6-Hydroxyflavone and Derivatives Exhibit Potent Anti-Inflammatory Activity among Mono-, Di- and Polyhydroxylated Flavones in Kidney Mesangial Cells

• DOI: 10.1371/journal.pone.0116409
• Publication Date: 2015-03-19T18:08:11Z
• Authors: Xing Wang; Zhiwei Wang; Preetpal Singh Sidhu; Umesh R. Desai; Qibing Zhou
• Keywords: Flavonoids; Lipopolysaccharides; 0303 health sciences; Science; Q; R; Anti-Inflammatory Agents; Pharmacy and Pharmaceutical Sciences; Flavones; Rats; 3. Good health; 03 medical and health sciences; Mesangial Cells; Medicine; Animals; Nitric Oxide Synthase; Research Article

Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS) as the inflammatory stimuli. 6-Hydroxyflavone and 4',6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the most potent with an IC50 of 192 nM. Mechanistic study indicated that the anti-inflammatory activity of 6-methoxyflavone arose via the inhibition of LPS-induced downstream inducible NO synthase in mesangial cells. The identification of 6-hydroxyflavone and 6-methoxyflavone with potent anti-inflammatory activity in kidney mesangial cells provides a new flavone scaffold and direction to develop naturally derived products for potential nephritis prevention and treatment.