Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review

Abstract

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.

Endogenous circadian time genes expressions in the liver of mice under constant darkness

“…Cyp4a14 is responsible for fatty acid metabolism, and its period was downregulated under L-DD. Cyp7a1 is involved in bile acid biosynthesis [34], and Cyp51 is an essential enzyme in sterol biosynthesis [35]. Periods of the two genes significantly increased under L-DD.…”

Mechanisms of Interactions between Bile Acids and Plant Compounds—A Review

“…The referenced studies indicate that plant polyphenols may interact with bile acids on a molecular level, which may be due to hydrophobic interactions. Besides these direct polyphenol-induced alterations of the bile acid pool, polyphenols are described to significantly change microbiota compositions and affect gen expressions linked to bile acid metabolism [108][109][110]. For instance, resveratrol was reported to decrease ileal bile acid contents, repress FXR, and increase CYP7A1 and bile acid synthesis.…”

<p>The Mechanism of Traditional Chinese Medicine for the Treatment of Obesity</p>

“…59 Polyphenols extracted from puerarin (Pueraria lobata), resveratrol, and quercetin can mediate cholesterol efflux and intestinal microbial changes, thereby regulating bile acid excretion and reducing fat production. 60,61 Scutellaria baicalensis can increase the expression of the rate-limiting enzyme cytochrome P450 family 7 subfamily A member 1 (CYP7A1) in the bile acid biosynthesis pathway, and CYP7A1 can prevent the obesity induced by a high-fat diet (the exact mechanism is not clear). 62 Clove, allspice, and aromatic ginger extracts can induce TGR5-mediated BAS weight loss effects.…”