Computational insights into Curcumin's modulation of Epithelial-mesenchymal transition in pulmonary fibrosis

Abstract

Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by excessive production and accumulation of extracellular matrix, resulting in permanent lung damage. The epithelial-mesenchymal transition (EMT) plays a central part in the development of fibrosis; however, therapeutic strategies targeting EMT remain limited. Curcumin, a natural polyphenol with known anti-inflammatory and anti-fibrotic properties, presents a promising candidate for modulating EMT. This study aimed to evaluate the potential of curcumin as an EMT-targeting agent in pulmonary fibrosis using computational approaches. Protein targets of curcumin were predicted using the SwissTargetPrediction and STITCH databases. Protein-protein interaction (PPI) networks were analysed via STRING. Molecular docking studies were performed using AutoDock Vina with EMT-related proteins (TGFBR1, EGFR, MAPK1, and MMP9). Drug-like and pharmacokinetic properties were assessed using SwissADME, while toxicity was evaluated through Protox-II. Curcumin demonstrated strong binding affinity for multiple EMT regulators, suggesting potential inhibitory activity. Network analysis revealed dense interconnectivity among curcumin targets, indicating a co-regulated EMT-related functional cluster. Curcumin also exhibited favourable drug-like parameters and a low predicted toxicity profile (LD50: 2000 mg/kg). This study supports the role of curcumin as a multitarget modulator of epithelial-mesenchymal transition (EMT) with therapeutic relevance in pulmonary fibrosis. The results warrant further experimental validation to confirm its efficacy and safety in preclinical models.