{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:25:20Z","timestamp":1790508320205,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Program for Changjiang Scholars of the Ministry of Education of the People's Republic of China","award":["T2016088"],"award-info":[{"award-number":["T2016088"]}]},{"name":"the National Natural Science Foundation for Distinguished Young Scholars","award":["81725021"],"award-info":[{"award-number":["81725021"]}]},{"name":"the Innovative Research Groups of the National Natural Science Foundation of China","award":["81721005"],"award-info":[{"award-number":["81721005"]}]},{"name":"the National Science &amp; Technology Major Project \u201cKey New Drug Creation and Manufacturing Program\u201d, China","award":["2019ZX09201001"],"award-info":[{"award-number":["2019ZX09201001"]}]},{"name":"the Technological Innovation Major Project of Hubei Province in 2018","award":["2018ACA115"],"award-info":[{"award-number":["2018ACA115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Cholestasis is an important predisposing factor of liver diseases, such as hepatocyte necrosis, liver fibrosis and primary biliary cirrhosis. In this study, we aimed to investigate the effects of Kinsenoside (KD), a natural active ingredient of Anoectochilus roxburghii, on estrogen-induced cholestatic liver injury in Sprague-Dawley rats and the underlying mechanism. The rats were randomly divided into six groups: control group, model group, low-dose KD group (50 mg\/kg body weight, KD-L), medium-dose KD group (100 mg\/kg body weight, KD-M), high-dose KD group (200 mg\/kg body weight, KD-H) and ursodeoxycholic acid group (40 mg\/kg body weight, UDCA). 17\u03b1-Ethinylestradiol (EE) was used to establish an experimental animal model of estrogen-induced cholestasis (EIC). The results demonstrated that KD alleviated liver pathologic damage, serum biochemical status and inhibited hepatocellular microstructure disorder and bile duct hyperplasia in EE-induced cholestatic rats. Mechanically, KD alleviated EE-induced cholestatic liver injury by inhibiting inflammatory responses and regulating bile acid homeostasis. Concretely, KD reduced the expression of IL-1\u03b2 and IL-6 by inhibiting NF-\u03baB p65 to suppress EE-mediated inflammation in rat liver. KD enhanced the expression of FXR and inhibited EE-mediated reduction of FXR in vitro and in vivo. It was the potential mechanism that KD mitigates cholestasis by increasing efflux and inhibiting uptake of bile acids via FXR-mediated induction of bile salt export pump (BSEP) and reduction of Na+-dependent taurocholate cotransport peptide (NTCP) to maintain bile acid homeostasis. Moreover, KD repressed the bile acid synthesis through reducing the expression of synthetic enzyme (CYP7A1), thereby normalizing the expression of metabolic enzyme (SULT2A1) of bile acid. In conclusion, our results revealed that KD may be an effective drug candidate for the treatment of cholestasis.<\/jats:p>","DOI":"10.3390\/ph14050452","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T11:30:16Z","timestamp":1620732616000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Kinsenoside Alleviates 17\u03b1-Ethinylestradiol-Induced Cholestatic Liver Injury in Rats by Inhibiting Inflammatory Responses and Regulating FXR-Mediated Bile Acid Homeostasis"],"prefix":"10.3390","volume":"14","author":[{"given":"Jiaxiong","family":"Ming","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Xu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Gao","sequence":"additional","affiliation":[{"name":"Biobank, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Deng","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yin","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-7230","authenticated-orcid":false,"given":"Qingyi","family":"Tong","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7222-2142","authenticated-orcid":false,"given":"Yonghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e234430","DOI":"10.1136\/bcr-2020-234430","article-title":"Prolonged cholestasis after acute viral hepatitis: Successfully treated with oral steroid","volume":"13","author":"Jayappa","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"771","DOI":"10.5009\/gnl16365","article-title":"Extrahepatic Manifestations of Primary Biliary Cholangitis","volume":"11","author":"Chalifoux","year":"2017","journal-title":"Gut Liver"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cld.2016.02.006","article-title":"The Pathology of Alcoholic Liver Disease","volume":"20","author":"Alpert","year":"2016","journal-title":"Clin. 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