Synthesis of 3,3’,4’,7-tetraacetate fisetin and evaluation of its anti-inflammatory effect on LPS-stimulated RAW264.7 macrophages

Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a bioactive flavonol found in various fruits and vegetables, particularly strawberries, apples, persimmons, grapes, onions, and cucumbers. It possesses various properties, such as antioxidant, cytoprotective, and anti-inflammatory properties. In this study,...

Full description

Saved in:
Bibliographic Details
Published in:Journal of applied biological chemistry 2024-12, Vol.67, p.204
Main Authors: Neupane Asmita, Hyehyun Hong, Byeong Min Choi, Tae-jin Park, Won-jae Chi, Seung-young Kim
Format: Article
Language:Korean
Subjects:
3
4
7-tetraacetate fisetin
Acetylation
Anti-inflammatory agent
Fisetin
Inhibitory effects
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a bioactive flavonol found in various fruits and vegetables, particularly strawberries, apples, persimmons, grapes, onions, and cucumbers. It possesses various properties, such as antioxidant, cytoprotective, and anti-inflammatory properties. In this study, we synthesized a compound, 3,3′,4′,7-tetraacetate fisetin (FTA), from fisetin using an acetylation approach for structural modification. We aimed to investigate whether acetylation enhances the anti-inflammatory activity of the natural flavonoid, fisetin. Cell viability and restraining effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production were superior in FTA-treated RAW264.7 cells than in the fisetin-treated equivalents. Furthermore, compared to the parent compound fisetin, the novel compound FTA efficiently inhibited the production of pro-inflammatory cytokines, namely prostaglandin E2, interleukin-6, and interleukin-1β, and decreased the protein expression levels of inducible NO synthase and cyclooxygenase-2 in a dose-dependent manner. FTA suppressed LPS-induced inflammation by downregulating the phosphorylation of nuclear factor-kappa B, extracellular signal-regulated kinase, and c-Jun N-terminal kinase via the regulation of the mitogenactivated protein kinase signaling pathway. Notably, acetylation strongly enhanced the anti-inflammatory activity of fisetin in this study and may be used as a promising strategy to increase the bioactivity of other natural products. Our data suggest that the acetylated flavonoid developed in this study can aid in future drug development of drugs, particularly as anti-inflammatory agents.
ISSN:1976-0442