Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis

摘要

Background: In addition to recognized antimalarial effects, Artemisia annua L. (Qinghao) possesses anticancer properties. The un-derlying mechanisms of this activity are unknown. The aim of our experiments was to investigate the effects of distinct types of com-pounds isolated from A. annua on the immune-activated production of major mediators of angiogenesis playing a crucial role ingrowth of tumors and formation of metastasis.Methods: Included in the study were the sesquiterpene lactones artemisinin and its biogenetic precursors arteannuin B and artemis-inic acid. The semi-synthetic analogue dihydroartemisinin was used for comparative purposes. The flavonoids were represented bycasticin 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-activatedproduction of prostaglandin E2(PGE2) and cytokines (VEGF, IL-1b, IL-6 and TNF-a) was determined in both rat peritoneal cellsand human peripheral blood mononuclear cells using ELISA.Results: All sesquiterpenes (artemisinin, dihydroartemisinin, artemisinic acid, arteannuin B) significantly reduced productionof PGE2. Arteannuin B also inhibited production of NO and secretion of cytokines. All NO, PGE2and cytokines were suppressed byflavonoids casticin and chrysosplenol D. The coumarin derivative, 4-methylesculetin, was ineffective to change the productionof any of these factors.Conclusions: The inhibition of immune mediators of angiogenesis by sesquiterpene lactones and flavonoids may be one ofthe mechanisms of anticancer activity of Artemisia annua L