Anti-inflammatory effect of YPE-01, a novel diarylheptanoid derivative, on dermal inflammation in mice.

OBJECTIVE AND DESIGN

We investigated the anti-inflammatory effect of YPE-01, a novel diarylheptanoid derivative in vitro and in vivo.

MATERIAL

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 cells lysate was incubated with 50 microM arachidonic acid (AA) and 0.01-100 microM test drugs for 15 min. RBL-1 cells were preincubated with 0.01-100 microM test drugs for 10 min before incubation with 0.5 microM calcium ionophore A23187 for 10 min. 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-tetradecanoylphorbol 13-acetate (TPA) application or 1 h before an AA application.

METHODS

In the in vitro study, the amounts of 5-hydroxyeicosatetraenoic acid and leukotrienes were measured by high-performance liquid chromatography and an enzyme immunoassay, respectively. In the in vivo study, a circular tissue sample from the ear of the mice was weighed. Statistical analysis was done using Dunnett's test.

RESULTS

YPE-01 inhibited the 5-lipoxygenase activity (IC50, 0.28 microM) and the leukotriene B4 (IC50, 0.035 microM) and C4 (IC50, 0.046 microM) production by RBL-1 cells without any inhibition of cyclooxygenase activity in vitro. The topical application of YPE-01 significantly suppressed both the AA- and TPA-induced ear edemas in vivo.

CONCLUSIONS

YPE-01 is a selective 5-lipoxygenase inhibitor with a suppressive effect against dermal inflammation.