Dieckol isolated from a brown alga, Eisenia nipponica, suppresses ear swelling from allergic inflammation in mouse
Corresponding Author
Yoshimasa Sugiura
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Correspondence
Yoshimasa Sugiura, Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, 2-7-1 Nagata-Honmachi, Shimonoseki, Yamaguchi 759-6595, Japan.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorMasakatsu Usui
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
Search for more papers by this authorHirotaka Katsuzaki
Laboratory of Bioorganic Chemistry, Graduate School of Bioresources, Mie University, Tsu, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
Search for more papers by this authorKunio Imai
Laboratory of Bioorganic Chemistry, Graduate School of Bioresources, Mie University, Tsu, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
Search for more papers by this authorRyusuke Tanaka
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Methodology, Writing - review & editing
Search for more papers by this authorTeruo Matsushita
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Data curation, Methodology, Writing - review & editing
Search for more papers by this authorMasaaki Miyata
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Data curation, Methodology, Supervision, Writing - review & editing
Search for more papers by this authorCorresponding Author
Yoshimasa Sugiura
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Correspondence
Yoshimasa Sugiura, Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, 2-7-1 Nagata-Honmachi, Shimonoseki, Yamaguchi 759-6595, Japan.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorMasakatsu Usui
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
Search for more papers by this authorHirotaka Katsuzaki
Laboratory of Bioorganic Chemistry, Graduate School of Bioresources, Mie University, Tsu, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
Search for more papers by this authorKunio Imai
Laboratory of Bioorganic Chemistry, Graduate School of Bioresources, Mie University, Tsu, Japan
Contribution: Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
Search for more papers by this authorRyusuke Tanaka
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Methodology, Writing - review & editing
Search for more papers by this authorTeruo Matsushita
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Data curation, Methodology, Writing - review & editing
Search for more papers by this authorMasaaki Miyata
Laboratory of Food Function and Biochemistry, Department of Food Science and Technology, National Research and Development Agency, Japan Fisheries Research and Education Agency, National Fisheries University, Shimonoseki, Japan
Contribution: Data curation, Methodology, Supervision, Writing - review & editing
Search for more papers by this authorFunding information
This work was supported by the grant of JSPS KAKENHI (Grant Number 25850099 and 17K07951).
Abstract
We previously found a lipophilic fraction of the methanol/chloroform extract of a brown alga, Eisenia nipponica, that had an antiallergic effect in a murine ear swelling test. In this study, we purified the active component from the lipophilic fraction using high performance liquid chromatography and analyzed the mass and nuclear magnetic resonance spectra. This uncovered the phlorotannin dieckol, which exhibited antiallergic effects in an ear swelling test using mice sensitized by arachidonic acid, 12-O-tetradecanoylphorbol-13-acetate, and oxazolone. Mechanistic investigations indicated that dieckol suppressed degranulation, chemical mediator release, and the expression of mRNA such as cyclooxygenase-2, interleukin-6, and tumor necrosis factor-α in rat basophilic leukemia-2H3 cells. In summary, we isolated dieckol from E. nipponica and demonstrated its antiallergic mechanisms.
Practical applications
As the incidence of allergies increases worldwide, so too does the demand for food components with antiallergic and anti-inflammatory properties. Given this trend, we focused on a brown alga that displays a variety of bioactivities. Here, we have isolated dieckol from the antiallergic lipophilic fraction of E. nipponica and found that it possesses diverse physiological activities that may prevent lifestyle-related diseases. Consequently, dieckol or the alga containing this phlorotannin could be used as a health food ingredient to combat not only allergies, but also variety of disorders including the undesirable effects of aging.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author, Y. Sugiura, upon reasonable request.
REFERENCES
- Ahn, G., Amagai, Y., Matsuda, A., Kang, S.-M., Lee, W., Jung, K., & Tanaka, A. (2015). Dieckol, a phlorotannin of Ecklonia cava, suppresses IgE-mediated mast cell activation and passive cutaneous anaphylactic reaction. Experimental Dermatology, 24, 968–970. https://doi.org/10.1111/exd.12814
- Carlson, R., Lynn, O.-N.-D., Chang, J., & Lewis, A. (1985). Modulation of mouse ear edema by cyclooxygenase and lipoxygenase inhibitors and other pharmacologic agents. Agents and Actions, 17, 197–204. https://doi.org/10.1007/BF01966592
- Chowdhury, M. T. H., Bangoura, I., Kang, J.-Y., Cho, J.-Y., Joo, J., Choi, Y.-S., & Hong, Y.-K. (2014). Comparison of Ecklonia cava, Ecklonia stolonifera and Eisenia bicyclis for phlorotannin extraction. Journal of Environmental Biology, 35, 713–719.
- Chung, L. Y., Soo, W. K., Chan, K. Y., Mustafa, M. R., Goh, S. H., & Imiyabir, Z. (2009). Lipoxygenase inhibiting activity of some Malaysian plants. Pharmaceutical Biology, 47, 1142–1148. https://doi.org/10.3109/13880200903008724
- Corona, G., Ji, Y., Anegboonlap, P., Hotchkiss, S., Gill, C., Yaqoob, P., Spencer, J. P. E., & Rowland, I. (2016). Gastrointestinal modifications and bioavailability of brown seaweed phlorotannins and effects on inflammatory markers. British Journal of Nutrition, 115, 1240–1253. https://doi.org/10.1017/S0007114516000210
- Fukuyama, Y., Miura, I., Kinzyo, Z., Mori, H., Kido, M., Nakayama, Y., & Ochi, M. (1985). Eckols, novel phlorotannins with a dibenzo-p-dioxin skeleton possessing inhibitory effects on α2-macroglobulin from the brown alga Ecklonia kurome Okamura. Chemistry Letters, 14, 739–742. https://doi.org/10.1246/cl.1985.739
- Funk, C. D. (2001). Prostaglandins and leukotrienes: Advances in eicosanoid biology. Science, 294, 1871–1875. https://doi.org/10.1126/science.294.5548.1871
- Hardy, H., Harris, J., Lyon, E., Beal, J., & Foey, A. D. (2013). Probiotics, prebiotics and immunomodulation of gut mucosal defences: Homeostasis and immunopathology. Nutrients, 5, 1869–1912. https://doi.org/10.3390/nu5061869
- Hirasawa, N., Ohsawa, Y., Katoh, G., Shibata, K., Ishihara, K., Seyama, T., & Ohuchi, K. (2009). Modification of the picryl chloride-induced allergic dermatitis model in mouse ear lobes by 12-O-tetradecanoylphorbol 13-acetate, and analysis of the role of histamine in the modified model. International Archives of Allergy and Immunology, 148, 279–288. https://doi.org/10.1159/000170381
- Hirasawa, N., Scharenberg, A., Yamamura, H., Beaven, M. A., & Kinet, J.-P. (1995). A requirement for Syk in the activation of the microtubule-associated protein kinase/phospholipase A2 pathway by FcϵR1 is not shared by a G protein-coupled receptor. Journal of Biological Chemistry, 270, 10960–10967. https://doi.org/10.1074/jbc.270.18.10960
- Ivetić Tkalčević, V., Čužić, S., Dominis Kramarić, M., Parnham, M. J., & Eraković Haber, V. (2012). Topical azithromycin and clarithromycin inhibit acute and chronic skin inflammation in sensitized mice, with apparent selectivity for Th2-mediated processes in delayed-type hypersensitivity. Inflammation, 35, 192–205. https://doi.org/10.1007/s10753-011-9305-9
- Jung, W.-K., Heo, S.-J., Jeon, Y.-J., Lee, C.-M., Park, Y.-M., Byun, H.-G., Choi, Y. H., Park, S.-G., & Choi, I.-W. (2009). Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells. Journal of Agricultural and Food Chemistry, 57, 4439–4446. https://doi.org/10.1021/jf9003913
