Skip to main content

The Immunomodulating Effect of Phlorotannins from a Brown Alga, Eisenia nipponica, on Mice Stimulated with Ovalbumin through T Cell Regulation

Abstract

The immunomodulating effect of phlorotannin was investigated in mice stimulated by ovalbumin. When analyzing the main components of phlorotannin concentrate (PTC) from Eisenia nipponica, seven phlorotannins [eckol, 6,6′-bieckol, 6,8′-bieckol, 8,8′-bieckol, dieckol, phlorofucofuroeckol (PFF)-A, and PFF-B] were detected. These phlorotannins accounted for approximately 80% of PTC. Oral administration of PTC to mice daily for 21 days reduced serum immunoglobulin E (IgE) and total IgG1 levels attributable to Th2 cells. The production of splenic cytokines [interleukin (IL)-10 and transforming growth factor-β1] and Treg cell-mediated expression of forkhead box protein P3 mRNA were significantly increased whereas the production of inflammatory cytokines (interferon-γ, IL-4, IL-5, and IL-17) by Th1, Th2, and Th17 cells was markedly suppressed. IL-21 production and basic leucine zipper ATF-like transcription factor mRNA expression attributable to follicular helper T (Tfh) cells were also suppressed. Flow cytometric analyses demonstrated increased number of Treg cells despite a decrease in the total T cell population. An increase in total B cells was also observed by the flow cytometric analyses in addition to increases in IL-10 production, which activates B cells. In contrast, the significantly suppressed production of inflammatory cytokines and moderate increase in Treg cell subpopulation indicated a direct impact of PTC on inflammatory lymphocytes (Th1, Th2, Th17, and Tfh). Thus, PTC may exert antiallergic effects by immunomodulation of T cells and inactivation of inflammatory lymphocyte.

Graphical abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Data Availability

The datasets generated in present study are available from the corresponding author on reasonable request.

Abbreviations

0.9 mg:

0.9 mg phlorotannin-orally administered test group

4.5 mg:

4.5 mg phlorotannin-orally administered test group

Batf:

Basic leucine zipper transcription factor

Bcl:

B-cell lymphoma

Foxp3:

Forkhead box protein P3

GATA3:

GATA binding protein 3

HPLC:

High performance liquid chromatography

IFN:

Interferon

IL:

Interleukin

LC-MS:

Liquid chromatography-mass spectrometry

NC:

Negative control group

OVA:

Ovalbumin

PC:

Positive control group

PFF:

Phlorofucofuroeckol

PTC:

Phlorotannin concentrate

RORγt:

Retinoic acid-related orphan receptor γt

T-bet:

Th1-specific T box transcription factor

Tfh:

Follicular helper T

TGF:

Transforming growth factor

Th1:

Type 1 helper T

Th2:

Type 2 helper T

Th17:

IL-17-producing helper T

Treg:

Regulatory T

References

  1. Platts-Mills TAE (2015) The allergy epidemics: 1870–2010. J Allergy Clin Immunol 136:3–13. https://doi.org/10.1016/j.jaci.2015.03.048

    Article  Google Scholar 

  2. Ragan M, Glombitza K (1986) Phlorotannins, brown algal polyphenols. In: Round FE, Chapman DJ (eds) Progress in phycological research, vol 4. Biopress Ltd, Bistrol, pp 129–241

  3. Sugiura Y, Imai K, Amano H (2011) The anti-allergic and anti-inflammatory effects of seaweed polyphenol (phlorotannin). Foods Food Ingredients J Jpn 216(1):46–55 (in Japanese)

    CAS  Google Scholar 

  4. Achiha H, Fujisaki K (1989) Commercial seaweeds in Aichi Prefecture, central Japan. Aquac Sci 37:71–76. https://doi.org/10.11233/aquaculturesci1953.37.71 (in Japanese)

    Article  Google Scholar 

  5. 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. Mar Drugs 16:267. https://doi.org/10.3390/md16080267

    CAS  Article  PubMed Central  Google Scholar 

  6. Venkatesan J, Keekan KK, Anil S, Bhatnagar I, Kim S-K (2019) Phlorotannins. In: Melton L, Shahidi F, Varelis P (Eds.) Encyclopedia of Food Chemistry, Oxford: Academic Press, pp 515–527. https://doi.org/10.1016/B978-0-08-100596-5.22360-3

  7. Sugiura Y, Matsuda K, Okamoto T, Kakinuma M, Amano H (2008) Anti-allergic effects of the brown alga Eisenia arborea on Brown Norway rats. Fish Sci 74:180–186. https://doi.org/10.1111/j.1444-2906.2007.01508.x

    CAS  Article  Google Scholar 

  8. Mosmann T, Cherwinski H, Bond M, Giedlin M, Coffman R (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    CAS  PubMed  Google Scholar 

  9. Orihara K, Nakae S, Pawankar R, Saito H (2008) Role of regulatory and proinflammatory T-cell populations in allergic diseases. World Allergy Organ J 1:9–14. https://doi.org/10.1097/wox.0b013e3181629ae3

    Article  PubMed  PubMed Central  Google Scholar 

  10. Crotty S (2014) T follicular helper cell differentiation, function, and roles in disease. Immunity 41:529–542. https://doi.org/10.1016/j.immuni.2014.10.004

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Ise W (2016) Development and function of follicular helper T cells. Biosci Biotechnol Biochem 80:1–6. https://doi.org/10.1080/09168451.2015.1056512

    CAS  Article  PubMed  Google Scholar 

  12. Sahoo A, Alekseev A, Tanaka K, Obertas L, Lerman B, Haymaker C, Clise-Dwyer K, McMurray JS, Nurieva R (2015) Batf is important for IL-4 expression in T follicular helper cells. Nat Commun 6:7997. https://doi.org/10.1038/ncomms8997

