LOX inhibitor HOEC interfered arachidonic acid metabolic flux in collagen-induced arthritis rats.

Arachidonic acid (AA) metabolic network generates a variety of products that mediate or modulate inflammatory reactions. (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate (HOEC), isolated from (Wehrhahn) Grierson, was found as an inhibitor of 5-LOX and 15-LOX in vitro. When evaluated in collagen-induced arthritis (CIA) rats, however, lowdose of HOEC (1 mg/kg) showed better efficacy than that of high dose (10 mg/kg). To study how HOEC interfered the AA metabolic pathway, in this study, we dynamically observed the changes of plasma AA metabolites (LTB4, LTC4, 15-HETE, PGE2, TXB2 and PGD2) in the CIA rats treated with different doses of HOEC by using enzyme-linked immunosorbent assay (ELISA). The results showed that eicosanoids were elevated synchronously at three time points in different treated rats. The incidence of arthritis had a higher correlation with LOX pathway while the COX pathway might be more important in the severity of arthritis. HOEC in all doses could inhibit LOX pathway in the beginning of arthritis while highdose of HOEC could induce the increase of COX metabolites in the later stage of disease. These dynamic changes of eicosanoids, depending on the regulation of metabolic flux, can be interfered by HOEC and thus affect the output of efficacy.