Ca2+ signaling is related to various diseases such as allergies, diabetes, and cancer. We explored Ca2+ signaling inhibitors in natural resources using a yeast-based screening method and found bakkenolide B from the flower buds of edible wild plant, Petasites japonicus, using the YNS17 strain (zds1Δ erg3Δ pdr1/3Δ). Bakkenolide B exhibited growth-restoring activity against the YNS17 strain and induced Li+ sensitivity of wild-type yeast cells, suggesting that it inhibits the calcineurin pathway. Additionally, bakkenolide B inhibited interleukin-2 production at gene and protein levels in Jurkat cells, a human T cell line, but not the in vitro phosphatase activity of human recombinant calcineurin, an upstream regulator of interleukin-2 production. Furthermore, bakkenolide A showed weak activity in YNS17 and Jurkat cells compared with bakkenolide B. These findings revealed new biological effects and the structure-activity relationships of bakkenolides contained in P. japonicus as inhibitors of interleukin-2 production in human T cells.

中文翻译：

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基于酵母的筛选系统鉴定出 Petasites japonicus 中含有的 bakkenolide B 是人类 T 细胞系中白细胞介素 2 产生的抑制剂。


Ca2+ 信号传导与多种疾病有关，例如过敏、糖尿病和癌症。我们使用基于酵母的筛选方法探索了自然资源中的 Ca2+ 信号抑制剂，并使用 YNS17 菌株 (zds1Δ erg3Δ pdr1/3Δ) 从可食用野生植物 Petaites japonicus 的花蕾中发现了 bakkenolide B。 Bakkenolide B 对 YNS17 菌株表现出生长恢复活性，并诱导野生型酵母细胞对 Li+ 敏感，表明它抑制钙调磷酸酶途径。此外，bakkenolide B 在人类 T 细胞系 Jurkat 细胞的基因和蛋白质水平上抑制白介素 2 的产生，但不抑制人重组钙调磷酸酶（白细胞介素 2 产生的上游调节因子）的体外磷酸酶活性。此外，与bakkenolide B相比，bakkenolide A在YNS17和Jurkat细胞中显示出较弱的活性。这些发现揭示了日本对虾中所含的bakkenolide作为人T细胞中白细胞介素2产生的抑制剂的新生物效应和构效关系。