{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:21:35Z","timestamp":1768882895578,"version":"3.49.0"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274091"],"award-info":[{"award-number":["82274091"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) stands as a globally common malignancy with persistently elevated incidence and mortality rates. It is known for being able to resist conventional chemotherapy. There is currently growing interest in natural products for the treatment of HCC, owing to their significant antitumor activity. Osthole, a naturally occurring O\u2010methylated coumarin in <jats:italic><jats:styled-content style=\"fixed-case\">Cnidium<\/jats:styled-content> monnieri<\/jats:italic> (L.) Cusson, showed potent antitumor effects on various types of cancer. It plays a therapeutic role in HCC by inducing apoptosis and inhibiting proliferation. Nevertheless, the anti\u2010HCC effect of osthole at the molecular level needs to be investigated. In this study, an ultraperformance liquid chromatography coupled with quadrupole time\u2010of\u2010flight mass spectrometry (UPLC\u2010Q\u2010TOF\u2010MS\/MS)\u2013based cell metabolomics approach was established to investigate the antitumor effect of osthole on HepG2 cells. The effect of osthole on the viability of HepG2 cells was found to be concentration and time\u2010dependent. Moreover, 43 differential metabolites were identified, involving the metabolic pathways of sphingolipid, glycerophospholipid, and tryptophan. It is suggested that osthole may have an anti\u2010HCC effect by affecting the function of normal cells, altering important cellular properties, reducing cellular activity, and inducing cellular apoptosis.<\/jats:p>","DOI":"10.1002\/bmc.70215","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T23:19:22Z","timestamp":1756941562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomics Study on the Antitumor Effect of Osthole on HepG2 Cells Using UPLC\u2010Q\u2010TOF\u2010MS\/MS"],"prefix":"10.1002","volume":"39","author":[{"given":"Wenhan","family":"Lin","sequence":"first","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion  Tianjin China"},{"name":"State Key Laboratory of Component\u2010based Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"State Key Laboratory of Component\u2010based Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijing","family":"Zhang","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Miao","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Zhao","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yameng","family":"Zhu","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huizi","family":"Ouyang","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion  Tianjin China"},{"name":"State Key Laboratory of Component\u2010based Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-9234","authenticated-orcid":false,"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component\u2010based Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2012.06.032"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-024-00994-y"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2015.16.16.7179"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-579X(02)00096-2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7643-0_2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1966"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/13880209.2013.850517"},{"key":"e_1_2_8_10_1","first-page":"46","volume-title":"Pharmacopoeia of the people's Republic of China","author":"Chinese Pharmacopoeia Commission","year":"2020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky310"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7MD00109F"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2010.06.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04984-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr501087x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.03.025"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-45328-2_3"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1208616"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2022.2087885"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2020.12.001"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.01.003"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2015.09.033"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5FO01479D"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00812-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.107"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00066-023-02173-8"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510240307"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.5604\/01.3001.0010.3824","article-title":"Pharmacological Features of Osthole","volume":"71","author":"Jarz\u0105b A.","year":"2017","journal-title":"Post\u0229py Higieny i Medycyny Do\u015bwiadczalnej (Online)"},{"key":"e_1_2_8_29_1","first-page":"192","article-title":"Osthole Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma HepG2 Cells by Upregulating Tumor Suppressor PTEN","volume":"35","author":"Jia T. Y.","year":"2019","journal-title":"Chin Journal of Immunology"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1076"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.15430\/JCP.2019.24.2.72"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2017.5403"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.02.005"},{"key":"e_1_2_8_34_1","first-page":"825","article-title":"Effect of Osthole on Proliferation, Apoptosis and Invasion of Hepatoma HepG Cells","volume":"32","author":"Long X. X.","year":"2022","journal-title":"Chin J Integr Trad West Med Liver Dis"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2006.01220.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172788"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-018-0074-6"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.12.006"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2023.10.004"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.2020-0356"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/np970430b"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2015.01.007"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-021-02775-w"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031006"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4MB00414K"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2307"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.004"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2019.2958"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02164-y"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.945627"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr300502v"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103484"},{"key":"e_1_2_8_54_1","first-page":"2747","article-title":"Osthole: A Multifunctional Natural Compound With Potential Anticancer, Antioxidant and Anti\u2010inflammatory Activities","volume":"21","author":"Zafar S.","year":"2021","journal-title":"Mini Reviews in Medicinal Chemistry"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/354671"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037865"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.3109\/08923973.2015.1035391"},{"key":"e_1_2_8_58_1","first-page":"729","article-title":"Anticancer Mechanism of Osthole and Its Dosage Form Research","volume":"33","author":"Zhang N.","year":"2019","journal-title":"Chinese Journal of Pharmacology and Toxicology"},{"key":"e_1_2_8_59_1","first-page":"119","article-title":"Experimental Study on the Antitumor Activity of Natural Osthole","volume":"2","author":"Zhou Z. W.","year":"2007","journal-title":"Carcinog. Teratog. Mutagen."},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2017.08.028"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.09.015"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:21:02Z","timestamp":1760041262000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.70215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":60,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/bmc.70215"],"URL":"https:\/\/doi.org\/10.1002\/bmc.70215","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"assertion":[{"value":"2025-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70215"}}