Chlorogenic acid attenuates idiopathic pulmonary fibrosis: An integrated analysis of network pharmacology, molecular docking, and experimental validation

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung condition, the cause of which remains unknown and for which no effective therapeutic treatment is currently available. Chlorogenic acid (CGA), a natural polyphenolic compound found in different plants and foods, has emerged as a promising agent due to its anti-inflammatory, antioxidant, and antifibrotic properties. However, the molecular mechanisms underlying the therapeutic effect of CGA in IPF remain unclear. The purpose of this study was to analyze the pharmacological impact and underlying mechanisms of CGA in IPF. Using network pharmacology analysis, genes associated with IPF and potential molecular targets of CGA were identified through specialized databases, and a protein-protein interaction (PPI) network was constructed. Molecular docking was performed to accurately select potential therapeutic targets. To investigate the effects of CGA on lung histology and key gene expression, a murine model of bleomycin-induced lung fibrosis was used. Network pharmacology analysis identified 384 were overlapped between CGA and IPF. Key targets including AKT1, TP53, JUN, CASP3, BCL2, MMP9, NFKB1, EGFR, HIF1A, and IL1B were identified. Pathway analysis suggested the involvement of cancer, atherosclerosis, and inflammatory processes. Molecular docking confirmed the stable binding between CGA and targets. CGA regulated the expression mRNA of EGFR, MMP9, AKT1, BCL2 and IL1B and attenuated pulmonary fibrosis in the mouse model. CGA is a promising multi-target therapeutic agent for IPF, which is supported by its efficacy in reducing fibrosis through the modulation of key pathways. This evidence provides a basis to further investigate CGA as an IPF potential treatment. •Network pharmacology reveals therapeutic potential of CGA in IPF through regulation of EGFR, MMP9, AKT1, BCL2 and IL1B.•Molecular docking confirms strong and stable interactions between CGA and the key targets EGFR, MMP9, AKT1, BCL2 and IL1B.•CGA attenuates BLM-induced pulmonary fibrosis, cellular infiltrate and collagen deposition in vivo.•CGA treatment egulates EGFR, MMP9, AKT1, BCL2 and IL1B mRNA expression in the BLM-induced pulmonary fibrosis mice model.•This research provides a theoretical and experimental basis that places CGA as a candidate for treating IPF.