{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:47:52Z","timestamp":1791863272848,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014472","name":"Scientific Research Foundation of Hunan Provincial Education Department","doi-asserted-by":"publisher","award":["24A0555"],"award-info":[{"award-number":["24A0555"]}],"id":[{"id":"10.13039\/100014472","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Polygonatum sibiricum<\/jats:italic>\n                    Delar. ex Redoute (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. sibiricum<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) is a traditional Chinese medicine with multiple health benefits in medicinal\u2013edible dual consumption. However, its toxicological profiles and underlying mechanisms remain poorly characterized, limiting its safe clinical and dietary applications. In this study, an ethanolic extract of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. sibiricum<\/jats:italic>\n                    <\/jats:styled-content>\n                    (PS) was obtained via a microwave\u2010assisted ethanol extraction method, and the flavonoid and saponin contents were quantitatively determined via colorimetric assays and high\u2010performance liquid chromatography (HPLC). After oral administration to mouse models, the main blood\u2010accessible constituents, acute, subacute and genetic toxicities, and potential mechanisms were systematically evaluated via HPLC, manifestation observations, routine blood tests, histopathological evaluations, and network toxicology analyses. The results demonstrated that the PS contained 1.138\u2010mg\/ml flavonoids and 9.152\u2010mg\/ml saponins. Approximately 10 blood\u2010accessible constituents among 15 components were discovered, including diosgenin, 3\u2032\u2010methoxydaidzein, baicalein, (2R)\u20107\u2010hydroxy\u20102\u2010(4\u2010hydroxyphenyl) chroman\u20104\u2010one, 4\u2032,5\u2010dihydroxyflavone, (+)\u2010syringaresinol\u2010O\u2010beta\u2010D\u2010glucoside, zhonghualiaoine 1, methylprotodioscin_qt, sibiricoside A_qt and\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010sitosterol. Although PS did not cause acute lethality, high\u2010dose exposure induced obvious behavioural changes and chromosomal damage. Subacute administration elicited time\u2010dependent biochemical disturbances and structural lesions in the liver, kidney and spleen. Bioinformatic results linked hepatotoxicity to PI3K\u2010AKT signalling, nephrotoxicity to HIF\u20101 and MAPK cascades, and splenotoxicity to convergent PI3K\u2013AKT, NF\u2010\u03baB and MAPK pathways. Molecular docking revealed robust interactions between PS constituents and the predicted toxicity\u2010related targets. Taken together, these findings suggest that PS is nonlethal but potentially has genetic and multiorgan toxicities. Multitarget and multipathway mechanisms are involved in PS\u2010induced toxicities. These findings provide a comprehensive toxicological reference for the rational and safe use of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. sibiricum<\/jats:italic>\n                    <\/jats:styled-content>\n                    in both medicine and diet.\n                  <\/jats:p>","DOI":"10.1002\/jat.70013","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:44:54Z","timestamp":1764895494000},"page":"2106-2123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Excessive Use of\n                    <i>Polygonatum sibiricum<\/i>\n                    Causes No Acute Lethality but Induces Multiple Toxic Effects in Mice"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0213-0365","authenticated-orcid":false,"given":"Juzuo","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Biological and Food Engineering\/Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province\/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food Huaihua University  Huaihua China"},{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biological and Food Engineering\/Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province\/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food Huaihua University  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Biological and Food Engineering\/Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province\/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food Huaihua University  Huaihua China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Shu","sequence":"additional","affiliation":[{"name":"College of Biological and Food Engineering\/Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province\/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food Huaihua University  Huaihua China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biological and Food Engineering\/Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province\/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food Huaihua University  Huaihua China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-661X","authenticated-orcid":false,"given":"Wenhu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan China"},{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparation, School of Pharmaceutical Science Changsha Medical University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfei","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Biological and Food Engineering\/Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province\/Hunan Provincial Higher Education Key Laboratory of Intensive Processing Research on Mountain Ecological Food Huaihua University  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