Correlation between the biological activities and the chemical structures of conidendrin-related compounds: (-)-β-conidendrin inhibits degranulation of RBL-2H3 cells.

Abstract

Conidendrin, a metabolite of lariciresinol (a lignan in dietary plants), has eight stereoisomers with three asymmetric carbon atoms. However, the relationship between the chemical structure and biological activity of these stereoisomers remains unclear. Since strong cytotoxicity against rat basophilic cell line RBL-2H3 cells has been observed in four stereoisomers, the degranulation inhibitory effect of the other conidendrin isomers possessing no cytotoxicity was investigated. Significant degranulation inhibitory effect was observed on all four stereoisomers especially on (-)-β-conidendrin, suggesting that conidendrin exhibits stereospecific cytotoxic and degranulation inhibitory activities, and (-)-β-conidendrin is the most structurally effective isomer on anti-degranulation. Additionally, (-)-β-conidendrin inhibited the antigen-induced increase in intracellular Ca2+ concentration and phosphorylation levels of Syk, PLCγ, and Akt, indicating that (-)-β-conidendrin inhibits Ca2+ influx into cells by downregulating the Syk/PLCγ and PI3K/Akt signaling pathways, thereby suppressing degranulation. Our findings suggest that conidendrin may be useful as an anti-allergic functional food ingredient.