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Thus, modulating microglial activity is a critical therapeutic goal. In this study, we explored how Ginsenoside Rg1 (Rg1) protects against the inflammation seen in Parkinson\u2019s disease (PD). Our experiments utilized MPTP-challenged mice and lipopolysaccharide (LPS)-stimulated BV2 cells. Our data show that Rg1 restores motor function and preserves dopaminergic neurons in the substantia nigra. Notably, Rg1 treatment reconfigures the neuroinflammatory milieu, characterized by the targeted suppression of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6) and a reciprocal elevation of the anti-inflammatory marker (IL-10). This effect stems from a precise rebalancing of Wnt signaling. Rg1 activates the Wnt3a\/\u03b2-catenin pathway while suppressing the Wnt5a\/ROR2\/JNK axis. Such regulation promotes the transition of microglia to a protective M2 phenotype. When we knocked down Wnt3a and ROR2 using siRNA, the benefits of Rg1 were largely lost. In short, Rg1 alleviates neuroinflammation by recalibrating Wnt signals, offering a potential strategy for PD intervention.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c04447","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T07:02:29Z","timestamp":1786345349000},"page":"25252-25271","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Rg1\nAttenuates Neuroinflammation in Parkinson\u2019s\nDisease Models via Concomitant Modulation of Canonical and Noncanonical\nWnt Pathways in Microglial M1\/M2 Polarization"],"prefix":"10.1021","volume":"74","author":[{"given":"Wenshan","family":"Li","sequence":"first","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlang","family":"Yu","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiakang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Jin","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Jiang","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-2599","authenticated-orcid":true,"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210022"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"9","key":"2026081910182401000_cit1","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.1093\/brain\/awad150","article-title":"Advances in understanding the function of alpha-synuclein:\nimplications for Parkinson\u2019s disease","volume":"146","author":"Calabresi","year":"2023","journal-title":"Brain"},{"issue":"5","key":"2026081910182401000_cit2","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","article-title":"Challenges in the diagnosis\nof Parkinson\u2019s disease","volume":"20","author":"Tolosa","year":"2021","journal-title":"Lancet Neurol."},{"issue":"12","key":"2026081910182401000_cit3","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/S1474-4422(16)30230-7","article-title":"The epidemiology of Parkinson\u2019s disease: risk\nfactors and prevention","volume":"15","author":"Ascherio","year":"2016","journal-title":"Lancet Neurol."},{"issue":"1","key":"2026081910182401000_cit4","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/j.1468-1331.2008.02056.x","article-title":"Non-motor\nsymptoms in Parkinson\u2019s disease","volume":"22","author":"Poewe","year":"2008","journal-title":"Eur\nJ Neurol."},{"issue":"11","key":"2026081910182401000_cit5","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and immune\ndysfunction in Parkinson disease","volume":"22","author":"Tansey","year":"2022","journal-title":"Nat. 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