Zhichuanling injection improves bronchial asthma by attenuation airway inflammation and epithelia-mesenchymal transition

Abstract

Ethnopharmacological relevance: Zhichuanling (ZCL) Injection, is a compound formulation containing extracts of mahuang (Herba Ephedrae, dried stem or aerial part of Ephedra sinica Stapf), bitter almond (Semen Armeniacae Amarum, seeds of Prunus armeniaca var. sibirica (L.) K. Koch), yangjinhua (flower of Datura metel L.) and Fructus Forsythiae (fruits of Forsythia suspensa (Thunb.) Vahl). Intramuscular injection of ZCL has been used in the clinical practice to control asthma. The aerosol inhalation of ZCL has been shown to be effective on allergic bronchial asthma. However, the underlying mechanisms remain established.

Aim of the study: To investigate the underling mechanism by which ZCL inhibits the pathogenesis of bronchial asthma.

Methods: The guinea pig tracheal rings and human bronchial epithelial (16HBE) cells were used to assess ZCL's impact on acetylcholine (Ach) induced tracheal contraction, tumor necrosis factor α (TNF-α) induced bronchial inflammation, and transforming growth factor-β1 (TGF-β1) induced airway remodeling. Cell viability and gene expression were assessed using MTT assays, qPCR. RNA-seq (gene expression analysis) was employed to explore the novel mechanisms of ZCL in OVA-induced bronchial asthma.

Results: In this study, we found that ZCL reduces Ach-induced contraction of isolated guinea pig trachea, suppress TNF-α-induced interleukin (IL)-1β, IL-6, and IL-8 and TGF-β1-induced E-cadherin, α-SMA, Vimentin, N-cadherin mRNA expression in the 16HBE. Transcriptomic analysis of lung tissue from mice with OVA-induced bronchial asthma suggests that ZCL may alleviate asthma symptoms by modulating BPIFA1, HIF3Α, CTXN3, GRFA3, PPEF1, KSR2, and CDSN.

Conclusion: ZCL alleviates asthma by suppressing tracheal contractions, inflammation, and epithelial-to-mesenchymal transition. ZCL effect on asthma is likely through the upregulation of BPIFA1 expression thus providing the molecular insight for the treatment of asthma. The findings suggest that ZCL holds promise as a asthma therapeutic approach, and further research is needed to explore its full clinical potential. Future studies should focus on optimizing dosage, evaluating long-term efficacy, and investigating potential synergistic effects with existing treatments to enhance asthma management and patient outcomes.

Keywords: 16HBE; Asthma; BPIFA1; Bronchial epithelium; Zhichuanling injection.