Function-structural study of anti-LDL-oxidation effects of flavonoid phytochemicals

As a large group of polyphenolic phytochemicals with excellent anti-oxidation properties, the dietary flavonoid intakes have been shown to be negatively correlated with the incidence of coronary artery disease. Flavonoid compounds potentially inhibit the oxidation of low-density lipoprotein (Ox-LDL) that triggers the generation of a series of oxidation byproducts playing important roles in atherosclerosis development. The diverse inhibitory effects of different flavonoid phytochemicals on Ox-LDL might be closely associated with their intrinsic structures. In current work, we investigated the effects of eight flavonoid phytochemicals in high purity (>95%) with similar core structure on the susceptibility of LDL to Cu2+-induced oxidative modification. The results indicated that quercetin, rutin, isoquercitrin, hesperetin, naringenin, hesperidin, naringin and icariin could reduce the Cu2+-induced-LDL oxidation by59.56±7.03, 46.53±2.09, 40.52±4.65, 22.67±1.68, 20.87±2.43, 12.34±2.09, 10.87±1.68 and 3.53±3.20%, respectively. The function-structure relation study indicated that: (1) for structure similar flavonoids, the flavonoids with more free phenolic hydroxyl groups showed relative higher anti-Ox-LDL activities; (2) the free 3-OH in the C ring of flavones was important for the anti-Ox-LDL activities of flavonol (quercetin) and flavones (rutin and isoquercitrin) as their activities were decreased by ~22 and ~32% following the b-Glc and b-Glc-a-Rha modifications of 3-OH; (3) the 7-OH of A ring was important for anti-Ox-LDL capacities of flavanone compounds. The substitution of b-Glc-a-Rha with the hydrogen of 7-OH made the anti-Ox-LDL abilities for hesperidin and naringin reduced by 45.6 and 47.9%; (4) function and structure comparison also indicated that the C ring C2-C3 double bond and the 4’-OH might benefit the protection of Cu2+-induced LDL oxidation by flavonoids. Taken together, the anti-Ox-LDL activities of flavonoids were closely associated with their intrinsic structures/conformations. This study might provide clues to estimate/evaluate the contribution impacts of different functional groups of flavonoids on anti-LDL oxidation, which might also help in selecting effective and favorable dietary flavonoid drugs in the prevention and treatment of coronary artery disease and similar diseases.   Key words: Flavonoid phytochemicals, low-density lipoprotein (LDL) oxidation, antioxidant, function, structure.