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The objective of this study was to evaluate the hepatoprotective effects of LQ in cholestatic mice. LQ (40 or 80\u2009mg\/kg) was intragastrically administered to mice once daily for 6\u00a0days, and mice were treated intragastrically with a single dosage of ANIT (75\u2009mg\/kg) on the 5th day. On the 7th day, mice were sacrificed to collect blood and livers. The mRNA and protein levels were determined by qRT\u2010PCR and western blot assay. We also conducted systematical assessments of miRNAs expression profiles in the liver. LQ ameliorated ANIT\u2010induced cholestatic liver injury, as evidenced by reduced serum biochemical markers and attenuated pathological changes in liver. Pretreatment of LQ reduced the increase of malondialdehyde, TNF\u2010\u03b1, and IL\u20101\u03b2 induced by ANIT. Moreover, ANIT suppressed the expression of Sirt1 and FXR in liver tissue, which was weakened in the LQ pre\u2010treatment group. LQ enhanced the nuclear expression of Nrf2, which was increased in the ANIT group. LQ also increased the mRNA expressions of bile acid transporters <jats:italic>Bsep<\/jats:italic>, <jats:italic>Ntcp<\/jats:italic>, <jats:italic>Mrp3<\/jats:italic>, and <jats:italic>Mrp4<\/jats:italic>. Furthermore, a miRNA deep sequencing analysis revealed that LQ had a global regulatory effect on the hepatic miRNA expression. Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the differentially expressed miRNAs were mainly related to metabolic pathways, endocytosis, and MAPK signaling pathway. Collectively, LQ attenuated hepatotoxicity and cholestasis by regulating the expression of Sirt1\/FXR\/Nrf2 and the bile acid transporters, indicating that LQ might be an effective approach for cholestatic liver diseases.<\/jats:p>","DOI":"10.1002\/jat.4385","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:33:39Z","timestamp":1661474019000},"page":"350-359","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Liquiritin alleviates alpha\u2010naphthylisothiocyanate\u2010induced intrahepatic cholestasis through the Sirt1\/FXR\/Nrf2 pathway"],"prefix":"10.1002","volume":"43","author":[{"given":"Miao","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Second Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiating","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingli","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Birth Defects Research, Prevention and Treatment Hunan Provincial Maternal and Child Health Care Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyan","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Affiliated Yantai Yuhuangding Hospital of Qingdao University  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Gu","sequence":"additional","affiliation":[{"name":"Chia Tai Tianqing Pharmaceutical Group Co. 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