{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T12:28:08Z","timestamp":1763123288800,"version":"3.45.0"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["PL2024H015"],"award-info":[{"award-number":["PL2024H015"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study investigated whether Ginsenoside Rg1 (Rg1) alleviates autism\u2010like behaviors in mice prenatally exposed to valproic acid (VPA) via Sirt2\/Foxo1 signaling. Pregnant C57BL\/6J mice received a single intraperitoneal injection of VPA (600\u2009mg\/kg) on embryonic Day 12.5 to establish an autism model. At 8\u2009weeks of age, male offspring were randomly divided into four groups: Normal, VPA, VPA\u2009+\u2009Rg1 (5\u2009mg\/kg), and VPA\u2009+\u2009Rg1 (10\u2009mg\/kg). Rg1 was administered once daily for 28\u2009days. Behavioral assessments included grooming, rearing, locomotor activity, social interaction, novel object recognition, open field, and marble\u2010burying tests. Molecular assays measured Sirt2\/Foxo1 expression, inflammatory cytokines, oxidative stress markers in the hippocampus and prefrontal cortex. Nissl staining was performed to evaluate neuronal integrity in the prefrontal cortex and hippocampus. Rg1 administration significantly ameliorated core autism\u2010like behaviors in VPA\u2010exposed mice, including deficits in social interaction, recognition memory, and anxiety\u2010 and compulsive\u2010like behaviors, as well as excessive grooming and marble\u2010burying. VPA reduced Sirt2\/Foxo1 expression, increased levels of interleukin (IL)\u20101\u03b2, IL\u20106, tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), and malondialdehyde (MDA), and decreased superoxide dismutase (SOD) activity in both brain regions. Rg1 treatment reversed these alterations in a dose\u2010responsive manner, with the 10\u2009mg\/kg dose yielding more pronounced behavioral and molecular improvements than the 5\u2009mg\/kg dose. Nissl staining revealed significant neuronal loss in VPA\u2010exposed mice, which was partially restored by Rg1 treatment. These findings suggest that Rg1 alleviates VPA\u2010induced behavioral and neuropathological abnormalities, potentially via Sirt2\/Foxo1\u2010mediated regulation of neuroinflammation and oxidative stress, and may represent a promising therapeutic strategy for autism spectrum disorder.<\/jats:p>","DOI":"10.1002\/kjm2.70078","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T12:40:32Z","timestamp":1751892032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Rg1 Restores Sirt2\/Foxo1 Expression and Alleviates Autism\u2010Like Behaviors in a Valproic Acid Induced Male Mouse Model"],"prefix":"10.1002","volume":"41","author":[{"given":"Fan\u2010Xu","family":"Song","sequence":"first","affiliation":[{"name":"Pediatric Health Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing\u2010Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Traditional Rehabilitation Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Pan","sequence":"additional","affiliation":[{"name":"Medical Administration Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Speech Therapy Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Pediatric Health Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Speech Therapy Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zong\u2010Yao","family":"Yu","sequence":"additional","affiliation":[{"name":"Speech Therapy Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Ning","sequence":"additional","affiliation":[{"name":"Speech Therapy Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6103-7957","authenticated-orcid":false,"given":"Lan\u2010Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Pediatric Health Department, Rehabilitation Medicine College Jiamusi University; Jiamusi University Affiliated Third Hospital; Heilongjiang Province Key Laboratory of Children's Neurorehabilitation  Jiamusi Heilongjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"issue":"4","key":"e_1_2_7_2_1","first-page":"100","article-title":"Autistic Disturbances of Affective Contact","volume":"35","author":"Kanner L.","year":"1968","journal-title":"Acta Paedopsychiatrica"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-024-02004-z"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252011283"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.2696"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03617-3"},{"issue":"7","key":"e_1_2_7_7_1","article-title":"Emerging Treatments and Therapies for Autism Spectrum Disorder: A Narrative Review","volume":"16","author":"Kaye A. 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