Salidroside Promotes Vascular Regeneration In Hind-limb Ischemia Mice Through Activation Of Multiple Angiogenesis Factor

Rhodiola rosea is a commonly used medicine for treatment high altitude sickness, mountain malhypoxia, and anoxia. Researchers have also illustrated that Rhodiola rosea has anti-fatigue, anti-oxidation effect and enhance cell survival. Furthermore, recent studies reported that salidroside, one of the main active compound of Rhodiola could stabilize HIFpromote human bone marrow-derived endothelial progenitor cells migration and proliferation, and then promote angiogenesis. However, the knowledge regarding ites molecular mechanisms is still very limted. Moreover, whether or not salidroside could induce mature and functional blood vessels and subsequently, could be used for treating hind limb ischemia diseases had not been elucidated yet.Atherosclerosis-induced arterial diseases are one leading cause of morbidity and mortality. Peripheral artery disease is a disease caused by the obstructions in the arteries due to the atherosclerosis, limiting blood supply to organs besides heart and brain. Lower extremity is the most common location for peripheral artery disease, suffers from pain even at rest, ulcer, gangrene, poor prognosis, high amputation and mortality rates, and low quality of life. There is no systematic drug-based treatment for hindlimb ischemia at present. Current clinical treatments mainly depend on surgical-based revascularization, however, a significant number of patients, most of them had and extremely poor prognosis for major amputation and mortality, have been deemed as no option for revascularization. Thus, there is an urgent necessity to develop an effective clinical treatment for this disease.In our study, we found that salidroside promote hindlimb ischemia mice model perfusion recovery and promote angiogenesis through intramuscular injection. Salidroside promoted the expression of angiogenesis factors in gastrocnemius. We also found that salidroside not only promote angiogenesis factors that are HIF-dependent, but also promote angiogenesis factors that are HIF-independent. Other important biological effect of salidroside is that salidroside promote migration of skeletal muscle cell and proliferation. The proliferation and migration of skeletal muscle is very important to tissue repair.Collectively, we had shown that salidroside has a protential effect for the treatment of hindlimb ischemia disease. The molecular mechanism of salidroside promote angiogenesis provide a novel method for the treatment of peripheral artery disease.