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 21alpha-methylmelianodiol and 21beta-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. 21alpha-Methylmelianodiol and 21beta-methylmelianodiol inhibited IL-5-dependent growth of Y16 cells in a dose-dependent manner with IC (50) values of 17 microM and 15 microM, respectively. A positive control, tyrphostin AG-490, exhibited an IC (50) value of 23 microM on IL-5 bioactivity. Further, we have documented that 21alpha-methylmelianodiol and 21beta-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.
Lee
In Jeong
IJ
College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.
Xu
Guang-Hua
GH
Ju
Jung-Hun
JH
Kim
Jeong Ah
JA
Kwon
Soon-Woo
SW
Lee
Seung Ho
SH
Han
Sang-Bae
SB
Kim
Youngsoo
Y
D002460:Cell Line; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D032104:Poncirus / Q000737:chemistry*; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*
C525645:21-methylmelianodiol; D015848:Interleukin-5; D014315:Triterpenes