Atherosclerosis, the main contributor to coronary heart disease, is characterised by an accumulation of lipids such as cholesterol in the arterial wall. Reverse cholesterol transport (RCT) reduces cholesterol via its conversion into bile acids (BAs). During RCT in non-hepatic peripheral tissues, cholesterol is transferred to high-density lipoprotein (HDL) particles and returned to the liver for conversion into BAs predominantly via the rate-limiting enzyme, cholesterol 7 α-hydroxylase (CYP7A1). Numerous reports have described that polyphenol induced increases in BA excretion and corresponding reductions in total and LDL cholesterol in animal and in-vitro studies, but the process whereby this occurs has not been extensively reviewed. There are three main mechanisms by which BA excretion can be augmented: (1) increased expression of CYP7A1; (2) reduced expression of intestinal BA transporters; and (3) changes in the gut microbiota. Here we summarise the BA metabolic pathways focusing on CYP7A1, how its gene is regulated via transcription factors, diurnal rhythms, and microRNAs. Importantly, we will address the following questions: (1) Can polyphenols enhance BA secretion by modulating the CYP7A1 biosynthetic pathway? (2) Can polyphenols alter the BA pool via changes in the gut microbiota? (3) Which polyphenols are the most promising candidates for future research? We conclude that while in rodents some polyphenols induce CYP7A1 expression predominantly by the LXRα pathway, in human cells, this may occur through FXR, NF-KB, and ERK signalling. Additionally, gut microbiota is important for the de-conjugation and excretion of BAs. Puerarin, resveratrol, and quercetin are promising candidates for further research in this area.

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PON1 gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity (p ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (−22%, p < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.

Scope Some dietary interventions with berry fruits, berry fruit extracts, and purified anthocyanins have been reported to beneficially alter lipoprotein profiles in hyperlipidemic participants. The major anthocyanins in human diets are glycosides of cyanidin and delphinidin, and structure can influence both absorption and bioactivity. The aim of this study is to determine the effects of two major types of anthocyanins on low‐density lipoprotein cholesterol and other cardiometabolic markers for cardiovascular disease (CVD) risk in hyperlipidemic individuals. Methods and results Fifty‐two hyperlipidemic participants complete this randomized, placebo‐controlled, double‐blind, three arm crossover trial. Participants ingest capsules containing 320 mg of anthocyanins (bilberry trihydroxy‐type or black rice dihydroxy‐type) or placebo once daily for 28 days. Biomarkers of CVD risk are measured before and after the intervention period. Compared to the placebo, neither anthocyanin treatment significantly (p < 0.05) changes circulating levels of lipoproteins (total‐/high‐density lipoprotein (HDL)‐/low‐density lipoprotein (LDL)‐cholesterol, triglycerides, Apolipoprotein B (ApoB)), biomarkers of glycemic control (fasting glucose, fructosamine), biomarkers of HDL function (ApoA1, HDL3, paraoxonase‐1 (PON1) arylesterase, and lactonase activities), or plasma bile acids. Conclusions These data do not support the notion that regular consumption of anthocyanins beneficially affects glycemic control or lipoprotein profiles or functions. It is possible the no effect observation is due to the relatively short duration of treatments.