{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T16:28:44Z","timestamp":1767025724207,"version":"3.48.0"},"reference-count":92,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Multi\u2010glycoside from\n                    <jats:italic>Tripterygium\u2009wilfordii<\/jats:italic>\n                    Hook.f. (GTW) has shown clinical efficacy in suppressing immunological dysfunction, but is associated with severe hepatotoxicity. Phospholipids derived from marine organisms, particularly enriched in long\u2010chain polyunsaturated fatty acids, possess various beneficial bioactivities and significant medicinal value. However, the antagonistic action of phospholipids against GTW\u2010induced hepatotoxicity remains unclear. In this study, we explored the protective effect of squid gonads\u2013derived phospholipids (SPLs) against GTW\u2010induced hepatotoxicity using a zebrafish model. We evaluated the changes in a range of parameters following SPLs co\u2010treatment, including liver morphology, histology, transaminase activities, microRNA\u2010122 (miR\u2010122) transcript level, and expressions of genes related to liver injury. The results indicated that SPLs significantly attenuated GTW\u2010induced malformations and changes in the liver and yolk sac areas of zebrafish. The abnormal elevation of transaminase activities and dramatic downregulation of miR\u2010122 induced by GTW were remarkably reversed by SPLs. Histological and ultrastructural examinations showed SPLs alleviated GTW\u2010induced abnormalities in the liver tissue, including loose cell\u2010to\u2010cell contact, vacuolar structures, focal necrosis, and mitochondrial ultrastructural abnormalities. Moreover, SPLs significantly reversed the abnormal expressions of genes related to inflammation within the Myd88\/NF\u2010\u03baB signaling pathway, and those involved in drug\/xenobiotic metabolism. Molecular docking simulations revealed that these key inflammatory and drug metabolic regulators exhibited stable docking affinities with seven major components of SPLs. These findings suggest that SPLs may exert protective effects against GTW\u2010induced hepatotoxicity, potentially through the inhibition of inflammatory responses and the restoration of GTW metabolism. Therefore, SPLs may serve as a promising therapeutic candidate for mitigating GTW\u2010induced hepatotoxicity.\n                  <\/jats:p>","DOI":"10.1002\/jat.4830","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T02:08:54Z","timestamp":1749780534000},"page":"2145-2164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects of Squid Gonad Phospholipids Against Hepatotoxicity Induced by Multi\u2010Glycoside From\n                    <i>Tripterygium\u2009wilfordii<\/i>\n                    (GTW): Inhibition of Inflammatory Response and Boost of GTW Metabolism in Zebrafish"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5714-4917","authenticated-orcid":false,"given":"Ning","family":"Li","sequence":"first","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6269-4268","authenticated-orcid":false,"given":"Jibin","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Te","family":"Zheng","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Overseas Fisheries Association  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2104-9909","authenticated-orcid":false,"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-515X","authenticated-orcid":false,"given":"Qing","family":"Xia","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rostyslav","family":"Stoika","sequence":"additional","affiliation":[{"name":"Department of Regulation of Cell Proliferation and Apoptosis Institute of Cell Biology, National Academy of Sciences of Ukraine  Lviv Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kechun","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2709-4297","authenticated-orcid":false,"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"},{"name":"Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109130"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.12887"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413417"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2021.166101"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants9101345"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsfa.13225"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141550"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.02.011"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.646491"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875\u20105364(21)60078\u2010X"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.10.018"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2020.09.013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3791\/55630"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010023\u201002868\u2010z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.8b00312"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1079\/cabicompendium.54360"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2024.2309212"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.01.008"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012344"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001757\u20109"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.115911"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/08982104.2022.2069809"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.6039\/j.issn.1001\u20100408.2016.13.38"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/09637486.2024.2437469"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2020.114844"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.113517"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.11.008"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4031"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165677"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2023.2248680"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12092769"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110524"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2018.09.032"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906\u2010023\u201003836\u2010w"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2018.08.018"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2020.110806"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113513"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.723940"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010019\u20100085\u20102"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22111964"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109128"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast\u20102019\u2010000341"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2018.12.009"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811403"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14225703"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1930"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2021.117329"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249\u2010024\u201002813\u2010x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20109420\u20105_18"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6503"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20246359"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2021.100973"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2fo02672d"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2022.103868"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010019\u20100567\u20108"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12182246"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.157665"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B1900607"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13606"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010022\u201004448\u20107"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109808"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0np00054j"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2020.1779701"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2018.1527370"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9fo01677e"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2016.11.012"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102020\u2010322526"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1043836"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814139116"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520941634"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.20884\/1.sb.2017.4.2.420"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40495\u2010018\u20100147\u20100"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944\u2010022\u201001698\u20108"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440\u2010024\u201000595\u20104"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2020.100592"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2021.110456"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2021.112213"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8284107"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods10071569"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.08.027"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2023.00446"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2019.124705"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906\u2010021\u201003210\u20108"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010019\u201002572\u2010w"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpim.78"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2019.100997"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2019.108928"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.18636"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118888"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.10.011"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2508952"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010023\u201004020\u20109"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4830","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T16:25:55Z","timestamp":1767025555000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":92,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/jat.4830"],"URL":"https:\/\/doi.org\/10.1002\/jat.4830","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"type":"print","value":"0260-437X"},{"type":"electronic","value":"1099-1263"}],"subject":[],"published":{"date-parts":[[2025,6,12]]},"assertion":[{"value":"2025-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}