Fangxiao Formula alleviates airway inflammation and remodeling in rats with asthma via suppression of transforming growth factor-β/Smad3 signaling pathway

• Published in: Biomedicine & pharmacotherapy Vol. 119; p. 109429
• Main Authors: Ge, Yuqing, Cheng, Rubin, Sun, Siya, Zhang, Saijun, Li, Lan, Jiang, Jianping, Yang, Chenxi, Xuan, Xiaobo, Chen, Jian
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.11.2019; Elsevier
• Subjects: Airway inflammation; Airway Remodeling - drug effects; Animals; Asthma; Asthma - physiopathology; Bronchoalveolar Lavage Fluid; Collagen - metabolism; Cytokines - metabolism; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Fangxiao Formula; Hyperplasia; Inflammation - drug therapy; Inflammation - physiopathology; Lung - drug effects; Lung - pathology; Lung - physiopathology; Male; Proliferating Cell Nuclear Antigen - metabolism; Rats, Sprague-Dawley; Remodeling; Signal Transduction - drug effects; Smad3 Protein - metabolism; TGF-β/Smad3 pathway; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Transforming Growth Factor beta - metabolism; Fangxiao Formula; Airway inflammation; TGF-β/Smad3 pathway; Remodeling; Asthma
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109429

Asthma is a common obstructive airway disease characterized by inflammation and remodeling with a progressive decline in lung function. Fangxiao Formula (FXF) is an herbal medicine that has achieved significant clinical benefits toward asthma patients, but the relevant mechanism has not yet been clarified. The aim of this study was to determine the inhibitory effects of FXF on airway inflammation and remodeling, and investigate the activities of TGF‑β/Smads signaling pathway in the rat asthma model. Rats were sensitized by ovalbumin (OVA) for six weeks to establish the asthma experimental model. OVA-challenged animals were randomly divided into 5 groups and received different concentrations of FXF or dexamethasone. The animals in blank control group received saline only. Lung tissues were collected and analyzed for determining the inflammatory cells infiltration, HE and PAS staining, airway wall thickness and collagen deposition. The productions of inflammatory cytokine productions were analyzed by ELISA in the bronchoalveolar lavage (BAL) fluid. Immunohistochemical analysis was performed to measure the expression of α-SMA and PCNA in lung tissue after the treatment of FXF. The levels of TGF-β were assessed by both immunohistology and western blotting, and the expression of p-Smad2/3 proteins were determined by western blotting analysis. Our results indicated that FXF attenuated the infiltration of inflammatory cells, decreased the production of Th2 cytokines and simultaneously increased the levels of Th1 cytokine in the asthma rat model. In addition, FXF reduced allergen-induced increased airway wall thickness, goblet cell hyperplasia and collagen deposition. Furthermore, the expression levels of TGF-β and p-Smad3 were obviously reduced after the treatment of FXF. These results indicate that FXF alleviates airway inflammation and remodeling by restoring the balance of Th1/Th2 cytokines and the TGF-β/Smad-3 pathway, therefor providing potential therapeutic approach for asthmatic patients.