{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:08:54Z","timestamp":1785413334037,"version":"3.56.0"},"reference-count":35,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Development Fund, Macau SAR","award":["0001\/2024\/RDP"],"award-info":[{"award-number":["0001\/2024\/RDP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmazie"],"abstract":"<jats:p>Background:Pulmonary fibrosis (PF) is a chronic and progressive respiratory disorder marked by aberrant activation of pulmonary fibroblasts and the occurrence of epithelial\u2013mesenchymal 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.Methods: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-\u03b21) 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.Results: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-\u03b21\/Smad2\/3 pathway and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway.Conclusions:The ameliorative action of SCM198 on BLM-induced pulmonary fibrosis is associated with suppression of the TGF-\u03b21\/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.<\/jats:p>","DOI":"10.31083\/pharmazie52723","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:42:49Z","timestamp":1785411769000},"source":"Crossref","is-referenced-by-count":0,"title":["SCM198 Alleviates Pulmonary Fibrosis Through Downregulation of the TGF-\u03b21\/Smad Signalling Pathway and Activation of Nrf2-Mediated Antioxidant Defenses During EMT"],"prefix":"10.31083","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7097-6339","authenticated-orcid":true,"given":"Jie","family":"Liang","sequence":"first","affiliation":[{"name":"Faculty of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"},{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"},{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"},{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"},{"name":"School of Pharmacy, Macau University of Science and Technology, 999078 Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhun","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, 999078 Macau, China"},{"name":"School of Pharmacy, Macau University of Science and Technology, 999078 Macau, China"},{"name":"Shanghai Key Laboratory of Bioactive Small Molecules and Department of Pharmacology, School of Pharmacy, Fudan University, 200000 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, et al. 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Evaluation of lung protection of Sanghuangporus sanghuang through TLR4\/NF-\u03baB\/MAPK, keap1\/Nrf2\/HO-1, CaMKK\/AMPK\/Sirt1, and TGF-\u03b2\/SMAD3 signaling pathways mediating apoptosis and autophagy. Biomedicine & Pharmacotherapy. 2023; 165: 115080.","DOI":"10.1016\/j.biopha.2023.115080"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Patel D, Yadav P, Singh SK, Tanwar SS, Sehrawat A, Khurana A, et al. Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2\/HO-1\/NLRP3 and TGF-\u03b2 expression. 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