Combined network pharmacology, transcriptomics and machine learning suggests Danggui Buxue Tang may suppress oxidative stress and inflammation through Nrf2/HO-1 and IL-17 pathways in pulmonary fibrosis

Ethnopharmacological relevance Danggui Buxue Tang (DBT), a classical Chinese herbal formula of Astragalus membranaceus (Fisch.) Bunge and Angelica sinensis (Oliv.) Diels in a 5:1 ratio, has long been used for qi and blood deficiency . Its mechanism against pulmonary fibrosis (PF) remains unclear. Aim of the study This study examined how DBT treats silica-induced PF, combining network pharmacology, transcriptomics, machine learning and experimental validation. Materials and methods We built a rat PF model by intratracheal silica instillation. Network pharmacology and weighted gene co-expression network analysis (WGCNA) identified candidate therapeutic targets. Four machine learning algorithms screened diagnostic signature genes (DSGs). We profiled immune infiltration with CIBERSORT, modeled compound–target binding by molecular docking, and confirmed key genes and pathways by Western blotting. Results DBT treatment significantly attenuated silica-induced lung pathology, evidenced by improved pulmonary function, reduced alveolitis and fibrosis scores, diminished collagen deposition, and downregulated expression of α-smooth muscle actin, collagen I, and fibronectin. Furthermore, DBT markedly suppressed inflammatory responses (decreasing TNF-α, IL-6, IL-1β, and TGF-β1 while elevating IL-10) and mitigated oxidative stress (lowering MDA levels while enhancing SOD, GSH-Px, and T-AOC activities). Bioinformatic analyses identified three core DSGs—MMP7, MMP13, and TNF—as candidate therapeutic targets. Enrichment analyses highlighted the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and IL-17 signaling as the primary mechanistic routes. Immune profiling revealed that DBT's therapeutic effects correlate with specific shifts in immune cell subsets. Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry detected 11 prototype constituents in serum; notably, the Ononin, Methylnissolin-3-O-glucoside, and Isomucronulatol-7-O-glucoside exhibited strong binding affinities to MMP7, MMP13, and TNF. DBT inhibited the profibrotic IL-17 cascade while activating the antioxidant Nrf2/HO-1 axis. Conclusion Our data suggest that DBT may ease silica-induced PF through multiple targets that act on oxidative stress and inflammation. The DSGs ( MMP7 , MMP13 , TNF ) and pathways (Nrf2/HO-1, IL-17) help explain how DBT works and point to new targets for treating PF. The approach also provides a reusable workflow for studying other complex herbal formulas in fibrosis.