{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T04:44:50Z","timestamp":1782621890747,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ibrain"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Berberine (BBR) exerts an effective protection for diabetic retinopathy (DR), but the underlying key molecular mechanism remains unknown; this study investigated the protective mechanism of BBR on DR by alleviating cell pyroptosis. A rat DR model was established and treated with BBR, and histological analyses, including hematoxylin and eosin staining, Nissl staining, and immunofluorescence, were executed to evaluate tissue changes. Core target genes were identified using the GeneCards database, Venn diagram analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein\u2010protein interaction networks, and molecular docking. Validation of key genes was performed via reverse transcription\u2010quantitative polymerase chain reaction (RT\u2010qPCR), Western blot, and RNA interference. BBR improved retinal morphology, reduced edema, and restored the arrangement of retinal ganglion cells in DR rats. BBR significantly reduced the levels of pyroptosis markers such as IL\u20101\u03b2 and IL\u201018, which were elevated in DR. Network pharmacology identified 10 hub genes, with six genes (\n                    <jats:italic>JUN<\/jats:italic>\n                    ,\n                    <jats:italic>STAT3<\/jats:italic>\n                    ,\n                    <jats:italic>AKT1<\/jats:italic>\n                    ,\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>IL\u20101B<\/jats:italic>\n                    ,\n                    <jats:italic>EGFR<\/jats:italic>\n                    ) further analyzed. BBR reversed DR\u2010induced upregulation of\n                    <jats:italic>JUN<\/jats:italic>\n                    ,\n                    <jats:italic>STAT3<\/jats:italic>\n                    , and\n                    <jats:italic>AKT1<\/jats:italic>\n                    at both the mRNA and protein levels, as confirmed by RT\u2010qPCR and Western blot. Silencing these genes enhanced cell viability and amplified BBR's protective effects. Altogether, BBR alleviates retinal inflammation and pyroptosis in diabetic retinal ganglion cells by targeting\n                    <jats:italic>JUN<\/jats:italic>\n                    ,\n                    <jats:italic>STAT3<\/jats:italic>\n                    , and\n                    <jats:italic>AKT1<\/jats:italic>\n                    , providing insights into its therapeutic potential for DR.\n                  <\/jats:p>","DOI":"10.1002\/ibra.70018","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:20:10Z","timestamp":1774588810000},"page":"222-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Berberine alleviates pyroptosis of retinal ganglion cells in diabetic retinopathy by regulating AKT1, JUN, and STAT3"],"prefix":"10.1002","volume":"12","author":[{"given":"Na","family":"Li","sequence":"first","affiliation":[{"name":"M. Kandiah Faculty of Medicine and Health Sciences Universiti Tunku Abdul Rahman Kajang Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3256-5204","authenticated-orcid":false,"given":"Yi\u2010Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Fan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatin Athirah","family":"Pauzi","sequence":"additional","affiliation":[{"name":"M. Kandiah Faculty of Medicine and Health Sciences Universiti Tunku Abdul Rahman Kajang Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song\u2010Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Yi Hsan","family":"Saik","sequence":"additional","affiliation":[{"name":"M. Kandiah Faculty of Medicine and Health Sciences Universiti Tunku Abdul Rahman Kajang Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Han\u2010Kiat","family":"Ong","sequence":"additional","affiliation":[{"name":"M. Kandiah Faculty of Medicine and Health Sciences Universiti Tunku Abdul Rahman Kajang Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"issue":"5","key":"e_1_2_11_2_1","first-page":"4227","article-title":"Berberine protects against diabetic retinopathy by inhibiting cell apoptosis via deactivation of the NF\u2011\u03baB signaling pathway","volume":"22","author":"Zhai J","year":"2020","journal-title":"Mol Med Rep"},{"issue":"2","key":"e_1_2_11_3_1","first-page":"53","article-title":"Diabetic retinopathy","volume":"28","author":"Moreno A","year":"2013","journal-title":"Nutr 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