{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:13:24Z","timestamp":1792260804512,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"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":["81973613"],"award-info":[{"award-number":["81973613"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130120"],"award-info":[{"award-number":["82130120"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Total astragalus saponins (TAS) are the main active components of <jats:italic>astragali radix<\/jats:italic>, and have potent anti\u2010hepatic fibrosis effect. However, the therapeutic efficacy of TAS and their potential mechanisms in the treatment of primary sclerosing cholangitis (PSC) remain unclear. In this study, two mouse models of PSC, including 3,5\u2010Diethoxycarbonyl\u20101,4\u2010Dihydro\u20102,4,6\u2010Collidine (DDC)\u2010induced PSC and <jats:italic>Mdr2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> spontaneous PSC, and the <jats:italic>Tgr5<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice were used to investigate the therapeutic effect and mechanisms of TAS. Treatment with TAS, particularly with a dose of 56\u2009mg\/kg, significantly ameliorated the PSC\u2010related liver injury, cholestasis, collagen deposition, ductular reaction (DR), and fibrosis in the DDC\u2010induced and <jats:italic>Mdr2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>spontaneous PSC mice. Furthermore, treatment with TAS significantly mitigated the PSC\u2010related inflammatory responses in vivo and HIBEpiC cells by inhibiting the expression of TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2. Mechanistically, treatment with TAS rescued the PSC\u2010decreased hepatic TGR5 expression to attenuate the NF\u2010\u03baB p65 phosphorylation. Notably, the therapeutic efficacy of TAS on PSC in DDC\u2010induced mice was abrogated in <jats:italic>Tgr5<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, suggesting the anti\u2010PSC effect of TAS may depend on enhancing TGR5 expression. In conclusion, TAS ameliorated DR, inflammation and liver fibrosis in both models of PSC mice by rescuing TGR5 expression. Our findings may aid in the design of new therapeutic strategies for the treatment of PSC.<\/jats:p>","DOI":"10.1002\/ptr.8297","type":"journal-article","created":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T08:45:57Z","timestamp":1721465157000},"page":"4502-4518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Total astragalus saponins attenuate primary sclerosing cholangitis in mice by upregulation of <scp>TGR5<\/scp>"],"prefix":"10.1002","volume":"38","author":[{"given":"Qun","family":"Zhou","sequence":"first","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadong","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongping","family":"Mu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-9610","authenticated-orcid":false,"given":"Jiamei","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31211"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32771"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.112895"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28707"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30300-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.05.009"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233782"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14800"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31067"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061463"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.lab.0000097190.56734.fe"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315259"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00690-y"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-014-8443-x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.02.033"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20022"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001651"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.09.189"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155116"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.06.027"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14427"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.04.015"},{"key":"e_1_2_10_24_1","volume-title":"Primary sclerosing cholangitis","author":"Rawla P.","year":"2023"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.03.029"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1179\/1351000214y.0000000115"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100230"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322362"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-020-01681-z"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24525"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2023.2216942"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104559"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-2631"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0207"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.965914"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116833"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.11.004"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.06.011"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.8297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T13:49:45Z","timestamp":1729691385000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.8297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,20]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/ptr.8297"],"URL":"https:\/\/doi.org\/10.1002\/ptr.8297","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,20]]},"assertion":[{"value":"2023-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}