Graduate School of Agriculture, Iwate University, Morioka 020-8550, Japan.
Center for Liberal Arts and Sciences, Iwate Medical University, Yahaba 028-3694, Japan.
Fitoterapia. 2018 Jun;127:263-270. doi: 10.1016/j.fitote.2018.02.033. Epub 2018 Mar 5.
Amber is fossilized tree resin and several biologically active compounds were isolated from ambers using the growth-restoring activity of the mutant yeast [Saccharomyces cerevisiae (zds1∆ erg3∆ pdr1∆ pdr3∆)] involving Ca-signal transduction. The aim of this study is to investigate the anti-allergic effect of both the methanol extract of Kuji amber (MEKA) and its main biologically active constituent, kujigamberol (15,20-dinor-5,7,9-labdatrien-18-ol) having activity against the mutant yeast. Both MEKA and kujigamberol inhibited the degranulation of RBL-2H3 cells by stimulation of thapsigargin (Tg) (IC = 15.0 μg/ml and 29.1 μM) and A23187 (IC = 19.6 μg/ml and 24.9 μM) without cytotoxicity, but not by stimulation of IgE + DNP-BSA (Ag) (IC > 50.0 μg/ml and 50.0 μM). However, both inhibited Ca-influx in RBL-2H3 cells by all three stimulations in a dose dependent manner. Leukotriene C production in RBL-2H3 cells stimulated by A23187 was also inhibited by both through the inhibition of ERK1/2 phosphorylation. In an ovalbumin-induced rhinitis model of guinea pigs, nasal administration of MEKA and kujigamberol inhibited nasal blockade in a dose-dependent manner and the effect was about 5 times potent than that of a steroid clinical drug, mometasone furoate. The growth-restoring activity of MEKA and kujigamberol against the mutant yeast is involved in the anti-allergic activities against cells and animals, and both are expected to be candidates for the development of new anti-allergy agents.
琥珀是石化的树树脂，使用涉及钙信号转导的突变酵母 [酿酒酵母（zds1∆ erg3∆ pdr1∆ pdr3∆）] 的生长恢复活性，从琥珀中分离出几种生物活性化合物。本研究旨在研究库吉琥珀甲醇提取物（MEKA）及其主要生物活性成分库吉醇（15,20-二降-5,7,9-拉巴二烯-18-醇）对突变酵母的抗过敏作用。MEKA 和 kujigamberol 均通过刺激 Tg（IC = 15.0 µg/ml 和 29.1 µM）和 A23187（IC = 19.6 µg/ml 和 24.9 µM）抑制 RBL-2H3 细胞脱颗粒，而没有细胞毒性，但不通过刺激 IgE + DNP-BSA（Ag）（IC > 50.0 µg/ml 和 50.0 µM）。然而，两者均通过所有三种刺激以剂量依赖的方式抑制 RBL-2H3 细胞中的 Ca 内流。A23187 刺激的 RBL-2H3 细胞中白三烯 C 的产生也被两者通过抑制 ERK1/2 磷酸化而抑制。在豚鼠卵清蛋白诱导的鼻炎模型中，MEKA 和 kujigamberol 的鼻内给药以剂量依赖性方式抑制鼻阻塞，其作用约为皮质类固醇临床药物糠酸莫米松的 5 倍。MEKA 和 kujigamberol 对突变酵母的生长恢复活性与细胞和动物的抗过敏活性有关，两者都有望成为开发新型抗过敏药物的候选药物。
