Tanshinone II-A inhibits low density lipoprotein oxidation in vitro

Tanshinone II-A (TSII-A) is a major component of Salvia miltorrhiza Bunge w hich has long been used for preventing and ameliorating anginal pain in Chi na. However the effect of TSII-A on low density lipoprotein (LDL) oxidation has not been studied. The present study was performed to investigate the e ffects of TSII-A on LDL oxidation using four oxidizing systems, including c opper-, peroxyl radical- and peroxynitrite-initiated and macrophage-mediate d LDL oxidation. LDL oxidation was measured in terms of formation of thioba rbituric acid-reactive substances (TBARS), relative electrophoretic mobilit y (REM) on agarose gel and lag time. In all four systems, TSII-A has appare nt antioxidative effects against LDL oxidation, as evidenced by its dose-de pendent inhibition of TEARS formation, prolongation of lag time and suppres sion of increased REM. Regarding the mechanism underlying its antioxidative effect, TSII-A neither scavenged superoxide nor peroxynitrite. It also did not chelate copper. Bu t it has mild peroxyl radical scavenging activity. The direct binding to LD L particles and conformational change of LDL structure by TSII-A were sugge sted, because it increased negative charge of LDL which was shown by increa sed REM on agarose gel. In conclusion, TSII-A is an effective antioxidant a gainst LDL oxidation in vitro. The underlying mechanism appears to be relat ed to its peroxyl radical scavenging and LDL binding activity.