title: 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.affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Je
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Hyun Gyu
authors.initials: HG
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Hui-Hun
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Jin Kyeong
authors.initials: JK
authors.lastname: Choi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, CHA Gumi Medical Center, CHA University, Gumi 730-040, Republic of Korea.
authors.forename: Sung-Wan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, CHA Gumi Medical Center, CHA University, Gumi 730-040, Republic of Korea.
authors.forename: Duk-Sil
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Woosuk University, Jeonju 565-701, Republic of Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
authors.affiliation: Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Republic of Korea. Electronic address: dkhang@gachon.ac.kr.
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Khang
authors.affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea. Electronic address: shkim72@knu.ac.kr.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D035801:Amomum; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006967:Hypersensitivity; D051550:I-kappa B Kinase / Q000096:biosynthesis; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000840:Anisoles; D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; C088469:1,2,4,5-tetramethoxybenzene; D051550:I-kappa B Kinase
keywords: Active systemic anaphylaxis; Allergic inflammation; Histamine; Mast cells; Pro-inflammatory cytokine