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Procyanidins are potent inhibitors of LOX-1: a new player in the French Paradox.

Nishizuka T, Fujita Y, Sato Y, Nakano A, Kakino A, Ohshima S, Kanda T, Yoshimoto R, Sawamura T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2011)

Bottom Line: Indeed, purified procyanidins significantly inhibited oxLDL binding to LOX-1 while other ingredients of apple polyphenols did not.Moreover, chronic administration of oligomeric procyanidins suppressed lipid accumulation in vascular wall in hypertensive rats fed with high fat diet.These results suggest that procyanidins are LOX-1 inhibitors and LOX-1 inhibition might be a possible underlying mechanism of the well-known vascular protective effects of red wine, the French Paradox.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Physiology, National Cerebral and Cardiovascular Center, Osaka, Japan.

ABSTRACT
Lectin-like oxidized LDL receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL (oxLDL) and plays multiple roles in the development of cardiovascular diseases. We screened more than 400 foodstuff extracts for identifying materials that inhibit oxLDL binding to LOX-1. Results showed that 52 extracts inhibited LOX-1 by more than 70% in cell-free assays. Subsequent cell-based assays revealed that a variety of foodstuffs known to be rich in procyanidins such as grape seed extracts and apple polyphenols, potently inhibited oxLDL uptake in Chinese hamster ovary (CHO) cells expressing LOX-1. Indeed, purified procyanidins significantly inhibited oxLDL binding to LOX-1 while other ingredients of apple polyphenols did not. Moreover, chronic administration of oligomeric procyanidins suppressed lipid accumulation in vascular wall in hypertensive rats fed with high fat diet. These results suggest that procyanidins are LOX-1 inhibitors and LOX-1 inhibition might be a possible underlying mechanism of the well-known vascular protective effects of red wine, the French Paradox.

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Related in: MedlinePlus

DiI-oxLDL (10 µg/mL) binding in LOX-1-CHO cells in the presence of apple polyphenols (A) and each ingredient of apple polyphenols (C, 100 ng/mL each). Figure 2B represents the relative contents of each ingredient in apple polyphenols. The graph was created according to the reference.20) * represents statistical significance from control.
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fig02: DiI-oxLDL (10 µg/mL) binding in LOX-1-CHO cells in the presence of apple polyphenols (A) and each ingredient of apple polyphenols (C, 100 ng/mL each). Figure 2B represents the relative contents of each ingredient in apple polyphenols. The graph was created according to the reference.20) * represents statistical significance from control.

Mentions: In the next series of experiments, we characterized the profiles of apple polyphenols as a representative containing a large amount of procyanidins. Apple polyphenols dose-dependently and completely inhibited the DiI-oxLDL (10 µg/mL) binding to LOX-1-CHO cells with an IC50 value of 102 ng/mL (Fig. 2A). As apple polyphenol contains catechin/epicatechin ((epi)catechin), phenolcarboxylic acids, and other ingredients as well as procyanidins (Fig. 2B), we examined which of the ingredients inhibited DiI-oxLDL binding to LOX-1. As shown in Fig. 2C, the fractions containing procyanidins and (epi)catechin significantly inhibited the DiI-oxLDL binding while phenolcarboxylic acids and others did not. These results clearly indicated that procyanidins and/or (epi)catechin were active ingredients for the inhibition of oxLDL binding to LOX-1. Neither apple polyphenol nor procyanidins displayed cytotoxic effects up to 10 µg/mL (data not shown).


Procyanidins are potent inhibitors of LOX-1: a new player in the French Paradox.

Nishizuka T, Fujita Y, Sato Y, Nakano A, Kakino A, Ohshima S, Kanda T, Yoshimoto R, Sawamura T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2011)

DiI-oxLDL (10 µg/mL) binding in LOX-1-CHO cells in the presence of apple polyphenols (A) and each ingredient of apple polyphenols (C, 100 ng/mL each). Figure 2B represents the relative contents of each ingredient in apple polyphenols. The graph was created according to the reference.20) * represents statistical significance from control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066543&req=5

fig02: DiI-oxLDL (10 µg/mL) binding in LOX-1-CHO cells in the presence of apple polyphenols (A) and each ingredient of apple polyphenols (C, 100 ng/mL each). Figure 2B represents the relative contents of each ingredient in apple polyphenols. The graph was created according to the reference.20) * represents statistical significance from control.
Mentions: In the next series of experiments, we characterized the profiles of apple polyphenols as a representative containing a large amount of procyanidins. Apple polyphenols dose-dependently and completely inhibited the DiI-oxLDL (10 µg/mL) binding to LOX-1-CHO cells with an IC50 value of 102 ng/mL (Fig. 2A). As apple polyphenol contains catechin/epicatechin ((epi)catechin), phenolcarboxylic acids, and other ingredients as well as procyanidins (Fig. 2B), we examined which of the ingredients inhibited DiI-oxLDL binding to LOX-1. As shown in Fig. 2C, the fractions containing procyanidins and (epi)catechin significantly inhibited the DiI-oxLDL binding while phenolcarboxylic acids and others did not. These results clearly indicated that procyanidins and/or (epi)catechin were active ingredients for the inhibition of oxLDL binding to LOX-1. Neither apple polyphenol nor procyanidins displayed cytotoxic effects up to 10 µg/mL (data not shown).

Bottom Line: Indeed, purified procyanidins significantly inhibited oxLDL binding to LOX-1 while other ingredients of apple polyphenols did not.Moreover, chronic administration of oligomeric procyanidins suppressed lipid accumulation in vascular wall in hypertensive rats fed with high fat diet.These results suggest that procyanidins are LOX-1 inhibitors and LOX-1 inhibition might be a possible underlying mechanism of the well-known vascular protective effects of red wine, the French Paradox.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Physiology, National Cerebral and Cardiovascular Center, Osaka, Japan.

ABSTRACT
Lectin-like oxidized LDL receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL (oxLDL) and plays multiple roles in the development of cardiovascular diseases. We screened more than 400 foodstuff extracts for identifying materials that inhibit oxLDL binding to LOX-1. Results showed that 52 extracts inhibited LOX-1 by more than 70% in cell-free assays. Subsequent cell-based assays revealed that a variety of foodstuffs known to be rich in procyanidins such as grape seed extracts and apple polyphenols, potently inhibited oxLDL uptake in Chinese hamster ovary (CHO) cells expressing LOX-1. Indeed, purified procyanidins significantly inhibited oxLDL binding to LOX-1 while other ingredients of apple polyphenols did not. Moreover, chronic administration of oligomeric procyanidins suppressed lipid accumulation in vascular wall in hypertensive rats fed with high fat diet. These results suggest that procyanidins are LOX-1 inhibitors and LOX-1 inhibition might be a possible underlying mechanism of the well-known vascular protective effects of red wine, the French Paradox.

Show MeSH
Related in: MedlinePlus