title: Coptisine from Coptis chinensis inhibits production of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells.
abstract: Coptis chinensis has been used for the treatment of inflammatory diseases in China and other Asian countries for centuries. However, the chemical constituents and mechanism underlying the anti-inflammatory activity of this medicinal plant are poorly understood. Here, coptisine, the main constituent of C. chinensis, was shown to potently inhibit the production of nitric oxide (NO) by suppressing the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Coptisine also inhibited the production of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) by suppressing expression of cytokine mRNA. Coptisine suppressed the degradation of inhibitor of nuclear factor κBα (IκBα) and phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase/Akt (PI3K/Akt). Coptisine had no effect on the expression of toll-like receptor 4 (TLR-4) and myeloid differentiation factor 88 (MyD88) as well as LPS binding to TLR-4. Coptisine also inhibited carrageenan-elicited rat paw edema and reduced the release of TNF-α and NO in rat inflamed tissue. These results suggest that coptisine inhibits LPS-stimulated inflammation by blocking nuclear factor-kappa B, MAPK, and PI3K/Akt activation in macrophages, and can be used as an agent for the prevention and treatment of inflammatory diseases.
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
authors.forename: Jiasi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China. Electronic address: wangfei@cib.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China. Electronic address: xlm9999@hotmail.com.
authors.forename: Xianli
authors.initials: X
authors.lastname: Meng
mesh_terms: D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D039323:Coptis / Q000737:chemistry*; D004487:Edema / Q000188:drug therapy; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C034384:coptisine; D001599:Berberine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Coptis chinensis; Coptisine; Inflammation; Macrophage; Nitric oxide