Scopoletin ameliorates bleomycin-induced pulmonary fibrosis by modulating oxidative stress, inflammatory signaling, and epithelial–mesenchymal transition

Title : Scopoletin ameliorates bleomycin-induced pulmonary fibrosis by modulating oxidative stress, inflammatory signaling, and epithelial–mesenchymal transition

Abstract:

Pulmonary Fbrosis (PF) is a progressive interstitial lung disease characterised by chronic inflammation and excessive Extracellular Matrix (ECM) remodelling. Scopoletin (SCO), a naturally occurring coumarin with diverse pharmacological activities, remains unexplored for its potential effects against pf. This study examines the therapeutic efficacy of sco in pf through a comprehensive approach that integrates computational analysis, in vitro studies, and in vivo validation. Network pharmacology was performed to predict sco gene targets associated with pf and the molecular pathways regulated by these targets. Sco targets 93 pf-related gene products involved in the regulation of key inflammatory and fibrotic signalling pathways. Subsequently, molecular docking analysis suggested potential interactions between sco and key protein targets. The effect of sco on epithelial mesenchymal transition (emt) was evaluated in bleomycin (blm) stimulated human alveolar epithelial (a549) cells. Pf was induced in c57bl/6 mice by intratracheal (i.t) instillation of blm, and sco (10 and 30 mg/kg, p.o.) was administered for 14 days. In BLM challenged mice, sco markedly alleviated histopathological injury and reduced immune cell infiltration. Sco upregulated the expression of nrf2 and ho-1, thereby reducing oxidative stress and inflammatory responses through the downregulation of nf-κb, aim2 axis. This upstream modulation subsequently reduces the expression of tgf-β1, p-smad2/3, snail, and slug, thus mitigating emt associated changes. In vitro experiments further confirmed that sco suppressed emt in blm-induced a549 cells. Anti-fibroic effects of sco associacted with modulation of nrf2/ho-1 antioxidant pathway, suppressing oxidative stress, inflammation, and tgf-β1-driven emt, highlighting its potential as a promising antifibrotic agent. 

Keywords: Pulmonary Fibrosis, Scopoletin, Nrf2, Aim2, Tgf-Β1.

Biography:

Yuvaraj D K is an Integrated I-PG-phd researcher in the Department of Pharmacology and Toxicology at the National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, India, under the supervision of Dr Ravinder Kumar Kaundal. My research focuses on the pharmacological investigation of pulmonary fibrosis, with particular emphasis on oxidative stress, inflammatory signaling, epithelial–mesenchymal transition, and fibrotic remodeling. My work involves evaluating bioactive natural compounds as potential therapeutic candidates for pulmonary fibrosis using complementary in- vitro and in- vivo experimental models. My research interests include understanding molecular mechanisms involved in pulmonary fibrosis and exploring novel pharmacological strategies for the development of effective anti-fibrotic therapies.