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

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.