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Ethanol Extract of <i>Inonotus obliquus</i> Inhibits Lipopolysaccharide-Induced Inflammation in RAW 264.7 Macrophage Cells

Ho-Gyoung KimDepartment of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of KoreaDeok‐Hyo YoonDepartment of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of KoreaChun-Hoi KimDepartment of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of KoreaBhushan ShresthaDivision of Applied Biology, Kangwon National University, Republic of KoreaWoochul ChangCardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of KoreaSoyeon LimCardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of KoreaWon‐Ho LeeDivision of Applied Biology, Kangwon National University, Republic of KoreaSang-Guk HanDivision of Applied Biology, Kangwon National University, Republic of KoreaJe-O LeeDivision of Applied Biology, Kangwon National University, Republic of KoreaMi‐Hee LimDepartment of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of KoreaGi‐Young KimDepartment of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of KoreaSunga ChoiDepartment of Life Science, Hallym University, ChuncheonWon O. SongDepartment of Food Science and Human Nutrition, Michigan State University, East Lansing, MichiganJae‐Mo SungDivision of Applied Biology, Kangwon National University, Republic of KoreaKi‐Chul HwangCardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of KoreaTae‐Woong KimDepartment of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of Korea

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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.

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DOI: 10.1089/jmf.2006.156

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