QiShen YiQi and its components attenuate acute thromboembolic stroke and carotid thrombosis by inhibition of CD62P/PSGL-1-mediated platelet-leukocyte aggregate formation.

BACKGROUND: QiShen YiQi (QSYQ) dropping pill, a component-based Chinese medicine consisting of benefiting Qi (YQ) and activating blood (HX) components, has been reported to exert a beneficial effect on cerebral ischemia-induced stroke. However, its efficacy and pharmacological mechanism on acute thromboembolic stroke is not clear. PURPOSE: This study is to explore the preventative effect and pharmacological mechanism of QSYQ and its YQ/HX components on the formation of platelet-leukocyte aggregation (PLA) in acute thromboembolic stroke. STUDY DESIGN AND METHODS: In vivo thromboembolic stroke model and FeCl3-induced carotid arterial occlusion models were used. Immunohistochemistry, Western blot, RT-qPCR, and flow cytometry experiments were performed to reveal the pharmacological mechanisms of QSYQ and its YQ/HX components. RESULTS: In thromboembolic stroke rats, QSYQ significantly attenuated infarct area, improved neurological recovery, reduced PLA formation, and inhibited P-selection (CD62P)/ P-selectin glycoprotein ligand-1 (PSGL-1) expressions. The YQ component preferentially down-regulated PSGL-1 expression in leukocyte, while the HX component preferentially down-regulated CD62P expression in platelet. In carotid arterial thrombosis mice, QSYQ and its YQ/HX components inhibited thrombus formation, prolonged vessel occlusion time, reduced circulating leukocytes and P-selectin expression. PLA formation and platelet/leukocyte adhesion to endothelial cell were also inhibited by QSYQ and its YQ/HX components in vitro. CONCLUSION: QSYQ and YQ/HX components attenuated thromboembolic stroke and carotid thrombosis by decreasing PLA formation via inhibiting CD62P/PSGL-1 expressions. This study shed a new light on the prevention of thromboembolic stroke.

Identification of linoleic acid as an antithrombotic component of Wenxin Keli via selective inhibition of p-selectin-mediated platelet activation.

Atrial fibrillation significantly increases the risk of thromboembolism and stroke. Wenxin Keli (WXKL) is a widely used Chinese patent medicine against arrhythmia but if it has antithrombotic activity is unknown. Since platelet activation is a critical factor in thrombosis and the key target for many antithrombotic drugs, this study aims to demonstrate the antithrombotic efficacy of WXKL. In vitro platelet activation experiments showed that WXKL significantly inhibited platelet adhesion and aggregation. The potential active monomers in WXKL were screened by in silico prediction and in vitro platelet aggregation/adhesion assays. From WXKL chemical fractions and more than 40 monomers, linoleic acid (LA) was identified as the strongest antiplatelet compound. Oral administration of WXKL (1.2 g/kg/day) and LA (50 mg/kg/day) for 7 days significantly improved FeCl3-induced carotid thrombus formation in ICR mice without prolonging bleeding time. Flow cytometry showed that both WXKL and LA inhibited the release of p-selectin after platelet activation. ELISA showed that WXKL and LA also inhibited the expression of 6-Keto-PGF1α in plasma of mice with thrombus, but had no obvious effect on the expression of TXB2. WXKL inhibited platelet activation by broadly inhibiting the phosphorylation of protein kinase B (Akt), mitogen-activated protein kinases (MAPKs) and phospholipase C (PLC) ß3. In contrast, LA only inhibited the phosphorylation of PLCß3. In conclusion, WXKL and its active component LA showed good antiplatelet and antithrombotic efficacy in vivo and in vitro. Mechanistically, the multicomponent Chinese medicine WXKL acts on multiple targets in the platelet activation pathway whereas its active monomer linoleic acid acts specifically on phospholipase C ß3.

Recyclable and Green Triboelectric Nanogenerator.

A recyclable and green triboelectronic nanogenerator (TENG) is developed based on triboelectrification and designed cascade reactions. Once triggered by water, the TENG can fully dissolve and degrade into environmentally benign end products. With features of rapid dissolution, reproductivity, and green electronic, the TENG has potential of serving as clearable energy harvester and nanosensor for health monitoring and motion sensing.