9E Health-Promoting Effects of Wine Phenolics 579
(Baba et al. 2007a; Jung et al. 2003), post-menopausal women (Zern et al. 2005),
and hemodialysis patients (Castilla et al. 2006). Increased HDL cholesterol caused
by polyphenols has also been reported in healthy individuals and patients (Baba
et al. 2007b; Castilla et al. 2006; Covas et al. 2006; Mursu et al. 2004). In vitro
models have provided evidence of other mechanisms that may explain these effects
(Fig. 9E.1). A reduced synthesis and secretion of apolipoprotein B (ApoB) has been
observed in both CaCo-2 enterocytes and HepG2 hepatocytes following treatment
with polyphenols (Pal et al. 2005; Vidal et al. 2005; Takechi et al. 2004); such
an effect could attenuate the synthesis and secretion of proatherogenic intestinal
lipoproteins. Inhibition of microsomal transfer protein, diacylglycerol acyltransferase,
Fig. 9E.1Effects of polyphenols on cholesterol homeostasis. Low-density lipoprotein (LDL) is
taken up by the LDL receptor (LDLr) and transported through a complex vesicular pathway,
from early endosomes to late endosomes and lysosomes. From there, cholesterol can enter the
plasma membrane or reach the endoplasmic reticulum (ER), where cholesterol-sensing machinery
regulates cholesterol homeostasis through the sterol regulatory element-binding protein (SREBP)
pathway. Low levels of free cholesterol in the ER activate the SREBP pathway, leading to increased
transcription of target genes including the LDLr. Excess free cholesterol is stored as cholesteryl
ester in lipid droplets through the action of acyl coenzyme A cholesterol acyltransferase (ACAT).
Microsomal triglyceride transfer protein (MTP) is necessary for lipoprotein assembly. Intracellular
excess of free cholesterol activates cholesterol efflux by ATP-binding cassette (ABC) transporter
proteins. Polyphenols have been reported to inhibit MTP (1), change cholesterol distribution in
lipid rafts (2), inhibit the ubiquitin-proteasome pathway (3), enhance SREBP processing (4),
increase liver x receptor-mediated expression of ABC efflux proteins (5), increase sterol elimi-
nation through bile acid excretion (6), disrupt endocytic LDL trafficking (7), and increase LDLr
expression and activity (8)