{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:09:22Z","timestamp":1785431362281,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304897"],"award-info":[{"award-number":["82304897"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82304897"],"award-info":[{"award-number":["82304897"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Special Program for Young Scientific and Technological Talents of Jiaxing","award":["2023AY40008"],"award-info":[{"award-number":["2023AY40008"]}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ21H280007"],"award-info":[{"award-number":["LQ21H280007"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"award":["LQ21H280007"],"award-info":[{"award-number":["LQ21H280007"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurological disorders, particularly Parkinson\u2019s disease (PD), represent a pressing global health challenge with limited disease-modifying therapies. While Achyranthes bidentata exhibits neuroprotective potential, its bioactive constituents against PD remain poorly characterized. This study integrated phytochemical isolation and in silico target prediction to identify eight compounds from A. bidentata, followed by neuroprotective evaluation in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-challenged SH-SY5Y cells. Among these, 25R-inokosterone significantly downregulated Monoamine oxidase B (MAOB) and Glycogen synthase kinase-3\u03b2 (GSK-3\u03b2) expression and showed superior neuroprotection compared to \u03b2-ecdysterone. It markedly restored mitochondrial membrane potential, suppressed Bcl-2-associated X protein (Bax)\/Cysteinyl aspartate specific proteinase 3 (caspase-3) apoptotic signaling, and alleviated oxidative stress. Mechanistically, Nuclear factor erythroid 2-related factor 2 (Nrf2)\/Heme oxygenase 1 (HO-1) activation was the dominant and indispensable mechanism for neuroprotection, while MAOB\/GSK-3\u03b2 expression downregulation served as an upstream synergistic regulatory event, as evidenced by the abolition of neuroprotection following Nrf2 knockdown in SH-SY5Y cells. These findings identify 25R-inokosterone as a promising multi-target natural lead for PD, which exerts antioxidant and anti-apoptotic effects predominantly by activating Nrf2, accompanied by the upstream modulation of MAOB\/GSK-3\u03b2 expression.<\/jats:p>","DOI":"10.3390\/ijms27104204","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:17:42Z","timestamp":1778519862000},"page":"4204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["25R-Inokosterone from Achyranthes bidentata Ameliorates Parkinson\u2019s Disease Pathology Predominantly via Nrf2\/HO-1 Activation with Coordinated MAOB\/GSK-3\u03b2 Expression Downregulation: An In Vitro and In Silico Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Ding","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Ye","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Yang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7350-4773","authenticated-orcid":false,"given":"Liu-Tian","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Xia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Kun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41582-021-00486-9","article-title":"Prodromal Parkinson disease subtypes\u2014Key to understanding heterogeneity","volume":"17","author":"Berg","year":"2021","journal-title":"Nat. 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