title: Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-κB inactivation in RAW264.7 macrophages and protects mice against endotoxin shock.
abstract: Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6 N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner, while CA up to 200 μM did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of IκB-α and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-κB to the nucleus, transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-κB and MAPK signaling pathways, suggesting that CA may be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Park
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Keun Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Jung
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Jung
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Mohamed Antar Aziz
authors.initials: MA
authors.lastname: Mohamed
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: In Sik
authors.initials: IS
authors.lastname: Chung
authors.affiliation: Graduate School of Biotechnology and College of Life Science, Kyung Hee University, Yongin 446-701, Korea jkim@khu.ac.kr.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000276:immunology* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C403944:cynandione A; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Cynanchum wilfordii; Inflammation; MAPK pathway; NF-κB; cynandione A