{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:02:37Z","timestamp":1778194957378,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science foundation committee of China","award":["81560648"],"award-info":[{"award-number":["81560648"]}]},{"name":"National Natural Science foundation committee of China","award":["81760575"],"award-info":[{"award-number":["81760575"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Euodia rutaecarpa is a common traditional Chinese medicine (TCM) in clinical practice, having the ability to suppress pain and cease coughing; however, with the increasing reports showing that it is toxic, particularly hepatotoxic, the concerns raised by what cause its toxicity is growing. In the current study, an analysis method based on the spectrum effect has been employed to screen the major hepatotoxic components in Euodia rutaecarpa so that the toxic material\u2019s basis would be elucidated. A fingerprinting method of the Euodia rutaecarpa extracts (which were petroleum ether, chloroform, ethyl acetate, n-butanol, and water) using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF\/MS) has been developed. Orthogonal partial least squares (OPLS) was used to establish the spectrum-toxicity relationship with the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice serum as evaluation indices for liver injury. The UHPLC-MS fingerprint was established and the OPLS analytical results suggested that coniferin, 1-methyl-2-undecyl-4(1H)-quinolone, 1-methyl-2-[(6Z,9Z,12E)-pentadeca triene]-4(1H)-quinolone, evocarpine, 1-methyl-2-[(Z)-7-tridecenyl]-4(1H)-quinolone, dihydroevocarpine, and 1-methyl-2-tetradecy-4-(1H)-quinolone probably associated with the hepatotoxicity of Euodia rutaecarpa. This paper offered considerable methods and insight for the fundamental research of the toxic material basis of similar toxic TCMs.<\/jats:p>","DOI":"10.3390\/molecules22081264","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T11:28:40Z","timestamp":1501154920000},"page":"1264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Screening Hepatotoxic Components in Euodia rutaecarpa by UHPLC-QTOF\/MS Based on the Spectrum-Toxicity Relationship"],"prefix":"10.3390","volume":"22","author":[{"given":"Jian","family":"Liang","sequence":"first","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Xiong","sequence":"additional","affiliation":[{"name":"Jiangxi Province Center for Disease Control and Prevention, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankang","family":"Li","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahao","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinbin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Lab of Modern Preparations of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1665-2681(19)30796-3","article-title":"Traditional Chinese medicine and herbal hepatotoxicity: A tabular compilation of reported cases","volume":"14","author":"Teschke","year":"2015","journal-title":"Ann. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rolf, T., Dominique, L., Dieter, M., and Gaby, D. (2016). Traditional Chinese medicine (TCM) and herbal hepatotoxicity: RUCAM and the role of novel diagnostic biomarkers such as microRNAs. Medicines, 3.","DOI":"10.3390\/medicines3030018"},{"key":"ref_3","unstructured":"Committee for the Pharmacopoeia of People\u2019s Republic of China (2015). Pharmacopoeia of People\u2019s Republic of China, Chemical Industry Publishing House. [2015 ed.]. Part 1."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.3390\/molecules18021826","article-title":"Pharmacological actions of multi-target-directed evodiamine","volume":"18","author":"Yu","year":"2013","journal-title":"Molecules"},{"key":"ref_5","first-page":"641","article-title":"A review of studies on chemical constituents of Evodia rutaecarpa","volume":"45","author":"Wang","year":"2014","journal-title":"Chin. Pharm. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21168","DOI":"10.3390\/molecules191221168","article-title":"Toxicity of Evodiae fructus on rat liver mitochondria: The role of oxidative stress and mitochindrial permeability transition","volume":"19","author":"Cai","year":"2014","journal-title":"Molecules"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.jep.2013.12.006","article-title":"Subchronic oral toxicity of evodia fruit powder in rats","volume":"151","author":"Kim","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","first-page":"1317","article-title":"Toxic logical assessment on safety of water and 70% ethanolic extracts of nearly ripe fruit of Evodia rutaecarpa","volume":"33","author":"Yang","year":"2008","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_9","first-page":"2176","article-title":"Study on analgesic and accompanying toxic and side effects of Euodiae fructus based on clinical eficacy dose","volume":"38","author":"Huang","year":"2013","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_10","first-page":"129","article-title":"Experimental comparison study on mice\u2019s acute toxicity of different composition in Evodia fructus","volume":"7","author":"Huang","year":"2008","journal-title":"Chin. J. Pharmacovigil."},{"key":"ref_11","first-page":"55","article-title":"\u201cDose-time-toxicity\u201d relationship study on hepatotoxicity caused by single dose volatile oil of Evodia fructus to mice","volume":"28","author":"Sun","year":"2012","journal-title":"Pharmacol. Clin. Chin. Mater. Med."