{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:16:16Z","timestamp":1791486976478,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)","award":["RS-2024-00353812"],"award-info":[{"award-number":["RS-2024-00353812"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)","award":["RS-2022-NR070856"],"award-info":[{"award-number":["RS-2022-NR070856"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Endothelial cells play a crucial role in cardiovascular health by maintaining vascular homeostasis, regulating blood flow and vascular wall permeability, and protecting against external stressors. Oxidative stress, particularly excessive reactive oxygen species (ROS), disrupts cellular homeostasis and contributes to endothelial cell dysfunction. Rutaecarpine (RUT), an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has cytoprotective potential. However, the molecular mechanism underlying its cytoprotective activity in endothelial cells remains unclear. In this study, we investigated the protective effects of RUT against H2O2-induced apoptosis in human EA.hy926 endothelial cells and explored its underlying mechanism of action. RUT enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) activation by increasing its expression and phosphorylation, resulting in the upregulation of antioxidant enzymes (GCLC, NQO1, and HO-1). RUT increased the level of the anti-apoptotic marker (Bcl-2) while inhibiting apoptotic markers (cleaved caspase-3 and Bax) in H2O2-induced apoptotic cells. Mechanistic analysis revealed that RUT activates Nrf2 through two pathways: TRPV1-mediated PKC\u03b4\/Akt phosphorylation and aryl hydrocarbon receptor (AhR)-dependent Nrf2 expression. These findings suggest that RUT exerts protective effects against oxidative-stress-induced apoptosis by controlling the Nrf2 signaling pathway in endothelial cells.<\/jats:p>","DOI":"10.3390\/antiox14050616","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T13:59:43Z","timestamp":1747835983000},"page":"616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rutaecarpine Protects Human Endothelial Cells from Oxidative-Stress-Induced Apoptosis via TRPV1- and AhR-Mediated Nrf2 Activation"],"prefix":"10.3390","volume":"14","author":[{"given":"Chae Yeon","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2739-5942","authenticated-orcid":false,"given":"Anh Thi Ngoc","family":"Bui","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8020-8914","authenticated-orcid":false,"given":"Hye Gwang","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1253\/circj.CJ-08-1102","article-title":"Endothelial function and oxidative stress in cardiovascular diseases","volume":"73","author":"Higashi","year":"2009","journal-title":"Circ. 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