A yeast-based screening system identified bakkenolide B contained in Petasites japonicusas an inhibitor of interleukin-2 production in a human T cell line

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 vitrophosphatase 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. japonicusas inhibitors of interleukin-2 production in human T cells.Graphical AbstractPetasites japonicusshowed inhibitory effect against Ca2+signaling of mutant yeast YNS17 strain. Bakkenolide B, an active component, suppressed interleukin-2 production in Jurkat cells.