Prostaglandins, Leukotrienes and Essential Fatty Acids 72 (2005) 195–201 Effect of Cleome arabica leaf extract, rutin and quercetin on soybean lipoxygenase activity and on generation of inflammatory eicosanoids by human neutrophils H. Bouriche a,Ã , E.A. Miles b , L. Selloum a , P.C. Calder b a Laboratory of Applied Biochemistry, Department of Biology, Faculty of Sciences, University of Ferhat Abbas, 19000 Setif, Algeria b Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK Received 3 June 2004; accepted 22 October 2004 Abstract The effects of Cleome arabica leaf extract, rutin and quercetin on soybean lipoxygenase (Lox) activity and on calcium ionophore (A23187)-stimulated generation of the leukotriene B 4 and prostaglandin E 2 by human neutrophils were examined. The extract (25 mg/ml), rutin (25 mM) and quercetin (25 mM) inhibited LTB 4 synthesis at all concentrations of A23187 used. The extract at 1–100 mg/ml and rutin at 1–100 mM inhibited LTB 4 generation by neutrophils stimulated with 1 mM A23187 by about 50%. PGE 2 production in response to different concentrations of A23187 was affected in a biphasic manner by the extract and rutin. Quercetin at 1–100 mM caused concentration-dependent inhibition of LTB 4 and PGE 2 production. The extract, rutin and quercetin caused concentration-dependent inhibition of soybean Lox activity. These results indicate that rutin, quercetin and an extract of C. arabica containing these compounds inhibit Lox activity, consequently decreasing LTB 4 production. Thus, these compounds or extracts containing them may be beneficial for the treatment of inflammatory conditions, particularly those characterised by excessive leukotriene generation. r 2004 Elsevier Ltd. All rights reserved. 1. Introduction Upon appropriate stimulation of neutrophils, arachi- donic acid (AA) is cleaved from membrane phospholi- pids. The AA that is released can be converted into leukotrienes (LTs) or prostaglandins (PGs) through 5- lipoxygenase (5-Lox) or cyclooxygenase (Cox) path- ways, respectively [1,2]. Neutrophils are a major source of the potent chemotatic agent LTB 4 [3,4], which increases vascular permeability, local blood flow, and lysosomal enzyme, oxygen radical and inflammatory cytokine release [5,6]. Thus, LTB 4 is a potent mediator of inflammation, amplifying recruitment and activation of inflammatory cells [4]. Therefore, LTB 4 generation is considered to be important in the pathogenesis of neutrophil-mediated inflammatory diseases [7]. Indeed, increased LTB 4 generation and concentration has been demonstrated in inflammation, with a marked relation to the severity of the disease [8]. Human neutrophils can also synthesize PGs from endogenous AA [1,2]. PGE 2 plays a major role in mediating inflammation and regulates macrophage and lymphocyte functions [9,10]. High levels of PGs produced via the Cox-2 pathway are present in pathologic conditions, such as acute or chronic inflammation [2,10]. PGE 2 has many proinflammatory actions, contributing to pain and swelling during inflammation through induction of hyperalgesia and increased vascular permeability [11]. On the other hand, recent studies have reported that PGE 2 inhibits 5-Lox activity, so preventing the generation of the inflammatory 4-series LTs [12]. Furthermore, PGE 2 was found to induce generation of ARTICLE IN PRESS www.elsevier.com/locate/plefa 0952-3278/$-see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.plefa.2004.10.018 Ã Corresponding author. Tel./fax: +21336925122. E-mail address: Bouriche_ha@yahoo.fr (H. Bouriche).