The mechanisms by which Yiqi Huoxue compound treats pulmonary inflammation and fibrosis in scleroderma: Based on bioinformatics and network pharmacology

Objective To identify the effective components and key molecules of Yiqi Huoxu compound(YQHX) in the treatment of pulmonary inflammation and fibrosis in scleroderma, providing basis for the development of drug targets for scleroderma. Methods A mouse model of pulmonary fibrosis was established by a single tracheal perfusion of bleomycin. Twenty-four mice were randomly divided into four groups, i.e. intragastric PBS, bleomycin alone, intragastric Yiqi Huoxue compound, and control. HE staining and Masson staining were used to verify the therapeutic effect of Yiqi Huoxue compound on lung inflammation and fibrosis. The active components and target genes of anti-fiber salvia miltiorrhiza were obtained from TCMSP database. PPI network, GO/KEGG enrichment analysis, molecular docking and other bioinformatics analyses were integrated to identify the main active ingredients and key targets of salvia miltiorrhiza in the treatment of scleroderma, and to analyze the relevant signaling pathways. The expression levels of CD3 antibody, p-PI3K antibody and p-AKT antibody were analyzed by immunohistochemistry to verify the effects of Yiqi Huoxu compound on inflammation and key pathways. Results The results of HE staining and Masson staining showed that the severity of fibrosis and inflammatory infiltration were decreased, suggesting that Yiqi Huoxue compound could significantly improve the pulmonary fibrosis, inflammation and tissue damages. The key component of salvia miltiorrhiza was mainly luteolin. PPI network analysis showed that AKT1, EGFR, ESR1, TNF and IL6 were the core targets of salvia miltiorrhiza in the treatment of scleroderma. KEGG enrichment analysis showed that the genes were mainly enriched in the PI3K-AKT pathway. Molecular docking analysis showed the potential binding sites between luteolin and four key targets. The immunohistochemical results showed that YQHX significantly decreased bleomycin-induced CD3+T cell infiltration, p-PI3K and p-AKT levels in mouse lung tissue. Conclusions YQHX has significant therapeutic effects on lung inflammation and fibrosis. Luteolin may be a key effective molecule in YQHX, and treat scleroderma lung inflammation and fibrosis by targeting the PI3K-AKT pathway.