{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:04:01Z","timestamp":1779685441753,"version":"3.53.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Oxidative stress-mediated retinal pigment epithelial (RPE) cell injury is a key pathological feature of age-related macular degeneration (AMD). Ferroptosis\u2014an iron-dependent form of regulated cell death driven by lipid peroxidation\u2014has been increasingly identified as a critical executor of RPE degeneration and a key pathogenic mechanism in AMD. This study aimed to investigate the mechanism by which Salvianolic acid A (SalA) alleviates ferroptosis in RPE cells under sodium iodate (NaIO\n                      <jats:sub>3<\/jats:sub>\n                      )-induced damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using\n                      <jats:italic>in vitro<\/jats:italic>\n                      (ARPE-19 cells) and\n                      <jats:italic>in vivo<\/jats:italic>\n                      (mice) NaIO\n                      <jats:sub>3<\/jats:sub>\n                      -induced injury models. We assessed cell viability, ferroptosis markers (iron, lipid peroxidation, glutathione), mitochondrial ultrastructure, and key protein expression via biochemical assays, flow cytometry, transmission electron microscopy, and Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SalA pretreatment effectively mitigated NaIO\n                      <jats:sub>3<\/jats:sub>\n                      -induced ferroptosis, reducing lipid peroxidation, iron overload, and mitochondrial damage. Mechanistically, SalA upregulated the key ferroptosis regulators SLC7A11 and GPX4. Critically, this protection was significantly attenuated by the SLC7A11 inhibitor erastin, confirming the essential role of this axis.\n                      <jats:italic>In mice<\/jats:italic>\n                      , SalA attenuated NaIO\n                      <jats:sub>3<\/jats:sub>\n                      -induced retinal structural damage and enhanced SLC7A11\/GPX4 expression in retina tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies SalA as a potent inhibitor of ferroptosis in RPE cells, primarily through activation of the SLC7A11\/GPX4 axis. These findings suggest that SalA may hold therapeutic potential for AMD and provide a preliminary pharmacological basis for further exploration in retinal degenerative diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1803187","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:45:42Z","timestamp":1779684342000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Salvianolic acid a attenuates sodium iodate-induced ferroptosis in age-related macular degeneration models via the SLC7A11\/GPX4 axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chengdu Sixth People\u2019s Hospital","place":["Chengdu, China"]},{"name":"The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]},{"name":"The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.preteyeres.2009.11.003","article-title":"The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited","volume":"29","author":"Anderson","year":"2010","journal-title":"Prog. 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