{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:41:27Z","timestamp":1790224887699,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82405153"],"award-info":[{"award-number":["82405153"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104644"],"award-info":[{"award-number":["82104644"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2022\u2010JYB\u2010XJSJJ003"],"award-info":[{"award-number":["2022\u2010JYB\u2010XJSJJ003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) is a neurodegenerative disorder that worsens progressively. Different pathological mechanisms are involved in the progression of PD, including the loss of dopaminergic (DA) neurons and exacerbated oxidative damage in the nigrostriatal path. Da\u2010Bu\u2010Yin\u2010Wan combined with Qian\u2010Zheng\u2010San is called Bu\u2010Yin\u2010Qian\u2010Zheng Formula (BYQZF), which is a prescription for PD used in traditional Chinese medicine, but its neuroprotective effects and mechanisms are not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The purpose of this study was to explore how BYQZF can activate the Keap1\/Nrf2\/HO\u20101 pathway to effectively lessen oxidative damage, providing insights into its potential anti\u2010PD effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The chemical constituents and pharmacokinetics of BYQZF were analyzed by ultraperformance liquid chromatography in tandem with mass spectrometry (UPLC\u2010MS\/MS). Then, we evaluated the toxicity and safety of BYQZF treatment. After establishing MPTP\u2010induced PD mouse models and the administration of BYQZF treatment, PD\u2010like behaviors were assessed through the pole test, rotarod test and open field experiment. DA neuron loss and apoptosis in the nigrostriatal path were detected via immunofluorescence and western blotting analysis. Oxidative stress levels and the dissociation state of Keap1\u2010Nrf2 in these brain areas were assessed by ELISA, immunofluorescence Co\u2010IP, RT\u2010qPCR, and western blot analysis. We constructed Nrf2\u2010knockdown PD cell models. The transcriptional and Nrf2 protein expression levels were determined using both real\u2010time quantitative PCR and western blot analysis. We further assessed cellular viability, intracellular ATP content, apoptotic cell ratio, as well as the expression levels of CAT and GSH following MPP\n                      <jats:sup>+<\/jats:sup>\n                      , and BYQZF exposure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The chemical constituents of BYQZF were systematically characterized using UPLC\u2010MS\/MS technology. The results of pharmacokinetic evaluation suggested that the pathological conditions of PD significantly affected the pharmacokinetic behavior of BYQZF in\u00a0vivo. BYQZF treatment ultimately improved the movement disorders in MPTP\u2010induced PD mice, by alleviating the damage of dopaminergic neurons within the nigrostriatal path. In addition, BYQZF reduced the damage caused by oxidative stress by decreasing the 8\u2010OHdG level and increasing the CAT, GSH\/GSSG, HO\u20101, NQO1, and GCLM levels. Further, BYQZF treatment advanced the dissociation of Keap1 and Nrf2 and the nuclear translocation of Nrf2. Finally, functional experiments by Nrf2\u2010knockdown PD cell models demonstrated that the neuroprotective effect of BYQZF depends on the integrity of Nrf2, and Nrf2 deficiency significantly weakened its antioxidant and anti\u2010apoptotic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study elucidated that BYQZF improved PD through the Keap1\/Nrf2\/HO\u20101 signaling pathway and alleviated oxidative stress, which is beneficial for inspiring new strategies for drug development targeting PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70681","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T10:57:07Z","timestamp":1765277827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Da\u2010Bu\u2010Yin\u2010Wan and Qian\u2010Zheng\u2010San Alleviate Parkinson's Disease by Activating the Keap1\/Nrf2\/\n                    <scp>HO<\/scp>\n                    \u20101 Pathway to Positively Regulate Oxidative Stress"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-6382","authenticated-orcid":false,"given":"Huimin","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate School of the First Clinical Medical College Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Beijing University of Chinese Medicine  Beijing 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