Anti-allergic property of dietary phytoestrogen secoisolariciresinol diglucoside through microbial and β-glucuronidase-mediated metabolism

Kento Sawane; Takahiro Nagatake; Koji Hosomi; Jun Kunisawa

doi:10.1016/j.jnutbio.2022.109219

Anti-allergic property of dietary phytoestrogen secoisolariciresinol diglucoside through microbial and β-glucuronidase-mediated metabolism

J Nutr Biochem. 2023 Feb:112:109219. doi: 10.1016/j.jnutbio.2022.109219. Epub 2022 Nov 11.

Authors

Kento Sawane¹, Takahiro Nagatake², Koji Hosomi³, Jun Kunisawa⁴

Affiliations

¹ Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
² Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan; Laboratory of Functional Anatomy, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa, Japan; Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine, NIBIOHN.
³ Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan; Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine, NIBIOHN.
⁴ Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine, NIBIOHN; Graduate School of Medicine, Graduate School of Science and Graduate School of Dentistry, Osaka University, Osaka, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology and International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Electronic address: kunisawa@nibiohn.go.jp.

PMID: 36375731
DOI: 10.1016/j.jnutbio.2022.109219

Abstract

Phytoestrogens play pivotal roles in controlling not only the endocrine system but also inflammatory metabolic disorders. However, the effects of dietary phytoestrogens on allergic diseases and underlying mechanisms remain unclear. In this study, we revealed the unique metabolic conversion of phytoestrogen to exert anti-allergic properties, using an ovalbumin-induced allergic rhinitis mouse model. We found that dietary secoisolariciresinol diglucoside (SDG), a phytoestrogen abundantly present in flaxseed, alleviated allergic rhinitis by the microbial conversion to enterodiol (ED). We also found that ED circulated mainly in the glucuronide form (EDGlu) in blood, and deconjugation of EDGlu to ED aglycone occurred in the nasal passage; this activity was enhanced after the induction of allergic rhinitis, which was mediated by β-glucuronidase. We further found that IgE-mediated degranulation was inhibited by ED aglycone, but not by EDGlu, in a G protein-coupled receptor 30 (GPR30)-dependent manner. These results provide new insights into the anti-allergic properties of phytoestrogens and their metabolism in vivo for the development of novel therapeutic strategies against allergic rhinitis.

Keywords: GPR30; allergic rhinitis; degranulation; phytoestrogen; secoisolariciresinol diglucoside; β-glucuronidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Allergic Agents* / pharmacology
Anti-Allergic Agents* / therapeutic use
Glucuronidase
Mice
Phytoestrogens / metabolism
Phytoestrogens / pharmacology
Phytoestrogens / therapeutic use
Rhinitis, Allergic* / drug therapy

Substances

secoisolariciresinol diglucoside
Phytoestrogens
Glucuronidase
Anti-Allergic Agents