    CAS  Article  PubMed  Google Scholar 

  13. Harada Y, Tanaka S, Motomura Y, Harada Y, Ohno S-I, Ohno S, Yanagi Y, Inoue H, Kubo M (2012) The 3′ enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral immunity in follicular helper T cells. Immunity 36:188–200. https://doi.org/10.1016/j.immuni.2012.02.002

    CAS  Article  PubMed  Google Scholar 

  14. McCarron MJ, Marie JC (2014) TGF-β prevents T follicular helper cell accumulation and B cell autoreactivity. J Clin Invest 124:4375–4386. https://doi.org/10.1172/jci76179

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ahn G, Amagai Y, Matsuda A, Kang S-M, Lee W, Jung K, Oida K, Jang H, Ishizaka S, Matsuda K, Jeon Y-J, Jee Y, Matsuda H, Tanaka A (2015) Dieckol, a phlorotannin of Ecklonia cava, suppresses IgE-mediated mast cell activation and passive cutaneous anaphylactic reaction. Exp Dermatol 24:968–970. https://doi.org/10.1111/exd.12814

    Article  PubMed  Google Scholar 

  16. Han EJ, Kim H-S, Sanjeewa KKA, Herath KHINM, Jeon Y-J, Jee Y, Lee J, Kim T, Shim S-Y, Ahn G (2020) Eckol from Ecklonia cava suppresses immunoglobulin E-mediated mast cell activation and passive cutaneous anaphylaxis in mice. Nutrients 12:1361. https://doi.org/10.3390/nu12051361

    CAS  Article  PubMed Central  Google Scholar 

  17. Yang G, Oh J-W, Lee Hye E, Lee BH, Lim K-M, Lee JY (2016) Topical application of dieckol ameliorates atopic dermatitis in NC/Nga mice by suppressing thymic stromal lymphopoietin production. J Invest Dermatol 136:1062–1066. https://doi.org/10.1016/j.jid.2015.12.046

    CAS  Article  PubMed  Google Scholar 

  18. Oh S, Shim M, Son M, Jang JT, Son KH, Byun K (2021) Attenuating effects of dieckol on endothelial cell dysfunction via modulation of Th17/Treg balance in the intestine and aorta of spontaneously hypertensive rats. Antioxidants 10:298. https://doi.org/10.3390/antiox10020298

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Corona G, Ji Y, Anegboonlap P, Hotchkiss S, Gill C, Yaqoob P, Spencer JPE, Rowland I (2016) Gastrointestinal modifications and bioavailability of brown seaweed phlorotannins and effects on inflammatory markers. Br J Nutr 115:1240–1253. https://doi.org/10.1017/S0007114516000210

    CAS  Article  PubMed  Google Scholar 

  20. Go NF, Castle BE, Barrett R, Kastelein R, Dang W, Mosmann TR, Moore KW, Howard M (1990) Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med 172:1625–1631. https://doi.org/10.1084/jem.172.6.1625

    CAS  Article  PubMed  Google Scholar 

  21. Catalán D, Mansilla MA, Ferrier A, Soto L, Oleinika K, Aguillón JC, Aravena O (2021) Immunosuppressive mechanisms of regulatory B cells. Front Immunol 12:654. https://doi.org/10.3389/fimmu.2021.611795

    CAS  Article  Google Scholar 

  22. Okada Y, Oh-Oka K, Nakamura Y, Ishimaru K, Matsuoka S, Okumura K, Ogawa H, Hisamoto M, Okuda T, Nakao A (2012) Dietary resveratrol prevents the development of food allergy in mice. PLoS ONE 7:e44338. https://doi.org/10.1371/journal.pone.0044338

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Wang J, Ren Z, Xu Y, Xiao S, Meydani SN, Wu D (2012) Epigallocatechin-3-gallate ameliorates experimental autoimmune encephalomyelitis by altering balance among CD4+ T-cell subsets. Am J Pathol 180:221–234. https://doi.org/10.1016/j.ajpath.2011.09.007

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Yang E-J, Lee J, Lee S-Y, Kim E-K, Moon Y-M, Jung YO, Park S-H, Cho M-L (2014) EGCG attenuates autoimmune arthritis by inhibition of STAT3 and HIF-1α with Th17/Treg control. PLoS ONE 9:e86062. https://doi.org/10.1371/journal.pone.0086062

Download references

Acknowledgements

We thank Ms. M. Fuse, Mr. M. Ishibashi, Mr. S. Kedo, Mr. R. Ota, Mr. Y. Tanaka, and Ms. E. Yurino (National Fisheries University) for their technical assistance. The authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

This work was supported by the grant of JSPS KAKENHI (Grant Number 23880036, 25850099, and 17K07951).

Author information

Authors and Affiliations

Authors

Contributions

Yoshimasa Sugiura performed the study and drafted the manuscript; Yuta Matsuura, Hirotaka Katsuzaki, Makoto Kakinuma, Masakatsu Usui and Ryusuke Tanaka analyzed and interpreted the data; Hideomi Amano, Teruo Matsushita, and Masaaki Miyata supervised the study and drafted the manuscript. All authors approved the final manuscript.

Corresponding author

Correspondence to Yoshimasa Sugiura.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 144 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sugiura, Y., Matsuura, Y., Katsuzaki, H. et al. The Immunomodulating Effect of Phlorotannins from a Brown Alga, Eisenia nipponica, on Mice Stimulated with Ovalbumin through T Cell Regulation. Plant Foods Hum Nutr 77, 307–316 (2022). https://doi.org/10.1007/s11130-022-00974-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11130-022-00974-3

Keywords

  • Brown algae
  • Phlorotannins
  • Immunomodulation
  • Antiallergy