In vitro inhibition of 5-lipoxygenase by natural quinone compounds

Abstract

Dual inhibition of cyclooxygenase (COX) and lipoxygenase (LOX) pathways is promising approach in treatment of inflammatory diseases. Drugs able to block production of prostanoids together with leukotrienes should provide better anti-inflammatory properties and fewer side effects than non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors [1,2]. Our previous studies revealed that some natural quinone compounds such as primin, alkannin, or shikonin are potent in vitro COX inhibitors [3]. In the current study, we tested 19 quinone compounds for 5-lipoxygenase (5-LOX) inhibition using in vitro assay according to [4] where neutrophile granulocytes with 5-LOX activity isolated from the human blood are incubated with arachidonic acid (substrate) and tested samples. After the incubation, the amount of leukotriene B4 (LTB4) is determined by commercial LTB4 EIA kit (Assay Designs). The most active quinone 5-LOX inhibitors were benzoquinone primin and naphthoquinone shikonin which decreased LTB4 production by 93 and 87% at 50µM concentration, respectively. Reference inhibitor zileuton reduced LTB4 production by 91% at the same concentration. Based on these preliminary results obtained in 5-LOX assay together with data from previous studies targeted on COX inhibition the plant quinones such as primin and shikonin should be considered for further studies aimed on their potential of dual COX/LOX inhibition.