SCM198 Alleviates Pulmonary Fibrosis Through Downregulation of the TGF-β1/Smad Signalling Pathway and Activation of Nrf2-Mediated Antioxidant Defenses During EMT.
Pulmonary fibrosis (PF) is a chronic and progressive respiratory disorder marked by aberrant activation of pulmonary fibroblasts and the occurrence of epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AECs). This disease process is primarily driven by inflammation and oxidative stress (OS), leading to excessive deposition of the extracellular matrix (ECM). Current treatments provide limited efficacy and are associated with significant side effects. Leonurine and its sulfate derivative SCM198, derived from Herba Leonuri, exhibit anti-inflammatory and antioxidant properties. However, their therapeutic effects and mechanisms of action in PF remain poorly understood.
Bleomycin (BLM) was delivered intratracheally to mice to establish a model of PF. Human Fetal Lung fibroblast-1 (HFL-1) fibroblasts and A549 AECs were subjected to transforming growth factor-beta 1 (TGF-β1) exposure for in vitro assays. This study comprehensively evaluated the effects of SCM198 on PF and explored its underlying molecular mechanisms through metabolomics analysis, western blotting, and additional biological techniques.
SCM198 significantly ameliorated lung pathology and micro-Computed Tomography (CT) findings and reduced collagen deposition in BLM-treated mice. Furthermore, the levels of inflammatory markers and cytokines were decreased in lung tissue and Bronchoalveolar Lavage Fluid (BALF). In vitro, SCM198 inhibited fibroblast activation, EMT, and OS. It also down-regulated the TGF-β1/Smad2/3 pathway and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway.
The ameliorative action of SCM198 on BLM-induced pulmonary fibrosis is associated with suppression of the TGF-β1/Smad2/3 signaling axis and activation of Nrf2-mediated antioxidant defenses during the EMT process. However, further studies are needed to confirm the direct involvement of these pathways.
Bleomycin (BLM) was delivered intratracheally to mice to establish a model of PF. Human Fetal Lung fibroblast-1 (HFL-1) fibroblasts and A549 AECs were subjected to transforming growth factor-beta 1 (TGF-β1) exposure for in vitro assays. This study comprehensively evaluated the effects of SCM198 on PF and explored its underlying molecular mechanisms through metabolomics analysis, western blotting, and additional biological techniques.
SCM198 significantly ameliorated lung pathology and micro-Computed Tomography (CT) findings and reduced collagen deposition in BLM-treated mice. Furthermore, the levels of inflammatory markers and cytokines were decreased in lung tissue and Bronchoalveolar Lavage Fluid (BALF). In vitro, SCM198 inhibited fibroblast activation, EMT, and OS. It also down-regulated the TGF-β1/Smad2/3 pathway and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway.
The ameliorative action of SCM198 on BLM-induced pulmonary fibrosis is associated with suppression of the TGF-β1/Smad2/3 signaling axis and activation of Nrf2-mediated antioxidant defenses during the EMT process. However, further studies are needed to confirm the direct involvement of these pathways.