Sesamin Catechol Glucuronides Exert Anti-inflammatory Effects by Suppressing Interferon β and Inducible Nitric Oxide Synthase Expression through Deconjugation in Macrophage-like J774.1 Cells

J Agric Food Chem. 2019 Jul 10;67(27):7640-7649. doi: 10.1021/acs.jafc.8b07227. Epub 2019 Apr 16.

Abstract

Sesamin, a representative sesame lignan, has health-promoting activities. Sesamin is converted into catechol derivatives and further into their glucuronides or sulfates in vivo, whereas the biological activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin metabolites on the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse macrophage-like J774.1 cells and found that a monocatechol derivative SC1, (7α,7'α,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane, has a much higher activity than sesamin and other metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced, associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides and SC1 attenuated the expression of inducible NO synthase (iNOS) and upstream interferon-β (IFN-β) in the LPS-stimulated macrophages. The inhibitory effects of SC1 glucuronides against NO production were canceled by the β-glucuronidase inhibitor and enhanced by the catechol-O-methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the anti-inflammatory effects by inhibiting the IFN-β/iNOS signaling through macrophage-mediated deconjugation.

Keywords: anti-inflammation; deconjugation; macrophage; nitric oxide; sesamin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents*
  • Catechol O-Methyltransferase / metabolism
  • Catechols / chemistry
  • Catechols / metabolism
  • Catechols / pharmacology*
  • Cell Line
  • Cytochrome P-450 Enzyme System / metabolism
  • Dioxoles / metabolism
  • Dioxoles / pharmacology*
  • Glucuronidase / metabolism
  • Glucuronides / chemistry
  • Glucuronides / pharmacology*
  • Interferon-beta / antagonists & inhibitors*
  • Lignans / metabolism
  • Lignans / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Molecular Structure
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents
  • Catechols
  • Dioxoles
  • Glucuronides
  • Lignans
  • Interferon-beta
  • Cytochrome P-450 Enzyme System
  • Nitric Oxide Synthase Type II
  • Catechol O-Methyltransferase
  • Glucuronidase
  • sesamin