title: Flavonoids casticin and chrysosplenol D from Artemisia annua L. inhibit inflammation in vitro and in vivo.
abstract: BACKGROUND
  The aim of our experiments was to investigate the anti-inflammatory properties of casticin and chrysosplenol D, two flavonoids present in Artemisia annua L.
  
  
  METHODS
  Topical inflammation was induced in ICR mice using croton oil. Mice were then treated with casticin or chrysosplenol D. Cutaneous histological changes and edema were assessed. ICR mice were intragastrically administrated with casticin or chrysosplenol D followed by intraperitoneal injection of lipopolysaccharide (LPS). Mouse Raw264.7 macrophage cells were incubated with casticin or chrysosplenol D. Intracellular phosphorylation was detected, and migration was assessed by trans-well assay. HT-29/NFκB-luc cells were incubated with casticin or chrysosplenol D in the presence or absence of LPS, and NF-κB activation was quantified.
  
  
  RESULTS
  In mice, administration of casticin (0.5, 1 and 1.5μmol/cm(2)) and chrysosplenol D (1 and 1.5μmol/cm(2)) inhibited croton oil-induced ear edema (casticin: 29.39-64.95%; chrysosplenol D: 37.76-65.89%, all P<0.05) in a manner similar to indomethacin (0.5, 1 and 1.5μmol/cm(2); 55.63-84.58%). Casticin (0.07, 0.13 and 0.27mmol/kg) and chrysosplenol D (0.07, 0.14 and 0.28mmol/kg) protected against LPS-induced systemic inflammatory response syndrome (SIRS) in mice (all P<0.05), in a manner similar to dexamethasone (0.03mmol/kg). Casticin and chrysosplenol D suppressed LPS-induced release of IL-1 beta, IL-6 and MCP-1, inhibited cell migration, and reduced LPS-induced IκB and c-JUN phosphorylation in Raw264.7 cells. JNK inhibitor SP600125 blocked the inhibitory effect of chrysosplenol D on cytokine release.
  
  
  CONCLUSIONS
  The flavonoids casticin and chrysosplenol D from A. annua L. inhibited inflammation in vitro and in vivo.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Weng
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xu-Cen
authors.initials: XC
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Kan
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: zhuxx59@163.com.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Zhu
authors.affiliation: Institute of Pharmacology and Toxicology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Kmoníèková
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeòská 1083, 142 20 Prague, Czech Republic.
authors.forename: Zdenìk
authors.initials: Z
authors.lastname: Zídek
mesh_terms: D000818:Animals; D031172:Artemisia annua; D003872:Dermatitis / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000627:therapeutic use*; D004487:Edema / Q000188:drug therapy* / Q000473:pathology; D047309:Flavones / Q000302:isolation & purification / Q000627:therapeutic use*; D005419:Flavonoids / Q000302:isolation & purification / Q000627:therapeutic use*; D019073:HT29 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
chemical_list: D004365:Drugs, Chinese Herbal; D047309:Flavones; D005419:Flavonoids; C568008:chrysosplenol D; C054133:casticin
keywords: Artemisia annua L.; Casticin; Chrysosplenol D; Flavonoids; Inflammation