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NADPH oxidase is considered as an important contributor to the oxidative injury in several neurodegenerative disorders including HD. Thus, the present study explored the possible neuroprotective effects of diapocynin, a specific NADPH oxidase inhibitor, against 3-nitropropionic acid (3-NP) model of HD in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Animals received diapocynin (10 mg\/kg\/day, p.o), 30 min before 3-NP (10 mg\/kg\/day, i.p) over a period of 14 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Diapocynin administration attenuated 3-NP-induced oxidative stress with significant increase in reduced glutathione, glutathione-S-transferase, nuclear factor erythroid 2-related factor 2, and brain-derived neurotrophic factor striatal contents contrary to NADPH oxidase (NOX2; gp91phox subunit) diminished expression. Moreover, diapocynin mitigated 3-NP-associated neuroinflammation and glial activation with prominent downregulation of nuclear factor-\u041a\u03b2 p65 and marked decrement of inducible nitric oxide synthase content in addition to decreased immunoreactivity of ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein; markers of microglial and astroglial activation, respectively. Treatment with diapocynin hindered 3-NP-induced apoptosis with prominent decrease in tumor suppressor protein and Bcl-2-associated X protein contents whereas the anti-apoptotic marker; B-cell lymphoma-2 content was noticeably increased. Diapocynin neuroprotective effects could be attributed to silent information regulator 1 upregulation which curbed 3-NP-associated hazards resulting in improved motor functions witnessed during open field, rotarod, and grip strength tests as well as attenuated 3-NP-associated histopathological derangements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present findings indicated that diapocynin could serve as an auspicious nominee for HD management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphical abstract<\/jats:title><\/jats:sec>","DOI":"10.1007\/s10787-022-01004-z","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T04:02:36Z","timestamp":1653969756000},"page":"1745-1758","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Diapocynin neuroprotective effects in 3-nitropropionic acid Huntington\u2019s disease model in rats: emphasis on Sirt1\/Nrf2 signaling pathway"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-0318","authenticated-orcid":false,"given":"Weam W.","family":"Ibrahim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora O.","family":"Abdel Rasheed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"1004_CR1","doi-asserted-by":"publisher","first-page":"120480","DOI":"10.1016\/j.lfs.2022.120480","volume":"297","author":"NO Abdel Rasheed","year":"2022","unstructured":"Abdel Rasheed NO, Ibrahim WW (2022) Telmisartan neuroprotective effects in 3-nitropropionic acid Huntington\u2019s disease model in rats: Cross talk between PPAR-\u03b3 and PI3K\/Akt\/GSK-3\u03b2 pathway. 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