Haejun Pyun1, Unwoo Kang1, Eun Kyoung Seo1, Kyunglim Lee2. 1. Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea. 2. Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address: klyoon@ewha.ac.kr.
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.
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.
Authors: Douglas Kemboi; Moses K Langat; Xavier Siwe-Noundou; Tendamudzimu Tshiwawa; Rui W M Krause; Candace Davison; Christie Jane Smit; Jo-Anne de la Mare; Vuyelwa Jacqueline Tembu Journal: PLoS One Date: 2022-08-23 Impact factor: 3.752