Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB.

Persistent activation of nuclear factor-κB (NF-κB) has been associated with the development of asthma. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring bioactive flavonol, has been shown to inhibit NF-κB activity. We hypothesized that fisetin may attenuate allergic asthma via negative regulation of the NF-κB activity. Female BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Fisetin dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of adhesion molecules, chitinase, IL-17, IL-33, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. Fisetin blocked NF-κB subunit p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. In normal human bronchial epithelial cells, fisetin repressed TNF-α-induced NF-κB-dependent reporter gene expression. Our findings implicate a potential therapeutic value of fisetin in the treatment of asthma through negative regulation of NF-κB pathway.

Goh FY ，Upton N ，Guan S ，Cheng C ，Shanmugam MK ，Sethi G ，Leung BP ，Wong WS ... -  《-》

A novel antiinflammatory role for andrographolide in asthma via inhibition of the nuclear factor-kappaB pathway.

Bao Z ，Guan S ，Cheng C ，Wu S ，Wong SH ，Kemeny DM ，Leung BP ，Wong WS ... -  《-》

Glycogen synthase kinase-3beta inhibition attenuates asthma in mice.

Bao Z ，Lim S ，Liao W ，Lin Y ，Thiemermann C ，Leung BP ，Wong WS ... -  《AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE》

Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF-κB signaling pathway.

Huang W ，Li ML ，Xia MY ，Shao JY ... -  《-》

Anti-malarial drug artesunate attenuates experimental allergic asthma via inhibition of the phosphoinositide 3-kinase/Akt pathway.

Cheng C ，Ho WE ，Goh FY ，Guan SP ，Kong LR ，Lai WQ ，Leung BP ，Wong WS ... -  《PLoS One》