Salidroside, a scavenger of ROS, enhances the radioprotective effect of Ex-RAD® via a p53-dependent apoptotic pathway

Salidroside (Sal), the predominant component of a Chinese medicinal herb, Rhodiola rosea L., has become an attractive bioagent due to its significant anti-radiation, antioxidant and immune adjustment effects. We explored the radioprotective effect of Sal to ascertain whether it could enhance the anti-radiation effect of ON 01210.Na (Ex-RAD®) in vivo and in vitro, and elucidate its underlying mechanism. Our data demonstrated that Sal inhibited radiation-induced apoptosis, scavenged reactive oxygen species (ROS), and decreased the DNA damage of human umbilical vein endothelial cells (HUVECs). Sal downregulated the expression of Bax and p53 and increased the ratio of Bcl-2/Bax, which indicated that Sal inhibited the radiation-induced apoptosis through p53-dependent pathways. The radioprotection of the Sal pretreatment was also evidenced by an increasing survival rate of the mice, maintaining antioxidant enzyme levels in the liver, and accelerating hematopoietic recovery. The results suggest that Sal exhibits an excellent radioprotective effect with powerful antioxidant activity in vitro and in vivo. Sal enhanced the radioprotective effect of Ex-RAD by improving the antioxidant effect, the scavenging of ROS, by accelerating hematopoietic recovery and DNA repair as well as by regulating apoptotic and repair signaling pathways. Combined modality treatments were more effective than single-agent treatments, demonstrating the value of multiple-agent radioprotectants.