Inhibition of trypsin-induced mast cell activation by acanthoic acid.
Acanthoic acid (AA) is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum (Araliaceae). In the present study, we examined whether AA has the inhibitory effect on the production of inflammatory mediators and activating signals induced in trypsin-treated human leukemic mast cell-1 (HMC-1). HMC-1 cells were stimulated with trypsin (100 nM) in the presence or absence of AA (1, 10, and 100 microg/ml). We assessed the production of TNF-alpha and tryptase by enzyme-linked immunosorbent assay (ELISA) or reverse transcription-PCR, ERK activation by Western blot, and NF-kappaB activation by gel shift assay. AA (10 and 100 microg/ml) significantly inhibited production of both TNF-alpha and tryptase in a dose-dependent manner in trypsin-stimulated HMC-1. Furthermore, AA inhibited ERK phosphorylation and NF-kappaB activation induced by trypsin treatment without blocking of trypsin activity even with 100 microg/ml. These results suggest that AA may inhibit the production of inflammatory mediators through inhibition of ERK phosphorylation and NF-kappaB activation pathway in human mast cells. It supports the evidence that AA may be used to blocks the development of inflammation caused from mast cells.
Kang
Ok-Hwa
OH
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
Choi
Yeon-A
YA
Park
Hye-Jung
HJ
Kang
Chon-Sik
CS
Song
Bong-Seok
BS
Choi
Suck-Chei
SC
Nah
Yong-Ho
YH
Yun
Ki-Jung
KJ
Cai
Xing-Fu
XF
Kim
Young-Ho
YH
Bae
Ki-Hwan
KH
Lee
Young-Mi
YM
D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D053802:Tryptases / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D004224:Diterpenes; D016328:NF-kappa B; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; C099958:acanthoic acid; D048049:Extracellular Signal-Regulated MAP Kinases; D053802:Tryptases