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

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

  • J Ethnopharmacol. 2026 Mar 25:359:121125. doi: 10.1016/j.jep.2025.121125.
Yibu Kong 1,  Aiai Dong 2,  Xinyan Yu 3,  Ting Sun 2,  Hongjun Yu 2,  Chengxiang Zhang 3,  Chunyu Li 3,  Yongji Wang 4,  Yinan Guo 5
Affiliations

Affiliations

  • 1 Department of Pediatrics, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, Jilin, PR China; College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, PR China; Post-Doctoral Research Center, Jilin Aodong Pharmaceutial Group Company Limited, Dunhua, 133700, Jilin, PR China.
  • 2 Department of Pediatrics, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, Jilin, PR China; College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, PR China.
  • 3 College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, PR China.
  • 4 Department of Pediatrics, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, Jilin, PR China; College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, PR China. Electronic address: [email protected].
  • 5 Department of Pediatrics, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, Jilin, PR China; College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, PR China. Electronic address: [email protected].
PMID: 41475628 DOI: 10.1016/j.jep.2025.121125
Abstract

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.

Keywords

Airway remodeling; Bronchial epithelial cells; EHMT2; NEDD4L; YiQi GuBen formula.

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