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

Conidendrin, a metabolite of lariciresinol (a lignan in dietary plants), has 8 stereoisomers with 3 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 4 stereoisomers, the degranulation inhibitory effect of the other conidendrin isomers possessing no cytotoxicity was investigated. Significant degranulation inhibitory effect was observed on all 4 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 antidegranulation. 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 antiallergic functional food ingredient.