Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

AMP-Activated Protein Kinases/*metabolism ; Autophagy/*drug effects ; Ginsenosides/*therapeutic use ; Hypolipidemic Agents/*therapeutic use ; Lipid Metabolism/*drug effects ; Liver/*drug effects ; Non-alcoholic Fatty Liver Disease/*drug therapy ; Sirtuin 1/*metabolism; Animals ; Cells, Cultured ; Enzyme Activators/chemistry ; Enzyme Activators/pharmacology ; Enzyme Activators/therapeutic use ; Ginsenosides/chemistry ; Ginsenosides/pharmacology ; Glucose Intolerance/drug therapy ; Glucose Intolerance/metabolism ; Hep G2 Cells ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Humans ; Hypolipidemic Agents/chemistry ; Hypolipidemic Agents/pharmacology ; Liver/metabolism ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/metabolism ; Panax/chemistry

Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L) obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA)-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK) and silent information regulator 1 (sirt1). Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD) and glucose tolerance.
Competing Interests: The authors declare no conflict of interest.

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Keywords: AMPK; NAFLD; autophagy; ginsenoside Rb2; hepatosteatosis; sirt1; type 2 diabetes

0 (Enzyme Activators)
0 (Ginsenosides)
0 (Hypolipidemic Agents)
11021-13-9 (ginsenoside Rb2)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
EC 3.5.1.- (Sirt1 protein, mouse)
EC 3.5.1.- (Sirtuin 1)

Date Created: 20170524 Date Completed: 20180307 Latest Revision: 20181113

20231215

PMC5454975

10.3390/ijms18051063

28534819