Mammalian Lignans Research Articles

Inhibitory effect of 2,3-dibenzylbutane-l,4-diol, a mammalian lignan, on contraction induced by norepinephrine in rat aorta

Inhibitory effect of 2,3-dibenzylbutane-l,4-diol, a mammalian lignan, on contraction induced by norepinephrine in rat aorta

Diet and breast cancer.

It is a general opinion that the Western diet plays a significant role in increasing the risk of breast cancer in the Western World. Recently some likely mechanisms involved in increasing the risk have been disclosed. It has been found that a Western-type diet elevates plasma levels of sex hormones and decreases the sex hormone binding globulin concentration, increasing the availability of these steroids for peripheral tissues. The same diet results in low formation by intestinal bacteria of mammalian lignans and isoflavonoid phyotestrogens from plant precursors. These diphenolic compounds seem to affect hormone metabolism and production and cancer cell growth by many different mechanisms making them strong candidates for a role as cancer protective substances. The sex hormone pattern found in connection with a Western-type diet combined with low lignan and isoflavonoid excretion was found particularly in postmenopausal breast cancer patients and omnivores living in high-risk areas, and to a lesser degree in areas with less risk. However, the pattern observed was not entirely due to diet.

Mammalian lignan production from various foods

Mammalian lignans such as enterolactone and enterodiol, which are produced in the colon from precursors in foods, have been suggested as playing a role in the cancer-protective effect of vegetarian diets. Despite this, very little is known regarding the amount that is produced from different food products. Therefore, the objective of this study was to determine the production of mammalian lignans from 68 common plant foods by using the technique of in vitro fermentation with human fecal microbiota, which simulates colonic fermentation. Results showed a wide range (21-67,541 microgram(s)/100 g sample) in the amount of lignans produced. On the average as a group, the oilseeds produced the highest amounts (20,461 +/- 12,685), followed by the dried seaweeds (900 +/- 247), whole legumes (562 +/- 211), cereal brans (486 +/- 90), legume hulls (371 +/- 52), whole grain cereals (359 +/- 81), vegetables (144 +/- 23), and fruits (84 +/- 22). The vegetables produced the second highest concentration of lignans (1,546 +/- 280) when the data were expressed on a moisture-free basis. Flaxseed flour and its defatted meal were the highest producers of lignans (mean 60,110 +/- 7,431). Lignan production with the in vitro method related well to the urinary lignan excretion observed in rats and humans. The data should be useful in the estimation of lignan production from a given diet and in the formulation of high-lignan-producing diet for the purpose of reducing the cancer risk.

P-530 - Effect of 2,3-dibenzylbutane-1,4-diol(mammalian lignan) on Ca2+ mobilization and pH change in human neutrophils.

P-530 - Effect of 2,3-dibenzylbutane-1,4-diol(mammalian lignan) on Ca2+ mobilization and pH change in human neutrophils.

Effects of the mammalian lignan, 2,3-dibenzylbutane-1,4-diol, on contraction and Ca 2+ mobilization induced by noradrenaline in rat aorta

1. 1. In rat aorta, 2,3-dibenzylbutane-1,4-diol (DBB) inhibited noradrenaline (NA)-induced contraction in a concentration-dependent manner. The inhibitory effect of DBB was observed in verapamil-pretreated muscle, and did not differ from that in the high K + solution containing verapamil (1.0 μM). 2. 2. DBB inhibited not only contraction, but [Ca 2+] i elevation induced by NA (10 μM) with the same potency. 3. 3. The inhibitory effect of DBB on NA-induced contraction was reversed by methylene blue (3.2 μM) and enhanced by M&B 22,948 (10μM). 4. 4. DBB (100 μM) alone increased cyclic GMP levels. This effect was attenuated by methylene blue (3.2 μM) and augmented by M&B 22,948 (10 μM). 5. 5. From these results, the inhibitory effects of DBB on NA-induced contraction in rat aorta may be caused by an increase of cyclic GMP levels.

P-179 - Effects of the mammalian lignan, 2,3-dibenzylbutane-1,4-diol, on contraction and Ca2+ mobilization induced by noradrenaline in rat aorta.

