Elucidating the Mechanism of Buyanghuanwu Decoction Acting on Pulmonary Fibrosis Based on Network Pharmacology and Animal Studies

Background and Objective: Buyanghuanwu Decoction (BYHWD) is a clinically proven prescription effective in treating pulmonary fibrosis (PF), but the molecular mechanism underlying its action remains unclear. The network pharmacology analysis was performed to elucidate the acting substances and related pathways of BYHWD in treating bleomycin (BLM) induced PF mouse. Methods: First, the pharmacologically active components and corresponding targets in BYHWD were identified through the TCMSP database and literature review. Second, PF-related targets were identified through the DisGeNet database. Then, the components-targets network of BYHWD in PF treatment was constructed using Cytoscape. The DAVID database was used for the enrichment analysis of GO terms and KEGG pathways. At last, the therapeutic effect of BYHWD on BLMinduced PF mice were verified, and the mRNA and protein expression of related targets was determined through RT-PCR and western blotting, respectively. Results: The core component-target network contained 58 active components and 147 targets. Thirty-nine core targets were mainly involved in the regulation of biological functions and KEGG pathways, such as the positive regulation of nitric oxide biosynthesis and the TNF signaling pathway. These core targets were obtained through enrichment analysis. Moreover, animal studies revealed that BYHWD down-regulated the mRNA expression levels of TNF, IL-6, IL-1β, and NOS2 and inhibited NF-κB and p38 phosphorylation. Conclusion: The effects of BYHWD on PF mice are therapeutic, and its anti-PF mechanism mainly involves the effects on inflammatory factors and the NF-κB/p38 pathway.