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Preclinical studies have highlighted gentiopicroside's anti\u2010inflammatory activities in treating arthritis, colitis and pancreatitis, and its neuroprotective effects on neurological diseases such as\n                    <jats:sc>AD<\/jats:sc>\n                    , chronic neuropathic pain and ischemia. However, the effects and mechanisms of gentiopicroside on PD\u2010related conditions remain uncertain. Here, we evaluated the potential benefits of gentiopicroside using a unilateral 6\u2010OHDA rat model and a MPP\n                    <jats:sup>+<\/jats:sup>\n                    \u2010induced cell model. Our findings indicated that gentiopicroside improved motor deficits and restored nigral TH\u2010positive neurons in\u00a0vivo. Mechanistically, gentiopicroside ameliorated inflammatory responses of 6\u2010OHDA\u2010induced rats, decreased NF\u2010\u03baB and pro\u2010inflammatory cytokines levels and reduced Iba\u20101\u2010positive microglia in the substantia nigra. Furthermore, gentiopicroside regulated the levels of DMT1 and FPN1, thereby inhibiting iron accumulation in PD rats. In\u00a0vitro, gentiopicroside preserved the viability of MPP\n                    <jats:sup>+<\/jats:sup>\n                    \u2010treated SH\u2010SY5Y cells and suppressed NF\u2010\u03baB activity and its downstream factors' levels. Meanwhile, gentiopicroside inhibited lipid peroxidation and ROS production, while it upregulated the expression of GPX4 in MPP\n                    <jats:sup>+<\/jats:sup>\n                    \u2010treated cells. And these antiferroptosis effects were also linked to iron transporters regulation. Conclusively, gentiopicroside exhibits neuroprotective effects via alleviating neuroinflammation and iron\u2010dependent ferroptosis, offering promise for PD treatment.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.70036","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T06:29:11Z","timestamp":1745216951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gentiopicroside Attenuated Dopaminergic Neurodegeneration via Inhibiting Neuroinflammatory Responses and Ferroptosis in Experimental Models of Parkinson's Disease"],"prefix":"10.1111","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1985-0286","authenticated-orcid":false,"given":"Fangling","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University Beijing Municipal Geriatric Medical Research Center  Beijing 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Capital Medical University Beijing Municipal Geriatric Medical Research Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University Beijing Municipal Geriatric Medical Research Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University Beijing Municipal Geriatric Medical Research Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Center, Xuanwu Hospital of Capital Medical University Beijing Municipal Geriatric Medical Research Center  Beijing 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