title: An extract of Phellinus linteus grown on germinated brown rice inhibits inflammation markers in RAW264.7 macrophages by suppressing inflammatory cytokines, chemokines, and mediators and up-regulating antioxidant activity.
abstract: The immunomodulatory activity of an organic extract of Phellinus linteus grown on slightly germinated brown rice (PBR) was previously demonstrated. Here, we investigated the possible anti-inflammatory activity of the PBR extract by analyzing its effect on the expression of macrophage-derived cytokines, chemokines, and mediator genes that participate in immune and inflammatory responses and diseases. The extract profoundly inhibited the induction of cytokines and chemokines, including tumor necrosis factor-α, chemokine (C-X-C motif) ligand-10, granulocyte-macrophage colony-stimulating factor, and interleukin-6, in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage cells. It also greatly inhibited LPS-stimulated production of nitric oxide (NO) and prostaglandin E(2) in RAW264.7 cells by suppressing the expression of inducible NO synthase and cyclooxygenase-2. PBR extract inhibited NO production with a twofold lower half-maximal inhibitory concentration value than P. linteus extract. To elucidate the underlying mechanism of action, we examined the effect of the PBR extract on the LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in RAW264.7 cells. PBR extract greatly inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylation and slightly inhibited p38 MAPK phosphorylation. It also significantly increased intracellular glutathione peroxidase activity and heme oxygenase-1 protein expression. Thus, the PBR extract has anti-inflammatory activity in LPS-stimulated RAW264.7 cells by virtue of its ability to suppress the production of inflammatory cytokines and chemokines via inhibition of MAPK activation and up-regulation of antioxidant activities.
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea. hyejinpak@gmail.com
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Eun Su
authors.initials: ES
authors.lastname: Han
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Park
authors.forename: Chan
authors.initials: C
authors.lastname: Lee
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001487:Basidiomycota / Q000737:chemistry* / Q000254:growth & development; D015415:Biomarkers / Q000378:metabolism; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018525:Germination; D018836:Inflammation Mediators / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012275:Oryza / Q000254:growth & development / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D000084682:Phellinus; D010936:Plant Extracts; D011134:Polysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012639:Seeds / Q000254:growth & development / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; C526145:Phellinus linteus extract; D010936:Plant Extracts; D011134:Polysaccharides; D012333:RNA, Messenger; D010088:Oxidoreductases; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2