Sesamin The Antioxidant Effects And Mechanisms

Objective:Several studies have indicated that the metabolites of sesamin play an important antioxidative role in vitro. However, the preventive effect of sesamin on artherosclerosis (AS) in vivo and the cellular or molecular mechanisms have not been reported. The present study was conducted to determine whether sesamin consumption would result in the prevention of AS and to decide on the optimal dose. In addition, the cellular and molecular mechanisms involved in the prevention were also studied.Methods:Rats were allowed 1 week to adapt to their environment before being used for experiments.40 male SD rats were randomly divided into normal control group, high fat control and three sesamin groups according to the initial serum cholesterol and body weight. The rats in each group were 8 individuals. Rats in sesamin intervention groups were treated with sesamin 20,40,80mg/kg·d-1 by intragastric administration, respectively. Rats were executed on the end of 9 weeks and the levels of TC, TG, LDL-C, HDL-C, VitE, VitC, SOD, GSH-PX, MDA in serum were determined. Furthermore, morphology changes of aortic arch were observed and LOX-1 mRNA of aorta was also detected. In addition, the radical scavenging capacity of sesamin was checked by spectrophotometer in vitro.)Results:1. Body weights of rats submitted to sesamin treatment were similar to those of normal control and high fat control rats both at the beginning and at the end of the study.2. Compared with normal control group, the levels of TC and LDL-C were significantly higher in hyperlipidemia model group (p<0.01). The levels of HDL-C in the three sesamin treated groups were significantly higher and LDL-C were significantly lower than that of hyperlipidemia model group (p<0.01).)3. The IC50of sesamin on DPPH·., O2-'and OH'were 5mg/mL,29.7mg/mL,19.5mg/mL, respectively.4. Compared with model group, levels of VitC, VitE in serum of 20mg/kg·d-1 sesamin group was significantly increased. However, there were not significantly difference among 40mg/kg·d-1,80mg/kg·d-1 and model group.5. The activity of GSH-PX in sesamin high-dose group was markedly increased compared with that of model group. The levels of MDA in the three sesamin treated groups were significantly reduced. SOD activities were not different among all groups.6. Compared with normal control group, LOX-1 mRNA expression in aortic endodermis increased significantly in the model group. The expressions of LOX-1 mRNA were decreased in the three sesamin treated groups. Conclusion:The primary finding of this study is that sesamin treatment may prevent AS on rats by the following mechanisms:1) decreasing the level of LDL-C; 2) increasing the ability of scavenging free radical by itself (DPPH-, O2-' and OH'can be cleaned in vitro), antioxidase system (increasing the activity of GSH-Px) and non-antioxidase system (increasing the levels of VitC, VitE in the serum); 3) modulating the expression of LOX-1mRNA in the aorta of hyperlipidemic rats to inhibit the formation of foam cell.