Abstract
Although the lipidic extract of Serenoa repens (LESSr, Permixon ®, Sereprostat ®) is widely used in patients suffering from benign prostatic hypertrophy (BPH), its mechanism of action is not fully elucidated. It has been demonstrated that infiltration of the prostate by inflammatory cells is one of the aetiologic factors involved in the development of BPH. These inflammatory cell types, such as polymorphonuclear neutrophils (PMNs), produce chemotactic mediators and contribute to the development of the disease. Among the chemotactic factors generated by inflammatory cell types, the derivatives of arachidonic acid have been extensively studied. For instance, leukotriene (LT) B 4 is one of the most potent chemotactic factors for PMNs and also exhibits a wide range of biological activities. In order to investigate the potential action of LESSr on arachidonate metabolism, and particularly on the synthesis of LTB 4, the effect of this extract on the in vitro synthesis of LT by human PMNs stimulated with the calcium ionophore A23187 was investigated. LESSr significantly inhibits the production of 5-lipoxygenase metabolites (5-HETE, 20-COOH LTB 4, LTB 4 and 20-OH LTB 4) at concentrations as low as 5 μg/ml. Such an effect of LESSr was also observed in the presence of exogenous arachidonic acid (20 μg/ml) and when f-MLP was used as the agonist, suggesting that inhibition of LTB 4 production by the extract was unrelated to phospholipase A 2 blockade and independent of the stimulating agent. The capability of LESSr to antagonize 5-lipoxygenase metabolites production may contribute, at least partly, to the understanding of its therapeutic activity on the inflammatory component of BPH.
Published Version
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