Dehydrocostus lactone, a sesquiterpene from Saussurea lappa Clarke, suppresses allergic airway inflammation by binding to dimerized translationally controlled tumor protein
- 주제(키워드) Allergic diseases , Dehydrocostus lactone , Dimerized TCTP , Histamine releasing factor , Saussurea lappa Clarke
- 주제(기타) Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy
- 설명문(일반) [Pyun, Haejun; Kang, Unwoo; Seo, Eun Kyoung; Lee, Kyunglim] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 ELSEVIER GMBH, URBAN & FISCHER VERLAG
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000151495
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.phymed.2018.03.045
초록/요약
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 K-D value was 5.33 +/- 0.03 mu M 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-kappa B activation. Conclusion: DCL's therapeutic potential in allergic airway inflammation is based on its anti-inflammatory activity of suppressing the function of dTCTP.
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