{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:18:04Z","timestamp":1790104684881,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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>Cerebral ischemic injury includes ischemic stroke in adults and hypoxic-ischemic encephalopathy (HIE) in newborns. Delphinidin-3-O-glucoside (Dp3G) is a bioactive anthocyanin abundant in vibrantly colored plant-based foods and known for its potent antioxidant properties. Previous studies have shown that Dp3G suppresses oxidative stress and inflammation in atherosclerosis, protects against myocardial ischemic injury, and sensitizes glioblastoma to temozolomide by reducing drug resistance. However, its role and mechanisms in hypoxic-ischemic brain injury remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study investigated the neuroprotective effects and mechanisms of Dp3G using\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      models. An oxygen\u2013glucose deprivation (OGD) model in microglia was used for in vitro assessment. In vivo, a neonatal KM mouse model of HIE was employed. Techniques included transcriptomic analysis and molecular docking to elucidate the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a microglial oxygen\u2013glucose deprivation (OGD) model, Dp3G reduced apoptosis, inflammatory responses, and oxidative stress. Transcriptomic analysis suggested that Dp3G promotes metabolic reprogramming and inhibits NF-\u03baB signaling via NLRC3, shifting microglial polarization toward an anti-inflammatory phenotype. Molecular docking indicated a potential interaction between Dp3G and NLRC3. In a neonatal KM mouse model of HIE, Dp3G treatment reduced neuronal damage and cerebral infarction and restored regional cerebral blood flow, with mechanistic evidence supporting microglial polarization regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dp3G exerts significant neuroprotective effects in models of hypoxic-ischemic brain injury. Its mechanism involves the modulation of microglial polarization, and interaction with NLRC3 and subsequent inhibition of NF-\u03baB signaling. These findings identify Dp3G as a promising neuroprotective candidate in preclinical models of hypoxic-ischemic brain injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1797078","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:32:05Z","timestamp":1777872725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Delphinidin-3-O-glucoside attenuates neonatal hypoxic-ischemic encephalopathy in a neonatal mouse model by reprogramming microglial polarization"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiacan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, the 960th Hospital of PLA (General Hospital of Jinan Military Command)","place":["Jinan, Shandong, China"]},{"name":"Department of Histology and Embryology, School of Basic Medical Science, Qilu College of Medicine, Shandong University","place":["Jinan, 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