YiQi GuBen formula targets EHMT2 and enhances NEDD4L transcription to combat epithelial-mesenchymal transition and airway remodeling in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have highlighted the anti-inflammatory properties of YiQi GuBen Formula (YQGBF), a blend of multiple bioactive herbal ingredients, in asthma.

AIM OF THE STUDY: This study investigated the role of YQGBF in asthma and the potential mechanism.

METHODS

Ovalbumin (OVA)-sensitized asthmatic mice were established (n = 8/group) and gavaged with a low dose (1.1 g/kg) or high dose (2.2 g/kg) of YQGBF once daily throughout the entire experimental period. DMSO served as the control. Human or mouse epithelial cells were exposed to TGF-β1 for in vitro modeling.

RESULTS

YQGBF suppressed EHMT2 expression (36 % reduction in EHMT2 mRNA expression and 28 % decrease in positive expression in mice), alleviated airway inflammation in asthmatic mice (47 % reduction in inflammation score at low-dose treatment), inhibited airway remodeling, and blocked epithelial-mesenchymal transition (EMT) (37 % reduction in airway fibrosis, increased E-cadherin expression by 68 %, and decreased vimentin expression by 35 % at low-dose treatment). EHMT2 suppressed NEDD4L mRNA expression (by 46 %) by methylating histone H3K9me2. Overexpression of NEDD4L reversed the exacerbation of airway remodeling and EMT induced by EHMT2 overexpression (reducing airway fibrosis by 38 % in mice, E-cadherin expression increased by 81 %, and vimentin expression decreased by 50 %). Further, either NEDD4L overexpression or β-catenin inhibition ameliorated both EMT and airway remodeling.

CONCLUSION

YQGBF inhibits EHMT2 expression to activate NEDD4L transcription, thereby blocking Wnt/β-catenin signaling and alleviating asthma development. Treatment with YQGBF, combined with intervention targeting the EHMT2/NEDD4L/Wnt/β-catenin signaling pathway, may emerge as a novel therapeutic strategy for asthma-related allergic responses.