Dehydrocostus lactone, a sesquiterpene from Saussurea lappa Clarke, suppresses allergic airway inflammation by binding to dimerized translationally controlled tumor protein

Haejun Pyun, Unwoo Kang, Eun Kyoung Seo, Kyunglim Lee

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: We previously reported that the biologically active form of histamine releasing factor (HRF) is dimerized translationally controlled tumor protein (dTCTP) which is involved in a number of allergic diseases. Hypothesis/purpose: Hoping that agents that modulate dTCTP may provide new therapeutic targets to allergic inflammatory diseases, we screened a library of natural products for substances that inhibit dTCTP. One such inhibitor we found was dehydrocostus lactone (DCL), a natural sesquiterpene present in rhizome of Saussurea lappa Clarke, the subject of this study. Methods: We evaluated the therapeutic efficacy of DCL in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation, employing the ELISA system using BEAS-2B cells and splenocytes, and confirmed that DCL interacts with dTCTP using SPR assay. Results: DCL inhibited dTCTP-induced secretion of IL-8 in BEAS-2B cells. From kinetic analysis of dTCTP and DCL, we found that KD value was 5.33 ± 0.03 μM between dTCTP and DCL. DCL also significantly reduced inflammatory lung eosinophilia, type 2 cytokines in BALF, as well as OVA specific IgE and mucus production in a mouse model of ovalbumin induced allergy. Moreover, DCL suppressed NF-κB activation. Conclusion: DCL's therapeutic potential in allergic airway inflammation is based on its anti-inflammatory activity of suppressing the function of dTCTP.

Original languageEnglish
Pages (from-to)46-54
Number of pages9
JournalPhytomedicine
Volume43
DOIs
StatePublished - 1 Apr 2018

Keywords

  • Allergic diseases
  • Dehydrocostus lactone
  • Dimerized TCTP
  • Histamine releasing factor
  • Saussurea lappa Clarke

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