Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in...

Area of Science:

• Biochemistry
• Immunology
• Pharmacology

Background:

• Fisetin is a flavonoid with known anti-inflammatory properties.
• The precise molecular mechanisms underlying fisetin's anti-inflammatory effects remain unclear.

Purpose of the Study:

• To elucidate the anti-inflammatory mechanism of fisetin.
• To investigate the role of GSK-3β/β-catenin and NF-κB signaling pathways in fisetin's action.

Main Methods:

• Utilized lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish larvae models.
• Assessed the expression of inflammatory mediators (NO, PGE2) and cytokines (IL-6, TNF-α).
• Investigated the activation of NF-κB, GSK-3β, and β-catenin signaling pathways.

Main Results:

• Fisetin significantly inhibited LPS-induced production of NO, PGE2, IL-6, and TNF-α in macrophages.
• Fisetin reduced LPS-induced mortality and inflammatory cell recruitment in zebrafish larvae.
• Fisetin suppressed NF-κB nuclear translocation by activating GSK-3β/β-catenin signaling.

Conclusions:

• Fisetin exhibits potent anti-inflammatory effects against LPS-induced inflammation and endotoxic shock.
• The mechanism involves the inhibition of NF-κB signaling via the GSK-3β/β-catenin pathway.
• Fisetin represents a promising therapeutic agent for inflammatory conditions.