Andrographolide Modulates Fibrogenic and Oxidative Stress Responses in Human Lung Fibroblasts

Pulmonary fibrosis is a progressive lung disorder characterized by fibroblast activation and excessive extracellular matrix deposition. Andrographolide (ANDRO) has been reported to attenuate pulmonary fibrosis, but the underlying molecular mechanisms remain incompletely understood. In this study, we investigated the effects of ANDRO on transforming growth factor-beta 1 (TGF-β1)-induced fibrogenesis in human lung fibroblasts. Comprehensive transcriptomic analysis revealed that ANDRO reversed TGF-β1-perturbed genes associated with fibrogenesis and glutathione (GSH) metabolism. Functionally, ANDRO restored TGF-β1-inhibited total GSH levels and suppressed TGF-β1-induced reactive oxygen species (ROS) accumulation. Together, these findings identify GSH metabolism as a previously unrecognized mechanism underlying the antifibrotic effects of ANDRO in human lung fibroblasts.