- Kang, H. S., Chung, H. Y., Jung, J. H., Son, B. W., & Choi, J. S. (2003). A new phlorotannin from the brown alga Ecklonia stolonifera. Chemical & Pharmaceutical Bulletin, 51, 1012–1014. https://doi.org/10.1248/cpb.51.1012
- Kang, N.-J., Koo, D.-H., Kang, G.-J., Han, S.-C., Lee, B.-W., Koh, Y.-S., Hyun, J.-W., Lee, N.-H., Ko, M.-H., Kang, H.-K., & Yoo, E.-S. (2015). Dieckol, a component of Ecklonia cava, suppresses the production of MDC/CCL22 via down-regulating STAT1 pathway in interferon-γ stimulated HaCaT human keratinocytes. Biomolecules and Therapeutics, 23, 238–244. https://doi.org/10.4062/biomolther.2014.141
- Kawai, H., Akita, S., Hashimoto, K., & Hanyuda, T. (2020). A multigene molecular phylogeny of Eisenia reveals evidence for a new species, Eisenia nipponica (Laminariales), from Japan. European Journal of Phycology, 55, 234–241. https://doi.org/10.1080/09670262.2019.1692911
- Kim, T. H., Ku, S.-K., & Bae, J.-S. (2012). Antithrombotic and profibrinolytic activities of eckol and dieckol. Journal of Cellular Biochemistry, 113, 2877–2883. https://doi.org/10.1002/jcb.24163
- Kim, T. H., Ku, S.-K., Lee, T., & Bae, J.-S. (2012). Vascular barrier protective effects of phlorotannins on HMGB1-mediated proinflammatory responses in vitro and in vivo. Food and Chemical Toxicology, 50, 2188–2195. https://doi.org/10.1016/j.fct.2012.03.082
- Kujubu, D. A., Fletcher, B. S., Varnum, B. C., Lim, R. W., & Herschman, H. R. (1991). TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. Journal of Biological Chemistry, 266, 12866–12872. https://doi.org/10.1016/S0021-9258(18)98774-0
- Kwak, J. H., Yang, Z., Yoon, B., He, Y., Uhm, S., Shin, H.-C., Lee, B. H., Yoo, Y. C., Lee, K. B., Han, S.-Y., & Kim, J. S. (2015). Blood-brain barrier-permeable fluorone-labeled dieckols acting as neuronal ER stress signaling inhibitors. Biomaterials, 61, 52–60. https://doi.org/10.1016/j.biomaterials.2015.04.045
- Le, Q.-T., Li, Y., Qian, Z.-J., Kim, M.-M., & Kim, S.-K. (2009). Inhibitory effects of polyphenols isolated from marine alga Ecklonia cava on histamine release. Process Biochemistry, 44, 168–176. https://doi.org/10.1016/j.procbio.2008.10.002
- Lee, S.-H., Park, M.-H., Heo, S.-J., Kang, S.-M., Ko, S.-C., Han, J.-S., & Jeon, Y.-J. (2010). Dieckol isolated from Ecklonia cava inhibits α-glucosidase and [alpha]-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Food and Chemical Toxicology, 48, 2633–2637. https://doi.org/10.1016/j.fct.2010.06.032
- Maruyama, H., Tamauchi, H., Hashimoto, M., & Nakano, T. (2005). Suppression of Th2 immune responses by Mekabu fucoidan from Undaria pinnatifida Sporophylls. International Archives of Allergy and Immunology, 137, 289–294. https://doi.org/10.1159/000086422
- Matsui, T., Ito, C., Furukawa, H., Okada, T., & Itoigawa, M. (2013). Lansiumamide B and SB-204900 isolated from Clausena lansium inhibit histamine and TNF-α release from RBL-2H3 cells. Inflammation Research, 62, 333–341. https://doi.org/10.1007/s00011-012-0586-8
- Matsuo, N., Yamada, K., Shoji, K., Mori, M., & Sugano, M. (1997). Effect of tea polyphenols on histamine release from rat basophilic leukemia (RBL-2H3) cells: The structure–inhibitory activity relationship. Allergy, 52, 58–64. https://doi.org/10.1111/j.1398-9995.1997.tb02546.x
- Meurer, R., Opas, E. E., & Humes, J. L. (1988). Effects of cyclooxygenase and lipoxygenase inhibitors on inflammation associated with oxazolone-induced delayed hypersensitivity. Biochemical Pharmacology, 37, 3511–3514. https://doi.org/10.1016/0006-2952(88)90704-6
