Yamazaki R, Aiyama R, Matsuzaki T, Hashimoto S, Yokokura T
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Inflamm Res. 1998 Apr;47(4):182-6. doi: 10.1007/s000110050315.
We investigated the anti-inflammatory effect of YPE-01, a novel diarylheptanoid derivative in vitro and in vivo.
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.
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.
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.
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.
YPE-01 is a selective 5-lipoxygenase inhibitor with a suppressive effect against dermal inflammation.
我们在体外和体内研究了新型二芳基庚烷衍生物YPE - 01的抗炎作用。
体外研究使用大鼠嗜碱性白血病（RBL - 1）细胞。体内研究使用ICR和ddY小鼠（雄性，7周龄）。
体外研究中，将RBL - 1细胞裂解物的上清液与50微摩尔花生四烯酸（AA）和0.01 - 100微摩尔受试药物孵育15分钟。RBL - 1细胞在与0.5微摩尔钙离子载体A23187孵育10分钟前，先与0.01 - 100微摩尔受试药物预孵育10分钟。体内研究中，在应用12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）的同时或在应用AA前1小时，将YPE - 01（0.1 - 3毫克/耳）涂抹于小鼠耳部。
体外研究中，分别通过高效液相色谱法和酶免疫测定法测量5 - 羟基二十碳四烯酸和白三烯的含量。体内研究中，称取小鼠耳部的圆形组织样本重量。采用邓尼特检验进行统计分析。
YPE - 01在体外抑制RBL - 1细胞的5 - 脂氧合酶活性（IC50，0.28微摩尔）以及白三烯B4（IC50，0.035微摩尔）和C4（IC50，0.046微摩尔）的产生，而对环氧化酶活性无任何抑制作用。YPE - 01局部应用在体内显著抑制了AA和TPA诱导的耳部水肿。
YPE - 01是一种选择性5 - 脂氧合酶抑制剂，对皮肤炎症具有抑制作用。
