Salidroside inhibits platelet function and thrombus formation through AKT/GSK3β signaling pathway.

Guangyu Wei,Kailin Xu,Wen Ju,Huan Tong,Yangyang Ding,Xiamin Wang,Chunling Fu,Jianlin Qiao,Lingyu Zeng,Zhenyu Li,Yuting Chen,Xiaoqi Xu,Sixuan Zhang

doi:10.18632/aging.103131

Abstract

Salidroside is the main bioactive component in Rhodiola rosea and possesses multiple biological and pharmacological properties. However, whether salidroside affects platelet function remains unclear. Our study aims to investigate salidroside’s effect on platelet function. Human or mouse platelets were treated with salidroside (0-20 μM) for 1 hour at 37°C. Platelet aggregation, granule secretion, and receptors expression were measured together with detection of platelet spreading and clot retraction. In addition, salidroside (20 mg/kg) was intraperitoneally injected into mice followed by measuring tail bleeding time, arterial and venous thrombosis. Salidroside inhibited thrombin- or CRP-induced platelet aggregation and ATP release and did not affect the expression of P-selectin, glycoprotein (GP) Ibα, GPVI and αIIbβ3. Salidroside-treated platelets presented decreased spreading on fibrinogen or collagen and reduced clot retraction with decreased phosphorylation of c-Src, Syk and PLCγ2. Additionally, salidroside significantly impaired hemostasis, arterial and venous thrombus formation in mice. Moreover, in thrombin-stimulated platelets, salidroside inhibited phosphorylation of AKT (T308/S473) and GSK3β (Ser9). Further, addition of GSK3β inhibitor reversed the inhibitory effect of salidroside on platelet aggregation and clot retraction. In conclusion, salidroside inhibits platelet function and thrombosis via AKT/GSK3β signaling, suggesting that salidroside may be a novel therapeutic drug for treating thrombotic or cardiovascular diseases.

Highlights

Platelets are well known regulators in the pathological thrombosis and physiological hemostasis
Through incubation with human washed platelets with salidroside (0, 5, 10 and 20 μM), we investigated whether salidroside affects platelet aggregation in response to thrombin (0.03 U/ml) or Collagen-related peptide (CRP) (1 μg/ml) stimulation
To further investigate whether salidroside influences ATP release which simultaneously occurs along with platelet aggregation, we detected ATP release and found significantly reduced ATP release from thrombin or CRP-stimulated platelets after salidroside treatment compared with vehicle treatment (Figure 1A, 1B), with more reduction being observed in platelets treated with the highest dose of salidroside (20 μM)

Summary

Introduction

Platelets are well known regulators in the pathological thrombosis and physiological hemostasis. Circulating platelets will adhere and attach to the damaged area through binding to collagen and VWF by glycoprotein (GP)VI and GPIbα [1,2,3]. As a small genus of the Crassulaceae family, Rhodiola rosea L. has been widely used as a botanical medicine for a long time for prevention and treatment of multiple diseases, such as fatigue, pains, Alzheimer’s disease, depression, and anxiety [7, 8]. It is used as a cardiopulmonary protective agent in traditional folk medicine [9]. Whether salidroside plays a role in platelet function is unclear

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