2. Academic Validation
  3. Effects of 101BHG-D01, a novel M receptor antagonism, on allergic rhinitis in animal models and its mechanism

Effects of 101BHG-D01, a novel M receptor antagonism, on allergic rhinitis in animal models and its mechanism

  • Eur J Pharmacol. 2023 Jul 6;175902. doi: 10.1016/j.ejphar.2023.175902.
Huijuan Shen 1,  Hao Wei 2,  Junxia Jiang 1,  Hongyi Yao 1,  Yongliang Jia 3,  Jian Shen 3,  Yanyou Li 4,  Qiangmin Xie 5,  Xiaoping Chen 6,  Yicheng Xie 7,  Haibin Dai 8
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China; Department of Pharmacy, Xuzhou Medical University, Xuzhou, China.
  • 3 Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Beijing Showby Pharmaceutical Co., LTD, Beijing, China.
  • 5 Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China; Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou, China.
  • 6 Beijing Showby Pharmaceutical Co., LTD, Beijing, China. Electronic address: [email protected].
  • 7 Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China. Electronic address: [email protected].
  • 8 The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: [email protected].
PMID: 37422119 DOI: 10.1016/j.ejphar.2023.175902
Abstract

Allergic rhinitis (AR) is a nasal mucosal disease with sneezing and nasal itching as the main symptoms. Although AR treatment continues to improve, there remains a lack of effective drugs. There are still controversies regarding whether anticholinergic drugs can effectively and safely relieve the symptoms of AR and reduce inflammation in the nasal mucosa. Here, we synthesized 101BHG-D01, which is a novel anticholinergic drug that mainly targets the M3 receptor and may reduce the adverse effects of other anticholinergic drugs on the heart. We evaluated the effects of 101BHG-D01 on AR and investigated the potential molecular mechanism of anticholinergic therapy for AR. We found that 101BHG-D01 effectively alleviated AR symptoms, reduced the infiltration of inflammatory cells and attenuated the expression of inflammatory factors (IL-4, IL-5, IL-13, etc.) in various AR animal models. In addition, 101BHG-D01 reduced the activation of mast cells and the release of histamine from rat peritoneal mesothelial cells (RPMCs) challenged by IgE. Moreover, 101BHG-D01 reduced the expression of MUC5AC in IL-13-challenged rat nasal epithelial cells (RNECs) and human nasal epithelial cells (HNEpCs). Furthermore, IL-13 stimulation significantly increased JAK1 and STAT6 phosphorylation, which was suppressed by 101BHG-D01. We demonstrated that 101BHG-D01 reduced mucus secretion and inflammatory cell infiltration in the nasal mucosa, which may occur through a reduction in activation of the JAK1-STAT6 signaling pathway, indicating that 101BHG-D01 is a potent and safe anticholinergic therapy for AR.

Keywords

Allergic rhinitis; Anticholinergic drug; JAK1; STAT6.

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