Cellular & Molecular Biology Letters

, Volume 17, Issue 3, pp 479–499 | Cite as

Cannabinoid-like anti-inflammatory compounds from flax fiber

  • Monika Styrczewska
  • Anna KulmaEmail author
  • Katarzyna Ratajczak
  • Ryszard Amarowicz
  • Jan Szopa
Research Article


Flax is a valuable source of fibers, linseed and oil. The compounds of the latter two products have already been widely examined and have been proven to possess many health-beneficial properties. In the course of analysis of fibers extract from previously generated transgenic plants overproducing phenylpropanoids a new terpenoid compound was discovered.

The UV spectra and the retention time in UPLC analysis of this new compound reveal similarity to a cannabinoid-like compound, probably cannabidiol (CBD). This was confirmed by finding two ions at m/z 174.1 and 231.2 in mass spectra analysis. Further confirmation of the nature of the compound was based on a biological activity assay. It was found that the compound affects the expression of genes involved in inflammatory processes in mouse and human fibroblasts and likely the CBD from Cannabis sativa activates the specific peripheral cannabinoid receptor 2 (CB2) gene expression. Besides fibers, the compound was also found in all other flax tissues. It should be pointed out that the industrial process of fabric production does not affect CBD activity.

The presented data suggest for the first time that flax products can be a source of biologically active cannabinoid-like compounds that are able to influence the cell immunological response. These findings might open up many new applications for medical flax products, especially for the fabric as a material for wound dressing with anti-inflammatory properties.

Key words

Flax Linum usitatissimum Linen Cannabinoid Inflammation Terpenoids Flax fibers Cannabinoid signaling 

