Zhi Chuan Ling oral liquid alleviates Th2-type asthma via IL-4-JAK1-STAT6 and KIT signaling pathways.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi Chuan Ling Oral Liquid (ZCL) has long been used in traditional Chinese medicine for the treatment of asthma. However, how ZCL acts on Th2-type asthma and its active components remain unclear. AIM OF THE STUDY: This study is to investigate the mechanism and potential active substances of ZCL in intervening Th2-type asthma using an ovalbumin (OVA)-induced Th2-type asthma model. MATERIALS AND METHODS: An OVA-sensitized and challenged Th2-type asthma mouse model was established to evaluate the effects of ZCL on airway hyperresponsiveness, Th2-type inflammatory effector cells and cytokines in bronchoalveolar lavage fluid (BALF). Proteomics was employed to identify potential targets of ZCL intervention in Th2-type asthma, and validation was performed in vitro and in vivo using molecular biology, bioinformatics, and LC-MS. RESULTS: ZCL alleviated airway hyperresponsiveness and airway inflammation in Th2-type asthmatic mice, and downregulated TGF-β mRNA expression in lung tissue, decreased the numbers of eosinophils, mast cells and Th2 cytokines in BALF. Proteomic analysis suggested that ZCL may modulate Th2-type asthma via IL-4 and KIT signaling pathways. Western blotting showed that ZCL reduced the IL-4's downstream p-JAK1/JAK1 and p-STAT6/STAT6 ratios and decreased the expression of KIT and Tryptase in lung tissue. Bioinformatics analysis, LC-MS, and in vitro experiments suggest that rutin, forsythiaside, and isoforsythiaside may be the key components of ZCL responsible for intervening in the aforementioned targets. CONCLUSIONS: ZCL can ameliorate Th2-type asthma by suppressing IL-4 and KIT signaling pathways. Rutin, isoforsythiaside and forsythiaside are likely to be key bioactive components mediating these protective effects.