{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:04:38Z","timestamp":1782129878413,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T00:00:00Z","timestamp":1563408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>Cardiac fibrosis plays a crucial role in the pathogenesis of myocardial infarction (MI). It has been found that differentiation of cardiac fibroblasts (CFs) into myofibroblasts is a major event in the process of cardiac fibrosis. In the present study, we aimed to investigate the effects of protocatechuic acid (PCA), a cardiac protective agent, on the CFs differentiation in vitro. The results showed that PCA exhibited inhibitory effects on the cell proliferation and migration in angiotensin II (Ang II)\u2010induced CFs. PCA treatment suppressed the Ang II\u2010induced expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), which is a hallmark of myofibroblasts. In addition, the production of extracellular matrix (ECM) proteins, including type I collagen (Col I) and connective tissue growth factor (CTGF), were significantly decreased in the PCA\u2010treated CFs. The Ang II\u2010induced increased levels of matrix metalloproteinase (MMP)\u20102, and MMP\u20109 were reduced by PCA. Furthermore, PCA resulted in decrease in reactive oxygen species (ROS) generation, as well as the expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme 4 (NOX4) and p\u2010p38 in Ang II\u2010induced CFs. These findings showed that PCA treatment prevented the Ang II\u2010induced cardiac fibrosis by inhibiting the NOX4\/ROS\/p38 signaling pathway in vitro, suggesting that PCA might be a therapeutic agent for MI.<\/jats:p>","DOI":"10.1002\/ptr.6435","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T09:06:39Z","timestamp":1563440799000},"page":"2440-2447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Protocatechuic acid attenuates angiotensin II\u2010induced cardiac fibrosis in cardiac fibroblasts through inhibiting the NOX4\/ROS\/p38 signaling pathway"],"prefix":"10.1002","volume":"33","author":[{"given":"Hui","family":"Song","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Ankang Vocational and Technical College Affiliated Hospital  Ankang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4876-0899","authenticated-orcid":false,"given":"Jie","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine the First Affiliated Hospital of Xi'an Jiaotong University; Key Laboratory of Molecular Cardiology, Shaanxi Province; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00251"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)88507-5"},{"key":"e_1_2_6_4_1","article-title":"Berberine inhibit cardiac fibrosis through p38 MAPK pathway","author":"Cai S. 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