- Myung, C. S., Shin, H. C., Bao, H. Y., Yeo, S. J., Lee, B. H., & Kang, J. S. (2005). Improvement of memory by dieckol and phlorofucofuroeckol in ethanol-treated mice: Possible involvement of the inhibition of acetylcholinesterase. Archives of Pharmacal Research, 28, 691–698. https://doi.org/10.1007/BF02969360
- Nakamura, T., Nagayama, K., Uchida, K., & Tanaka, R. (1996). Antioxidant activity of phlorotannins isolated from the brown alga Eisenia bicyclis. Fisheries Science, 62, 923–926. https://doi.org/10.2331/fishsci.62.923
- Nigorikawa, K., Hazeki, K., Guo, Y., & Hazeki, O. (2014). Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells. PLoS One, 9, e111698. https://doi.org/10.1371/journal.pone.0111698
- Platts-Mills, T. A. E. (2015). The allergy epidemics: 1870–2010. Journal of Allergy and Clinical Immunology, 136, 3–13. https://doi.org/10.1016/j.jaci.2015.03.048
- Ragan, M., & Glombitza, K. (1986). Phlorotannins, brown algal polyphenols. In D. J. Chapman (Ed.), Progress in phycological research, Vol. 4 (pp. 129–241). Biopress Ltd.
- Rao, T. S., Currie, J. L., Shaffer, A. F., & Isakson, P. C. (1993). Comparative evaluation of arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation. Inflammation, 17, 723–741. https://doi.org/10.1007/BF00920477
- Sakai, S., Sugawara, T., Matsubara, K., & Hirata, T. (2009). Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptors. Journal of Biological Chemistry, 284, 28172–28179. https://doi.org/10.1074/jbc.M109.001099
- Schwartz, L., Lewis, R., Seldin, D., & Austen, K. (1981). Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. The Journal of Immunology, 126, 1290–1294.
- Shibata, T., Nagayama, K., Tanaka, R., Yamaguchi, K., & Nakamura, T. (2003). Inhibitory effects of brown algal phlorotannins on secretory phospholipase A2s, lipoxygenases and cyclooxygenases. Journal of Applied Phycology, 15, 61–66. https://doi.org/10.1023/A:1022972221002
- Sugiura, Y., Kinoshita, Y., Abe, M., Murase, N., Tanaka, R., Matsushita, T., Usui, M., Hanaoka, K.-I., & Miyata, M. (2016). Suppressive effects of the diethyl ether fraction from a brown alga Sargassum fusiforme on allergic and inflammatory reactions. Fisheries Science, 82, 369–377. https://doi.org/10.1007/s12562-016-0969-9
- Sugiura, Y., Matsuda, K., Okamoto, T., Kakinuma, M., & Amano, H. (2008). Anti-allergic effects of the brown alga Eisenia arborea on Brown Norway rats. Fisheries Science, 74, 180–186. https://doi.org/10.1111/j.1444-2906.2007.01508.x
- Sugiura, Y., Matsuda, K., Okamoto, T., Yamada, Y., Imai, K., Ito, T., Kakinuma, M., & Amano, H. (2009). The inhibitory effects of components from a brown alga, Eisenia arborea, on degranulation of mast cells and eicosanoid synthesis. Journal of Functional Foods, 1, 387–393. https://doi.org/10.1016/j.jff.2009.08.002
- Sugiura, Y., Matsuda, K., Yamada, Y., Nishikawa, M., Shioya, K., Katsuzaki, H., & Amano, H. (2006). Isolation of a new anti-allergic phlorotannin, phlorofucofuroeckol-B, from an edible brown alga, Eisenia arborea. Bioscience, Biotechnology, and Biochemistry, 70, 2807–2811. https://doi.org/10.1271/bbb.60417
- Sugiura, Y., Matsuda, K., Yamada, Y., Nishikawa, M., Shioya, K., Katsuzaki, H., Imai, K., & Amano, H. (2007). Anti-allergic phlorotannins from the edible brown alga, Eisenia Arborea. Food Science and Technology Research, 13, 54–60. https://doi.org/10.3136/fstr.13.54
