{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:45:46Z","timestamp":1782456346457,"version":"3.54.5"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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                      Baicalin is the most abundant flavonoid in the traditional Chinese heat-clearing botanical drug\n                      <jats:italic>Scutellaria baicalensis<\/jats:italic>\n                      Georgi. and has been demonstrated to exert a protective role in various brain diseases. Baicalin capsules (BC), a preparation composed primarily of baicalin, have been widely used in the clinical treatment of acute bronchitis, chronic hepatitis, hypertension, cerebral ischemia sequelae, diabetic retinopathy, and other conditions. Nevertheless, the effects of BC on diabetic encephalopathy remain largely unexplored. The aim of this study was to investigate the therapeutic effects and underlying mechanisms of BC on diabetic encephalopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HT22 cells were treated with glucose and palmitic acid to mimic neuronal damage in type 2 diabetes mellitus (T2DM). The CCK-8 assay and oxidative stress-related detection kits were employed to measure cell viability and cellular oxidative stress levels. The ultrastructure was observed using transmission electron microscopy (TEM). The baicalin content in BC was detected through high-performance liquid chromatography. The cognitive ability was evaluated using the Morris water maze in db\/db mice. Nissl staining, TEM, and TUNEL staining were performed to assess neuronal injury. The expression of Nrf2 signaling and apoptosis-related proteins was determined by western blotting and immunofluorescence colocalization analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We successfully established an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model of type 2 diabetic encephalopathy.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments revealed that baicalin significantly enhanced the cell viability, reduced ROS production, and attenuated apoptosis.\n                      <jats:italic>In vivo<\/jats:italic>\n                      results demonstrated that BC improved learning and memory dysfunction in db\/db mice. BC markedly increased the number of Nissl bodies, reduced ROS and MDA levels, and increased SOD and GSH-Px activities in the frontotemporal cortex of db\/db mice. Furthermore, BC attenuated neuronal apoptotic characteristics, and decreased the ratio of TUNEL-positive neurons and the expression of cleaved caspase-3. Additionally, BC stimulated Nrf2 activation by increasing the expression of Nrf2, HO-1, NQO1, and GPX4 proteins, as well as promoting the colocalization of neuronal nuclei marker-NeuN with Nrf2 or GPX4.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BC ameliorated diabetic encephalopathy in db\/db mice. The underlying mechanisms were closely associated with Nrf2 activation in neurons of the frontotemporal cortex, along with the inhibition of oxidative stress-induced neuronal apoptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1740727","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:46:16Z","timestamp":1782452776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of Nrf2 signaling and suppression of oxidative stress-induced neuronal apoptosis: mechanisms for baicalin capsules relieving diabetic encephalopathy"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruimin","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Pharmacology, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Pan","sequence":"additional","affiliation":[{"name":"Chongqing Three Gorges Medical College","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Lian","sequence":"additional","affiliation":[{"name":"School of Pharmacy, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejia","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyun","family":"Xi","sequence":"additional","affiliation":[{"name":"School of Anesthesiology, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"466","DOI":"10.3389\/fnins.2018.00466","article-title":"Targeting Nrf2 to suppress ferroptosis and mitochondrial dysfunction in neurodegeneration","volume":"12","author":"Abdalkader","year":"2018","journal-title":"Front. 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