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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

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

Author(s): Huimin Lao*, Mengqi Chen, Xuanyu Liu, Libo Li, Qian Li and Baoqing Zhang

Volume 21, Issue 5, 2024

Published on: 01 March, 2023

Page: [897 - 904] Pages: 8

DOI: 10.2174/1570180820666230117141701

Price: $65

Abstract

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-β1, were analyzed using ELISA. The gene transcriptions and expressions of MMP-9, TIMP-1, VEGF, HIF-1α, NF-kB, and β-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-β1, 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-1α 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-β1/Smad2/3 signaling pathway and suppressing the oxidative stress-mediated NF-kB/HIF-1α/MMPs signaling pathway.

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