21-Methylmelianodiols from Poncirus trifoliata as inhibitors of interleukin-5 bioactivity in pro-B cells

Interleukin (IL)-5 plays an important role in the progression of allergic inflammation. Here, we have isolated 21α-methylmelianodiol and 21β-methylmelianodiol from Poncirus trifoliata (L.) Raf., a plant of the Rutaceae family, as the inhibitors of IL-5-dependent growth of Y16 pro-B cells by bioassay-guided fractionation. 21α-Methylmelianodiol and 21β-methylmelianodiol inhibited IL-5-dependent growth of Y16 cells in a dose-dependent manner with IC₅₀ values of 17 μM and 15 μM, respectively. A positive control, tyrphostin AG-490, exhibited an IC ₅₀ value of 23 μM on IL-5 bioactivity. Further, we have documented that 21α-methylmelianodiol and 21β-methylmelianodiol cause G1 arrest of IL-5-induced cell cycle progression of Y16 cells, and also reduce IL-5-dependent survival of the cells by apoptosis. This study could provide a pharmacological potential for P. trifoliata in treatment of IL-5-associated inflammatory disorders.