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


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.

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Data Availability

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


0.9 mg:

0.9 mg phlorotannin-orally administered test group

4.5 mg:

4.5 mg phlorotannin-orally administered test group


Basic leucine zipper transcription factor


B-cell lymphoma


Forkhead box protein P3


GATA binding protein 3


High performance liquid chromatography






Liquid chromatography-mass spectrometry


Negative control group




Positive control group




Phlorotannin concentrate


Retinoic acid-related orphan receptor γt


Th1-specific T box transcription factor


Follicular helper T


Transforming growth factor


Type 1 helper T


Type 2 helper T


IL-17-producing helper T


Regulatory T


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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 ( for the English language review.


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

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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.

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Correspondence to Yoshimasa Sugiura.

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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).

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  • Brown algae
  • Phlorotannins
  • Immunomodulation
  • Antiallergy