title: Eugenol--the active principle from cloves inhibits 5-lipoxygenase activity and leukotriene-C4 in human PMNL cells.
abstract: Polymorphonuclear leukocytes (PMNL) play an important role in the modulation of inflammatory conditions in humans. PMNL cells recruited at the site of inflammation, release inflammatory mediators such as leukotrienes, proteolytic enzymes and reactive oxygen species. Among these, leukotrienes are implicated in pathophysiology of allergic and inflammatory disorders like asthma, allergic rhinitis, arthritis, inflammatory bowel disease and psoriasis. 5-lipoxygenase (5-LO) is the key enzyme in biosynthetic pathway of leukotrienes. Our earlier studies showed that spice phenolic active principles significantly inhibit 5-LO enzyme in human PMNLs. In this study we have further characterized the inhibitory mechanism of eugenol, the active principle of spice-clove on 5-LO enzyme and also its effect on leukotriene C((4)) (LTC(4)). Substrate dependent enzyme kinetics showed that the inhibitory effect of eugenol on 5-LO was of a non-competitive nature. Further, eugenol was found to significantly inhibit the formation of LTC(4) in calcium ionophore A23187 and arachidonic acid (AA) stimulated PMNL cells. These data clearly suggest that eugenol inhibits 5-LO by non-competitive mechanism and also inhibits formation of LTC(4) in human PMNL cells and thus may have beneficial role in modulating 5-LO pathway in human PMNL cells.
authors.affiliation: Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Cheluvamba Mansion, Mysore, Karnataka 570 020, India.
authors.forename: H
authors.initials: H
authors.lastname: Raghavenra
authors.forename: B T
authors.initials: BT
authors.lastname: Diwakr
authors.forename: B R
authors.initials: BR
authors.lastname: Lokesh
authors.forename: K A
authors.initials: KA
authors.lastname: Naidu
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D045783:Clove Oil / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D017997:Leukotriene C4 / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D045783:Clove Oil; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D017997:Leukotriene C4; D005054:Eugenol; D001094:Arachidonate 5-Lipoxygenase