{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:04:41Z","timestamp":1779689081332,"version":"3.53.1"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Tardive dyskinesia (TD) is a persistent hyperkinetic movement disorder associated with prolonged dopamine D2 receptor blockade, particularly during chronic haloperidol (HP) exposure. Emerging evidence suggests that TD-like pathology is sustained by an interconnected redox\u2013mitochondrial\u2013inflammatory network within striatal circuits; however, the regulatory architecture of this network remains incompletely defined. Hyperoside (HS), a flavonol glycoside with cytoprotective properties, has been implicated in cellular stress-response modulation, yet its role in antipsychotic-induced motor dysfunction remains unclear. In this study, a six-group mechanistic design was employed in which rats received HP (1 mg\/kg, i.p., 21 days) to induce TD-like orofacial dyskinesia (OD), quantified by vacuous chewing movements (VCMs) and tongue protrusions (TPs). HS (30 mg\/kg, i.p.) was administered alone or in combination with HP, with or without pharmacological inhibition of nuclear factor erythroid 2\u2013related factor 2 (Nrf2) using ML385. HP exposure induced progressive dyskinetic behavior accompanied by oxidative and nitrosative stress, mitochondrial dysfunction, increased pro-inflammatory cytokines, and elevated caspase-3 activity in the striatum. HS significantly attenuated behavioral abnormalities while restoring redox balance, preserving mitochondrial enzyme activities, and reducing inflammatory and apoptotic signaling. Notably, Nrf2 inhibition intensified molecular pathology without proportionally worsening behavioral outcomes, indicating a dissociation between biochemical vulnerability and overt motor expression. Furthermore, ML385 markedly attenuated HS-mediated protection across multiple endpoints. Collectively, these findings support a potential protective role for Nrf2-related regulatory mechanisms in limiting network destabilization in TD-like pathology, while highlighting the importance of integrated stress-response pathways in modulating disease progression.<\/jats:p>","DOI":"10.3390\/life16050814","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperoside Stabilizes Redox\u2013Mitochondrial\u2013Inflammatory Networks in a Haloperidol-Induced Tardive Dyskinesia\u2013Like Model"],"prefix":"10.3390","volume":"16","author":[{"given":"Hsiang-Chien","family":"Tseng","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao-Hsien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, En Chu Kon Hospital, New Taipei City 23702, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chi","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Taiwan Instrument Research, National Applied Research Laboratories, Hsinchu 300092, Taiwan"},{"name":"Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei 10608, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Pei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery, Hsinchu Br. of Mackay Memorial Hospital, Hsinchu City 30071, Taiwan"},{"name":"Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e001170","DOI":"10.1136\/bmjno-2025-001170","article-title":"Patient and physician perceptions of the burden of tardive dyskinesia: An international survey","volume":"7","author":"Chepke","year":"2025","journal-title":"BMJ Neurol. 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