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

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-α and interleukin (IL)-4 at both the transcriptional and translational levels. Increased expression of these cytokines was caused by translocation of nuclear factor-κB into the nucleus, and it was hindered by suppressing activation of IκB 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.

• Authors: In-Gyu Je, Hyun Gyu Choi, Hui-Hun Kim, Soyoung Lee, Jin Kyeong Choi, Sung-Wan Kim, Duk-Sil Kim, Taeg Kyu Kwon, Tae-Yong Shin, Pil-Hoon Park, Dongwoo Khang, Sang-Hyun Kim
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 287 Issue 2 Pg. 119-127 (Sep 01 2015) ISSN: 1096-0333 [Electronic] United States
• PMID: 25981167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anisoles
• Cytokines
• Inflammation Mediators
• Plant Extracts
• 1,2,4,5-tetramethoxybenzene
• I-kappa B Kinase

Topics

• Amomum
• Animals
• Anisoles (pharmacology)
• Cell Degranulation (drug effects)
• Cytokines (antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Hypersensitivity
• I-kappa B Kinase (biosynthesis)
• Inflammation (drug therapy, physiopathology)
• Inflammation Mediators (antagonists & inhibitors)
• Male
• Mast Cells (drug effects)
• Mice
• Plant Extracts (pharmacology)
• Rats
• Rats, Sprague-Dawley