PMID- 36091227
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220913
IS  - 2296-861X (Print)
IS  - 2296-861X (Electronic)
IS  - 2296-861X (Linking)
VI  - 9
DP  - 2022
TI  - Gypenosides ameliorate high-fat diet-induced non-alcoholic steatohepatitis via 
      farnesoid X receptor activation.
PG  - 914079
LID - 10.3389/fnut.2022.914079 [doi]
LID - 914079
AB  - BACKGROUND: Gypenosides (Gyps), the major botanical component of Gynostemma 
      pentaphyllum, was found to up-regulate the farnesoid X receptor (FXR) in a mouse 
      model of non-alcoholic steatohepatitis (NASH). However, the exact role of FXR and 
      underlying mechanisms in Gyps-mediated effects on NASH remain to be elucidated. 
      PURPOSE: This study investigated whether Gyps attenuates NASH through directly 
      activating FXR in high-fat diet (HFD)-induced NASH, and delineated the molecular 
      pathways involved. STUDY DESIGN: A mouse model of HFD-induced NSAH was used to 
      examine effects of Gyps on NASH with obeticholic acid (OCA) as a positive 
      control, and the role of FXR in its mechanism of action was investigated in 
      wild-type (WT) and FXR knockout (KO) mice. METHODS: WT or FXR KO mice were 
      randomly assigned into four groups: normal diet (ND) group as negative control, 
      HFD group, HFD + Gyps group, or HFD + OCA group. RESULTS: Treatment with Gyps and 
      OCA significantly improved liver histopathological abnormalities in HFD-induced 
      NASH, reduced the non-alcoholic fatty liver disease (NAFLD) activity score (NAS), 
      and lowered hepatic triglyceride (TG) content compared with the HFD group. In 
      agreement with these liver tissue changes, biochemical tests of blood samples 
      revealed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
      TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting 
      blood glucose (FBG), and fasting insulin (FINS) levels were significantly lower 
      in the HFD + Gyps vs. HFD group. Furthermore, Gyps and OCA treatment 
      significantly up-regulated hepatic FXR, small heterodimer partner (SHP), 
      carnitine palmitoyltransferase 1A (CPT1A), and lipoprotein lipase (LPL) 
      expression, and significantly down-regulated sterol-regulatory element binding 
      protein 1 (SREBP1), fatty acid synthetase (FASN), and stearoyl-CoA desaturase 1 
      (SCD1) protein levels compared with the HFD group in WT mice but not in FXR KO 
      mice. Notably, Gyps- and OCA-mediated pharmacological effects were significantly 
      abrogated by depletion of the FXR gene in FXR KO mice. CONCLUSION: Gyps 
      ameliorated HFD-induced NASH through the direct activation of FXR and 
      FXR-dependent signaling pathways.
CI  - Copyright (c) 2022 Li, Xi, Liu and Xin.
FAU - Li, Hongshan
AU  - Li H
AD  - Liver Disease Department of Integrative Medicine, Hwa Mei Hospital, University of 
      Chinese Academy of Sciences, Ningbo, China.
AD  - Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang 
      Province, Ningbo, China.
FAU - Xi, Yingfei
AU  - Xi Y
AD  - Liver Disease Department of Integrative Medicine, Hwa Mei Hospital, University of 
      Chinese Academy of Sciences, Ningbo, China.
FAU - Liu, Hongliang
AU  - Liu H
AD  - Liver Disease Department of Integrative Medicine, Hwa Mei Hospital, University of 
      Chinese Academy of Sciences, Ningbo, China.
FAU - Xin, Xin
AU  - Xin X
AD  - Shuguang Hospital, Institute of Liver Disease, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20220824
PL  - Switzerland
TA  - Front Nutr
JT  - Frontiers in nutrition
JID - 101642264
PMC - PMC9449333
OTO - NOTNLM
OT  - farnesoid X receptor
OT  - gypenosides
OT  - high-fat diet
OT  - mice
OT  - non-alcoholic steatohepatitis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/13 06:00
MHDA- 2022/09/13 06:01
PMCR- 2022/01/01
CRDT- 2022/09/12 03:58
PHST- 2022/04/06 00:00 [received]
PHST- 2022/08/08 00:00 [accepted]
PHST- 2022/09/12 03:58 [entrez]
PHST- 2022/09/13 06:00 [pubmed]
PHST- 2022/09/13 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnut.2022.914079 [doi]
PST - epublish
SO  - Front Nutr. 2022 Aug 24;9:914079. doi: 10.3389/fnut.2022.914079. eCollection 
      2022.