{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:03:27Z","timestamp":1785301407888,"version":"3.55.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>\n                      Drug-induced liver injury remains a major clinical challenge due to the lack of effective therapeutic options.\n                      <jats:italic>Polygonatum odoratum<\/jats:italic>\n                      extract (PO), derived from the traditional medicinal and edible plant\n                      <jats:italic>Polygonatum odoratum (Mill.) Druce<\/jats:italic>\n                      , has long been used in folk practices in forms such as herbal soups and tea infusions. However, its protective effect against acetaminophen (APAP)-induced liver injury has not yet been investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study evaluated the preventive effects of PO against APAP-induced acute liver injury in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>An APAP-induced acute liver injury model was established in C57BL\/6 mice. The hepatoprotective effects of PO were validated via histopathological analysis, oxidative stress assays,and serum biomarkers Multi-omics approaches, including 16\u00a0S rDNA sequencing, transcriptomics, and network pharmacology, were integrated with molecular biology techniques and pseudo-germ-free (PGF) mouse models to elucidate the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PO significantly alleviated hepatic histopathological damage, oxidative stress, and reduced serum ALT, AST, and LDH. PO remodeling gut microbiota, mitigated colonic inflammation and oxidative stress, and improved intestinal morphology, effects abolished by microbiota depletion. Mechanistically, PO maybe inhibited hepatic ferroptosis via the gut microbiota\u2013ceramide axis, evidenced by upregulation of GPX4 and FSP1, NRF2\/KEAP1 pathway activation, downregulation of ACSL4, TFRC\/TFR2, and DUOX2, restored iron homeostasis, and decreased lipid peroxidation and ROS.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , PO demonstrated anti-ferroptotic effects in APAP- or RSL3-treated AML12 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>PO confers hepatoprotection via the gut\u2013liver axis, which is associated with changes in ceramide metabolism and ferroptosis-related markers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1907173","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:44:35Z","timestamp":1785300275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Polygonatum odoratum extract ameliorates acetaminophen-induced acute liver injury by modulating the gut-liver axis and remodeling microbial and ceramide metabolism to suppress hepatic ferroptosis: insights from multi-omics"],"prefix":"10.3389","volume":"17","author":[{"given":"Huanghui","family":"Qin","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Shi","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caibin","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Bin","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoming","family":"Zeng","sequence":"additional","affiliation":[{"name":"Engineering Technology Research Center of Natural Medicine R&D for Prevention and Treatment of Metabolic Chronic Diseases in Huaihua City","place":["Huaihua, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Deng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Medical Laboratory Science,Hunan University of Medicine","place":["Huaihua, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanyu","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102726","DOI":"10.1016\/j.redox.2023.102726","article-title":"The KEAP1-NRF2 pathway: targets for therapy and role in cancer","volume":"63","author":"Adinolfi","year":"2023","journal-title":"Redox Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3377","DOI":"10.1007\/s00204-021-03142-9","article-title":"Delayed administration of N-acetylcysteine blunts recovery after an acetaminophen overdose unlike 4-methylpyrazole","volume":"95","author":"Akakpo","year":"2021","journal-title":"Arch. 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