Background: Cardiovascular disease (CVD) is currently the leading cause of death globally. The
metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density
lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a
significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to
as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity,
diabetes, and insulin resistance. NAFLD initially presents as relatively benign, non-progressive hepatic steatosis,
but it may, in certain individuals, progress to nonalcoholic steatohepatitis, fibrosis, cirrhosis, or hepatocellular
carcinoma. Currently, there are no validated treatments for NAFLD. Polyphenols are important bioactive dietary
compounds and may represent a natural complementary and integrative therapy for the treatment of CVDassociated
risk factors, including elevated serum cholesterol and triglyceride levels, as well as NAFLD. Understanding
their molecular mechanisms of action is important in the design of future human intervention studies.
Methods: Several studies utilizing in vitro and in vivo models have helped to identify underlying molecular
mechanisms of action of polyphenols.
Results: This review will highlight recent advances regarding the molecular actions of dietary procyanidins, with
a special focus on those originating from procyanidin-rich grape seed extracts, with a focus on the signaling
pathways utilized to exert beneficial metabolic effects.
Conclusion: Modulation of nuclear receptor activity and histone deacetylase inhibition has been identified as
underlying mechanisms contributing to procyanidin-mediated amelioration of dyslipidemia and steatosis.