Effects of (+)-2-(1-hydroxyl-4-oxocyclohexyl)ethyl caffeate at different doses on rat arthritis model and whole blood inflammation model

AIM:To evaluate the pharmacodynamics of (+)-2-(1-hydroxyl-4-oxocyclohexyl)ethyl caffeate (HOEC), and to explore the possible causes of non-dose-dependent effects of HOEC on collagen-induced arthritis (CIA) rats using the arachidonic acid (AA) metabolic model in rat whole blood. METHODS:The rat CIA model was used to study the treatment with HOEC at 3 doses. The expression of cytoplasmic phospholipase A₂ (cPLA₂), 5-lipoxygenase (5-LOX) and cyclo-oxygenase-2 (COX-2) was assayed by immunohistochemical method. The effects of HOEC and its in vivo metabolite caffeic acid (CA) on AA metabolite in rat whole blood were measured by ELISA. RESULTS:HOEC had a therapeutic effect on rat CIA, but the curative effect at low dose and middle dose (1 and 3 mg/kg) was better than that at high dose (10 mg/kg). The expression levels of cPLA₂, 5-LOX and COX-2 in joint tissues were decreased. HOEC inhibited the metabolites of LOX and COX pathways in the rat whole blood AA metabolic model, while the inhibitory effect of CA on these metabolites was weaker than that of HOEC. CONCLUSION:The anti-inflammatory effect of HOEC on rat CIA may be associated with the inhibition of cPLA₂, 5-LOX and COX-2 expression in the joint tissues. The non-dose-dependent therapeutic effect of HOEC on rat CIA may due to the weaker inhibitory activity of CA on AA metabolic model in rat whole blood than that of HOEC.