Yeast Ca^{2 +}-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca^{2 +}-influx

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• 作者：Tomomi Abe^a ; ¹ ; Miki Kobayashi^a ; ¹ ; Yusuke Okawa^a ; Tomoki Inui^a ; Jun Yoshida^b ; Hironori Higashio^b ; Hisao Shinden^c ; Shota Uesugi^d ; Hiroyuki Koshino^e ; Ken-ichi Kimura^a ; ^d ; ^{kimurak@iwate-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dominican amber ; 3-Cleroden-15-oic acid ; Saccharomyces cerevisiae ; GSK-3β ; Calcineurin ; RBL-2H3 cells
• 刊名：Fitoterapia
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：113
• 期：Complete
• 页码：188-194
• 全文大小：1133 K

文摘

A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca^2 +-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC₅₀ = 40.0, 21.2 and 34.2 μM) and glycogen synthase kinase-3β (GSK-3β) (IC₅₀ = 48.9, 43.8 and 41.1 μM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca^2 +-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds.