Molecular and Cellular Biochemistry

, Volume 202, Issue 1–2, pp 91–100 | Cite as

Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone

  • D.D. Kitts
  • Y.V. Yuan
  • A.N. Wijewickreme
  • L.U. Thompson


The antioxidant activities of the flaxseed lignan secoisolariciresinol diglycoside (SDG) and its mammalian lignan metabolites, enterodiol (ED) and enterolactone (EL), were evaluated in both lipid and aqueous in vitro model systems. All three lignans significantly (p ≤ 0.05) inhibited the linoleic acid peroxidation at both 10 and 100 μM over a 24-48 h of incubation at 40°C. In a deoxyribose assay, which evaluates the non site-specific and site-specific Fenton reactant-induced ·OH scavenging activity, SDG demonstrated the weakest activity compared to ED and EL at both 10 and 100 μM; the greatest ·OH scavenging for ED and EL was observed at 100 μM in both assays. The incubation of pBR322 plasmid DNA with Fenton reagents together with SDG, ED or EL showed that the inhibition of DNA scissions was concentration dependent. The greatest non site-specific activity of lignans was at 100 μM, thus, confirming the results of the deoxyribose test. In contrast, the protective effect of SDG and EL in the site-specific assay was lost and that of ED was minimal. Therefore, the results indicate a structure-activity difference among the three lignans with respect to specific antioxidant efficacy. All three lignans did not exhibit reducing activity compared to ascorbic acid, therefore, did not possess indirect prooxidant activity related to potential changes in redox state of transition metals. The efficacy of SDG and particularly the mammalian lignans ED and EL to act as antioxidants in lipid and aqueous in vitro model systems, at relatively low concentrations (i.e. 100 μM), potentially achievable in vivo, is an evidence of a potential anticarcinogenic mechanism of flaxseed lignan SDG and its mammalian metabolites ED and EL.

flaxseed secoisolariciresinol diglycoside (SDG) mammalian lignans enterodiol (ED) enterolactone (EL) site-specific and non-site-specific hydroxyl radical scavenging DNA nicking 


