{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:10:48Z","timestamp":1791933048553,"version":"4.3.4"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003668","name":"Ministry of Agriculture, Food and Rural Affairs","doi-asserted-by":"publisher","award":["RS-2024-00400380"],"award-info":[{"award-number":["RS-2024-00400380"]}],"id":[{"id":"10.13039\/501100003668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS-2024-00344269"],"award-info":[{"award-number":["RS-2024-00344269"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS-2024-00349668"],"award-info":[{"award-number":["RS-2024-00349668"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Astrocytic redox-inflammatory signaling has been implicated in Parkinson\u2019s disease (PD) pathology and may constrain hippocampal neurogenesis. We previously identified an astrocytic NOX4\u2013MPO\u2013OPN axis associated with impaired neurogenic capacity. Here, we tested whether a saffron-derived antioxidant (SDA; Crocus sativus extract) and Passiflora incarnata L. extract (PI) modulate this pathway in an MPTP-induced PD mouse model. Methods: Male C57BL\/6J mice were randomized to Sham, MPTP, and treatment groups (n = 9\/group for behavior; n = 4\u20135\/group for histology\/immunoblotting). SDA or PI (50 mg\/kg\/day, oral, 5 weeks) was administered, with resveratrol as a positive control. Behavioral, histological, and molecular analyses were performed by investigators blinded to group allocation where feasible. Results: SDA and PI were associated with reduced NOX4\/MPO\/OPN signals, mainly in GFAP-positive astrocytes, along with recovery of neurogenesis markers (Ki67, DCX, BrdU\/NeuN) and synaptic markers (PSD95, synaptophysin), and improved motor performance. Mitochondrial and oxidative injury markers (TIM23, TOM20, OXPHOS subunits; 4-HNE) and apoptotic markers (Bax, cleaved caspase-3, Bcl-2) also shifted toward Sham levels. Given previous reports of Passiflora extracts\u2019 sedative effects, we note that metabolic measures (body weight, food intake, and water intake) were similar across groups; however, specific tests for sedation or arousal were not conducted. Conclusions: These findings offer preclinical evidence that SDA and PI modulate redox-inflammatory and mitochondrial stress signatures and are associated with neurogenic, synaptic, and behavioral improvements in an acute MPTP model. Further validation in chronic\/genetic PD models and pharmacokinetic\/brain exposure studies will be necessary to confirm their translational potential.<\/jats:p>","DOI":"10.3390\/nu18010055","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:22:14Z","timestamp":1766575334000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oral Administration of Astrocyte-Targeted Natural Antioxidants Suppress NOX4-Driven Neuroinflammation and Restore Hippocampal Neurogenesis in MPTP-Induced Parkinson\u2019s Disease Mouse Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Miri","family":"Jo","sequence":"first","affiliation":[{"name":"BK21 Four Program, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4368-2600","authenticated-orcid":false,"given":"Kayoung","family":"Ko","sequence":"additional","affiliation":[{"name":"BK21 Four Program, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seohee","family":"Choi","sequence":"additional","affiliation":[{"name":"BK21 Four Program, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhye","family":"Kim","sequence":"additional","affiliation":[{"name":"Central Lab, iCONNECTOME Co., Ltd., Suwon 16229, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyuhee","family":"Park","sequence":"additional","affiliation":[{"name":"Gyeonggi Business & Science Accelerator, Suwon 16229, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac Jinwon","family":"Yi","sequence":"additional","affiliation":[{"name":"Neuroscience and Behavioral Biology Program (NBB), College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Seop","family":"Nahm","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4879-5207","authenticated-orcid":false,"given":"Kiyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"BK21 Four Program, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4752-2810","authenticated-orcid":false,"given":"Woosuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8568-0954","authenticated-orcid":false,"given":"Sun-Shin","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea"},{"name":"Central Lab, iCONNECTOME Co., Ltd., Suwon 16229, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, M., Chen, M., Li, H., Gao, D., Zhao, L., and Zhu, M. 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