Inhibition of angiogenic factors by laserolide, a sesquiterpene lactone from Laser trilobum Borkh. ex Gaertn

Sesquiterpene lactones (SLs) are plant secondary metabolites, widely distributed within the families of Asteraceae and Apiaceae. SLs have received ever increasing attention for their beneficial effects in pathologies etiologically associated with angiogenesis, such as chronic inflammation and cancer. We have investigated the interference of SLs isolated from the non-pharmacopoeia C./E. European plant Laser trilobum Borkh. ex Gaertn., i.e. laserolide, isolaserolide, eudeslaserolide, archangelolide and 2-deangeloyl-archangelolide with production of angiogenic factors such as nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines vascular endothelial growth factor (VEGF), interleukins IL-1β and IL-6. The recognized SL costunolide was included for comparative purposes. The cytocidal effects of the compounds were evaluated as well. The immunobiological experiments were done under in vitro conditions using rat resident peritoneal cells. They were cultured at a density of 2×10⁶/mL in RPMI-1640 medium for 24h. The production of NO, PGE2 and cytokines were triggered by lipopolysaccharide (1µg/mL). Formation of NO was assayed using Griess reagent. Concentrations of PGE2 and cytokines were determined by ELISA. In contrast to costunolide, the SLs from L. trilobum. are devoid of cytocidal effects up to a concentration of 50µM. Laserolide may be considered as a promising candidate for further preclinical investigations because its immunosuppressive effectiveness is very close to that exhibited by costunolide. It inhibits the cytokine (including the major angiogenic factor VEGF), PGE2 and NO production at IC50s of approximately 5–10µM.

Keywords: Laser trilobum; laserolide; nitric oxide; prostaglandins; cytokines

Acknowledgement: The work was supported by the grant 305/07/0061 from GACR.