Huatan Tongluo Decoction Inhibits Inflammatory Infiltration and Airway Remodeling by Attenuating TGF-β1/Smad2/3 and Oxidative Stress-mediated NF-kB/HIF-1α/MMPs Signaling Pathway in Chronic Asthma Mice

Background Asthma is a common chronic respiratory disorder characterized by inflammation and remodeling of the airways. Aims This study aimed to identify the inhibitory effects of Huatan Tongluo decoction (HTTLD) on airway inflammation and associated remodeling mechanisms. Methods Mice were immunized with ovalbumin (OVA) for 8 weeks to generate chronic asthma mouse models (CAS), which were randomly divided into 4 groups administrated with pachyman, dexamethasone (DEX), HTTLD, and without anything (CAS model), while mice who administrated saline were assigned as the control group. Hematoxylin-eosin (H&E) and Masson trichrome were used to determine inflammatory infiltration and airway remodeling (fiber deposition). Inflammatory cytokines, including VEGF, PDGF, and TGF-beta 1, were analyzed using ELISA. The gene transcriptions and expressions of MMP-9, TIMP-1, VEGF, HIF-1 alpha, NF-kB, and beta-actin were evaluated using RT-PCR and Western blot, while the expression of p-Smad2/3 was determined by Western blot. Results HTTLD inhibited inflammatory infiltration and airway remodeling (reducing airway wall thickness and decreasing fiber deposition) of lung tissues in the CAS mouse model. HTTLD markedly attenuated levels of TGF-beta 1, VEGF, and PDGF compared to those of mice in the CAS model group (p < 0.05). HTTLD significantly reduced the secretion of matrix metalloproteinases (MMP-9 and TIMP-1) and the expression of NF-kB/HIF-1 alpha compared to mice in the CAS model group (p < 0.05). HTTLD prominently downregulated phosphorylated levels of the Smad2/3 molecule (ratio of p-Smad3/2/Smad2/3) compared to mice in the CAS group (p < 0.05). Conclusion HTTLD inhibited inflammatory infiltration and airway remodeling in an OVA-induced chronic asthma mouse model by attenuating the TGF-beta 1/Smad2/3 signaling pathway and suppressing the oxidative stress-mediated NF-kB/HIF-1 alpha/MMPs signaling pathway.