{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:13:46Z","timestamp":1788588826232,"version":"build-2803163510"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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                      Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-\u03b2 (A\u03b2) plaques and pervasive cognitive decline. Bavachinin, a natural flavonoid derived from the traditional medicinal herb Psoralea corylifolia, has previously been demonstrated to inhibit A\u03b2 aggregation\n                      <jats:italic>in vitro<\/jats:italic>\n                      . However, its potential to alleviate cognitive impairment, restore large-scale brain network dysfunctions, and mitigate AD-related pathology\n                      <jats:italic>in vivo<\/jats:italic>\n                      remains elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we systematically evaluated the therapeutic efficacy of bavachinin on AD-associated pathology, cortical slow-wave activity (SWA), and behavioral phenotypes in 5xFAD transgenic mice. We utilized behavioral assessments to evaluate learning and memory, mesoscopic wide-field calcium imaging to assess cortical network dynamics, and histological analyses to measure cerebral A\u03b2 deposition. Furthermore, pharmacological inhibition was employed to investigate the mechanistic role of mitochondrial oxidative phosphorylation (OXPHOS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Behavioral assessments revealed that bavachinin administration significantly rescued deficits in learning and memory. Mesoscopic wide-field calcium imaging further demonstrated that bavachinin substantially enhanced the synchrony of cortical SWA while reducing its frequency in 5xFAD mice, indicating a restoration of network-level dynamics. Histological analyses confirmed a marked reduction in cerebral A\u03b2 deposition, which occurred independent of A\u03b2 production pathways. Mechanistically, bavachinin bolstered microglial A\u03b2 phagocytosis and chemotactic migration by promoting mitochondrial OXPHOS, thereby revitalizing cellular energy metabolism. Notably, pharmacological inhibition of OXPHOS partially abrogated the therapeutic benefits of bavachinin, suggesting that the augmentation of mitochondrial function is a requisite for its anti-AD effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In summary, bavachinin alleviates cognitive impairment and neuropathology in AD model mice by driving microglial metabolic reprogramming and facilitating A\u03b2 clearance. These findings highlight its robust potential as a therapeutic candidate for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1839602","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:56:12Z","timestamp":1779962172000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Microglial metabolic reprogramming drives the therapeutic effects of bavachinin on brain network function and memory in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Zou","sequence":"first","affiliation":[{"name":"Center for Medical Research, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Lin","sequence":"additional","affiliation":[{"name":"Neurology Department, The First People\u2019s Hospital of Yulin, the Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine and Advanced Institute for Brain and Intelligence, School of Medicine, Guangxi University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Medical Research, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Medical Research, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehan","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Medical Research, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Liang","sequence":"additional","affiliation":[{"name":"Center for Medical Research, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liang","sequence":"additional","affiliation":[{"name":"Center for Medical Research, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]},{"name":"Center for Respiratory Medicine, the First People\u2019s Hospital of Yulin, The Sixth Affiliated Hospital of Guangxi Medical University","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","article-title":"A breakdown in metabolic reprogramming causes microglia dysfunction in alzheimer's disease","volume":"30","author":"Baik","year":"2019","journal-title":"Cell Metab."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1038\/s42255-025-01404-9","article-title":"The neuron-astrocyte metabolic unit as a cornerstone of brain energy metabolism in health and disease","volume":"7","author":"Bola\u00f1os","year":"2025","journal-title":"Nat. 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