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Bioactive Constituents, Metabolites, and Functions
Sesamin catechol glucuronides exert anti-inflammatory effects by suppressing IFN-# and iNOS expression through the deconjugation in macrophage-like J774.1 cells Naomi Abe-Kanoh, Yumi Lee, Daisuke Takemoto, Yoshiko Ono, Hiroshi Shibata, Kohta Ohnishi, and Yoshichika Kawai J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.8b07227 • Publication Date (Web): 05 Apr 2019 Downloaded from http://pubs.acs.org on April 7, 2019
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Journal of Agricultural and Food Chemistry
Sesamin catechol glucuronides exert anti-inflammatory effects by suppressing
and
iNOS expression through the deconjugation in macrophage-like J774.1 cells Naomi Abe-Kanoh*,†,‡, Yumi Lee§, Daisuke Takemoto , Yoshiko Ono*, , Hiroshi Shibata , Kohta Ohnishi†, , Yoshichika Kawai†
†
Department of Food Science, Institute of Biomedical Sciences, Tokushima University Graduate
School, Tokushima 770-8503, Japan ‡ Department
of Public Health and Applied Nutrition, Institute of Biomedical Sciences,
Tokushima University Graduate School, Tokushima 770-8503, Japan §
Department of Food Science, School of Medical Nutrition, Tokushima University, Tokushima
770-8503, Japan Institute for Health Care Science, Suntory Wellness, Ltd., 8-1-1 Seikadai, Seika-cho, Sorakugun, Kyoto 619-0284, Japan Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan Corresponding author: *(Y O) E-mail:
[email protected], Tel.: +81-774-66-1110. Fax: +81-774-98-6262. *(N A-K) E-mail:
[email protected], Tel./Fax: +81-88-633-7450 1 ACS Paragon Plus Environment
Journal of Agricultural and Food Chemistry
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ABSTRACT
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Sesamin, a representative sesame lignan, has health promoting activities. Sesamin is converted into
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catechol derivatives and further into their glucuronides or sulfates in vivo, whereas the biological
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activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin
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metabolites on the lipopolysaccharide (LPS)-induced NO production in mouse macrophage-like
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J774.1 cells and found that a mono-catechol derivative SC1, =-F -GF /F /GF>-3,4-dihydroxy-3’,4’-
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methylenedioxy-7,9’:7’,9-diepoxylignane, has a much higher activity than sesamin and other
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metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced,
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associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides
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and SC1 attenuated the expression of the inducible NO synthase (iNOS) and the upstream
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#
H =&$
H> in the LPS-stimulated macrophages. The inhibitory effects of SC1
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glucuronides against NO production were cancelled by the H 8(
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by the catechol-O-methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the
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anti-inflammatory effects by inhibiting the &$
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mediated deconjugation.
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KEYWORDS: Sesamin / Deconjugation / Macrophage / Anti-inflammation / Nitric oxide
HE
%
inhibitor and enhanced
signaling through the macrophage-
2 ACS Paragon Plus Environment
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Journal of Agricultural and Food Chemistry
INTRODUCTION
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Seeds and oils of sesame (Sesamum indicum L.) have long been recognized as traditional
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healthy foods in East Asian countries. Sesame seeds are a rich source of various nutrients, such as
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lipids, proteins, vitamins and minerals
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have attracted significant attention for their contribution to the biological activities and are
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commercially available as nutraceuticals in the form of capsules for an antioxidant function. The
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major sesame lignans are lipophilic sesamin and sesamolin in sesame oils and hydrophilic
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sesaminol glucosides in sesame seed cakes 3.
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Sesamin, =-F -GF /F /GF> 1
