PMID- 32198087 OWN - NLM STAT- MEDLINE DCOM- 20200526 LR - 20231015 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 324 DP - 2020 Jun 1 TI - Ginsenoside Rg1 alleviates ANIT-induced intrahepatic cholestasis in rats via activating farnesoid X receptor and regulating transporters and metabolic enzymes. PG - 109062 LID - S0009-2797(19)31928-3 [pii] LID - 10.1016/j.cbi.2020.109062 [doi] AB - Ginsenoside Rg1 is an active ingredient extracted from the roots of ginsenoside, and an alpha-naphthylisothiocyanate (ANIT)-induced rat model of intrahepatic cholestasis was used to investigate the protective effect of Rg1 on cholestasis. 48 SD male rats were randomly divided into 6 groups: control group, model group, UDCA group (ursodeoxycholic acid), low-dose Rg1 group (10 mg/kg), medium-dose Rg1 group (20 mg/kg) and high-dose Rg1 group (40 mg/kg). The model group, the UDCA group and all the Rg1 group were then intragastrically administered with 80 mg/kg ANIT, and the control group were given equal volume of olive oil. Then the pathological changes in liver tissue were observed, the secretion of bile in the bile duct was measured, and the biochemical markers in serum were quantified, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transfer peptidase (GTP) and the content of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA). The contents of inflammatory mediators in serum were quantified, including tumor necrosis factor (TNF-alpha), gamma-interferon (IFN-gamma) and interleukin-1beta (IL-1beta). The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver homogenate were quantified. Expression of farnesoid X receptor (FXR), transporters and metabolic enzymes in liver tissue was monitored. Rg1 treatment improved liver tissue pathological damage, promoted bile secretion and significantly reduced serum levels of the intrahepatic cholestasis markers ALT, AST, ALP, GTP, TBIL, DBIL and TBA. Rg1 increased the activity of SOD and GSH-Px in liver homogenate, while, reducing the serum levels of MDA and inflammatory mediators. Rg1 also regulated the expression of FXR, bile acid transporters and metabolic enzymes. Overall, Rg1 alleviated liver injury by improving secretion of bile and normalizing the activity of enzymes in the serum. The protective mechanism appeared to be related to the activation of FXR and regulation of liver transporters and metabolic enzymes. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Xiao, Qing AU - Xiao Q AD - Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhang, Shujun AU - Zhang S AD - Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Ren, Huina AU - Ren H AD - Department of General Medicine, People's Hospital of Chongqing Bishan District, Chongqing, China. FAU - Du, Ruoyang AU - Du R AD - Department of Urology, Chongqing Emergency Medical Center, Chongqing, China. FAU - Li, Jiajun AU - Li J AD - Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhao, Jinqiu AU - Zhao J AD - Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Gao, Yue AU - Gao Y AD - Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhu, Yali AU - Zhu Y AD - Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Huang, Wenxiang AU - Huang W AD - Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: wenxiang_huang@163.com. LA - eng PT - Journal Article DEP - 20200318 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Ginsenosides) RN - 0 (Membrane Transport Proteins) RN - 0 (Protective Agents) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Ugt1a1 protein, rat) RN - 0C5V0MRU6P (farnesoid X-activated receptor) RN - 4Y8F71G49Q (Malondialdehyde) RN - 551-06-4 (1-Naphthylisothiocyanate) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.14.14.1 (Cyp3a2 protein, rat) RN - EC 1.14.14.1 (Cytochrome P-450 CYP3A) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.4.1.17 (Glucuronosyltransferase) RN - EC 2.8.2.- (Sulfotransferases) RN - EC 2.8.2.2 (alcohol sulfotransferase) RN - PJ788634QY (ginsenoside Rg1) SB - IM EIN - Chem Biol Interact. 2023 Nov 1;385:110697. PMID: 37839352 MH - 1-Naphthylisothiocyanate MH - Animals MH - Bile/metabolism MH - Biomarkers/metabolism MH - Cholestasis, Intrahepatic/chemically induced/*drug therapy/pathology MH - Cytochrome P-450 CYP3A/metabolism MH - Cytokines/metabolism MH - Ginsenosides/*pharmacology MH - Glucuronosyltransferase/metabolism MH - Glutathione Peroxidase/metabolism MH - Liver/pathology MH - Male MH - Malondialdehyde/metabolism MH - Membrane Transport Proteins/*metabolism MH - Protective Agents/*pharmacology MH - Rats, Sprague-Dawley MH - Receptors, Cytoplasmic and Nuclear/*metabolism MH - Sulfotransferases/metabolism MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - Bile acid metabolism OT - Farnesoid X receptor (FXR) OT - Ginsenoside Rg1 OT - Intrahepatic cholestasis OT - Metabolic enzyme OT - Transporter COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/03/22 06:00 MHDA- 2020/05/27 06:00 CRDT- 2020/03/22 06:00 PHST- 2019/11/20 00:00 [received] PHST- 2020/03/10 00:00 [revised] PHST- 2020/03/16 00:00 [accepted] PHST- 2020/03/22 06:00 [pubmed] PHST- 2020/05/27 06:00 [medline] PHST- 2020/03/22 06:00 [entrez] AID - S0009-2797(19)31928-3 [pii] AID - 10.1016/j.cbi.2020.109062 [doi] PST - ppublish SO - Chem Biol Interact. 2020 Jun 1;324:109062. doi: 10.1016/j.cbi.2020.109062. Epub 2020 Mar 18.