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  1. 1.
    Setchell KDR, Lawson FL, Mitchell H, Adlercreutz HT, Kirk DN, Axelson M: Lignans in man and animal species. Nature 287: 740–742, 1980PubMedGoogle Scholar
  2. 2.
    Ames BM, Shigena MK, Hagen TM: Oxidants, antioxidants and the degenerative diseases of aging. Proc Natl Acad Sci USA 90: 7915–7922, 1993PubMedGoogle Scholar
  3. 3.
    Prasad K, Kalara J, Lee P: Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: Effect of probucol. Intern J Angiol 3: 100–112, 1994Google Scholar
  4. 4.
    Meyer AS, Yi O-S, Pearson DA, Waterhouse AL, Frankel EN: Inhibition of human low-density lipoprotein oxidation in relation to composition of phenolic antioxidants in grapes (Vitis vinifera). J Agric Food Chem 45: 1638–1643, 1997Google Scholar
  5. 5.
    Horvath PM, Ip C: Synergistic effect of vitamin E and selenium in the chemoprevention of mammary carcinogenesis in rats. Cancer Res 43: 5335–5341, 1983PubMedGoogle Scholar
  6. 6.
    Kamal-Eldin A, Pettersson D, Appelqvist L-Å: Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids 30: 499–505, 1995PubMedGoogle Scholar
  7. 7.
    Ip SP, Poon MKT, Wu SS, Che CT, Ng KH, Kong YC, Ko KM: Effect of Schisandrin B on hepatic glutathione antioxidant system in mice: Protection against carbon tetrachloride toxicity. Planta Med 61: 398–401, 1995PubMedGoogle Scholar
  8. 8.
    Lu H, Liu G-T: Anti-oxidant activity of dibenzocyclooctene lignans isolated from schisandraceae. Planta Med 58: 311–313, 1992PubMedGoogle Scholar
  9. 9.
    Amarowicz R, Wanasundara U, Wanasundara J, Shahidi F: Antioxidant activity of ethanolic extracts of flaxseed in a β-carotene-linoleate model system. J Food Lipids 1: 111–117, 1993Google Scholar
  10. 10.
    Prasad K: Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol Cell Biochem 168: 117–123, 1997PubMedGoogle Scholar
  11. 11.
    Serraino M, Thompson LU: Flaxseed supplementation and early markers of colon carcinogenesis. Cancer Lett 63: 159–165, 1992PubMedGoogle Scholar
  12. 12.
    Jenab M, Thompson LU: The influence of flaxseed and lignans on colon carcinogenesis and β-glucuronidase activity. Carcinogenesis 17: 1343–1348, 1996PubMedGoogle Scholar
  13. 13.
    Serraino M, Thompson LU: The effect of flaxseed supplementation and early markers of mammary carcinogenesis. Cancer Lett 60: 135–142, 1991PubMedGoogle Scholar
  14. 14.
    Thompson LU, Seidl MM, Rickard SE, Orcheson LJ, Fong HHS: Antitumorigenic effect of a mammalian lignan precursor from flaxseed. Nutr Cancer 26: 159–165, 1996PubMedGoogle Scholar
  15. 15.
    Thompson LU, Rickard SE, Orcheson LJ, Seidl MM: Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis 17: 1121–1126, 1996PubMedGoogle Scholar
  16. 16.
    Rickard SE, Orcheson LJ, Seidl MM, Luyengi L, Fong HHS, Thompson LU: Dose-dependent production of mammalian lignans in rats and in vitro from the purified precursor secoisolariciresinol diglycoside in flaxseed. J Nutr 126: 2012–2019, 1996PubMedGoogle Scholar
  17. 17.
    Kirk DN, McLaughlin LM, Lawson AM, Setchell KDR, Patel SK: Synthesis of the [2H]-labelled urinary lignans enterolactone and enterodiol. J Chem Soc Perkin Trans I: 35–37, 1985Google Scholar
  18. 18.
    Asamari AM, Addis PB, Epley RJ, Krick TP: Wild rice hull antioxidants. J Agric Food Chem 44: 126–130, 1996Google Scholar
  19. 19.
    Halliwell B, Gutteridge JMC, Aruoma OI: The deoxyribose method: A simple 'test tube' assay for determination of rate constants for reaction of hydroxyl radicals. Anal Biochem 165: 215–219, 1987PubMedGoogle Scholar
  20. 20.
    Aruoma OI: Deoxyribose assay for detecting hydroxyl radicals. Meth Enzymol 233: 57–66, 1994Google Scholar
  21. 21.
    Wijewickreme AN, Kitts DD: Influence of reaction conditions on the oxidative behaviour of model Maillard reaction products. J Agric Food Chem 45: 4571–4576, 1997Google Scholar
  22. 22.
    Axelson M, Setchell KDR: The excretion of lignans in rats – evidence for an intestinal bacterial source for this new group of compounds. FEBS Lett 123: 337–342, 1981PubMedGoogle Scholar
  23. 23.
