{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:05:29Z","timestamp":1780380329258,"version":"3.54.1"},"reference-count":73,"publisher":"SAGE Publications","issue":"1-3","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Ministry of Education, Taiwan","award":["CMRC-CENTER-7"],"award-info":[{"award-number":["CMRC-CENTER-7"]}]},{"name":"National Science and Technology Council","award":["NSTC 111-2813-C-039-161-B"],"award-info":[{"award-number":["NSTC 111-2813-C-039-161-B"]}]},{"name":"National Science and Technology Council","award":["NSTC 113-2320-B-039-029"],"award-info":[{"award-number":["NSTC 113-2320-B-039-029"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      To determine whether physalin A (PA) safeguards the outer blood\u2013retinal barrier under diabetic stress by engaging nuclear factor erythroid 2-related factor 2 (Nrf2) to restore redox balance and restrain ferroptosis in human retinal pigment epithelial (hRPE) cells and C57BLKS\/J Iar \u2212+Lepr\n                      <jats:sup>db<\/jats:sup>\n                      \/+Lepr\n                      <jats:sup>db<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In high-glucose challenged hRPE cells, PA dose-dependently preserved viability, maintained claudin-1\/occludin\/zonula occludens-1 abundance and membrane localization, and reversed ferroptosis hallmarks (restored solute carrier family 7 member 11 [SLC7A11], SLC3A2, and glutathione peroxidase 4; reduced ferrous iron [Fe\n                      <jats:sup>2+<\/jats:sup>\n                      ] overload and lipid peroxidation). PA restored glutathione levels, reduced malondialdehyde (MDA), and enhanced the antioxidant defense pathway mediated by Nrf2, including upregulation of heme oxygenase 1, NAD(P)H quinone dehydrogenase 1, and superoxide dismutase 2. Silencing Nrf2 abolished the effects of PA on barrier integrity and ferroptosis suppression, with rebounds in reactive oxygen species, MDA, Fe\n                      <jats:sup>2+<\/jats:sup>\n                      , and tight junction loss. In db\/db mice treated systemically for 20 weeks, PA reduced Evans Blue leakage, increased retinal thickness, restored RPE tight junction proteins, and normalized mitochondrial architecture by transmission electron microscopy. PA rebalanced mitochondrial dynamics (dynamin 1-like, optic atrophy 1, fission 1, mitofusin 1, FUN14 domain containing 1), increased retinal mitochondrial DNA copy number, and partially stabilized glycemia and weight.\n                    <\/jats:p>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" orientation=\"portrait\" position=\"float\" xlink:href=\"10.1177_15230864261442217-fig9.tif\"\/>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      PA restores redox tone, restrains ferroptosis, and preserves junctional integrity to protect the diabetic retina, with Nrf2 being indispensable for these benefits. These findings position PA as a promising adjunctive candidate for early diabetic retinopathy and support Nrf2-centered strategies to reinforce the outer blood\u2013retinal barrier.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      45, 5\u201327.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261442217","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:02:58Z","timestamp":1778310178000},"page":"5-27","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Physalin A Restores Redox and Mitochondrial Homeostasis to Protect against Diabetic Retinopathy"],"prefix":"10.1177","volume":"45","author":[{"given":"Yan-Ru","family":"Xiao","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine, China Medical University, Taichung City, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yow-Wen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, China Medical University Hospital, Taichung City, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Yong","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Sheng","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, National Chung Cheng University, Chiayi, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Cheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, National Chung Cheng University, Chiayi, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Ying","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, China Medical University Hospital, China Medical University, Taichung City, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Hsiung","family":"Kuo","sequence":"additional","affiliation":[{"name":"Chinese Medicine Research Center, China Medical University, Taichung City, Taiwan."},{"name":"Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dah-Yuu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung City, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2330-8898","authenticated-orcid":false,"given":"Wen-Tsong","family":"Hsieh","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, China Medical University, Taichung City, Taiwan."},{"name":"Chinese Medicine Research Center, China Medical University, Taichung City, Taiwan."},{"name":"Department of Pharmacology, School of Medicine, China Medical University, Taichung City, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"issue":"1","key":"e_1_3_4_2_1","first-page":"99","article-title":"Anti-oxidative and Reno-restorative effects of physalis angulata (whole plant extract) in alloxan-induced diabetic male Wistar rats","volume":"45","author":"Adewoye EO","year":"2016","unstructured":"Adewoye EO, , Oguntola MA, , Ige AO. 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