},{"key":"ref_12","first-page":"4865","article-title":"Study on molecular mechanism of Euodia fructus on liver toxicity in mice","volume":"39","author":"Liao","year":"2014","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_13","first-page":"120","article-title":"Effects of ethanol extract from Evodia rutaecarpa on acute toxicity and hepatotoxicity in rats","volume":"29","author":"Li","year":"2013","journal-title":"Pharmacol. Clin Chin. Mater. Med."},{"key":"ref_14","first-page":"2600","article-title":"Toxicity of repeated doses of alcohol extract of evodia in target organs","volume":"42","author":"Ying","year":"2015","journal-title":"Mod. Pre-Med."},{"key":"ref_15","first-page":"2915","article-title":"Preliminary study on effective components of Tripterygium wilfordii for liver toxicity based on spectrum-effect correlation analysis","volume":"41","author":"Zhao","year":"2016","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_16","first-page":"26","article-title":"Application of spectrum-effect relationship in Chinese medicine research and related thinking","volume":"38","author":"Qin","year":"2013","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.jep.2014.04.027","article-title":"Investigation on the spectrum-effect relationships of Da-Huang-Fu-Zi-Tang in rats by UHPLC-ESI-Q-TOF-MS method","volume":"154","author":"Liu","year":"2014","journal-title":"J. Ethnopharmcol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.jep.2014.03.011","article-title":"Spectrum-effect relationships between UPLC fingerprints and bioactivities of crude secondary roots of aconitum Carmichaelii debeaux (Fuzi) and its three processed products on mitochondrial growth coupled with canonical correlation analysis","volume":"153","author":"Zheng","year":"2014","journal-title":"J. Ethnopharmcol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2016.00164","article-title":"Toxic constituents index: A toxicity-calibrated quantitative evaluation approach for the precise toxicity prediction of the hypertoxic phytomedicine-aconite","volume":"7","author":"Zhang","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, Y.H., Li, Y., Zhang, Y., Feng, G., Yang, Z.X., Guang, Q.X., Wang, R., and Han, F.J. (2017). Multi-dimensional spectrum-effect relationship of the impact of Chinese herbal formula Lichong Shengsui Yin on ovarian cancer. Molecules, 22.","DOI":"10.3390\/molecules22060979"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5331","DOI":"10.1039\/C6RA26281C","article-title":"An activity-calibrated chemical standardization approach for quality evaluation of Salvia miltiorrhiza Bge","volume":"7","author":"Liu","year":"2017","journal-title":"RSC Adv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchromb.2016.10.014","article-title":"Component analysis and target cell-based neuroactivity screening of panax ginseng by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry","volume":"1038","author":"Yuan","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1002\/bmc.3774","article-title":"Screening and identification of hepatotoxic component in Evodia rutaecarpa based on spectrum\u2013effect relationship and UPLC-Q-TOFMS","volume":"30","author":"Li","year":"2016","journal-title":"Biomed. Chromatogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1093\/chromsci\/bmw109","article-title":"Identification and structural characterization of acyl gluconic acids, flavonol glycosides, limonoids and alkaloids from the fruits of Evodia rutaecarpa by high performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry","volume":"54","author":"Ling","year":"2016","journal-title":"J. Chromatogr. Sci."},{"key":"ref_25","first-page":"694","article-title":"Chemical constituents of fruits from Evodia delavayi","volume":"51","author":"Xia","year":"2016","journal-title":"Chin. Pharm. J."},{"key":"ref_26","first-page":"45","article-title":"Chemical components of alkaloids from euodiafructus and their anti-angiogenic activities","volume":"22","author":"Yi","year":"2016","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"ref_27","first-page":"179","article-title":"Comparison of analgesic effect and active ingredient content of Evodia fructus extracts","volume":"25","author":"Cai","year":"2014","journal-title":"Tradit. Chin. Drug Res. Clin. Pharmacol."},{"key":"ref_28","first-page":"183","article-title":"Pharmacological research progress on the effective constituents of Evodia fructus","volume":"20","author":"Gong","year":"2009","journal-title":"Tradit. Chin. Drug Res. Clin. Pharmacol."},{"key":"ref_29","first-page":"366","article-title":"Research thinking on toxicity of Evodia rutaecarpa based on efficacy and material basis","volume":"8","author":"Zhu","year":"2011","journal-title":"Tradit. Chin. Drug Res. Clin. Pharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/8\/1264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:44:14Z","timestamp":1760208254000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/8\/1264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,27]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["molecules22081264"],"URL":"https:\/\/doi.org\/10.3390\/molecules22081264","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,27]]}}}