{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:26:25Z","timestamp":1790508385021,"version":"4.1.0"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100010876","name":"Shanghai University of Traditional Chinese Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010876","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2021,4]]},"DOI":"10.1016\/j.phymed.2021.153513","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T04:16:13Z","timestamp":1613708173000},"page":"153513","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":38,"special_numbering":"C","title":["Pharmacokinetics-based comprehensive strategy to identify multiple effective components in Huangqi decoction against liver fibrosis"],"prefix":"10.1016","volume":"84","author":[{"given":"Yahang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiakai","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weian","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7701-0846","authenticated-orcid":false,"given":"Yueming","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2021.153513_bib0001","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5604\/16652681.1226814","article-title":"Management strategies for liver fibrosis","volume":"16","author":"Altamirano-Barrera","year":"2017","journal-title":"Ann. Hepatol."},{"key":"10.1016\/j.phymed.2021.153513_bib0002","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5152\/tjg.2018.17330","article-title":"Liver fibrosis","volume":"29","author":"Ayd\u0131n","year":"2018","journal-title":"Turk. J. Gastroenterol."},{"key":"10.1016\/j.phymed.2021.153513_bib0003","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1139\/cjpp-2018-0474","article-title":"Inhibition effect of phytoestrogen calycosin on TGF-\u03b2 1-induced hepatic stellate cell activation, proliferation, and migration via estrogen receptor \u03b2","volume":"96","author":"Deng","year":"2018","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0004","doi-asserted-by":"crossref","DOI":"10.3390\/cells8111419","article-title":"TGF-\u03b2 in hepatic stellate cell activation and liver fibrogenesis-updated 2019","volume":"8","author":"Dewidar","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.phymed.2021.153513_bib0005","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/10715762.2017.1290233","article-title":"Astragaloside IV synergizes with ferulic acid to suppress hepatic stellate cells activation in vitro","volume":"51","author":"Dong","year":"2017","journal-title":"Free Radic. Res."},{"key":"10.1016\/j.phymed.2021.153513_bib0006","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1472-6882-12-33","article-title":"Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway","volume":"12","author":"Du","year":"2012","journal-title":"BMC Complement. Altern. Med."},{"key":"10.1016\/j.phymed.2021.153513_bib0007","unstructured":"Food and Drug Administration Guidence for Industry: Bioanalytical Method Validation. 2018. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/bioanalytical-method-validation-guidance-industry."},{"key":"10.1016\/j.phymed.2021.153513_bib0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2019.153108","article-title":"Liquiritigenin suppresses the activation of hepatic stellate cells via targeting miR-181b\/PTEN axis","volume":"66","author":"Geng","year":"2020","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2021.153513_bib0009","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/3156267","article-title":"Glycyrrhetinic acid-induced MiR-663a alleviates hepatic stellate cell activation by attenuating the TGF-beta\/Smad signaling pathway","volume":"2020","author":"Guo","year":"2020","journal-title":"Evid. Based Complement Alternat. Med."},{"key":"10.1016\/j.phymed.2021.153513_bib0010","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1124\/dmd.113.051391","article-title":"Combinatorial metabolism notably affects human systemic exposure to ginsenosides from orally administered extract of Panax notoginseng roots (Sanqi)","volume":"41","author":"Hu","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.phymed.2021.153513_bib0011","doi-asserted-by":"crossref","first-page":"21786","DOI":"10.1039\/C4RA14148B","article-title":"Identification and pharmacokinetics of the major constituents of Fugan Fang in rat plasma","volume":"5","author":"Jiang","year":"2015","journal-title":"RSC Adv."},{"key":"10.1016\/j.phymed.2021.153513_bib0012","article-title":"Analysis of cell viability by the MTT Assay","author":"Kumar","year":"2018","journal-title":"Cold Spring Harb. Protoc."},{"key":"10.1016\/j.phymed.2021.153513_bib0013","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2018.12.003","article-title":"Liquiritigenin inhibits hepatic fibrogenesis and TGF-beta1\/Smad with Hippo\/YAP signal","volume":"62","author":"Lee","year":"2019","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2021.153513_bib0014","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2019.112442","article-title":"Advances in anti hepatic fibrotic therapy with Traditional Chinese Medicine herbal formula","volume":"251","author":"Li","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2019.152948","article-title":"Protective effect of herbal medicine Huangqi decoction against chronic cholestatic liver injury by inhibiting bile acid-stimulated inflammation in DDC-induced mice","volume":"62","author":"Li","year":"2019","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2021.153513_bib0016","first-page":"12","article-title":"Huangqi decoction inhibits apoptosis and fibrosis, but promotes Kupffer cell activation in dimethylnitrosamine-induced rat liver fibrosis","volume":"24","author":"Liu","year":"2012","journal-title":"BMC Complement. Altern. Med."