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Abstract Title:

Flavonoids reduces lipopolysaccharide-induced release of inflammatory mediators in human bronchial epithelial cells: Structure-activity relationship.

Abstract Source:

Eur J Pharmacol. 2019 Oct 11 ;865:172731. Epub 2019 Oct 11. PMID: 31610186

Abstract Author(s):

Peng Zhang, Judith Cw Mak, Ricky Yk Man, Susan Ws Leung

Article Affiliation:

Peng Zhang

Abstract:

Flavonoids are polyphenolic compounds that are widely present in food and Chinese medicine. The aim of the present study was to identify the flavonoids with anti-inflammatory effects in the airway; and to determine the role of anti-oxidant and cyclic adenosine monophosphate (cAMP) in the anti-inflammatory effect. Human bronchial epithelial BEAS-2B cells were exposed to bacterial endotoxin lipopolysaccharide (LPS) in the absence or presence of different flavonoids, which are categorized according to their chemical structures in seven subclasses [anthocyanidins, chalcones, flavanes, flavanones, flavones, flavonols, isoflavones]. Among the 17 flavonoids tested, only apigenin (flavones), luteolin (flavones), daidzein (isoflavones) and genistein (isoflavones) reduced LPS-induced release of inflammatory cytokines/chemokines interleukin (IL)-6, IL-8 and monocyte chemoattractant protein-1 in BEAS-2B cells. Quercetin caused further increase in LPS-induced IL-6 and IL-8 levels. It alone significantly increased nuclear factor-kappa B (NF-κB) p65 activity and the cellular oxidative stress marker malondialdehyde (MDA) level in BEAS-2B cells. By contrast, apigenin and genistein reduced LPS-induced increases in nuclear NF-κB activity and MDA level. Apigenin and genistein, but not quercetin, increased the cAMP level in BEAS-2B cells, and the cell-permeable cAMP analogue, 8-Br-cAMP, inhibited LPS-induced increase of IL-8 level. These findings suggest that the presence of C5-OH, C7-OH, C2=C3 and C4=O functional groups in the flavonoids is associated with greater anti-inflammatory effect, while that of C3-OH or glycosylation group at the A-ring greatly decreased the anti-inflammatory effect. The anti-inflammatory effect of these flavonoids may be related to their anti-oxidant properties, and partly to their ability in increasing cAMP level.

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