In Vitro Hypocholesterolemic Effect of Coffee Compounds

(1) Background: Cholesterol bioaccessibility is an indicator of cholesterol that is available for absorption and therefore can be a measure of hypocholesterolemic potential. In this work, the effect of commercial espresso coffee and coffee extracts on cholesterol solubility are studied in an in vitro model composed by glycodeoxycholic bile salt, as a measure of its bioaccessibility. (2) Methods: Polysaccharide extracts from coffees obtained with different extraction conditions were purified by selective precipitation with ethanol, and their sugars content were characterized by GC-FID. Hexane extraction allowed us to obtain the coffee lipids. Espresso coffee samples and extracts were tested regarding their concentration dependence on the solubility of labeled 13C-4 cholesterol by bile salt micelles, using quantitative 13C NMR. (3) Results and Discussion: Espresso coffee and coffee extracts were rich in polysaccharides, mainly arabinogalactans and galactomannans. These polysaccharides decrease cholesterol solubility and, simultaneously, the bile salts’ concentration. Coffee lipid extracts were also found to decrease cholesterol solubility, although not affecting bile salt concentration. (4) Conclusions: Coffee soluble fiber, composed by the arabinogalactans and galactomannans, showed to sequester bile salts from the solution, leading to a decrease in cholesterol bioaccessibility. Coffee lipids also decrease cholesterol bioaccessibility, although the mechanism of action identified is the co-solubilization in the bile salt micelles. The effect of both polysaccharides and lipids showed to be additive, representing the overall effect observed in a typical espresso coffee. The effect of polysaccharides and lipids on cholesterol bioaccessibility should be accounted on the formulation of hypocholesterolemic food ingredients.

Why Is Very High Cholesterol Content Beneficial for the Eye Lens but Negative for Other Organs?

The plasma membranes of the human lens fiber cell are overloaded with cholesterol that not only saturates the phospholipid bilayer of these membranes but also leads to the formation of pure cholesterol bilayer domains. Cholesterol level increases with age, and for older persons, it exceeds the cholesterol solubility threshold, leading to the formation of cholesterol crystals. All these changes occur in the normal lens without too much compromise to lens transparency. If the cholesterol content in the cell membranes of other organs increases to extent where cholesterol crystals forma, a pathological condition begins. In arterial cells, minute cholesterol crystals activate inflammasomes, induce inflammation, and cause atherosclerosis development. In this review, we will indicate possible factors that distinguish between beneficial and negative cholesterol action, limiting cholesterol actions to those performed through cholesterol in cell membranes and by cholesterol crystals.

Abstract 447: β-cyclodextrin Reduces Cholesterol Crystal-induced Inflammation Through Modulating Complement Activation

Atherosclerosis is an inflammatory condition and the underlying cause for cardiovascular disease. Cholesterol crystals (CC) are found to be abundant in atherosclerotic plaques and we have previously shown that CC initiate an inflammatory response via the complement system and inflammasome activation. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (BCD) is a compound that solubilizes lipophilic substances and is commonly used in pharmaceuticals or drug delivery. BCD is reported to increase cholesterol solubility and to promote the removal of cholesterol from foam cells. However, it remains unknown whether BCD has any effect on crystalline cholesterol. We here show that BCD attenuates the CC -induced inflammatory cytokine response as well as regulates a range of CC-related genes in human peripheral blood mononuclear cells. BCD binds to CC and prevents deposition of complement factors on CC in human plasma. Furthermore, BCD also decreases the formation of soluble terminal complement complex (TCC) and the expression of complement receptor 3 in response to CC stimulation in human whole blood. Induction of TCC by mono sodium urate crystals or zymosan was not affected by BCD. Of interest, after 1 hr of incubation, BCD is starting to dissolve the CC. These data demonstrate that BCD is a strong inhibitor of CC-induced inflammation, which might be explained by BCD-mediated attenuation of complement activation. These data suggest that BCD is a potential candidate for treatment of atherosclerosis.

Comment on “Cholesterol solubility limit in lipid membranes probed by small angle neutron scattering and MD simulations” by S. Garg et al., Soft Matter, 2014, 10, 9313

As consistently described in the literature, the solubility limit of cholesterol in phospholipid bilayers is defined by its phase separation and crystallization.

Response to “Reply to the ‘Comment on “Cholesterol Solubility Limit in Lipid Membranes probed by Small Angle Neutron Scattering and MD Simulations by Ursula Perez-Salas, Soft Matter, 2014, 10, 9313–9317”’”

As authors of the “Comment on ‘Cholesterol solubility limit in lipid membranes probed by small angle neutron scattering and MD simulations’”, we wish to comment on both the form and content of the Reply cited above.