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Currently, therapeutic interventions effectively mitigate motor symptoms; however, they fail to impede the progression of neurodegeneration. Enzymatically modified isoquercitrin (EMIQ) is a variant of isoquercitrin with enhanced bioavailability and potentially greater health benefits. Sodium R-Lipoate (NaRLA) is a modified form of lipoic acid with improved stability and efficacy. The current work assessed EMIQ and NaRLA neuroameliorative properties in a rotenone (ROT) model of PD in rats. The study employed open field and hanging tests to evaluate motor effects, and used dopamine (DA) estimation and tyrosine hydroxylase (TH) immunoreactivity to confirm motor abnormalities and neurodegeneration. Furthermore, neuroinflammation was evaluated through ELISA of proinflammatory cytokines (IL-1\u03b2, IL-6), expression of Toll-like receptor 4 (TLR4) via qRT-PCR, and immunoreactivity of ionized calcium-binding adaptor molecule 1 (IBA1). The findings indicated that the use of EMIQ and NaRLA with ROT reduced the neuroinflammation via decreasing: the expression level of TLR4, IL-1\u03b2 and IL-6 levels, and the number of IBA1\n                    <jats:sup>+<\/jats:sup>\n                    microglial cells. Moreover, EMIQ and NaRLA ameliorated motor impairments induced with ROT through the enhancement of rats\u2019 behavior, increasing DA concentration and TH immunoreactivity in the striatum. In the light of the findings of the current investigation, EMIQ and NaRLA exerted neuroameliorative effects against the ROT\u2010induced PD model. These results provide support for the potential impact of EMIQ and NaRLA in the treatment of PD and other diseases related to mitochondrial dysfunction and neuroinflammation.\n                  <\/jats:p>","DOI":"10.1007\/s11064-026-04715-9","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:44:50Z","timestamp":1774431890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Neuroameliorative Effects of Enzymatically Modified Isoquercitrin and Sodium R-lipoate on the Rotenone rat Model of Parkinson\u2019s Disease"],"prefix":"10.1007","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9988-716X","authenticated-orcid":false,"given":"Imam","family":"Hassouna","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4257-4232","authenticated-orcid":false,"given":"Omar H.","family":"Hassanein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6047-4505","authenticated-orcid":false,"given":"Ibrahim A.","family":"El-Elaimy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5137-0058","authenticated-orcid":false,"given":"Hany M.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"4715_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1589760","volume":"16","author":"Y Li","year":"2025","unstructured":"Li Y, Hu B, Mao Q, Liang B (2025) Global trends of early-onset Parkinson\u2019s disease from 1990 to 2021, and projections until to 2030: a systematic analysis of the global burden of disease study 2021. 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