Abbreviations used


α-linoleic acid


cannabinoid receptor 1


cannabinoid receptor 2




cannabichromenic acid




cannabidiolic acid


cannabigerolic acid




chalcone isomerise


chalcone synthase


cAMP response element-binding


differentially expressed genes


dihydroflavonol reductase


Dulbecco’s Modified Eagle Medium




glyceraldehyde-3-phosphate dehydrogenase


gas chromatography-mass spectrometry


geranyl pyrophosphate


high-performance liquid chromatography


interleukin 1β


interleukin 6


interleukin 8


interferon γ


isopentenyl diphosphate




monocyte chemotactic protein 1


nuclear factor κB


normal human dermal fibroblasts


olivetolic acid


phosphate buffered saline


protein kinase A


polyunsaturated fatty acids


relative quantification


real-time polymerase chain reaction


standard deviation


secoisolariciresinol diglucoside


standard error


suppressor of cytokine signaling 1


trifluoroacetic acid




Δ9-tetrahydrocannabinolic acid


Toll-like receptor 4


tumor necrosis factor α


TNF receptor


ultra performance liquid chromatography


  1. 1.
    Prasad, K. Flaxseed and cardiovascular health. J. Cardiovasc. Pharmacol. 54 (2009) 369–377.PubMedCrossRefGoogle Scholar
  2. 2.
    Prasad, K. Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol. Cell. Biochem. 168 (1997) 117–123.PubMedCrossRefGoogle Scholar
  3. 3.
    Wang, L., Chen, J. and Thompson, L.U. The inhibitory effect of flaxseed on the growth and metastasis of estrogen receptor negative human breast cancer xenograftsis attributed to both its lignan and oil components, Int. J. Cancer 116 (2005) 793–798.CrossRefGoogle Scholar
  4. 4.
    Muir, A.D. and Westcott, N.D. Flax, the genus Linum, Saskatchewan: T.F. Group, 2003.Google Scholar
  5. 5.
    Huwiler, A. and Pfeilschifter, J. Lipids as targets for novel antiinflammatory therapies. Pharmacol. Ther. 124 (2009) 96–112.PubMedCrossRefGoogle Scholar
  6. 6.
    Russo, G.L. Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem. Pharmacol. 77 (2009) 937–946.PubMedCrossRefGoogle Scholar
  7. 7.
    Skorkowska-Telichowska, K., Zuk, M., Kulma, A., Bugajska-Prusak, A., Ratajczak, K., Gasiorowski, K. and Szopa, J. New dressing materials derived from transgenic flax products to treat long-standing venous ulcersa pilot study. Wound. Repair. Regen. 18 (2010) 168–719.PubMedCrossRefGoogle Scholar
  8. 8.
    Lorenc-Kukula, K., Amarowicz, R., Oszmianski, J., Doermann, P., Starzycki, M., Skala, J., Zuk, M., Kulma, A. and Szopa, J. Pleiotropic effect of phenolic compounds content increases in transgenic flax plant. J. Agric. Food Chem. 53 (2005) 3685–3692.PubMedCrossRefGoogle Scholar
  9. 9.
    Raharjo, T.J., Chang, W.-T., Choi, Y.H., Peltenburg-Looman, A.M.G. and Verpoorte, R. Olivetol as product of a polyketide synthase in Cannabis sativa L. Plant Sci. 166 (2004) 381–385.CrossRefGoogle Scholar
  10. 10.
    Sirikantaramas, S., Taura, F., Morimoto, S. and Shoyama, Y. Recent advances in Cannabis sativa research: biosynthetic studies and its potential in biotechnology. Curr. Pharm. Biotechnol. 8 (2007) 237–243.PubMedCrossRefGoogle Scholar
  11. 11.
    Mechoulam, R., Peters, M., Murillo-Rodriguez, E. and Hanus, L.O. Cannabidiol-recent advances. Chem. Biodivers. 4 (2007) 1678–1692.PubMedCrossRefGoogle Scholar
  12. 12.
    Alexander, A., Smith, P.F. and Rosengren, R.J. Cannabinoids in the treatment of cancer. Cancer Lett. 285 (2009) 6–12.PubMedCrossRefGoogle Scholar
  13. 13.
    Ligresti, A., Petrosino, S. and Di Marzo, V. From endocannabinoid profiling to ‘endocannabinoid therapeutics’. Curr. Opin. Chem. Biol. 13 (2009) 321–331.PubMedCrossRefGoogle Scholar
  14. 14.
    Pacher, P., Batkai, S. and Kunos, G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol. Rev. 58 (2006) 389–462.PubMedCrossRefGoogle Scholar
  15. 15.
    Zoratti, C., Kipmen-Korgun, D., Osibow, K., Malli, R. and Graier, W.F. Anandamide initiates Ca(2+) signaling via CB2 receptor linked to phospholipase C in calf pulmonary endothelial cells. Br. J. Pharmacol. 140 (2003) 1351–1362.PubMedCrossRefGoogle Scholar
  16. 16.
    Rajesh, M., Mukhopadhyay, P., Batkai, S., Hasko, G., Liaudet, L., Huffman, J.W., Csiszar, A., Ungvari, Z., Mackie, K., Chatterjee, S. and Pacher, P. CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyteendothelial adhesion. Am. J. Physiol. Heart Circ. Physiol. 293 (2007) H2210–H2218.PubMedCrossRefGoogle Scholar
  17. 17.
