{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:05:22Z","timestamp":1792130722097,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010261","name":"Fok Ying Tung Education Foundation","doi-asserted-by":"publisher","award":["171036"],"award-info":[{"award-number":["171036"]}],"id":[{"id":"10.13039\/501100010261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703774; 81873058"],"award-info":[{"award-number":["81703774; 81873058"]}],"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":[[2021,6]]},"abstract":"<jats:p>Farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has emerged as a potential therapy for nonalcoholic fatty liver disease (NAFLD). However, the side effects of OCA may limit its application in clinics. We identified previously that isotschimgine (ITG) is a non\u2010steroidal FXR selective agonist and has potent therapeutic effects on NAFLD in mice. Here, we aimed to evaluate the therapeutic effects of ITG on nonalcoholic steatohepatitis (NASH) and fibrosis in mice. We used methionine and choline deficient (MCD) diet\u2010induced NASH mice, bile duct ligation (BDL), and carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010treated hepatic fibrosis mice to investigate the effects of ITG on NASH, fibrosis, and cholestatic liver injury. Our results showed that ITG improved steatosis and inflammation in the liver of MCD diet\u2010fed mice, as well as alleviated fibrosis and inflammation in the liver of CCl<jats:sub>4<\/jats:sub>\u2010treated mice. Furthermore, ITG attenuated serum bile acid levels, and reduced vacuolization, inflammatory infiltration, hepatic parenchymal necrosis, and collagen accumulation in the liver of BDL mice. Mechanistically, ITG increased the expression of FXR target genes. These data suggest that ITG is an FXR agonist and may be developed as a novel therapy for NASH, hepatic fibrosis, or primary biliary cholangitis.<\/jats:p>","DOI":"10.1002\/ptr.7055","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T23:30:45Z","timestamp":1617147045000},"page":"3351-3364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via <scp>FXR<\/scp> agonism in mice"],"prefix":"10.1002","volume":"35","author":[{"given":"Junxiao","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuhe","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baokai","family":"Dou","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chemical and Environmental Engineering Shanghai Institute of Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chemical and Environmental Engineering Shanghai Institute of Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Digestive Disease Longhua Hospital, Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-2943","authenticated-orcid":false,"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2012.05.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e32832e0a2f"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24537"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.023"},{"issue":"1","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1515\/znc-2001-1-218","article-title":"Pathogenesis of carbon tetrachloride\u2010induced hepatocyte injury bioactivation of CCI4 by cytochrome P450 and effects on lipid homeostasis","volume":"56","author":"Boll M.","year":"2001","journal-title":"Zeitschrift f\u00fcr Naturforschung. Teil C: Biochemie, Biophysik, Biologie, Virologie"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42801"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510258200"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13306"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gcb.2009.05.003"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2019_227"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399409000994"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00345"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000445268"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S170518"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308321200"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3977-1"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20100246"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90242-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2016.00068"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4829"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.10.169"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2012.07222.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5418.1362"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.07.025"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0616-x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.05.042"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61933-4"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13302"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2018-0441"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756284818787400"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677215571192"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60383-9"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.42.30028"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2018.1530110"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3791\/52438"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2016.1102889"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.143"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28991"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30509"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-153X-4-8"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00907"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33070-1"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33453"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22519"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/713611034"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.08.015"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00342"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201584200"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.025"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506982103"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201700059"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/Molecules23061473"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.7055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T10:11:23Z","timestamp":1746007883000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.7055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/ptr.7055"],"URL":"https:\/\/doi.org\/10.1002\/ptr.7055","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]},"assertion":[{"value":"2020-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}