The inhibitive effects of celastrol on LDL oxidation and HAEC cell oxidative damage / 中国药理学通报

ABSTRACT

Aim To evaluate the inhibitive effects of celastrol on LDL oxidation and HAEC cell oxidative damage. Methods The Cu2+-induced LDL oxidation model was employed to evaluate celastrol inhibitive effect on LDL oxidation in vitro, the oxidative reaction kinetic curves were determined, and the AUC, lag time,TBARS value were assayed. The AAPH-induced HAEC damaging cellular model was employed to evalu-ate the effect of celastrol on oxidative cellular damage. The safe dose of celastrol on normal cells was deter-mined by MTT method, and the effects of celastrol on HAEC oxidative damage were evaluated at the range of this safe dose. The LDH leakage,ROS level,SOD and GPX enzymatic activity,Nrf2 and HO-1 mRNA expres-sion were determined. Results At the dose range of 100 nmol · L-1 to 1 μmol · L-1 , celastrol effectively extended the lag time of LDL oxidative process induced by Cu2+, reduced the AUC of oxidative reaction kinet-ic curve and reduced the generation of lipid peroxide in the LDL oxidative process. In the cellular experiment, celastrol effectively reduced the LDH leakage induced by AAPH, increased the integrity of cell membrane and nucleus, enhanced the antioxidative enzyme activi-ties of cellular SOD,GPX and increased the expressions of Nrf2,HO-1 mRNA, celastrol also maintained the in-tegrity of cellular structure. Conlusion Celastrol can effectively inhibit LDL oxidation induced by Cu2+, and can inhibit HAEC cell oxidative damage induced by AAPH at the dose range of 100 to 400 nmol·L-1 .