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

Abstract

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.

• Authors: R Yamazaki, R Aiyama, T Matsuzaki, S Hashimoto, T Yokokura
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 47 Issue 4 Pg. 182-6 (Apr 1998) ISSN: 1023-3830 [Print] Switzerland
• PMID: 9628261 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Chemotactic Factors
• Diarylheptanoids
• Hydroxyeicosatetraenoic Acids
• Ionophores
• Ketones
• Lipoxygenase Inhibitors
• Phenols
• YPE 01
• Leukotriene B4
• Arachidonic Acid
• Calcimycin
• 5-hydroxy-6,8,11,14-eicosatetraenoic acid
• Arachidonate 5-Lipoxygenase
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Arachidonate 5-Lipoxygenase (metabolism)
• Arachidonic Acid
• Calcimycin
• Chemotactic Factors (analysis, metabolism)
• Chromatography, High Pressure Liquid
• Diarylheptanoids
• Ear
• Edema (chemically induced, drug therapy)
• Hydroxyeicosatetraenoic Acids (analysis, metabolism)
• Ionophores
• Ketones (pharmacology)
• Leukotriene B4 (analysis, metabolism)
• Lipoxygenase Inhibitors (pharmacology)
• Male
• Mice
• Mice, Inbred ICR
• Phenols (pharmacology)
• Rats
• Tetradecanoylphorbol Acetate
• Tumor Cells, Cultured