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This work aimed to verify the protective effects of BU against MPTP\/MPP<jats:sup>+<\/jats:sup>\u2010induced neurotoxicity and explore the mechanisms involved. The results showed that BU protected against MPTP\u2010induced motor dysfunction and decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels. Additionally, BU pretreatment improved PC12 cell viability and reduced MPP<jats:sup>+<\/jats:sup>\u2010induced PC12 cell apoptosis. BU treatment also attenuated MPP<jats:sup>+<\/jats:sup>\u2010stimulated oxidative stress and inflammatory response in PC12 cells. Furthermore, BU inhibited MPTP\/MPP<jats:sup>+<\/jats:sup>\u2010induced hyperactivation of the JAK2\/STAT3 signaling in mice and PC12 cells. Besides, a JAK2 agonist, Coumermycin A1 (C\u2010A1), substantially reversed BU\u2010mediated inhibition on JAK2\/STAT3 phosphorylation in MPP<jats:sup>+<\/jats:sup>\u2010challenged PC12 cells and abated BU\u2010induced repression on MPP<jats:sup>+<\/jats:sup>\u2010triggered apoptosis, oxidative stress, and inflammatory response in PC12 cells. To sum up, BU might exert neuroprotective effects against MPP<jats:sup>+<\/jats:sup>\/MPTP\u2010induced neurotoxicity by inactivating the JAK2\/STAT3 signaling.<\/jats:p>","DOI":"10.1002\/kjm2.12745","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:20:53Z","timestamp":1697073653000},"page":"1002-1010","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The gut microbiota metabolite butyrate mitigates <scp>MPTP<\/scp>\/<scp>MPP<\/scp><sup>+<\/sup>\u2010induced Parkinson's disease by inhibiting the <scp>JAK2<\/scp>\/<scp>STAT3<\/scp> signaling pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Li\u2010Li","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Neurology Jiangsu University Affiliated with Wujin Hospital (Wujin Clinical College of Xuzhou Medical University)  Changzhou 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