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Nonetheless, the safety profile of baicalin has not yet been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim of the study<\/jats:title><jats:p>The objective was to characterize the acute and subacute toxicity profiles of baicalin across various organ systems, thereby establishing safe therapeutic windows for its clinical application in the treatment of chronic neurodegenerative disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Acute toxicity was assessed at 4,000\u00a0mg\/kg (OECD 423), while subacute toxicity evaluated escalating doses (1,000\u20134,000\u00a0mg\/kg; OECD 407). Endpoints included survival, general behaviours, behavioral alterations, hematological\/biochemical parameters, organ coefficients, and histopathology of brain, liver, and kidney.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acute exposure showed no mortality (LD50 &amp;gt; 4,000\u00a0mg\/kg) or lasting physiological effects, with only transient gastrointestinal symptoms in one subject. Subacute administration caused temporary gastrointestinal issues and occasional compulsive behaviors, all resolving within 24\u00a0h. Behavioral assessments indicated intact neurocognitive function and emotional stability. Hematological profiles revealed sex-specific responses, with males showing higher lymphocyte percentages and females demonstrating renal changes. Biochemical analyses indicated liver metabolic changes, including alkaline phosphatase suppression and reduced triglycerides, along with mild nephrotoxic signs. Histopathological evaluations confirmed non-necrotic liver stress and unchanged hippocampal structure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Baicalin showed high acute safety with an LD50 over 4,000\u00a0mg\/kg in mice, and a subacute no-observed-adverse-effect level (NOAEL) of 2,000\u00a0mg\/kg, indicating its potential as a neuroprotective agent. However, 4,000\u00a0mg\/kg doses led to reversible hepatorenal toxicity and biochemical alterations, highlighting the need to monitor organ function during extended high-dose use.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1607919","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T05:28:38Z","timestamp":1755754118000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Integrated neurobehavioral and organ-specific safety profiling of baicalin: acute\/subacute toxicity studies"],"prefix":"10.3389","volume":"16","author":[{"given":"Jiali","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e9963","DOI":"10.15252\/emmm.201809963","article-title":"Dynorphin-based \u201crelease on demand\u201d gene therapy for drug-resistant temporal lobe epilepsy","volume":"11","author":"Agostinho","year":"2019","journal-title":"EMBO Mol. 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