{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:19:32Z","timestamp":1793042372023,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"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>Background<\/jats:title>\n                    <jats:p>\n                      Protocatechualdehyde (PCA), a phenolic compound derived from\n                      <jats:italic>Salvia miltiorrhiza<\/jats:italic>\n                      , exhibits anti-proliferative and antioxidant properties. However, its molecular mechanisms in reducing oxidative stress in diabetic cataract (DC) remain unclear. This study systematically investigated the role of PCA in modulating glyoxalase-1 (GLO1)-dependent suppression of advanced glycation end product (AGE)-receptor for AGE (RAGE) axis activation and oxidative stress in DC models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A galactose-induced DC rat model and high glucose-stimulated human lens epithelial cells (HLECs) were employed. Lens opacity was assessed using slit-lamp microscopy. GLO1, AGE, and RAGE expressions were analyzed through immunohistochemistry (IHC), immunofluorescence (IF), ELISA, and Western blotting. Molecular docking was performed to validate PCA\u2013GLO1 interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PCA administration (25\u00a0mg\/kg) significantly alleviated lens opacity and epithelial cell disorganization in DC rats (p &amp;lt; 0.01).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , PCA (10\u00a0\u03bcM) restored HLEC viability under hyperglycemic conditions (p &amp;lt; 0.05). Mechanistically, PCA upregulated GLO1 expression while suppressing AGE accumulation and RAGE activation in both models. Molecular docking revealed strong binding affinities between PCA and GLO1 (-CDOCKER energy: 26.41\u00a0kcal\/mol).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PCA ameliorates DC progression by enhancing the GLO1-mediated detoxification of AGE precursors, thereby inhibiting AGE\/RAGE-driven oxidative stress. These findings provide a foundation for PCA as a therapeutic candidate for DC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1586173","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T01:24:13Z","timestamp":1750814653000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Protocatechualdehyde attenuates oxidative stress in diabetic cataract via GLO1-mediated inhibition of AGE\/RAGE glycosylation"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiao","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41574-020-00451-4","article-title":"Current understanding of the molecular and cellular pathology of diabetic retinopathy","volume":"17","author":"Antonetti","year":"2021","journal-title":"Nat. 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