21-Methylmelianodiols from Poncirus trifoliata as Inhibitors of Interleukin-5 Bioactivity in Pro-B Cells

Abstract

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 IC₅₀ 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.

Key words

Poncirus trifoliata - Rutaceae - 21α-methylmelianodiol - 21β-methylmelianodiol - IL-5 inhibitor - pro-B cells

References

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