Buyang Huanwu Decoction attenuates silicosis progression via NF-κB/IL-17 signaling axis modulation: a network pharmacology and experimental validation study

Abstract

Background

Silicosis is a prevalent, irreversible occupational pulmonary fibrotic disease caused by crystalline silica dust inhalation. Buyang Huanwu Decoction (BYHWD), a classical Chinese herbal formula with anti-inflammatory and circulation-enhancing properties, shows potential in inhibiting pulmonary fibrosis. This study investigated its preventive mechanism against silicosis based on TCM’s "preventive treatment" principle.

Methods

Network pharmacology identified BYHWD-silicosis overlapping targets using TCMSP and disease databases. Protein-protein interaction (PPI) networks were constructed (STRING/Cytoscape), followed by GO/KEGG pathway enrichment (Metscape). Mechanistic validation employed in vivo silicosis models: Mice received preventive BYHWD administration prior to silica exposure. Lung fibrosis was assessed via H&E staining and immunohistochemistry (IHC). Key targets in the NF-κB/IL-17 pathway were quantified by Western blotting and qPCR. Liver/kidney toxicity was evaluated through serum biochemical analysis and histopathology.

Results

Network pharmacology analysis revealed that the therapeutic effects of BYHWD on silicosis are potentially mediated through regulation of the NF-κB/IL-17 signaling pathway. In vivo mechanistic studies confirmed that preventive administration of BYHWD prior to silica exposure significantly attenuated pulmonary fibrosis progression. This protective effect was associated with suppression of the NF-κB/IL-17 signaling axis. Additionally, BYHWD treatment did not induce significant impairment in liver or kidney function in mice.

Discussion

These findings support the therapeutic potential of Buyang Huanwu Decoction in intervening in silicosis progression. The study provides novel insights into the molecular mechanism underlying BYHWD's efficacy, specifically highlighting its role in modulating the NF-κB/IL-17 pathway. The lack of significant hepatorenal toxicity further suggests a favorable safety profile for BYHWD in this context. This study proposes a novel therapeutic strategy for targeting silicosis progression.