title: In vitro 12(S)-HETE and leukotriene metabolism inhibitory activity of sesquiterpenes of Warburgia ugandensis.
abstract: Twelve drimane and coloratane sesquiterpenes, isolated from the stem bark of Ethiopian Warburgia ugandensis, were evaluated for inhibition of 12( S)-HETE using human platelets and of leukotriene B (4) formation using activated human neutrophile granulocytes. Among the compounds examined for inhibition of 12-LOX, ugandensidial and muzigadial displayed potent inhibitory activity with IC (50) values of 3.3 and 20.2 microM, respectively, in comparison to the positive control baicalein with an IC (50) value of 20.0 microM. In the 5-LOX assay muzigadial and ugandensidial also exhibited a dose dependent and potent inhibitory effect on LTB (4) biosynthesis with an IC (50) value of 10.2 and 12.7 microM, respectively, compared to the well known 5-LOX inhibitor zileuton with an IC (50) value of 10.4 microM. In contrast, none of the other sesquiterpenoids showed significant inhibition of either 12( S)-HETE or LTB (4) metabolism.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Graz, Austria.
authors.forename: Abraham Abebe
authors.initials: AA
authors.lastname: Wube
authors.forename: Simon
authors.initials: S
authors.lastname: Gibbons
authors.forename: Kaleab
authors.initials: K
authors.lastname: Asres
authors.forename: Bernhard
authors.initials: B
authors.lastname: Streit
authors.forename: Michael
authors.initials: M
authors.lastname: Adams
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.forename: Franz
authors.initials: F
authors.lastname: Bucar
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000037:antagonists & inhibitors*; D001792:Blood Platelets / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D007975:Leukotriene B4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000378:metabolism*; D019684:Magnoliopsida; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018547:Plant Stems; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016166:Free Radical Scavengers; D015289:Leukotrienes; D010936:Plant Extracts; D012717:Sesquiterpenes; D007975:Leukotriene B4; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid