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Res."],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Huntington\u2019s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and behavioral impairments associated with striatal neuronal loss, for which effective symptom-attenuating therapies remain lacking. Artemisinin (ART), a natural sesquiterpene lactone with established antioxidant and anti-inflammatory actions, has recently gained attention as a potential neuroprotective agent. This study evaluated the therapeutic relevance of ART in a rat model of HD induced by 3-nitropropionic acid (3-NP). 3-NP administration caused severe behavioral deficits, including an 81.8% reduction in rearing and a 74.9% reduction in ambulation (p\u2009&lt;\u20090.0001), a 63.7% decrease in novel object exploration, and a 53.5% decline in Morris water maze target quadrant time versus controls. Biochemically, 3-NP elevated HMGB1 (4.8-fold), TLR4 (6.8-fold), RIPK1 (6.4-fold), RIPK3 (5.2-fold), MLKL (5.5-fold), p38-MAPK (4.2-fold), NF-\u03baB (2.1-fold), and TNF-\u03b1 (4.5-fold), while reducing GSH (57.6%), Nrf2 (77.7%), Sig1R (86.2%), D2R (64%), XIAP (77.8%), BDNF (57.6%) and SDH (61.44%) (all p\u2009&lt;\u20090.0001). Treatment with ART (100\u00a0mg\/kg) markedly restored behavioral performance, increasing rearing and ambulation by 3.2- and 2.6-fold, novel object exploration by 2.4-fold, and target quadrant time by 1.7-fold compared to the 3-NP group. At the molecular level, ART reduced HMGB1 (69.2%), TLR4 (60.4%), RIPK1 (66.3%), RIPK3 (66.4%), MLKL (58%), and TNF-\u03b1 (62.5%), while significantly restoring GSH (2.1-fold), Nrf2 (3.7-fold), Sig1R (5.2-fold), D2R (2.6-fold), XIAP (3.7-fold), BDNF (2.3-fold) and SDH (1.94-fold) relative to 3-NP-treated rats. Collectively, these results demonstrate that ART confers robust neuroprotection against 3-NP-induced HD-like pathology by attenuating oxidative stress, suppressing HMGB1\/TLR4\/NF-\u03baB signaling, inhibiting necroptosis, and upregulating neuroprotective markers. These findings highlight ART not only as a neuroprotective agent but also as a promising symptom-attenuating therapeutic candidate for Huntington\u2019s disease and other neurodegenerative disorders driven by oxidative and inflammatory stress.<\/jats:p>","DOI":"10.1007\/s12272-026-01604-1","type":"journal-article","created":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T07:27:49Z","timestamp":1774164469000},"page":"375-392","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Artemisinin attenuates 3-nitropropionic acid-induced neurodegeneration via HMGB1\/TLR4\/NF-\u03baB modulation in a rat model of huntington\u2019s disease"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-6318","authenticated-orcid":false,"given":"Aya M.","family":"Mustafa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Mudhafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"Elgindy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar M.","family":"Esmail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Atwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya M.","family":"Shaheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah F.","family":"Radwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nourhan","family":"Elfar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruaa Yasir Altayeb","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha M.","family":"Gamil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"1604_CR1","doi-asserted-by":"publisher","unstructured":"Abdel-Magid, A. 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