- Sugiura, Y., Tanaka, R., Katsuzaki, H., Imai, K., & Matsushita, T. (2013). The anti-inflammatory effects of phlorotannins from Eisenia arborea on mouse ear edema by inflammatory inducers. Journal of Functional Foods, 5, 2019–2023. https://doi.org/10.1016/j.jff.2013.08.010
- Sugiura, Y., Usui, M., Katsuzaki, H., Imai, K., Kakinuma, M., Amano, H., & Miyata, M. (2018). Orally administered phlorotannins from Eisenia arborea suppress chemical mediator release and cyclooxygenase-2 signaling to alleviate mouse ear swelling. Marine Drugs, 16, 267. https://doi.org/10.3390/md16080267
- Sugiura, Y., Usui, M., Katsuzaki, H., Imai, K., & Miyata, M. (2017). Anti-inflammatory effects of 6,6′-bieckol and 6,8′-bieckol from Eisenia arborea on mouse ear swelling. Food Science and Technology Research, 23, 475–480. https://doi.org/10.3136/fstr.23.475
- Sugiura, Y., Usui, M., & Miyata, M. (2017). The suppressive effect of the lipophilic fraction of Eisenia arborea on ear swelling in mice. Journal of National Fisheries University, 65, 245–251 [in Japanese].
- Tachibana, H. (2011). Green tea polyphenol sensing. Proceedings of the Japan Academy, Series B, 87, 66–80. https://doi.org/10.2183/pjab.87.66
- Takano-Ishikawa, Y., Goto, M., & Yamaki, K. (2006). Structure–activity relations of inhibitory effects of various flavonoids on lipopolysaccharide-induced prostaglandin E2 production in rat peritoneal macrophages: Comparison between subclasses of flavonoids. Phytomedicine, 13, 310–317. https://doi.org/10.1016/j.phymed.2005.01.016
- Taniguchi, M. (2012). Measures for allergic disease and medical network in Japan. Japanese Journal of Allergology, 61, 913–918 [in Japanese]. https://doi.org/10.15036/arerugi.61.913
- Yang, G., Oh, J.-W., Lee, H. E., Lee, B. H., Lim, K.-M., & Lee, J. Y. (2016). Topical application of dieckol ameliorates atopic dermatitis in NC/Nga mice by suppressing thymic stromal lymphopoietin production. Journal of Investigative Dermatology, 136, 1062–1066. https://doi.org/10.1016/j.jid.2015.12.046
- Yano, H., Nakanishi, S., Kimura, K., Hanai, N., Saitoh, Y., Fukui, Y., Nonomura, Y., & Matsuda, Y. (1993). Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. Journal of Biological Chemistry, 268, 25846–25856. https://doi.org/10.1016/S0021-9258(19)74466-4
- Yoon, J.-S., Kasin Yadunandam, A., Kim, S.-J., Woo, H.-C., Kim, H.-R., & Kim, G.-D. (2013). Dieckol, isolated from Ecklonia stolonifera, induces apoptosis in human hepatocellular carcinoma Hep3B cells. Journal of Natural Medicines, 67, 519–527. https://doi.org/10.1007/s11418-012-0709-0
- Yoshino, K., Yamazaki, K., & Sano, M. (2010). Preventive effects of black tea theaflavins against mouse type IV allergy. Journal of the Science of Food and Agriculture, 90, 1983–1987. https://doi.org/10.1002/jsfa.4035
- Young, J. M., Spires, D. A., Bedord, C. J., Wagner, B., Ballaron, S. J., & de Young, L. M. (1984). The mouse ear inflammatory response to topical arachidonic acid. Journal of Investigative Dermatology, 82, 367–371. https://doi.org/10.1111/1523-1747.ep12260709
- Zachariassen, L. F., Krych, L., Engkilde, K., Nielsen, D. S., Kot, W., Hansen, C. H. F., & Hansen, A. K. (2017). Sensitivity to oxazolone induced dermatitis is transferable with gut microbiota in mice. Scientific Reports, 7, 44385. https://doi.org/10.1038/srep44385