Inhibitory effect of 1,2,4,5-tetramethoxybenzene on mast cell-mediated allergic inflammation through suppression of I kappa B kinase complex

Title
Inhibitory effect of 1,2,4,5-tetramethoxybenzene on mast cell-mediated allergic inflammation through suppression of I kappa B kinase complex
Author(s)
박필훈김상현[김상현]제인규[제인규]최현규[최현규]김희훈[김희훈]이소영[이소영]최진경[최진경]김성완[김성완]김덕실[김덕실]권택규[권택규]신태용[신태용]강동우[강동우]
Keywords
AMOMUM-XANTHOIDES; GALLIC ACID; ANAPHYLACTIC RESPONSES; ATOPIC-DERMATITIS; NATURAL-PRODUCTS; DRUG DISCOVERY; IGE; ACTIVATION; CALCIUM; RAT
Issue Date
201509
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
TOXICOLOGY AND APPLIED PHARMACOLOGY, v.287, no.2, pp.119 - 127
Abstract
As the importance of allergic disorders such as atopic dermatitis and allergic asthma, research on potential drug candidates becomes more necessary. Mast cells play an important role as initiators of allergic responses through the release of histamine; therefore, they should be the target of pharmaceutical development for the management of allergic inflammation. In our previous study, anti-allergic effect of extracts of Amomum xanthioides was demonstrated. To further investigate improved candidates, 1,2,4,5-tetramethoxybenzene (TMB) was isolated from methanol extracts of A. xanthioides. TMB dose-dependently attenuated the degranulation of mast cells without cytotoxicity by inhibiting calcium influx. TMB decreased the expression of pro-inflammatory cytokines such as tumor necrosis factor-et and interleukin (IL)-4 at both the transcriptional and translational levels. Increased expression of these cytolcines was caused by translocation of nuclear factor-kappa B into the nucleus, and it was hindered by suppressing activation of I kappa B kinase complex. To confirm the effect of TMB in vivo, the ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and IgE-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA model, hypothermia was decreased by oral administration of TMB, which attenuated serum histamine, OVA-specific IgE, and IL-4 levels. Increased pigmentation of Evans blue was reduced by TMB in a dose-dependent manner in the PCA model. Our results suggest that TMB is a possible therapeutic candidate for allergic inflammatory diseases that acts through the inhibition of mast cell degranulation and expression of pro-inflammatory cytokines. (C) 2015 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/31023http://dx.doi.org/10.1016/j.taap.2015.05.006
ISSN
0041-008X
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약학대학 > 약학부 > Articles
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