Diosgenin as a Potential Therapeutic Agent for Bleomycin-Induced Pulmonary Fibrosis with Anti-Inflammatory, Antifibrotic and Antibacterial Activity

Idiopathic pulmonary fibrosis (IPF) is a severe long disease characterized by excessive extracellular matrix deposition, chronic inflammation, and irreversible lung remodeling. The study conducted in vivo anti-inflammatory, antifibrotic and antibacterial activity against bleomycin induced pulmonary fibrosis in mice. Pulmonary fibrosis was induced by intratracheal bleomycin administration, followed by prophylactic and therapeutic treatment with diosgenin. Histopathological analysis revealed severe lung injury with a 3.3 fold increase in fibrotic burden, which was significantly attenuated by diosgenin. Pulmonary inflammation was reduced by 39% and 33% in the prophylactic and therapeutic groups, respectively, while collagen deposition decreased by 80%, comparable to nintedanib (84%). Diosgenin suppressed neutrophil extracellular trap formation, reducing citrullinated histone H3 (CitH3) by 30%-40%, and significantly downregulated fibronectin, α-smooth muscle actin (α-SMA), collagen type I (Col1), and monocyte chemoattractant protein-1 (MCP1). Although TGF-β mRNA expression increased, no corresponding reduction in TGF-β protein levels was observed, suggesting post-transcriptional regulation. Pharmacokinetic analysis demonstrated preferential lung accumulation at 10 mg/kg, whereas higher systemic exposure occurred at 30 mg per kg (mg/kg). Antibacterial activity was evaluated using broth dilution and agar well diffusion assays against Escherichia coli, Bacillus subtilis, Bacillus cereus, and Salmonella typhi. Diosgenin significantly inhibited bacterial growth and produced inhibition zones of 23, 22, 20, and 19 mm, respectively, demonstrating broad-spectrum antibacterial activity. Collectively, these findings identify diosgenin as a promising multi-target therapeutic candidate with anti-inflammatory, antifibrotic, and antibacterial properties for the treatment of pulmonary fibrosis and associated bacterial infections.