 2010). EL and ED also possess antioxidant activity (Kitts et al, 1999;Prasad, 2000) which may contribute to a reduction in risk of diseases and conditions associated with increased inflammation and oxidative damage such as metabolic syndrome (Cornish et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

No evidence of hypoglycemia or hypotension in older adults during 6 months of flax lignan supplementation in a randomized controlled trial: A safety evaluation

Billinsky

Glew

Cornish

et al. 2013

Pharmaceutical Biology

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Context: The natural health product, BeneFlax, is a standardized flaxseed [Linum usitatissimum L. (Linaceae)] lignan enriched product with evidence of product quality and known quantity of the bioactive component, lignan. The acceptance of this natural health product for its various health benefits requires greater evidence of its safety in the general population. Objective: We determined whether flaxseed lignan causes clinical hypoglycemia or hypotension in healthy older adults as an important aspect of safety. Materials and methods: Participants aged 49-87 years were randomized in a double-blind trial to receive flaxseed lignan (543 mg/day in BeneFlax) or placebo while completing a 6-month walking program. The 94 participants who completed the study were stratified by age (565 years versus !65 years) and treatment category to determine whether older adults were more susceptible to adverse effects. Results: After 6 months of treatment, average plasma glucose level (5.4 AE 0.6 mmol/L), systolic blood pressure (127 AE 14 mm Hg), and diastolic blood pressure (80 AE 9 mm Hg) were within normal clinical range. Controlling for sex and body mass index covariates resulted in no observed differences between plasma glucose or blood pressure measurements between treatment or age groups (p40.05). No incidents of hypoglycemia or hypotension were observed during BeneFlax treatment, suggesting that 543 mg falls at or below the no observable adverse effect level (NOAEL). Discussion and conclusion: These data suggest the flaxseed lignan product BeneFlax does not pose a risk of hypoglycemia or hypotension in healthy adults aged 49-87 years.

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“…Based on a study examining the mechanism to interfere with ER by which enterolignans exert estrogenic and/or antiestrogenic effects, it indicated that enterolignans had distinct properties for transactivation of ERα and ERβ. ED, as estradiol (E2), induced ERα transcriptional activation through transactivation functions AF-1 and AF-2, while EL was less efficient in inducing AF-1 but acted predominantly through AF-2 82 .…”

Section: Estrogenic and Anti-estrogenic Effectsmentioning

confidence: 99%

The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans

Lin¹,

Krol²,

Alcorn

2013

NPJ

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The mammalian lignan, enterolactone (EL), is a gut microbe metabolite of plant lignan secoisolariciresinol diglucoside (SDG), which is most abundant in flaxseed. Numerous epidemiological, experimental and clinical studies suggest the protective effects of EL against various chronic diseases such as cancer, cardiovascular disease, and inflammation. However, EL's oral bioavailability is low and highly variable due to extensive first-pass metabolism, especially glucuronidation, which results in the large amount of glucuronide metabolites but low levels of free EL in human plasma. Hepatocytes and enterocytes express UDP-glucuronosyltransferases (UGT), the enzymes responsible for the conjugation of glucuronic acid to EL. To better understand the contribution of liver and intestine to the first-pass glucuronidation, I conducted an in vitro enzyme kinetic analysis of EL glucuronidation using hepatic and intestinal microsomal fractions from both human and rat.An intrinsic clearance (CL int ) value was calculated using the substrate depletion approach. In addition to monitoring substrate depletion, high-pressure liquid chromatography (HPLC) analysis allowed detection of EL glucuronides, which were further substantiated by LC-MS.EL monoglucuronide was identified in rat and human intestinal and liver microsomes.Enzyme kinetic studies indicated the extent of hepatic microsomal glucuronidation exceeded intestinal glucuronidation in both human and rat, while the human liver CL int value was slightly higher than that of rat liver. The CL int value generated in human intestinal microsomes was only one third of the value of human liver, whereas, the CL int of rat jejunum or colon was one-twentieth of rat liver, suggesting the human intestine makes a greater contribution to EL glucuronidation than rat intestine. These results suggest that both liver and intestine contribute to EL glucuronidation and the human intestine may exert a greater influence on the first-pass glucuronidation of EL than rat intestine, thereby significantly decreasing EL's oral bioavailability. The rat might underestimate the extent of intestinal metabolism of EL relative to human.iii

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Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERα transcriptional activation in human breast cancer cells

Cited by 83 publications

References 43 publications

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

No evidence of hypoglycemia or hypotension in older adults during 6 months of flax lignan supplementation in a randomized controlled trial: A safety evaluation

The Comparison of Rat and Human Intestinal and Hepatic Glucuronidation of Enterolactone Derived from Flaxseed Lignans

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