<p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with fibroblast proliferation, excessive extracellular matrix deposition, and oxidative stress, with limited treatment options available. The present study aimed to isolate and evaluate a flavonoid from <i>Cordia sinensis</i> for its potential antifibrotic-associated activity using integrated in vitro and in silico approaches. The isolated compound, kaempferol-3-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside, was assessed for its effects on cell viability, intracellular reactive oxygen species (ROS) levels, and fibrosis-associated protein expression in MRC-5 human lung fibroblasts. Molecular docking study was performed against selected IPF-related targets, including NOX4, KEAP1, EGFR, and TGFBR1. The compound exhibited concentration-dependent effects on MRC-5 cell viability and reduced intracellular ROS accumulation under oxidative stress conditions. Western blot analysis demonstrated decreased expression of COL1A1 and α-SMA, which are proteins associated with fibrotic remodeling and fibroblast activation. Molecular docking suggested favorable binding interactions with NOX4 and KEAP1, providing computational evidence for potential interactions with proteins involved in oxidative stress regulation. Collectively, these findings suggest that the isolated flavonoid exhibited antioxidant-associated activity and modulates fibrosis-associated cellular responses under the experimental conditions. However, the underlying molecular mechanisms, cellular selectivity, and in vivo efficacy remain to be established through further experimental investigations.</p>

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Biological activity assessment of isolated flavonoid from Cordia sinensis: in vitro and in silico evaluation against idiopathic pulmonary fibrosis

  • Pinkey Rawal,
  • Kavitha Jayaseelan,
  • Purnima Ashok

摘要

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with fibroblast proliferation, excessive extracellular matrix deposition, and oxidative stress, with limited treatment options available. The present study aimed to isolate and evaluate a flavonoid from Cordia sinensis for its potential antifibrotic-associated activity using integrated in vitro and in silico approaches. The isolated compound, kaempferol-3-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside, was assessed for its effects on cell viability, intracellular reactive oxygen species (ROS) levels, and fibrosis-associated protein expression in MRC-5 human lung fibroblasts. Molecular docking study was performed against selected IPF-related targets, including NOX4, KEAP1, EGFR, and TGFBR1. The compound exhibited concentration-dependent effects on MRC-5 cell viability and reduced intracellular ROS accumulation under oxidative stress conditions. Western blot analysis demonstrated decreased expression of COL1A1 and α-SMA, which are proteins associated with fibrotic remodeling and fibroblast activation. Molecular docking suggested favorable binding interactions with NOX4 and KEAP1, providing computational evidence for potential interactions with proteins involved in oxidative stress regulation. Collectively, these findings suggest that the isolated flavonoid exhibited antioxidant-associated activity and modulates fibrosis-associated cellular responses under the experimental conditions. However, the underlying molecular mechanisms, cellular selectivity, and in vivo efficacy remain to be established through further experimental investigations.