title: Anti-Inflammatory Effect of Ascochlorin in LPS-Stimulated RAW 264.7 Macrophage Cells Is Accompanied With the Down-Regulation of iNOS, COX-2 and Proinflammatory Cytokines Through NF-κB, ERK1/2, and p38 Signaling Pathway.
abstract: A natural compound C23 H32 O4 Cl, ascochlorin (ASC) isolated from an incomplete fungus, Ascochyta viciae has been known to have several biological activities as an antibiotic, antifungal, anti-cancer, anti-hypolipidemic, and anti-hypertension agent. In this study, anti-inflammatory activity has been investigated in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells, since ASC has not been observed on the inflammatory events. The present study has clearly shown that ASC (1-50 μM) significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2 ) and decreased the gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Moreover, ASC inhibited the mRNA expression and the protein secretion of interleukin (IL)-1β and IL-6 but not tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 macrophage cells. In addition, ASC suppressed nuclear translocation and DNA binding affinity of nuclear factor-κB (NF-κB). Furthermore, ASC down-regulated phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) and p-p38. These results demonstrate that ASC exhibits anti-inflammatory effects in RAW 264.7 macrophage cells.
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi-Do, Republic of Korea.
authors.forename: Sook-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi-Do, Republic of Korea.
authors.forename: Choong-Hwan
authors.initials: CH
authors.lastname: Kwak
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi-Do, Republic of Korea.
authors.forename: Sung-Kyun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi-Do, Republic of Korea.
authors.forename: Sun-Hyung
authors.initials: SH
authors.lastname: Ha
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi-Do, Republic of Korea.
authors.forename: Junyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan City, Gyeongsangnam-Do, Republic of Korea.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chung
authors.affiliation: Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan City, Gyeongsangnam-Do, Republic of Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi-Do, Republic of Korea.
authors.forename: Suk-Jong
authors.initials: SJ
authors.lastname: Suh
authors.affiliation: Research Institute of Biomedical Engineering, Department of Medicine, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Faculty of Pharmacy, Yeungnam University, Kyungsan, Republic of Korea.
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Faculty of Medicinal Biotechnology, Dong-A University, Busan, Republic of Korea.
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Kang
authors.affiliation: Magae Bioscience Institute, 49-4 Fujimidai, Tsukuba, 300-1263, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, Suwon City, Kyunggi-Do, Republic of Korea.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000475:Alkenes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D021381:Protein Transport; D004718:Saccharomycetales / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000475:Alkenes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010636:Phenols; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C415745:ascochlorin
keywords: ASCOCHLORIN; INFLAMMATION; LPS; RAW 264.7 MACROPHAGE CELLS