title: 6-Hydroxyflavone and derivatives exhibit potent anti-inflammatory activity among mono-, di- and polyhydroxylated flavones in kidney mesangial cells.
abstract: 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.
authors: Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Xing
authors: X
authors: Wang
authors: Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Zhiwei
authors: Z
authors: Wang
authors: Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors: Preetpal Singh
authors: PS
authors: Sidhu
authors: Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors: Umesh R
authors: UR
authors: Desai
authors: Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors: Qibing
authors: Q
authors: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D050527:Mesangial Cells / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats
chemical_list: C000593132:6-methoxyflavone; D000893:Anti-Inflammatory Agents; D047309:Flavones; D005419:Flavonoids; D008070:Lipopolysaccharides; C529356:6-hydroxyflavone; D019001:Nitric Oxide Synthase