Coronary artery disease develops as a result of risk factors such as increased plasma low-density lipoprotein (LDL) level and hypertension or LDL atherogenic modifications such as retention, oxidation, and aggregation. During early atherogenesis, circulating LDLs invade the arterial wall, where it binds to extracellular matrix proteoglycans, a process known as “LDL retention”.

 

1 LDL retention in the arterial wall may be a prerequisite to lipoprotein oxidative modification because retention of LDL to arterial proteoglycans increases its susceptibility to oxidation.

2 The process of LDL oxidation appears to occur within the artery wall, and all major artery wall cells including endothelial cells, smooth muscle cells and monocyte-derived macrophages, can oxidize LDL.

3 Extensive oxidation of LDL also leads to its aggregation,

4 and oxidized and aggregated LDL have been found in atherosclerotic lesions.

5 These LDL modifications are considered atherogenic because they contribute to macrophage cholesterol accumulation and foam cell formation, the hallmark of early atherosclerosis.

 

High-density lipoprotein (HDL), in contrast, is associated with antiatherogenic activity, and HDL levels are inversely related to the risk of developing atherosclerosis.
Paraoxonase (PON1) is an enzyme physically associated in serum with HDL and has been shown to protect LDL and HDL against oxidation.

6 Consumption of polyphenolic flavonoids in the diet was inversely associated with morbidity and mortality from coronary heart disease.7 Polyphenolic flavonoids may prevent coronary artery disease by reducing plasma cholesterol levels and their ability to inhibit LDL oxidation.

 

The antioxidant activity of flavonoids is related to their chemical structure as proven in privious studies on mice and human.

 

Licorice root derived from the plant Glycyrrhiza glabra is used widely in Asia as a sweetener or a spice. Licorice root contains flavonoids from the flavan and chalcone subclasses, which have lipophilic characteristics and antioxidative properties.
Among several flavonoids that were isolated and purified from licoriceroot extract, the isoflavan glabridin constituted the major flavonoid.20 We previously demonstrated that in vitro licorice extract and purified glabridin protect LDL from oxidation induced by copper ions or free radical–generating systems.21 Mechanistic studies have shown that licorice-derived glabridin binds to the LDL particle and protects it from oxidation because of its capacity to scavenge free radicals.21,22 Structural studies have found that the antioxidant effect of glabridin resides mainly in the 2-hydroxyl group of the isoflavan ring B.23 Glabridin accumulates in macrophages and inhibits cell-mediated oxidation of LDL due to the inhibition of macrophage nicotinamide adenine dinucleotide phosphate oxidase activity.24 In vivo studies have shown that supplementation of licorice extract or glabridin to atherosclerotic mice deficient in apolipoprotein E (E0) reduces the susceptibility of their LDL to oxidation and significantly reduces the development of aortic atherosclerotic lesions.

 

In the present study we extended our investigation on the anti-atherogenic properties of licorice-root extract in moderately hypercholesterolemic patients.
 

We found that licorice-root extract consumption by mildly hypercholesterolemic patients increases the resistance of their LDL against major atherogenic modifications and moderately reduces their plasma lipid levels and systolic blood pressures.