Abstract 216: The Effect of Fisetin on Lipopolysccharide-induced Inflammation and MMP Activity in Mouse Peritoneal Macrophages
Objective: Fisetin is a flavonoid that is prominent in strawberries. Fisetin has been shown to have several favorable effects, including anti-aging, anti-inflammatory and anti-carcinogenic. Fisetin is also known to have anti-oxidant properties as with other flavonoids. The purpose of this study was to investigate the influence of fisetin on lipopolysccharide (LPS) -induced inflammation and matrix metalloproteinase (MMP) activity in mouse peritoneal macrophages (MPMs) in vivo.
Methods and Results: MPMs were harvested from BALB/c mice and cultured. After 30 minutes incubation with fisetin (10, 30 or 100 uM), MPMs were incubated with LPS (10 ng/ml) for 15 minutes, 60 minutes or 24 hours. LPS incubation increased concentrations of nitric oxide in supernatants that was attenuated by fisetin in a concentration-dependent manner. Similarly, mRNA abundance of inflammatory genes, such as MCP-1, IL-1b and iNOS, were enhanced by LPS, but were decreased by fisetin incubation in a concentration-dependent manner. Gelatin zymography demonstrated that LPS increased MMP-9 activity in supernatants that were decreased by the highest fisetin concentration. LPS-enhanced mRNA abundance of MMP-2 and MMP-9 were also attenuated by the highest concentration of festin. Fisetin also decreased LPS increased protein abundance uPA, as determined by Western blotting, and uPAR gene expression. Furthermore, fisetin also attenuated LPS enhanced ERK and JNK phosphorylation.
Conclusion: Fisetin attenuated LPS-induced oxidative stress, inflammation, and MMPs activity in MPMs.
Author Disclosures: H. Takeuchi: None. H.A. Uchida: None. R. Umebayashi: None. Y. Kakio: None. Y. Okuyama: None. T. Okuyama: None. J. Wada: None.
- © 2015 by American Heart Association, Inc.