- Research Article
Cannabinoid-like anti-inflammatory compounds from flax fiber
Cellular & Molecular Biology Letters volume 17, pages 479–499 (2012)
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.
cannabinoid receptor 1
cannabinoid receptor 2
cAMP response element-binding
differentially expressed genes
Dulbecco’s Modified Eagle Medium
gas chromatography-mass spectrometry
high-performance liquid chromatography
monocyte chemotactic protein 1
nuclear factor κB
normal human dermal fibroblasts
phosphate buffered saline
protein kinase A
polyunsaturated fatty acids
- RT PCR:
real-time polymerase chain reaction
suppressor of cytokine signaling 1
Toll-like receptor 4
tumor necrosis factor α
ultra performance liquid chromatography
Prasad, K. Flaxseed and cardiovascular health. J. Cardiovasc. Pharmacol. 54 (2009) 369–377.
Prasad, K. Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol. Cell. Biochem. 168 (1997) 117–123.
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.
Muir, A.D. and Westcott, N.D. Flax, the genus Linum, Saskatchewan: T.F. Group, 2003.
Huwiler, A. and Pfeilschifter, J. Lipids as targets for novel antiinflammatory therapies. Pharmacol. Ther. 124 (2009) 96–112.
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.
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.
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.
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.
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.
Mechoulam, R., Peters, M., Murillo-Rodriguez, E. and Hanus, L.O. Cannabidiol-recent advances. Chem. Biodivers. 4 (2007) 1678–1692.
Alexander, A., Smith, P.F. and Rosengren, R.J. Cannabinoids in the treatment of cancer. Cancer Lett. 285 (2009) 6–12.
Ligresti, A., Petrosino, S. and Di Marzo, V. From endocannabinoid profiling to ‘endocannabinoid therapeutics’. Curr. Opin. Chem. Biol. 13 (2009) 321–331.
Pacher, P., Batkai, S. and Kunos, G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol. Rev. 58 (2006) 389–462.
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.
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.
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.
Klein, T.W. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat. Rev. Immunol. 5 (2005) 400–411.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Munro, S., Thomas, K.L. and Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365 (1993) 61–65.
McAllister, S.D. and Glass, M. CB1 and CB2 receptor-mediated signalling: a focus on endocannabinoids. Prostag. Leukotr. Ess. 66 (2002) 161–171.
Howlett, A.C. Cannabinoid receptor signaling. Handb. Exp. Pharmacol. (2005) 53–79.
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.
Kawai, T. and Akira, S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol. Med. 13 (2007) 460–469.
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.
Watts, T.H. TNF/TNFR family members in costimulation of T cell responses. Annu. Rev. Immunol. 23 (2005) 23–68.
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.
These authors contributed equally to this work
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Styrczewska, M., Kulma, A., Ratajczak, K. et al. Cannabinoid-like anti-inflammatory compounds from flax fiber. Cell Mol Biol Lett 17, 479–499 (2012). https://doi.org/10.2478/s11658-012-0023-6
- Linum usitatissimum
- Flax fibers
- Cannabinoid signaling