    Thompson LU, Robb P, Serraino M, Cheung F: Mammalian lignan production from various foods. Nutr Cancer 16: 43–52, 1991PubMedGoogle Scholar
  24. 24.
    Axelson M, Sjovall J, Gustaffson BF, Setchell KDR: Origin of lignans in mammals and identification of a precursor from plants. Nature 298: 659–660, 1982PubMedGoogle Scholar
  25. 25.
    Setchell KDR, Borriello SP, Gordon H, Lawson AM, Harkness R, Gordon H, Morgan DML, Kirk DN, Anderson LC, Adlercreutz H, Axelson M: Lignan formation in man-microbial involvement and possible roles in relation to cancer. Lancet 2: 4–7, 1981PubMedGoogle Scholar
  26. 26.
    Rickard SE, Thompson LU: Chronic exposure to secoisolariciresinol diglycoside alters lignan disposition in rats. J Nutr 128: 615–623, 1998PubMedGoogle Scholar
  27. 27.
    Sung MK, Lautens M, Thompson LU: Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res 18: 1405–1408, 1998PubMedGoogle Scholar
  28. 28.
    Halliwell B: How to characterize a biological antioxidant. Free Rad Res Commun 9: 1–32, 1992Google Scholar
  29. 29.
    Aruoma OI: Assessment of potential prooxidant and antioxidant actions. J Am Oil Chem Soc 73: 1617–1625, 1996Google Scholar
  30. 30.
    Aruoma OI, Chaudhary SS, Grootreld M, Halliwell B: Binding of iron (II) ions to pentose sugar 2-deoxyribose. J Inorg Biochem 35: 149–155, 1990Google Scholar
  31. 31.
    Gutteridge JMC: Reactivity of hydroxyl and hydroxyl-like radical discriminated by release of thiobarbituric acid-reactive material from deoxyribose, nucleosides and benzoate. Biochem J 224: 761–767, 1984PubMedGoogle Scholar
  32. 32.
    Halliwell B, Aeschbach R, Loliger J, Aruoma OI: The characteristics of antioxidants. Food Chem Toxicol 32: 671–683, 1994PubMedGoogle Scholar
  33. 33.
    Morel I, Gescoat G, Cogrel P, Sergent N, Pasdeloup P, Brissot P, Cillard P, Cillard J: Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 45: 13–19, 1993PubMedGoogle Scholar
  34. 34.
    Pool-Zobel BL, Abrahamse SL, Rechkemmer G: Cellular effects of phytohormones: Modulation of oxidative DNA damage and signal transduction in human colon cancer cells. Proc Am Assoc Cancer Res 39: (abst 4367) 641, 1998Google Scholar
  35. 35.
    Yang M-H, Schaich KM: Factors affecting DNA damage caused by lipid hydroperoxides and aldehydes. Free Rad Biol Med 20: 225–236, 1996PubMedGoogle Scholar
  36. 36.
    Ueda K, Kobayashi S, Morita J, Komano T: Site-specific DNA damage caused by lipid peroxidation products. Biochim Biophys Acta 824: 341–348, 1985PubMedGoogle Scholar
  37. 37.
    Nakayama T, Niimi T, Osawa T, Kawakishi S: The protective role of polyphenols in cytotoxicity of hydrogen peroxide. Mutation Res 281: 77–80, 1992PubMedGoogle Scholar
  38. 38.
    Foti M, Piattelli M, Baratta MT, Ruberto G: Flavonoids, coumarins, and cinnamic acids as antioxidants in a micellar system. Structure-activity relationship. J Agri Food Chem 44: 497–501, 1996Google Scholar
  39. 39.
    Rice-Evans EA, Miller NJ, Paganga G: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Rad Biol Med 20: 933–956, 1996PubMedGoogle Scholar
  40. 40.
    Laughton MJ, Halliwell B, Evans PJ, Hoult JRS: Antioxidant and prooxidant actions of the plant phenolics quercetin, gossypol and myricetin. Biochem Pharmacol 38: 859–865, 1989PubMedGoogle Scholar
  41. 41.
    Laudicina DC, Marnett LJ: Enhancement of hydroperoxide-dependent lipid peroxidation in rat liver microsomes by ascorbic acid. Arch Biochem Biophys 278: 73–80, 1990PubMedGoogle Scholar
  42. 42.
    Aruoma OI, Halliwell B, Aeschbach R, Loliger J: Antioxidant and pro-oxidant properties of active rosemary constituents: Carnosol and carnosic acid. Xenobiotics 22: 257–268, 1992Google Scholar
  43. 43.
    Mahoney JR, Graf E: Role of α-tocopherol, ascorbic acid and EDTA as oxidants in model systems. J Food Sci 51: 1293–1296, 1986Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • D.D. Kitts
    • 1
  • Y.V. Yuan
    • 2
  • A.N. Wijewickreme
    • 1
  • L.U. Thompson
    • 2
  1. 1.Food, Nutrition, and Health, Faculty of Agricultural ScienceUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Nutritional Sciences, Faculty of MedicineUniversity of TorontoTorontoCanada

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