{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:30:09Z","timestamp":1779183009459,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Natural Science Foundation of China","award":["82470063"],"award-info":[{"award-number":["82470063"]}]},{"name":"The National Natural Science Foundation of China","award":["82270069"],"award-info":[{"award-number":["82270069"]}]},{"name":"The National Natural Science Foundation of China","award":["82304856"],"award-info":[{"award-number":["82304856"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by the accumulation of fibrotic tissue in the lungs, leading to impaired gas exchange and respiratory failure, with a poor prognosis and limited treatment options. Oleuropein, a compound extracted from olive leaves, demonstrates a range of pharmacological activities, including benefits for non-alcoholic fatty liver disease and cardiac fibrosis. This study investigates the therapeutic potential of oleuropein for IPF and its underlying mechanisms. We first established a bleomycin-induced mouse model of pulmonary fibrosis and evaluated the in vivo efficacy of oleuropein. Our findings demonstrated that oleuropein significantly alleviated lung fibrosis and improved pulmonary function. Through in vitro experiments, we found that oleuropein inhibited TGF-\u03b21-induced fibroblast migration, activation, autophagy, and apoptotic resistance, and mechanistically, oleuropein could regulate the TGF-\u03b21\/Smad and TGF-\u03b21\/mTOR signaling pathways in fibroblasts. Additionally, molecular docking analysis indicated that FAP-\u03b1 is a potential target of oleuropein, displaying strong binding affinity. The effects of oleuropein on fibroblasts were markedly disrupted in FAP-\u03b1 knockout cells. In conclusion, oleuropein exerts its beneficial effects by targeting FAP-\u03b1 and inhibiting TGF-\u03b21-related signaling pathways, improving the pathological characteristics of pulmonary fibrosis in mouse models, and demonstrating promising application prospects for the treatment of IPF.<\/jats:p>","DOI":"10.3390\/biom15091211","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T11:50:31Z","timestamp":1755863431000},"page":"1211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oleuropein Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice by Targeting TGF-\u03b21 Signaling Pathway"],"prefix":"10.3390","volume":"15","author":[{"given":"Liang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yayue","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueze","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9293-0230","authenticated-orcid":false,"given":"Yuming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"},{"name":"Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoting","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"},{"name":"Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weidong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"},{"name":"Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-3422","authenticated-orcid":false,"given":"Honggang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tianjin First Central Hospital, College of Pharmacy, Nankai University, Tianjin 300353, China"},{"name":"Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1164\/rccm.202202-0399ST","article-title":"Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS\/ERS\/JRS\/ALAT Clinical Practice Guideline","volume":"205","author":"Raghu","year":"2022","journal-title":"Am. 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