title: Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis.
abstract: BACKGROUND
  In addition to recognized antimalarial effects, Artemisia annua L. (Qinghao) possesses anticancer properties. The underlying mechanisms of this activity are unknown. The aim of our experiments was to investigate the effects of distinct types of compounds isolated from A. annua on the immune-activated production of major mediators of angiogenesis playing a crucial role in growth of tumors and formation of metastasis.
  
  
  METHODS
  Included in the study were the sesquiterpene lactones artemisinin and its biogenetic precursors arteannuin B and artemisinic acid. The semi-synthetic analogue dihydroartemisinin was used for comparative purposes. The flavonoids were represented by casticin and chrysosplenol D, the coumarin type of compounds by 4-methylesculetin. Their effects on the lipopolysaccharide (LPS)-induced in vitro production of nitric oxide (NO) were analyzed in rat peritoneal cells using Griess reagent. The LPS-activated production of prostaglandin E2 (PGE2) and cytokines (VEGF, IL-1β, IL-6 and TNF-α) was determined in both rat peritoneal cells and human peripheral blood mononuclear cells using ELISA.
  
  
  RESULTS
  All sesquiterpenes (artemisinin, dihydroartemisinin, artemisinic acid, arteannuin B) significantly reduced production of PGE2. Arteannuin B also inhibited production of NO and secretion of cytokines. All NO, PGE2 and cytokines were suppressed by flavonoids casticin and chrysosplenol D. The coumarin derivative, 4-methylesculetin, was ineffective to change the production of any of these factors.
  
  
  CONCLUSIONS
  The inhibition of immune mediators of angiogenesis by sesquiterpene lactones and flavonoids may be one of the mechanisms of anticancer activity of Artemisia annua L.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Nanxiaojie 16, Dongzhimen Nei Avenue, Beijing 100700, China.
authors.forename: Xiaoxin X
authors.initials: XX
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.forename: Yujie J
authors.initials: YJ
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Petra
authors.initials: P
authors.lastname: Kostecká
authors.forename: Eva
authors.initials: E
authors.lastname: Kmoníčková
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Zídek
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D031172:Artemisia annua / Q000737:chemistry*; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D005419:Flavonoids; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; D009569:Nitric Oxide