Qufeng Xuanbi Formula Ameliorates Airway Remodeling in Asthmatic Mice by Suppressing Airway Smooth Muscle Cell Proliferation through MEK/ERK Signaling Pathway.

Bohan Wang,Xianhong Sun,Suofang Shi,Chunyang Liu,Lingling Tang,Ying Yang,Li Liu,Xiaona Zhang,Jintanaporn Wattanathorn

doi:10.1155/2022/1525110

Abstract

Asthma is a common chronic respiratory disease. The Qufeng Xuanbi formula (QFXBF), a Chinese herbal decoction, has shown efficacy in the management of asthma. The purpose of this study was to investigate the potential therapeutic effects of QFXBF in the treatment of asthma both in vitro and in vivo. Platelet-derived growth factor (PDGF)-induced airway smooth muscle cell (ASMC) proliferation and MTT assays were used to explore the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, ovalbumin (OVA) group, high QFXBF group, low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). A mouse allergic asthma model was established using the intranasally administered OVA sensitization method. Morphological changes in the lung tissue were examined by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Finally, the protein expression of alpha-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), phospho-mitogen-activated protein kinase (p-MEK1/2), mitogen-activated protein kinase (MEK1/2), phospho-extracellular signal-regulated kinases (p-ERK1/2), and extracellular signal-regulated kinases (ERK1/2) in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. PDGF significantly increased the viability of ASMCs. Compared with mice in the control group, the airway walls and airway smooth muscle of mice in the OVA group were thickened, and the number of inflammatory cells around the bronchus significantly increased. Moreover, the administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathological changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment with QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA, and PCNA. QFXBF inhibited the proliferation of ASMCs by suppressing MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.

Highlights

Asthma is a chronic respiratory disease that affects nearly 400 million individuals worldwide
Platelet-derived growth factor (PDGF) was purchased from Proteintech (Wuhan, China); U0126 was provided by Selleck Chemicals (Shanghai, China); fetal bovine serum (FBS), RPMI-1640, and penicillin-streptomycin solution were purchased from Gibco; ovalbumin (OVA) was obtained from Sigma-Aldrich (Saint Louis, MO, United States); and dexamethasone (DEX) was purchased from Xianju Pharmaceuticals (Zhejiang, China). p-ERK1/2, ERK1/2, and HRP-conjugated secondary antibodies were purchased from Cell Signaling Technology (Beverly, MA, USA); p-MEK1/2, MEK1/2, and β-actin antibodies were obtained from Affinity (Changzhou, China); proliferating cell nuclear antigen (PCNA), α-SMA, and GAPDH antibodies were purchased from Proteintech (Wuhan, China); and RIPA lysis buffer and bicinchoninic acid (BCA) protein assay kit were obtained from Beyotime (Shanghai, China)
Overexpression of PCNA and α-SMA is a significant hallmark of airway smooth muscle cells (ASMCs) proliferation; the protein expression of PCNA and α-SMA was detected by western blot assay

Summary

Introduction

Asthma is a chronic respiratory disease that affects nearly 400 million individuals worldwide. Chronic airway inflammation and airway remodeling are key pathological changes in the pathogenesis of asthma [2]. Airway remodeling is the main factor regulating the progression of asthma, which leads to an incomplete reversible obstruction of airflow [3]. Glucocorticoid drugs are still the first-line medication for the management of asthma; the safety issue remains to be solved, and whether glucocorticoid medications could fundamentally reduce the process of airway remodeling remains further investigation [4, 5]. Erefore, it is vital to explore the pathogenesis of airway remodeling in asthma and develop potential antiasthma therapies with improved therapeutic efficacy. Glucocorticoid drugs are still the first-line medication for the management of asthma; the safety issue remains to be solved, and whether glucocorticoid medications could fundamentally reduce the process of airway remodeling remains further investigation [4, 5]. erefore, it is vital to explore the pathogenesis of airway remodeling in asthma and develop potential antiasthma therapies with improved therapeutic efficacy.

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Conclusion