    Schatz, A.R., Lee, M., Condie, R.B., Pulaski, J.T. and Kaminski, N.E. Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system, Toxicol. Appl. Pharmacol. 142 (1997) 278–287.PubMedCrossRefGoogle Scholar
  18. 18.
    Klein, T.W. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat. Rev. Immunol. 5 (2005) 400–411.PubMedCrossRefGoogle Scholar
  19. 19.
    Klein, T.W., Lane, B., Newton, C.A. and Friedman, H. The cannabinoid system and cytokine network. Proc. Soc. Exp. Biol. Med. 225 (2000) 1–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Derocq, J.M., Jbilo, O., Bouaboula, M., Segui, M., Clere, C. and Casellas, P. Genomic and functional changes induced by the activation of the peripheral cannabinoid receptor CB2 in the promyelocytic cells HL-60. Possible involvement of the CB2 receptor in cell differentiation. J. Biol. Chem. 275 (2000) 15621–15628.PubMedCrossRefGoogle Scholar
  21. 21.
    Wrobel-Kwiatkowska, M., Zebrowski, J., Starzycki, M., Oszmianski, J. and Szopa, J. Engineering of PHB synthesis causes improved elastic properties of flax fibers. Biotechnol. Prog. 23 (2007) 269–277.PubMedCrossRefGoogle Scholar
  22. 22.
    Lorenc-Kukula, K., Wrobel-Kwiatkowska, M., Starzycki, M. and Szopa, J. Engineering flax with increased flavonoid content and thus Fusarium resistance. Physiol. Mol. Plant P. 70 (2007) 38–48.CrossRefGoogle Scholar
  23. 23.
    Boba, A., Kulma, A., Kostyn, K., Starzycki, M., Starzycka, E. and Szopa, J. The influence of carotenoid biosynthesis modification on the Fusarium culmorum and Fusarium oxysporum resistance in flax. Physiol. Mol. Plant P. 76 (2011) 39–47.CrossRefGoogle Scholar
  24. 24.
    Hazekamp, A., Peltenburg, A., Verpoorte, R. and Giroud, C. Chromatographic and Spectroscopic Data of Cannabinoids from Cannabis sativa L. J. Liq. Chromatog. R.T. 28 (2005) 2361–2382.CrossRefGoogle Scholar
  25. 25.
    Gredes, T., Kunert-Keil, C., Dominiak, M., Gedrange, T., Wrobel-Kwiatkowska, M. and Szopa, J. The influence of biocomposites containing genetically modified flax fibers on gene expression in rat skeletal muscle. Biomed. Tech. (Berl). 55 323–329.Google Scholar
  26. 26.
    Klein, T.W., Newton, C., Larsen, K., Lu, L., Perkins, I., Nong, L. and Friedman, H. The cannabinoid system and immune modulation. J. Leukoc. Biol. 74 (2003) 486–496.PubMedCrossRefGoogle Scholar
  27. 27.
    Klegeris, A., Bissonnette, C.J. and McGeer, P.L. Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. Br. J. Pharmacol. 139 (2003) 775–786.PubMedCrossRefGoogle Scholar
  28. 28.
    Matsuda, L.A., Lolait, S.J., Brownstein, M.J., Young, A.C. and Bonner, T.I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346 (1990) 561–564.PubMedCrossRefGoogle Scholar
  29. 29.
    Munro, S., Thomas, K.L. and Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365 (1993) 61–65.PubMedCrossRefGoogle Scholar
  30. 30.
    McAllister, S.D. and Glass, M. CB1 and CB2 receptor-mediated signalling: a focus on endocannabinoids. Prostag. Leukotr. Ess. 66 (2002) 161–171.CrossRefGoogle Scholar
  31. 31.
    Howlett, A.C. Cannabinoid receptor signaling. Handb. Exp. Pharmacol. (2005) 53–79.Google Scholar
  32. 32.
    Doyle, S.L. and O’Neill, L.A.J. Toll-like receptors: From the discovery of NF[kappa]B to new insights into transcriptional regulations in innate immunity. Biochem. Pharmacol. 72 (2006) 1102–1113.PubMedCrossRefGoogle Scholar
  33. 33.
    Kawai, T. and Akira, S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol. Med. 13 (2007) 460–469.PubMedCrossRefGoogle Scholar
  34. 34.
    Libermann, T.A. and Baltimore, D. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol. Cell. Biol. 10 (1990) 2327–2334.PubMedGoogle Scholar
  35. 35.
    Watts, T.H. TNF/TNFR family members in costimulation of T cell responses. Annu. Rev. Immunol. 23 (2005) 23–68.PubMedCrossRefGoogle Scholar
  36. 36.
    Ryo, A., Suizu, F., Yoshida, Y., Perrem, K., Liou, Y.C., Wulf, G., Rottapel, R., Yamaoka, S. and Lu, K.P. Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol. Cell 12 (2003) 1413–1426.PubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Wien 2012

Authors and Affiliations

  • Monika Styrczewska
    • 1
  • Anna Kulma
    • 1
    Email author
  • Katarzyna Ratajczak
    • 2
  • Ryszard Amarowicz
    • 3
  • Jan Szopa
    • 1
  1. 1.Faculty of BiotechnologyUniversity of WrocławWrocławPoland
  2. 2.Department of Traumatology and Hand SurgeryWrocław Medical UniversityWrocławPoland
  3. 3.Division of Food ScienceInstitute of Animal Reproduction and Food Research of the Polish Academy of SciencesOlsztynPoland

Personalised recommendations