[Inhibition of human low-density lipoprotein oxidation by salvianolic acid-A]

Oxidized low-density lipoprotein (LDL) is involved in the development of atherosclerosis. Oxidative modulation of serum LDL is related to oxygen free radicals. Antioxidants have beneficial effects on oxidative modulation of LDL and development of atherosclerosis. Salvia miltriorhiza (Danshen) preparations have been widely used in the treatment of cardio-cerebral vascular diseases in China. Salvianolic acid A (Sal-A), one of the components of Salvia miltriorhiza, was shown to have strong antioxidative activity. The aim of this investigation was to evaluate the effect of Sal-A on human LDL oxidative modulation mediated by copper ions.

Oxidation of human LDL was performed in pH 7.4 phosphate-buffered saline with 10 mumol.L-1 CuSO4 at 37 degrees C water for 20 h. The content of malondialdehyde (MDA), lipofuscin and vitamin E in LDL as well as the rate of electrophoretic mobility (REM) of LDL were measured. The generation of free radicals during LDL oxidation was detected by low level-chemiluminescence (LL-CL). The chelation of Cu2+ by Sal-A was detected by UV-spectrum scanning.

Sal-A (10(-6) to 10(-4) mol.L-1) was shown to markedly reduce the production of MDA and lipofuscin as well as the consumption of vitamin E during LDL oxidation. Sal-A (10(-4) mol.L-1) was also shown to inhibit the increase of REM of LDL caused by oxidative modification. In addition, the spectrum of LL-CL showed that Sal-A (10(-6) to 10(-5) mol.L-1) decreased the generation of free radicals during LDL oxidation in a dose dependent manner. The differential UV-spectrum of Sal-A in the presence of Cu2+ indicated that Sal-A could chelate copper ions.

Sal-A has inhibitory effect on Cu2+ mediated human LDL oxidation through chelating Cu2+ and scavenging free radicals.