Anti-inflammatory effect of YPE-01, a novel diarylheptanoid derivative, on dermal inflammation in mice.
OBJECTIVE
We investigated the anti-inflammatory effect of YPE-01, a novel diarylheptanoid derivative in vitro and in vivo.


METHODS
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.


METHODS
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.
Yamazaki
R
R
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Aiyama
R
R
Matsuzaki
T
T
Hashimoto
S
S
Yokokura
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid; D000001:Calcimycin; D002630:Chemotactic Factors / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D036381:Diarylheptanoids; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000378:metabolism*; D007476:Ionophores; D007659:Ketones / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000032:analysis / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002630:Chemotactic Factors; D036381:Diarylheptanoids; D006893:Hydroxyeicosatetraenoic Acids; D007476:Ionophores; D007659:Ketones; D016859:Lipoxygenase Inhibitors; D010636:Phenols; C114400:YPE 01; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D001094:Arachidonate 5-Lipoxygenase; D013755:Tetradecanoylphorbol Acetate