Effect of almond skin polyphenolics and quercetin on human LDL and apolipoprotein B-100 oxidation and conformation.

Almond skin polyphenolics (ASP) and vitamin C (VC) or E (VE) inhibit the Cu(2+)-induced generation of conjugated dienes in human low-density lipoprotein (LDL) in a synergistic manner. However, the mechanism(s) by which this synergy occurs is unknown. As modification of apolipoprotein (apo) B-100 is an early, critical step in LDL oxidation, we examined the effects of combining ASP or quercetin and antioxidant vitamins on the oxidation of this moiety as well as on the alteration of LDL conformation and electronegativity (LDL-). In a dose-dependent manner, ASP (0.12-2.0 micromol/L gallic acid equivalents) decreased tryptophan (Trp) oxidation by 6.7-75.7%, increased the generalized polarity (Gp) of LDL by 21.0-81.5% at 90 min and reduced the ratio of LDL- to total LDL (tLDL) by 38.2-83.8% at 5 h. The actions of ASP on these parameters were generally additive to those of VC and VE. However, a 10-25% synergy of ASP plus VC in protecting apo B-100 Trp against oxidation may result from their synergistic interaction in prolonging the lag time to oxidation. ASP and VE acted in synergy to reduce LDL-/tLDL by 24-43%. Quercetin's actions were similar to ASP, though more effective at inhibiting Trp oxidation. Thus, ASP and quercetin reduce the oxidative modification of apo B-100 and stabilize LDL conformation in a dose-dependent manner, acting in an additive or synergistic fashion with VC and VE.