P-179 - Effects of the mammalian lignan, 2,3-dibenzylbutane-1,4-diol, on contraction and Ca2+ mobilization induced by noradrenaline in rat aorta.

Priming effects of 2,3-dibenzylbutane-1,4-diol(mammalian lignan) on superoxide generation in human neutrophils

Priming effects of 2,3-dibenzylbutane-1,4-diol(mammalian lignan) on superoxide generation in human neutrophils

Priming effect of 2,3-dibenzylbutane-1,4-diol (mammalian lignan) on superoxide production in human neutrophils

We investigated the effect of 2,3-dibenzylbutane-1,4-diol(DBB), a mammalian lignan, on superoxide production and [Ca 2+]i mobilization in human neutrophils. DBB did not generate superoxide production by itself, but enhanced the FMLP or A23187-induced superoxide production in a dose dependent manner. DBB did not influence the OAG-induced superoxide production. The priming effect of DBB was inhibited by W-7 or trifluoroperazine, but not by H-7 or staurosporine. And the priming effect of DBB was observed in the presence or absence of extracellular Ca 2+. DBB enhanced the low dose FMLP-induced [Ca 2+]i mobilization. These results suggest that the priming effect of DBB in human neutrophils may be caused by the activation of the calcium-calmodulin pathway but not the protein kinase pathway.

P-571 - Effect of 2,3-dibenzylbutane-1,4-diol(mammalian lignan) on superoxide production in human neutrophil

P-571 - Effect of 2,3-dibenzylbutane-1,4-diol(mammalian lignan) on superoxide production in human neutrophil

P-464 - Inhibitory effect of mammalian lignan on the Ca2+ channel in vascular smooth muscle of rabbit femoral artery

P-464 - Inhibitory effect of mammalian lignan on the Ca2+ channel in vascular smooth muscle of rabbit femoral artery

Western diet and Western diseases: Some hormonal and biochemical mechanisms and associations

Breast cancer, prostate cancer, coronary heart disease and colon cancer belong to the so-called Western diseases and a general opinion is that diet is a significant or even the main factor increasing incidence and mortality of these diseases in the Western world. This review describes studies carried out in this department for about 10 years, many in collaboration with scientists abroad, and with the aim to clarify some of the connections between the diet and sex hormone, lipid and bile acid metabolism. A Western-type diet elevates plasma levels of sex hormones and decreases the sex hormone binding globulin concentration, increasing the bioavailability of these steroids. The same diet results in low formation of mammalian lignans and isoflavonic phytoestrogens. These diphenolic compounds seem to affect hormone metabolism and production and cancer cell growth by many different mechanisms making them candidates for a role as cancer protective substances. The precursors of these diphenols are to be found in fiber-rich unrefined grain products, various seeds, beans and probably also in pulses, peas and berries. Some types of fiber seem to influence sex hormone and bile acid metabolism mainly by partial interruption of the enterohepatic circulation, by alteration of intestinal metabolism and by increasing fecal excretion of these compounds. The sex hormone pattern found in connection with a Western-type diet is prevailing in the breast cancer patients, but is only partly a result of the diet.

Detection and identification of the plant lignans lariciresinol, isolariciresinol and secoisolariciresinol in human urine

The mammalian lignans enterolactone and enterodiol are regular constituents of human urine and are excreted daily in μmol amounts. They are produced by metabolic action of intestinal bacteria from natural plant lignan precursors which are constituents of various food plants. However, natural plant lignans seem to occur very seldom in detectable amounts in human urine. The present investigation shows that only in 5% of the 150 diphenolic fractions extracted from the urine of women plant lignans other than the previously identified matairesinol could be found. The lignans lariciresinol, isolariciresinol and secoisolariciresinol were identified for the first time by comparison of their GC characteristics and mass spectra with the corresponding results of authentic synthesized reference compounds. Secoisolariciresinol is one natural precursor of the mammalian lignan enterodiol. Of the two other plant lignans, no animal or human metabolic products are known. The occurrence of chemically unchanged plant lignans in some cases in human urine could be a result of an insufficient metabolic capacity of intestinal bacteria, resulting in a decreased detoxification of phenolic plant products.

Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG)

A brief account of our present knowledge on the enterohepatic metabolism of estrogens and on the origin, metabolism and biological effects of mammalian lignans and phytoestrogens is undertaken. Furthermore, recently published results on the effects of dietary fiber, fat and carbohydrates on estrogen metabolism are reviewed. New preliminary results are presented on quantitative assays of lignans and phytoestrogens in urine of women belonging to various dietary and population groups and in a group of chimpanzees. The highest values of lignans and phytoestrogens were found in the non-human primates, and in macrobiotic, lactovegetarian and Japanese women, all groups considered having a low risk for the development of breast and other hormone-dependent cancer. New results on correlations between intake of various fibers, lignan and phytoestrogen excretion and plasma levels of estrogens, free testosterone and SHBG in women are presented. There is a significant positive correlation between the intake of fiber and urinary excretion of lignans and phytoestrogens, and the concentration of plasma SHBG. Fiber intake and urinary excretion of lignans and equol correlated negatively with plasma percentage free estradiol. Enterolactone excretion correlated negatively with plasma free testosterone. It is concluded that dietary macro- and micronutrients seem to play an important role in estrogen metabolism.

Inhibition of the erythrocyte Na +, K +-pump by mammalian lignans

Several mammalian lignans, particularly enterolactone, 3 +-oxy-methyl enterolactone and prestegane B are able to inhibit Na +, K +-pump activity in human red cells with IC 50 of about 1 mM. The inhibition of Na +, K +-pump activity by mammalian lignans have the following properties: 1. i) the IC 50 for ouabain remains unchanged suggesting a non-competitive inhibition. 2. ii) the apparent affinity for internal Na + and maximal rate of cation translocation are both diminished. The above inhibition of the Na +, K +-pump was obtained at doses 2–3 orders of magnitude higher than those required for ouabain. However we cannot exclude that a glycosyl- (and/or butenolide)- derivative of enterolactone could be one endogenous ouabain-like factor.

Evidence that mammalian lignans show endogenous digitalis-like activities

Enterolactone, a lignan that has been identified in biological samples from man and several mammals, shares with ascorbic acid and cardiac glycosides a gamma-butyrolactone. It displaces 3H-ouabain from its binding sites on cardiac digitalis receptor and inhibits, dose dependently, the Na +,K +-ATPase activity of human and guinea-pig heart. The time dependence of this inhibition ressembles that of dihydroouabain, a cardiac glycoside in which the lactone ring does not contain conjugated double bonds. The active concentrations of enterolactone as inhibitor of Na +,K +-ATPase are in the 10 −4 M range and, at those concentrations, the cross-reactivity with antidigoxin antibodies is low. Lignans may contribute to the putative digitalis-like activity found in tissues, blood and urine of several mammals including man.

Origin of lignans in mammals and identification of a precursor from plants.

Lignans are a class of compounds with a dibenzylbutane skeleton1 which until recently had only been found in higher plants2,3. The first lignans to be identified in humans and animals were trans-2,3-bis(3-hydroxybenzyl)-γ-butyrolactone (enterolactone)4–6 and 2,3-bis(3-hydroxybenzyl)butane-1,4-diol (enterodiol)4,5. These structures differ from those of plant lignans by having aromatic rings substituted only in the meta position. Enterolactone and enterodiol are excreted in the urine and bile, predominantly as glucuronide conjugates7,8, and intestinal microflora is required for their formation8,9. It is not known, however, whether they are synthesized de novo by microorganisms or are formed from dietary precursors. We report here evidence that these mammalian lignans are formed by microbial action on precursor lignans which are present as dietary constituents of plant origin. Precursors are found in seeds of different species, being particularly abundant in linseed. From this source, 2,3-bis(3-methoxy-4-hydroxybenzyl)butane-1,4-diol (secoisolariciresinol) has been identified as a glycoside.

The dietary origin of the urinary lignan HPMF.

The influence of a synthetic diet devoid of plant fiber material on the occurrence of HPMF, a mammalian lignan, in rat urine was studied. The urine of rats on normal food contained significant amounts of HPMF. When the normal food was replaced by the synthetic diet the HPMF content fell to near-zero levels.