},{"key":"10.1016\/j.phymed.2021.153513_bib0017","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jep.2019.03.044","article-title":"Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 1: metabolic profiles from the liver-centric perspective","volume":"237","author":"Liu","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0018","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.2147\/DDDT.S203874","article-title":"Pharmacokinetics of the Yougui pill in experimental autoimmune encephalomyelitis model rats and its pharmacological activity in vitro","volume":"13","author":"Liu","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"10.1016\/j.phymed.2021.153513_bib0019","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.jep.2009.01.035","article-title":"Protective effects of astragaloside IV on porcine-serum-induced hepatic fibrosis in rats and in vitro effects on hepatic stellate cells","volume":"122","author":"Liu","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0020","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1021\/acs.jafc.8b00035","article-title":"Pharmacokinetics and bioavailability of the Isoflavones formononetin and ononin and their in vitro absorption in ussing chamber and CaCO-2 cell models","volume":"66","author":"Luo","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.phymed.2021.153513_bib0021","first-page":"262","article-title":"Efficacy of Huangqi decoction on patients with esophageal varices post hepatitis B cirrhosis: a double-blind placebo-controlled randomized clinical study","volume":"2","author":"Maimaitisidike","year":"2016","journal-title":"Chin. J. Integr. Tradit. West Med. Digest. (Chin.)"},{"key":"10.1016\/j.phymed.2021.153513_bib0022","first-page":"513","article-title":"Mechanism of hepatocytes transdifferentiation to bile duct epithelial cells and intervention of Huangqi decoction","volume":"30","author":"Qiu","year":"2010","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"10.1016\/j.phymed.2021.153513_bib0023","doi-asserted-by":"crossref","first-page":"11033","DOI":"10.3748\/wjg.v20.i32.11033","article-title":"Chronic hepatitis C and liver fibrosis","volume":"20","author":"Sebastiani","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.phymed.2021.153513_bib0024","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jep.2019.02.022","article-title":"Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl(4)-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro","volume":"236","author":"Tian","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0025","doi-asserted-by":"crossref","first-page":"708","DOI":"10.4254\/wjh.v10.i10.708","article-title":"Adiponectin as a novel biomarker for liver fibrosis","volume":"10","author":"Udomsinprasert","year":"2018","journal-title":"World J. Hepatol."},{"key":"10.1016\/j.phymed.2021.153513_bib0026","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.jep.2014.03.039","article-title":"Identification and pharmacokinetics of multiple constituents in rat plasma after oral administration of Yinchenzhufu decoction","volume":"153","author":"Wang","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0027","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jchromb.2014.12.028","article-title":"Metabolites identification of glycyrin and glycyrol, bioactive coumarins from licorice","volume":"983\u2013984","author":"Wang","year":"2015","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"10.1016\/j.phymed.2021.153513_bib0028","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/cpt.784","article-title":"Poly-pharmacokinetic study of a multicomponent herbal medicine in healthy Chinese volunteers","volume":"103","author":"Xie","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.phymed.2021.153513_bib0029","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1136\/gut.2004.042127","article-title":"Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis","volume":"54","author":"Xu","year":"2005","journal-title":"Gut"},{"key":"10.1016\/j.phymed.2021.153513_bib0030","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jep.2015.04.015","article-title":"Astragaloside prevents BDL-induced liver fibrosis through inhibition of notch signaling activation","volume":"169","author":"Yongping","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0031","doi-asserted-by":"crossref","first-page":"e4178","DOI":"10.1002\/bmc.4178","article-title":"Simultaneous quantification of multiple components in rat plasma by UPLC-MS\/MS and pharmacokinetic study after oral administration of Huangqi decoction","volume":"32","author":"Zeng","year":"2018","journal-title":"Biomed. Chromatogr."},{"key":"10.1016\/j.phymed.2021.153513_bib0032","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1124\/dmd.117.079673","article-title":"Pharmacokinetics-based identification of potential therapeutic phthalides from XueBiJing, a Chinese herbal injection used in sepsis management","volume":"46","author":"Zhang","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.phymed.2021.153513_bib0033","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12072-019-09997-6","article-title":"TAF and TDF attenuate liver fibrosis through NS5ATP9, TGF\u03b21\/Smad3, and NF-\u03baB\/NLRP3 inflammasome signaling pathways","volume":"14","author":"Zhao","year":"2020","journal-title":"Hepatol. Int."},{"key":"10.1016\/j.phymed.2021.153513_bib0034","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13020-019-0254-9","article-title":"Identifying the active components of Baihe-Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests","volume":"14","author":"Zhong","year":"2019","journal-title":"Chin. Med."},{"key":"10.1016\/j.phymed.2021.153513_bib0035","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jep.2016.06.011","article-title":"Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-\u03b21\/Smads signaling pathway modulation","volume":"190","author":"Zhou","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2021.153513_bib0036","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1089\/hum.2019.153","article-title":"Specific overexpression of mitofusin-2 in hepatic stellate cells ameliorates liver fibrosis in mice model","volume":"31","author":"Zhu","year":"2020","journal-title":"Hum. Gene Ther."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711321000556?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711321000556?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:27:22Z","timestamp":1760552842000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711321000556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":36,"alternative-id":["S0944711321000556"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2021.153513","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2021,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pharmacokinetics-based comprehensive strategy to identify multiple effective components in Huangqi decoction against liver fibrosis","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2021.153513","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"153513"}}