{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:13:06Z","timestamp":1790892786441,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973645"],"award-info":[{"award-number":["81973645"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104968"],"award-info":[{"award-number":["82104968"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204959"],"award-info":[{"award-number":["82204959"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274417"],"award-info":[{"award-number":["82274417"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82305225"],"award-info":[{"award-number":["82305225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["202201011196"],"award-info":[{"award-number":["202201011196"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515011707"],"award-info":[{"award-number":["2021A1515011707"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515110786"],"award-info":[{"award-number":["2021A1515110786"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515220010"],"award-info":[{"award-number":["2021A1515220010"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515011630"],"award-info":[{"award-number":["2022A1515011630"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515110870"],"award-info":[{"award-number":["2022A1515110870"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The liver plays a crucial role in the progression of sepsis in patients. Notably, it is the center of metabolism and detoxification, and is important for immune regulation and inflammatory response. Isoferulic acid (IFA), as a phenolic acid compound naturally found in Cimicifuga plants, is recognized for its anti\u2010inflammatory, antioxidant, and free radical\u2010scavenging properties. However, its protective mechanism underlying sepsis\u2010induced acute liver injury remains unknown. The present work focused on examining the effect of IFA on treating sepsis\u2010mediated liver injury and exploring its potential protective mechanism. In the in\u00a0vivo experiments, the cecal ligation and puncture (CLP) model was used to induce sepsis in mice. EX\u2010527 was administered through intraperitoneal injection, while IFA was given via intragastric administration. Thereafter, hepatic pathological damage was assessed through hematoxylin\u2013eosin staining. Lipid peroxidation levels were determined by measuring MDA, SOD, GSH, and ferrous iron contents. Meanwhile, relevant gene and target protein levels were analyzed using qPCR, immunohistochemistry, and Western blotting. For the in\u00a0vitro experiments, ferroptosis was induced in AML12 cells with erastin, followed by transfection with SIRT1\u2010siRNA and treatment with IFA. Subsequently, ROS levels were systematically assessed, the extent of mitochondrial membrane potential (MMP) damage was quantified, and Nrf2 immunofluorescence staining analysis was performed in AML12 cells. Finally, molecular docking and surface plasmon resonance (SPR) technologies were applied in confirming the SIRT1\u2010IFA interaction. From the in\u00a0vivo experiments, sepsis induced by CLP triggered hepatic ferroptosis. While intragastric administration of IFA reduced liver ferroptosis, the intraperitoneal injection of EX\u2010527 combined with intragastric administration of IFA reversed the protective effect of IFA. As revealed by the in\u00a0vitro experiments, IFA mitigated the erastin\u2010induced ferroptosis of AML12 cells. After transfection with SIRT1\u2010siRNA, the protective effect of IFA was reversed. IFA alleviated the sepsis\u2010induced acute liver injury through the SIRT1 signaling pathway.<\/jats:p>","DOI":"10.1002\/ptr.70098","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T03:05:45Z","timestamp":1758251145000},"page":"3-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sepsis\u2010Induced Liver Injury Mitigated by Isoferulic Acid Through Inhibition of Hepatic Ferroptosis via the\n                    <scp>SIRT1<\/scp>\n                    Signaling Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Jian","family":"Gan","sequence":"first","affiliation":[{"name":"Division of Hepatobiliopancreatic Surgery, Department of General Surgery Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliopancreatic Surgery, Department of General Surgery Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hua","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Xu","sequence":"additional","affiliation":[{"name":"Dongguan Hospital, Southern Medical University (Dongguan People's Hospital)  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlei","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Pang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-4723","authenticated-orcid":false,"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine (Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, State Key Laboratory of Respiratory Disease) the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2623-0472","authenticated-orcid":false,"given":"Yingchun","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"},{"name":"Department of Traditional Chinese Medicine Nanfang Hospital (ZengCheng Branch), Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.06.182"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010023\u201000689\u2010x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010022\u201000941\u20100"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210518"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14130"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010022\u201002400\u20106"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2011.01.001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19071985"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504\u20100781OC"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134777"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112230"},{"issue":"5","key":"e_1_2_11_13_1","first-page":"849","article-title":"Ferulic Acid Dimer Inhibits Lipopolysaccharide\u2010Stimulated Cyclooxygenase\u20102 Expression in Macrophages","volume":"19","author":"Hirata A.","year":"2005","journal-title":"In Vivo"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u201000324\u20108"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929\u2010023\u201000927\u20101"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab753"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.108948"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.12.026"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658\u2010020\u201000205\u20100"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.06.011"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.01.017"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906\u2010015\u20100874\u20102"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101328"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408347.2014.881250"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102317"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.100936"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/09629359990513"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.4103\/1735\u20105362.272561"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102655"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109158"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.168"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110004"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010020\u201000441\u20101"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2717"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S210220"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010019\u20100380\u2010z"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17300"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/1934578X1100600919"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113572"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7831"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154748"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.831168"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201014324\u2010x"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114925"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.06.035"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.7b00028"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70098","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70098","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70098","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T06:19:19Z","timestamp":1768285159000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/ptr.70098"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70098","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"assertion":[{"value":"2025-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}