title: Ethanol Extract of Sarcodon asparatus Mitigates Inflammatory Responses in Lipopolysaccharide-Challenged Mice and Murine Macrophages.
abstract: A number of compounds isolated from mushrooms have exhibited disease-modifying effects. We sought to investigate the mechanisms responsible for the anti-inflammatory effects of an extract from the mushroom species Sarcodon asparatus (SAE). Male BALB/c mice (N=42; 6 weeks old) were randomly assigned to four treatment groups. Intraperitoneal administration of SAE significantly attenuated lipopolysaccharide (LPS)-mediated increases in alanine aminotransferase (ALT) activity. LPS also increased serum levels of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, which were dose-dependently and significantly attenuated by SAE. Correlative relationships between serum ALT activity and proinflammatory cytokines suggested that SAE-mediated suppression of liver injury was partly attributable to the attenuation of serum inflammatory responses. SAE significantly decreased hepatic NO(•) production and subsequent 3-nitrotyrosine formation, and the hepatic NO(•) production significantly correlated with serum ALT and cytokine levels, suggesting that SAE mitigates liver injury in association with inflammatory processes, likely by suppressing NO(•) production. Anti-inflammatory activity and further mechanisms of SAE were evaluated using RAW264.7 with LPS challenge. Noncytotoxic levels of SAE significantly attenuated NO(•) production in RAW264.7 cells and also markedly suppressed the expression of iNOS and other proinflammatory mediators, including COX-2 and IL-6, which were upregulated in the presence of LPS. SAE inhibited the phosphorylation of p65, an observation that occurred independently of IKKαβ-mediated IκBα phosphorylation. Collectively, our results demonstrate that SAE suppressed NO(•)-mediated inflammation by inhibiting p65 transcriptional activation without affecting IKKαβ-mediated IκBα phosphorylation. Further studies are warranted to examine the major compounds responsible for these effects and the mechanisms responsible for the p65 phosphorylation observed.
authors.affiliation: 1 Korea Food Research Institute , Gyeonggi, Korea.
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Chung
authors.affiliation: 1 Korea Food Research Institute , Gyeonggi, Korea.
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Jung
authors.affiliation: 1 Korea Food Research Institute , Gyeonggi, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 1 Korea Food Research Institute , Gyeonggi, Korea.
authors.forename: Dong Hwa
authors.initials: DH
authors.lastname: Shon
authors.affiliation: 2 Department of Marine Life Science, Jeju National University, Jeju, Korea.
authors.forename: Hyun-Ku
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2
keywords: LPS; Sarcodon asparatus; inflammation; nitric oxide; nitrotyrosine; p65