The Effects Of Anti-psoriatic Drugs Or Compounds On The 5-Lipoxygenase Pathway Of Arachidonic Acid Metabolism

This research foculized on the 5-lipoxygenase (LO) pathway of arachidonic acid metabolism, which related to the inflammation in psoriasis. The effect of antipsoriatic drugs (or compounds) on the activity and content of 5-LO, of leukotriene (LT) A₄ hydrolase as well as leukocyte migration toward LTB₄ were determined in vitro. The compounds determined in this research included anthralin (ATL), cyclosporin A (CyA), tretinoin (RA), calcipotriol (Cal), clobetasol propionate (CP), methotrexate (MTX), erythromyin (Er), triptolide (To) and STW.The results showed that ATL, CyA, RA and To could inhibit 5-LO activity of circulating leukocyte (WBC). They inhibited the 5-LO products — LTB₄ and 5-hydroxyeicosatetraenoic acid (HETE) in a dose-dependent way. The 50% inhibitory concentration values (ICso) of LTB₄ production were 32. 71, 38. 81, 19. 09 or 1. 97X 10⁶μg/ml, respectively. And, the IC₅₀ of 5-HETE production were 0.28, 0.96, 5.72 or 1. 15×10⁶μg/ml, respectively. Cal, CP, MTX, Er and STW had no effects on 5-L0 activity. Moreover, these nine compounds did not influence 5-LO content on the transcriptional level.To could inhibit LTA₄ hydrolase activity in COLO 16 cell line in a dose-depedent pattern. The ICso of LTB₄ production were 2.58×10⁵μg/ml. ATL, CyA, RA, Cal, CP, MTX, Er and STW had no effects on LTA, hydrolase activity. Moreover, ATL could downregulate the mRNA expression of LTA₄ hydrolase on the transcriptional level in a dose-dependent pattern. The ICso of LTA₄ hydrolase mRNA expression was 2. 16μg/ml. CyA, RA, Cal, CP, MTX, Er, To and STW did not influence LTA₄ hydrolase content on the...