Hypolipidemic activity and mechanisms of the total phenylpropanoid glycosides from Ligustrum robustum (Roxb.) Blume by AMPK-SREBP-1c pathway in hamsters fed a high-fat diet

The aim of this study was to evaluate the hypolipidemic effect and mechanisms of total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) in hamsters fed a high-fat diet and to discover bioactive components in HepG2 cell model induced by oleic acid. LRTPG of high (1.2 g/kg), medium (0.6 g/kg), and low (0.3 g/kg) doses was administrated daily for 21 consecutive days in hamsters. We found that in hamsters fed a high-fat diet, LRTPG effectively reduced the concentrations of plasma triglycerides (TG), free fatty acid, total Cholesterol, low-density lipoprotein Cholesterol, and hepatic TG and total Cholesterol. And the compounds acteoside, ligupurpuroside A, ligupurpuroside C, and ligupurpuroside D significantly inhibited lipid accumulation in HepG2 cell at the concentration of 50 μmol/L. Mechanism research demonstrated that LRTPG increased the levels of phospho-AMP-activated protein kinase and phospho-sterol regulatory element binding protein-1c in liver, further to suppress the downstream lipogenic genes as stearoyl-CoA desaturase 1, glycerol-3-phosphate Acyltransferase, 1-acylglycerol-3-phosphate O-acyltransferase 2, and diacylglycerol Acyltransferase 2. In addition, LRTPG increased the hydrolysis of circulating TG by up-regulating lipoprotein Lipase activities. These results indicate that LRTPG prevents hyperlipidemia via activation of hepatic AMP-activated protein kinase-sterol regulatory element binding protein-1c pathway.

AMP-activated protein kinase (AMPK); hamster; hyperlipidemia; sterol regulatory element binding protein-1c (SREBP-1c); total phenylpropanoid glycoside from Ligustrum robustum (Roxb.) Blume (LRTPG); triglyceride.