Chamazulene: an antioxidant-type inhibitor of leukotriene B4 formation.
Matricine and its transformation product chamazulene are constituents of chamomile extracts. Both have been demonstrated to exert anti-inflammatory activity in vivo. Since preparations from chamomile are used for the treatment of inflammatory skin and bowel diseases, we studied the effects of these compounds on the leukotriene production in neutrophilic granulocytes. Chamazulene inhibited the formation of leukotriene B4 in intact cells and in the 105,000 x g supernatant fraction in a concentration-dependent manner. The IC50 values were 15 and 10 microM, respectively. Matricine showed no effect up to 200 microM. Chamazulene (IC50: 2 microM), but not matricine, blocked the chemical peroxidation of arachidonic acid. Additionally, matricine (up to 200 microM) had no effects on the cyclooxygenase and 12-lipoxygenase activities in human platelets. Therefore, it is concluded that chamazulene, but not matricine, may contribute to the anti-inflammatory activity of chamomile extracts by inhibiting the leukotriene synthesis and additional antioxidative effects.
Safayhi
H
H
Department of Pharmacology, University of Tübingen, Federal Republic of Germany.
Sabieraj
J
J
Sailer
E R
ER
Ammon
H P
HP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D052176:Azulenes; D001792:Blood Platelets / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D020843:Chamomile; D003508:Cycloheptanes / Q000494:pharmacology*; D005419:Flavonoids; D006801:Humans; D007783:Lactones; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009504:Neutrophils / Q000201:enzymology; D009822:Oils, Volatile; D010946:Plants, Medicinal; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane
D000975:Antioxidants; D052176:Azulenes; D003508:Cycloheptanes; D005419:Flavonoids; D007783:Lactones; D016859:Lipoxygenase Inhibitors; D009822:Oils, Volatile; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D007975:Leukotriene B4; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C039959:matricin; C013872:chamazulene