Trillin Protects Against Bleomycin-Induced Pulmonary Fibrosis via Suppressing Oxidative Stress and IL-1β/NLRP3 Inflammasome Positive Cycle

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease. Trillin, an active saponin component isolated from Trillium tschonoskii Maxim, exhibits various pharmacological properties. This study aimed to investigate the preventive effects of Trillin on bleomycin (BLM)-induced IPF and elucidate its underlying mechanisms. Methods BLM was administered via intratracheal injection to C57BL/6J mice to establish an IPF model. Different concentrations of Trillin were then administered as treatments. Network pharmacology and molecular docking approaches were employed to predict potential Trillin targets against IPF. A combination of histopathological examination, immunohistochemical analysis, Western Blotting, and other molecular biological techniques were utilized to assess Trillin's protective effect on BLM-induced IPF and to investigate underlying pathways. Results Trillin effectively inhibited lung tissue injury induced by BLM in mice, moderated inflammation and oxidative stress-related signaling pathways, and reduced the expression of IPF-associated proteins such as TGF-beta 1 and alpha-SMA. Network pharmacology analysis identified 18 core Trillin-IPF target genes. Molecular docking analysis suggested that pro-inflammatory cytokines IL-1 beta, IL-2, and TNF-alpha have high binding affinity with Trillin, suggesting their potential as anti-IPF targets. Additionally, experimental verification confirmed that Trillin suppressed NLRP3 inflammasome activation by reducing IL-1 beta release. Conclusions: This study demonstrates that Trillin effectively reduces oxidative stress and blocks the IL-1 beta/NLRP3 inflammasome positive feedback loop, providing protection against BLM-induced IPF. Consequently, our research underscores the potential of Trillin as a promising therapeutic agent for IPF and lays a theoretical foundation for its future clinical development and application in treating BLM-induced IPF.