Lignan metabolites

The presence of the oxidized metabolites is unique and may provide additional reasons for the health benefits of lignans. Classical antioxidant mechanisms show that the addition of an ortho hydroxyl group to a monophenol enhances the antioxidant activity of the original monophenol. Thus, some of the mammalian lignan metabolites may actually have greater or different activity than the parent lignan. Kitts et al (1999) reported that enterolactone and enterodiol had greater antioxidant activity than the parent... 

Kitts, D.D., Yuan, Y.V., Wijewickreme, A.N., and Thompson, L.U. 1999. Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol... 

The lignans enterodiol, enterolactone and NDGA and the lignan metabolite methyl p-hydroxyphenyllactate interfere with mitogenic and tumor promotional signal transduction pathways [153], NDGA and methyl p-hydroxyphenyllactate did not inhibit 12-G-tetradecanoylphorbol-13-acetate (TPA) mediated c-fos transcription, and enterolactone and enterodiol had only a weak inhibitory effect. NDGA at 0.1-10 p.mol/L increased c-fos mRNA levels. 

At least six different methods have been proposed for the analysis of lignans in flaxseed and products containing flaxseed, and three different methods for analysis of lignan metabolites in mammalian tissues and fluids since the lignan SDG was first isolated from flax by Bakke and Klosterman (1956). In addition, several variafions exist for many of these methods. Variations in extraction of lignans from flaxseed and products containing flaxseed further complicate its analysis. Results from these studies have been inconsistent mainly because of differences in methodology. 

Lignans are secondary plant metabolites possessing a variety of biological activities [1,2]. They are dimers of phenylpropenes, which are by definition connected between C(8) and C(8 ) [3]. Lignans are of great structural variety due to numerous potential oxidation states at the C(7)/C(7 ) and C(9)/C(9 ) positions, and to the possibility of aryl-aryl bond formation [1-3]. 

Gut microflora metabolites may also be important. As discussed above, the mammalian lignan aglycones, enterodiol and enterolactone, are estrogenic, and equol is more estrogenic than its dietary precursor, the isoflavone daidzein. ... 

Jacobs, E., Kulling, S.E., and Metzler, M., Novel metabolites of the mammalian lignans enterolactone and enterodiol in human urine, J. Steroid Biochem. Mol Biol, 68, 211, 1999. 

Using the technique of activity-guided chromatographic isolation, it is possible to generate many structurally novel bioactive plant secondary metabolites, and examples have been provided in this chapter of plant secondary metabolites with potential anticancer or potential cancer chemopreventive activity, comprised by compounds representative of the chal-cone, flavanone, flavone, furocoumarin, isoflavone, lignan, oligostilbenoid (resveratrol... 

The fully aromatic A,B-diheteropentalenes do not occur in nature. However, the reduced furofurans and pyrrolopyrroles are present in a variety of natural products such as lignans, fungal metabolites and alkaloids. It is beyond the scope of this chapter to present an exhaustive survey of these compounds. However, a few selected examples are presented in formulae (376)-(380). 

Oxidative coupling of dianions (12, 278). The oxidative coupling of dianions of carboxylic acids has been used for synthesis of enterolactone (6), a lignan urinary metabolite.1 Thus the dianion 2, generated from 1 with LDA, when treated with I2 (0.5 equiv.) couples to 3, obtained as a mixture of two isomers in a 4.5 1 ratio. This product is converted in 89% overall yield to the dimethyl ether (5) of enterolactone (6). 

Bannwart C, Adlercreutz H, Fotsis T, Wahala K, Hase T, Brunow G. 1984. Identification of o-desmethylangolensin, a metabolite of daidzein and of matairesinol, one likely plant precursor of the animal lignan enterolactone in human urine. Finn Chem Lett 4-5 120-125. 

Trachelogenin (lignan) Ipomoea cairica (Convolvulaceae) HIV-1 RT (Ca2+-CH) [metabolites inhibit HIV-INT]... 

Stilbenolignans are a third interesting group of non-conventional lignans produced by plants. Stilbenes, like flavonoids, are believed to be metabolites of mixed biosynthetic origin and derived from a cinnamoyl CoA and three malonate units... 

---