ANTIINFLAMMATORY EFFECT OF YPE-01, A NOVEL DIARYLHEPTANOID DERIVATIVE, ON DERMAL INFLAMMATION IN MICE

Objective and Design: We investigated the antiinflammatory effect of Y PE-01, a novel diarylheptanoid derivative in vitro and in vivo. Materi al: In the in vitro study, rat basophilic leukemia (RBL-1) cells were used. For the in vivo study, ICR and ddY mice (male, 7 weeks old) were used. Treatment: In the in vitro study, the supernatant of RBL-1 cell s lysate was incubated with 50 mu M arachidonic acid (AA) and 0.01-100 mu M test drugs for 15 min. RBL-1 cells were preincubated with 0.01-1 00 mu M test drugs for 10 min before incubation with 0.5 mu M calcium ionophore A23187 for 10min. In the in vivo study, YPE-01 (0.1-3 mg/ear ) was applied to the ear of mice at the same time as a 12-O-tetradecan oylphorbol 13-acetate (TPA) application or Ih before an AA application . Methods: In the in vitro study, the amounts of 5-hydroxyeicosatetrae noic acid and leukotrienes were measured by high-performance liquid ch romatography and an enzyme immunoassay, respectively. In the in vivo s tudy, a circular tissue sample from the ear of the mice was weighed. S tatistical analysis was done using Dunnett's test. Results: YPE-01 inh ibited the 5-lipoxygenase activity (IC50, 0.28 mu M) and the leukotrie ne B-4 (IC50, 0.035 mu M) and C-4 (IC50, 0.046 mu M) production by RBL -1 cells without any inhibition of cyclooxygenase activity in vitro. T he topical application of YPE-01 significantly suppressed both the AA- and TPA-induced ear edemas in vivo. Conclusions: YPE-01 is a selectiv e 5-lipoxygenase inhibitor with a suppressive effect against dermal in flammation.