A dose-response study of the bioavailability of grape seed proanthocyanidin in rat and lipid-lowering effects of generated metabolites in HepG2 cells

Identificador:  imarina:6387896

Handle: https://hdl.handle.net/20.500.11797/imarina6387896

Autors:  Margalef, Maria; Guerrero, Ligia; Pons, Zara; Isabel Bravo, Francisca; Arola, Lluis; Muguerza, Begona; Arola-Arnal, Anna

Resum:
Hyperlipidemia is one of the principal causes of cardiovascular disease and proanthocyanidins (PAs) regulate lipid homeostasis. This study aims to evaluate the concentration of PAs in rat serum after the administration of different doses of PAs and to determine the capacity of these metabolites to reduce de novolipid synthesis in HepG2 cells. Two hours after oral administration of different doses of a grape seed proanthocyanidin extract (GSPE) (1000, 375, 250 and 125. mg/kg), serum was semi-purified and characterised by HPLC-ESI-MS/MS before analysing the synthesis and secretion of lipids in HepG2 cells. Results showed a dose-dependent appearance of metabolised PAs in serum at doses up to 375. mg/kg and saturation at 1000. mg/kg of GSPE. A reduction in cholesterol esters (CE), free cholesterol (FC) and triglycerides (TG) synthesis was observed without dose-dependence when the cells were treated with PAs metabolites. Moreover, a low dose of metabolites (125. mg/kg) was sufficient to reduce FC and TG synthesis. In conclusion, the study demonstrated that PAs metabolise in a dose-dependent manner up to 370. mg/kg but not dose-dependent effect was shown in reducing the de novosynthesis of lipids. © 2014 Elsevier Ltd.