Transforming growth factor-β3/Smad2/Smad3 signaling pathway inhibition and autophagy by the Yunpi-Xiefei-Huatan decoction ameliorated airway inflammation and mucus hypersecretion in asthmatic rats
Wenzhou Wang , Zhu Chen , Kainan Cui , Na Chen , Qianqian Gao
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引用次数: 0
Abstract
Ethnopharmacological relevance
The Yunpi-Xiefei-Huatan decoction (YXHD) is a traditional Chinese medicine that can improve asthma-related symptoms, including cough, phlegm in the throat, and shortness of breath. However, the YXHD mechanism on asthma has not yet been elucidated.
Study aim
The aim of this study is to investigate the effect of YXHD on airway inflammation, mucus hypersecretion, and autophagy modulation in asthma.
Materials and methods
The YXHD chemical constituents were observed and analyzed using high-performance liquid chromatography-mass spectrometry. Ovalbumin sensitization and stimulation were used to establish an asthma rat model. A total of 80 Sprague-Dawley (SD) rats were segmented into eight groups at random: a Normal (NC) group, a Model (Mod) group, a YXHD low-dose group (10 g/kg/d), a YXHD moderate-dose group (20 g/kg/d), a YXHD high-dose group (40 g/kg/d), a Rapamycin group (4 mg/kg/d), a 3-methyladenine (3-MA) group (15 mg/kg/d), and a Dexamethasone (DEX) group (0.5 mg/kg/d). Whole-body plethysmography (WBP) detection was used to evaluate airway hyperresponsiveness. An enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors in the peripheral blood. Inflammatory cells in the bronchoalveolar lavage fluid (BALF) were also counted. Pathological changes in the lung tissues were marked using hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. The localization of MUC5AC and the co-localization of LC3B + MUC5AC were observed using immunofluorescence. The expressions of autophagy and the TGF-β3/Smad2/Smad3 pathway in the lung tissues were detected using a Western blot assay (WB) and qPCR, and the autophagosomes in the lung tissues were detected using a transmission electron microscope (TEM).
Results
Twenty signal peaks were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) technology. The TGF-β3/Smad2/Smad3 signal pathway activation was induced using ovalbumin (OVA) exposure in the rats. The upregulated expression of autophagy, enhanced MUC5AC fluorescence and LC3B fluorescence, and their co-localized expression in the airway epithelium indicated inflammatory cell infiltration and excessive mucus secretion in the lungs. This resulted in airway hyper-responsiveness. The YXHD inhibited the activation of the TGF-β3/Smad2/Smad3 signaling pathway, and autophagy expression reduced inflammatory factors, abnormal mucus secretion, and airway hyperresponsiveness.
Conclusion
The YXHD improved lung function, relieved lung inflammation, and inhibited airway mucus secretions in asthmatic rat models. Its mechanism may have been related to the blockage of the TGF-β3/Smad2/Smad3 signaling pathway and autophagy downregulation.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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