DW2008S and its major constituents from Justicia procumbens exert anti-asthmatic effect via multitargeting activity.

Jihyun Youm,Youngwoo Choi,Joobyoung Yoon,Hyunyong Lee

doi:10.1111/jcmm.13550

Jihyun Youm, Youngwoo Choi + Show 2 more

Open Access

https://doi.org/10.1111/jcmm.13550

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Abstract

Our previous study revealed that the ethanolic extract of Justicia procumbens ameliorates ovalbumin‐induced airway inflammation and airway hyper‐responsiveness in a mouse model of asthma. However, the mechanism of action of the extract remains unknown. In this study, we prepared DW2008S, an optimized and standardized powder extracted from J. procumbens using anhydrous ethanol, and investigated its anti‐asthmatic effect and mechanism of action. Our results showed that DW2008S contains two major ingredients, justicidin A (JA) and justicidin B (JB), which selectively inhibit T helper 2 (Th2) cell responses in concanavalin A‐activated spleen cells and polarized Th2 cells. Blockade of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine‐based inhibition motif domains (TIGIT) using a neutralizing antibody also selectively inhibited Th2 cell responses. Furthermore, DW2008S regulated TIGIT expression in the mice and cultured cells. Additionally, DW2008S and JA antagonized human adenosine receptor A3 (A3 AR), which mediates mast cell‐dependent inflammation and bronchoconstriction. DW2008S and JB inhibited human phosphodiesterase 4 (PDE4), which is known to cause bronchoconstriction; however, the required concentrations were higher than those needed to affect TIGIT . These findings suggest that DW2008S can potentially ameliorate Th2‐driven airway inflammation and bronchoconstriction through negative regulation of TIGIT and blockade of A3 AR and PDE4 activities.

Highlights

According to a recent report from the Global Initiative for Asthma, asthma is a heterogeneous chronic respiratory disease affecting 1%18% of the global population; it is characterized by chronic airway inflammation with variable expiratory airflow limitation.[1]
We initially found that DW2008S selectively suppressed T helper 2 (Th2) cytokines but not Th1/Th17 cytokines in concanavalin A-activated spleen cells
These results indicate that DW2008S possibly regulates TIGIT expression

Summary

| INTRODUCTION

According to a recent report from the Global Initiative for Asthma, asthma is a heterogeneous chronic respiratory disease affecting 1%18% of the global population; it is characterized by chronic airway inflammation with variable expiratory airflow limitation.[1]. There is evidence that Th2 immunity plays a crucial role in inflammation and airway hyper-responsiveness (AHR) in mouse models of allergic asthma.[2] Th2-type cytokines such as interleukin (IL)-4, IL-5 and IL-13 stimulate the production of allergen-specific immunoglobulin (Ig) E in B cells and infiltration of eosinophils into the lungs. We prepared DW2008S powder, which has better solubility and homogeneity characteristics than DW2008 has, and investigated its anti-asthmatic effect and mechanisms of action

| MATERIALS AND METHODS

| RESULTS

H2 BLT1 CYSLTR1 CYSLTR2

| DISCUSSION

Findings

CONFLICTS OF INTERESTS