{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:56:14Z","timestamp":1790546174576,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009103","name":"Education Department of Shaanxi Province","doi-asserted-by":"publisher","award":["No. 25JP047"],"award-info":[{"award-number":["No. 25JP047"]}],"id":[{"id":"10.13039\/501100009103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017605","name":"Shaanxi University of Chinese Medicine","doi-asserted-by":"publisher","award":["No. 2024\u2010LJRC\u201004"],"award-info":[{"award-number":["No. 2024\u2010LJRC\u201004"]}],"id":[{"id":"10.13039\/501100017605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Clofibrate (CF) is an effective lipid\u2010lowering drug, but its clinical use is restricted by hepatotoxicity. Molecular hybridization with paeonol may improve hepatic safety while preserving efficacy. To synthesize CF\u2010Paeonol and compare its lipid\u2010lowering activity and hepatic safety with CF. CF\u2010Paeonol was prepared by esterifying clofibric acid with paeonol. Its lipid\u2010lowering activity was assessed in Triton WR\u20101339\u2010induced hyperlipidemic mice, while hepatic safety was evaluated after 30 days of administration in normal mice. Plasma lipids, liver function, bile acids, oxidative stress, inflammation, histopathology, molecular docking, and hepatic YY1\/FXR expression were examined. CF\u2010Paeonol dose\u2010dependently reduced triglycerides and total cholesterol. At the high dose, levels decreased by 30.51% and 33.78%, respectively, versus the model group, while the equimolar dose showed efficacy comparable to CF. Compared with CF, CF\u2010Paeonol significantly lowered AST and ALT and reduced the liver histopathological score from 11 to 3. It also improved bile acid, oxidative stress, and inflammatory indices without obvious pathological changes in other organs. Docking predicted interactions with PPAR\u2010\u03b1 and YY1, and Western blot showed decreased YY1 and increased FXR expression. CF\u2010Paeonol retained lipid\u2010lowering activity with less hepatic injury than CF, warranting further pharmacokinetic, metabolic, and causal mechanistic studies for confirmation.<\/jats:p>","DOI":"10.1002\/cbdv.71657","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:24:31Z","timestamp":1789035871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Hepatotoxicity Evaluation of Paeonol Clofibrate"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7884-5596","authenticated-orcid":false,"given":"Haoyu","family":"Tu","sequence":"first","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiao","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuwen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinya","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"},{"name":"Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine Shaanxi Administration of Traditional Chinese Medicine  Xianyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiping","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"},{"name":"Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine Shaanxi Administration of Traditional Chinese Medicine  Xianyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9358-4864","authenticated-orcid":false,"given":"Yundong","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shaanxi University of Chinese Medicine, Xi'an\u2010xianyang New Ecomic Zone  Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"T.Cai X.Xu L.Dong et\u00a0al. \u201cOroxin A From Oroxylum Indicum Improves Disordered Lipid Metabolism by Inhibiting SREBPs in Oleic Acid\u2010Induced HepG2 Cells and High\u2010fat Diet\u2010Fed Non\u2010Insulin\u2010Resistant Rats \u201d Heliyon (Forthcoming) https:\/\/10.1016\/j.heliyon.2024.e29168."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-025-02759-4"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-022-01006-w"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232416224"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1111933"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12072056"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes15020190"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2024.10.019"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001457"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18020147"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2018.1537780"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(19)32419-9"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00632-3"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.31.653"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2024.2405163"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v7.i5.74"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156102"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2025.130309"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2025.130116"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.10.021"},{"key":"e_1_2_12_22_1","first-page":"124","article-title":"Prophylactic Impacts of Lotusine against Hyperglycaemia\u2010Induced Oxidative Stress in Hepatic Cells Isolated From Diabetic Rats via Irs\u20101\/Pi3 K\/Akt Pathway","volume":"45","author":"Alharthi N. S.","year":"2025","journal-title":"Pakistan Veterinary Journal"},{"key":"e_1_2_12_23_1","first-page":"1105","article-title":"Evaluating the Antidiabetic, Anticancer, Anti\u2010Alzheimer, Antiviral, and Antimicrobial Activities of Silymarin From Milk Thistle Extract: Hepatoprotective Properties, Histology and Gene Regulators in HgCl2\u2010Challenged Rats","author":"Alharbi A.","year":"2025","journal-title":"The Pakistan Veterinary Journal"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26092401"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117163"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.896874"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgac065"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12100956"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-024-03214-2"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.06.010"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0319721"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.70271"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.24171\/j.phrp.2021.0336"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2020.1764058"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28196918"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230390202353"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01165-4"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1581398"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13886"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.068"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155124"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/egastro-2024-100074"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2026.179060"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.5c00380"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13577"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S108526"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40643-025-00933-1"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.71657","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.71657","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.71657","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:58:05Z","timestamp":1790542685000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.71657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cbdv.71657"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.71657","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71657"}}