5, 7-Dihydroxyflavone Analogues May Regulate Lipopolysaccharide-Induced Inflammatory Responses by Suppressing IκBα-Linked Akt and ERK5 Phosphorylation in RAW 264.7 Macrophages. (30th April 2017)

• Record Type: Journal Article
• Authors: Nishina, Atsuyoshi; Shimizu, Kazue; Koketsu, Mamoru; Ninomiya, Masayuki; Sato, Daisuke; Suzuki, Takashi; Hayakawa, Satoshi; Kimura, Hirokazu
• Other Names: Williams Darren R. Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2017(2017)
• Publication Date: 2017-04-30
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2017/7898973
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : We studied the anti-inflammatory activity of twelve 5, 7-dihydroxyflavone analogues in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. We found that chrysin (1 ) and 4′-methoxytricetin (9 ) showed relatively significant anti-inflammatory activity and low cytotoxicity. Moreover, 1 and 9 recovered the expression levels of iNOS and COX2, as well as those of the intracellular inflammatory mediators IL-1 β and IL-6, which were upregulated by LPS stimulation. In addition, 1 and 9 actively regulated the phosphorylation of I κ B α, leading to the activation of NF κ B. Phosphorylation of Akt and ERK5 (upstream of NF κ B) by LPS stimulation was significantly regulated by 1 and 9, as well as by BIX 02189 and LY 294002, which are phosphorylation inhibitors of ERK5 and Akt, respectively. The results suggest that compounds 1 and 9 may suppress the levels of iNOS and COX2 by regulating phosphorylation of Akt, ERK5, and I κ B α and thus NF κ B-related signaling pathways, resulting in anti-inflammatory effects in the cells. Because 1 and 9 showed low cytotoxicity and regulated both PGE2 and NO production caused by inflammatory responses, they may hold promise as natural anti-inflammatory agents.