{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:28:11Z","timestamp":1779917291583,"version":"3.53.1"},"reference-count":24,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T00:00:00Z","timestamp":1569283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773691 & 81703815"],"award-info":[{"award-number":["81773691 & 81703815"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wenzhou Science and Technology Major Project, China","award":["ZS2017018"],"award-info":[{"award-number":["ZS2017018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alpinetin, a bioactive flavonoid, has been known to have a diverse therapeutic effect, with namely anti-inflammatory, anticancer and antioxidant effects with low systemic toxicity. This study aimed to obtain metabolic profiles of alpinetin in orally administrated rats. The metabolites of alpinetin were systematically analyzed and identified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The chromatographic separation was achieved on a High Strength Silica (HSS) T3 (1.8 \u03bcm, 2.1 \u00d7 100 mm) column with the mobile phase consisting of water containing 0.1% formic acid and acetonitrile with 0.1% formic acid via gradient elution. An extracted ion chromatogram strategy based on multiple prototype\/metabolite intermediate templates and 71 typical metabolic reactions was proposed to comprehensively profile the metabolites of alpinetin. With the metabolite profiling strategy, altogether 15 compounds were recognized from urine, plasma, bile and feces of rats after intragastric administration of alpinetin for the first time. The prototype, glucuronide conjugates and phenolic acids metabolites were the probable predominant form of alpinetin in rats. This work showed a comprehensive study of the probable metabolic pathways of alpinetin in vivo, which could provide meaningful information for future pharmacological studies.<\/jats:p>","DOI":"10.3390\/molecules24193458","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T03:51:18Z","timestamp":1569383478000},"page":"3458","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metabolic Profiling of Alpinetin in Rat Plasma, Urine, Bile and Feces after Intragastric Administration"],"prefix":"10.3390","volume":"24","author":[{"given":"Jieying","family":"Qiu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caihong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghui","family":"Chu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1158-5337","authenticated-orcid":false,"given":"Zheng","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.talanta.2006.03.032","article-title":"Separation and determination of alpinetin and cardamonin in Alpinia katsumadai Hayata by flow injection-micellar electrokinetic chromatography","volume":"71","author":"Chen","year":"2007","journal-title":"Talanta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.intimp.2015.08.002","article-title":"Alpinetin inhibits lipopolysaccharide-induced acute kidney injury in mice","volume":"28","author":"Huang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/s41419-018-0814-4","article-title":"Alpinetin exerts anti-colitis efficacy by activating AhR, regulating miR-302\/DNMT-1\/CREB signals, and therefore promoting Treg differentiation","volume":"9","author":"Lv","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.intimp.2018.07.010","article-title":"Alpinetin ameliorates inflammatory response in LPS-induced endometritis in mice","volume":"62","author":"Liang","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.amjms.2018.01.002","article-title":"Effects of alpinetin on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium-induced ulcerative colitis mice","volume":"355","author":"Tan","year":"2018","journal-title":"Am. J. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28370","DOI":"10.1038\/srep28370","article-title":"Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis","volume":"6","author":"He","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_7","first-page":"4030","article-title":"Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling","volume":"18","author":"Zhao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Malami, I., Abdul, A.B., Abdullah, R., Kassim, N.K., Rosli, R., Yeap, S.K., Waziri, P., Etti, I.C., and Bello, M.B. (2017). Crude extracts, flavokawain B and alpinetin compounds from the rhizome of alpinia mutica induce cell death via UCK2 enzyme inhibition and in turn reduce 18S rRNA biosynthesis in HT-29 cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173651"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9243","DOI":"10.1007\/s13277-016-4827-2","article-title":"Alpinetin targets glioma stem cells by suppressing Notch pathway","volume":"37","author":"Wang","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_10","first-page":"6119","article-title":"Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium","volume":"9","author":"Wu","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.biopha.2017.10.035","article-title":"Alpinetin improved high fat diet-induced non-alcoholic fatty liver disease (NAFLD) through improving oxidative stress, inflammatory response and lipid metabolism","volume":"97","author":"Zhou","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.micpath.2018.11.007","article-title":"Protective effects of alpinetin on lipopolysaccharide\/d-Galactosamine-induced liver injury through inhibiting inflammatory and oxidative responses","volume":"126","author":"Liu","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cbi.2019.04.031","article-title":"Activation of G protein-coupled receptor 30 by flavonoids leads to expression of acetylcholinesterase in cultured PC12cells","volume":"306","author":"Liu","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_14","first-page":"1610","article-title":"Alpinetin promotes the binding of PPAR and methyltransferase","volume":"33","author":"Hu","year":"2017","journal-title":"Xi bao yu fen zi mian yi xue za zhi = Chin. J. Cell. Mol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/bio.3531","article-title":"A sensitive resonance Rayleigh light scattering method for alpinetin using gold nanorods probes","volume":"33","author":"Bi","year":"2018","journal-title":"Luminescence"},{"key":"ref_16","first-page":"476","article-title":"Protection Mechanism of Alpinetin on Pulmonary Microvascular Endothelial Cells Injury","volume":"37","author":"Wang","year":"2017","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"ref_17","unstructured":"Ming-Jiang, W.U., Xiao-Lei, W.U., Zhang, D.Q., Ding, L.Q., Qiu, F., Hao-Ling, M.A., and Chen, X.Z. (2017). Identification of in vivo substances of rats after oral administration of mulberry leaves flavonoids by UPLC-Q-TOF\/MS. Chin. Tradit. Herb. Drugs."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1080\/00498254.2018.1440657","article-title":"Identification of UGTs and BCRP as potential pharmacokinetic determinants of the natural flavonoid alpinetin","volume":"49","author":"Qi","year":"2019","journal-title":"Xenobiotica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jpba.2017.12.046","article-title":"Quantification and pharmacokinetics of alpinetin in rat plasma by UHPLC-MS\/MS using protein precipitation coupled with dilution approach to eliminate matrix effects","volume":"152","author":"Ye","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_20","unstructured":"Jin, X.L., Fang, Z.Z., Yan-Qing, Q.U., Tang, B., Yang, L., and Wang, L.M. (2011). Study on the glucuronidation of alpinetin in human liver microsomes. Chin. J. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jpba.2010.07.049","article-title":"Determination of propofol UDP-glucuronosyltransferase (UGT) activities in hepatic microsomes from different species by UFLC-ESI-MS","volume":"54","author":"Liang","year":"2011","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.mam.2017.11.003","article-title":"Mechanisms of dietary flavonoid action in neuronal function and neuroinflammation","volume":"61","author":"Jaeger","year":"2018","journal-title":"Mol. Aspects Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5530","DOI":"10.1021\/acs.jafc.9b00330","article-title":"A systematic study of the metabolites of dietary acacetin in vivo and in vitro based on UHPLC-Q-TOF-MS\/MS analysis","volume":"67","author":"Yin","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1021\/acs.jafc.8b06929","article-title":"Comprehensive analyses of quercetin conjugates by LC\/MS\/MS revealed that isorhamnetin-7-O-glucuronide-4\u2032-O-sulfate is a major metabolite in plasma of rats fed with quercetin glucosides","volume":"67","author":"Tanaka","year":"2019","journal-title":"J. Agric. Food Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/19\/3458\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:23:26Z","timestamp":1760189006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/19\/3458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,24]]},"references-count":24,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["molecules24193458"],"URL":"https:\/\/doi.org\/10.3390\/molecules24193458","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,24]]}}}