title: Ethanol extract of Inonotus obliquus inhibits lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells.
abstract: Inonotus obliquus (Pers.:Fr.) Pil. is a white rot fungus that belongs to the family Hymenochaetaceae of Basidiomycetes. Extracts and fractions of this fungus have been known to have biological activities, including antimutagenic, anticancer, antioxidative, and immunostimulating effects. Recently, there have been reports that the anti-inflammatory and antinociceptive properties of the methanol extract of I. obliquus may be due to the inhibition of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression via the down-regulation of nuclear factor kappaB (NF-kappaB) binding activity. However, the effects of I. obliquus on Akt and mitogen-activated protein kinase (MAPK) activation of inflammatory mediator production have not yet been elucidated. In the present study, a 70% ethanol extract of I. obliquus (IOE70) showed antioxidative effects. We also tested the ability of the I. obliquus extract to inhibit the inflammatory cascades in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. The NO inhibition of IOE70 was better than that of other ethanol extracts from I. obliquus. To investigate the mechanism by which IOE 70 inhibits NO production and iNOS and COX-2 expression, we examined the activations of IkappaBalpha, Akt, and c-Jun NH(2) -terminal kinase (JNK) in LPS-activated macrophages. IOE70 markedly inhibited the phosphorylation of IkappaBalpha, Akt, and MAPKs in dose-dependent manners in LPS-activated macrophages. Taken together, these experiments demonstrated that IOE70 inhibition of LPS-induced expression of iNOS and COX-2 protein is mediated by Akt and JNK. Based on our findings, the most likely mechanism that can account for this biological effect of IOE70 involves the inhibition of NF-kappaB through the phosphatidylinositol 3-kinase/Akt/IkappaB pathway and the inhibition of JNK activation. Thus, IOE70 might have useful clinical applications in the management of inflammatory diseases and may also be useful as a medicinal food.
authors.affiliation: Department of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of Korea.
authors.forename: Ho-Gyoung
authors.initials: HG
authors.lastname: Kim
authors.forename: Deok-Hyo
authors.initials: DH
authors.lastname: Yoon
authors.forename: Chun-Hoi
authors.initials: CH
authors.lastname: Kim
authors.forename: Bhushan
authors.initials: B
authors.lastname: Shrestha
authors.forename: Woo-Chul
authors.initials: WC
authors.lastname: Chang
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Lim
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Lee
authors.forename: Sang-Guk
authors.initials: SG
authors.lastname: Han
authors.forename: Je-O
authors.initials: JO
authors.lastname: Lee
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Lim
authors.forename: Geun-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Sunga
authors.initials: S
authors.lastname: Choi
authors.forename: Won O
authors.initials: WO
authors.lastname: Song
authors.forename: Jae-Mo
authors.initials: JM
authors.lastname: Sung
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
authors.forename: Tae-Woong
authors.initials: TW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001487:Basidiomycota / Q000737:chemistry*; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases