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

Inhibitory effect of 1,2,4,5-tetramethoxybenzene on mast cell-mediated allergic inflammation... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Toxicology and Applied Pharmacology Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier Inc.
ISSN
0041-008x
D.O.I.
10.1016/j.taap.2015.05.006
Publisher site
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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.

Journal

Toxicology and Applied PharmacologyElsevier

Published: Sep 1, 2015

References

  • Natural compounds: leads or ideas? Bioinspired molecules for drug discovery
    Beghyn, T.; Deprez-Poulain, R.; Willand, N.; Folleas, B.; Deprez, B.
  • Oleanolic acid acetate inhibits atopic dermatitis and allergic contact dermatitis in a murine model
    Choi, J.K.; Oh, H.M.; Lee, S.; Park, J.W.; Khang, D.; Lee, S.W.; Lee, W.S.; Rho, M.C.; Kim, S.H.
  • Natural products: a continuing source of novel drug leads
    Cragg, G.M.; Newman, D.J.
  • Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity
    Galli, S.J.; Tsai, M.
  • IgE and mast cells in allergic disease
    Galli, S.J.; Tsai, M.
  • The development of allergic inflammation
    Galli, S.J.; Tsai, M.; Piliponsky, A.M.
  • Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation
    Kim, H.H.; Park, S.B.; Lee, S.; Kwon, T.K.; Shin, T.Y.; Park, P.H.; Lee, S.H.; Kim, S.H.

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