title: The açaí flavonoid velutin is a potent anti-inflammatory agent: blockade of LPS-mediated TNF-α and IL-6 production through inhibiting NF-κB activation and MAPK pathway.
abstract: Recent studies have shown that some flavonoids are modulators of proinflammatory cytokine production. In this study, velutin, a unique flavone isolated from the pulp of açaí fruit (Euterpe oleracea Mart.), was examined for its effects in reducing lipopolysaccharide-induced proinflammatory cytokine tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in RAW 264.7 peripheral macrophages and mice peritoneal macrophages. Three other structurally similar and well-studied flavones, luteolin, apigenin and chrysoeriol, were included as controls and for comparative purposes. Velutin exhibited the greatest potency among all flavones in reducing TNF-α and IL-6 production. Velutin also showed the strongest inhibitory effect in nuclear factor (NF)-κB activation (as assessed by secreted alkaline phosphatase reporter assay) and exhibited the greatest effects in blocking the degradation of inhibitor of NF-κB as well as in inhibiting mitogen-activated protein kinase p38 and JNK phosphorylation; all of these are important signaling pathways involved in production of TNF-α and IL-6. The present study led to the discovery of a strong anti-inflammatory flavone, velutin. This compound effectively inhibited the expression of proinflammatory cytokines TNF-α and IL-6 in low micromole levels by inhibiting NF-κB activation and p38 and JNK phosphorylation.
authors.affiliation: USDA Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Xie
authors.forename: Jie
authors.initials: J
authors.lastname: Kang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Li
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Schauss
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Nagarajan
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.forename: Xianli
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology; D028023:Arecaceae / Q000737:chemistry; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047309:Flavones; D005419:Flavonoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D047310:Apigenin; C577620:5,4'-dihydroxy-7,3'-dimethoxyflavone; D047311:Luteolin; C007054:chrysoeriol