Istituto di Biofisica     
Turchi G., Alagona G., Lubrano V. Protective activity of plicatin B against human LDL oxidation induced in metal ion-dependent and -independent processes. Experimental and theoretical studies. In: Phytomedicine, vol. 16 (11) pp. 1014 - 1026. Elsevier, 2009.
Oxidation of low-density lipoproteins (LDL) is thought to be a major factor in the pathophysiology of atherosclerosis. Natural antioxidants have been shown to protect LDL from oxidation and to inhibit atherogenic developments in animals. Structurally related prenylated pterocarpans, erybraedin C and bitucarpin A, and the prenylchalcone plicatin B were examined for their ability to inhibit LDL oxidation in vitro. The kinetic profile of peroxidation is characterized by the lag time of oxidation (tlag), the maximal rate of oxidation (Vmax) and the maximal accumulation of oxidation products (ODmax). Specific variation of the set of kinetic parameters by antioxidants may provide important information about the mechanism of inhibitory action of a given compound. At equimolar concentrations (1 μM) the prenylated derivatives tested were found toinhibit 1 μM copper sulphate-induced oxidation of LDL (50 μg protein/ml) in accordance with the following order of activity: plicatin B>erybraedin C≫bitucarpin A. Structural aspects, such as hydrogen-donating substituents, their number and arrangement in the aromatic ring moieties, and the prenyl and methoxy substituents, were investigated in order to explain the findings obtained. It is well known that the antioxidant activity of flavonoids is believed to be caused by a combination of transition metal chelation and free-radical-cavenging activities. To investigate these differences we comparatively studied the protective mechanism of plicatin B in copper-dependent or -independent LDL oxidation. The latter was mediated by 2,2'-azo-bis-(2-amidinopropane) dihydrochloride (ABAP). We measured the formation of conjugated dienes ( (OD)_234nm). Plicatin B (0.2-1.5 μM) delayed the (Cu)^2+ (1 μM) promoted oxidation as conjugate diene formation (tlag) of the LDL by 45.2-123.5 min and reduced V_max by 0.46-0.29 μM/min. In the ABAP (0.2 mM) promoted LDL oxidation tlag increased by 67.2-110.2 min through plicatin B (0.5-2.5 μM). In experiments in which (Cu)^2+ concentrations increased (0.5 - 3 μM) and the amount of plicatin B (1 μM) was maintained constant, a significant decrease in tlag and an increase in V_max was observed. In this study plicatin B appeared to exhibit a mixed mechanism, interfering with the formation of the radicals by chelating copper involved in the initiation/propagation reaction, but also by scavenging free hydroperoxyl radicals resulting from ABAP thermolysis. In addition, theoretical analysis indicated that plicatin B preferentially established the chelating complex with (Cu)^2+, because its affinity value is notably higher (by a factor of 5) than that for Cu+.
URL: http://www.elsevier.com/wps/find/journaldescription.cws_home/701794/description#description
DOI: 10.1016/j.phymed.2009.03.018
Subject LDL
Antioxidant mechanisms

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