Protective Mechanism Of Compound Danshen On Vascular Endothelial Cells Damaged By Active Oxygen

Compound Danshen (CD), composed of Salvia miltiorrhiza Bunge (SM), (Panaxnotoginseng (PN), and borneol, is used for the treatment of coronary heart disease andangina. However,the action mechanism CD is still unclear. Here, the antioxidation ofCD, SM, PN, salvianolic acid B (Sal B) and Danshensu was firstly checked, then,their protective effects on damaged vascular endothelial cells (VEC) induced byhydrogen peroxide were determined. Protective mechanism of CD was probed onintracellular radical oxygen species (ROS), oxidoreductase and signal transduction.Antioxidation of CD and its main components was inspected with eric freeradicals and reductive system in vitro. SM is significant in reductive effect, inscavenging DPPH and super oxygen negative radicals, and inhibiting the productionof hydroxyl radicals. While PN is significant in scavenging hydrogen peroxide andchaleting ferroporphyrin. CD has comprehensive efficacy than SM and PNindividually. Sal B and Danshensu are shown remarkable reductive effect, inscavenging DPPH, super oxygen negative radicals and inhibiting the production ofhydroxyl radicals.Intracellular antioxidation of CD and its main components was tested with theVEC damage induced by hydrogen peroxide. Protective effects on the damaged VECwere various on the drugs. CD, SM, Danshensu and Sal B are shown remarkableprotective effect, and Sal B is strongest in all, while PN is not. Sal B enhances theendogenous activities of SOD, CAT and GPX, and decreases the intracellular ROSlevel.The signal transduction of Sal B on H2O2 damaged VEC was detected usingWestern Blot analysis. The result shows that Sal B inhibits the activation of PKCα.Sal B inhibits the MAPK pathway with deactivation of JNK and p38, but not ERK.Furthermore, Sal B decreases the expression and secretion of ICAM-1 by blocking theactivation of NF-κB.It is likely that protective effects of CD on the VEC damage were associatedwith directly scavenging ROS, enhancing the activities of intracellular antioxidases,inhibiting the phosphorylation of PKCα, JNK and P38, and blocking the activationof nuclear transcriptional factor NF-κB. The decreased expression of adhesionmolecules of VEC will be helpful in keeping normal function. This study provided theimportant evidences on deciphering the molecular pharmacology of CD in its efficacy,on exploiting the second generation of Chinese traditional material medical.