Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion

AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.

Effects of Water-Soluble Tomato Concentrate on Platelet Aggregation

Objective:To investigate the antiplatelet aggregation effect of water-soluble tomato concentrate(WSTC)and explore the underlying molecular mechanisms.Materials and Methods:Platelet aggregometry was used to quantify rat platelet aggregation with the maximum aggregation rate in vitro and ex vivo.Then,the fibrinogen(FIB)binding assay was employed to detect the effect of WSTC on the activation of platelet integrinαIIβ3(GP IIb/IIIa).Furthermore,Western blot was performed to assess the platelet protein levels of phosphoinositide 3-kinase 110β(PI3 K110β),protein disulfide isomerase(PDI),platelet endothelial cell adhesion molecule 1(PECAM-1),andβ1-Tubulin.Results:WSTC inhibited adenosine diphosphate(ADP)and collagen-induced platelet aggregation in a concentration-dependent manner in vitro,at IC50 values of 3.05 g/L and 8.03 g/L,respectively.Significantly reduced ex vivo ADP induced platelet aggregation was observed after oral consumption of WSTC for 4 weeks in rats;average inhibition rates were 24.42%,21.48%,and 20.87%for 25 mg/Kg,75 mg/Kg,and 150 mg/Kg WSTC,respectively.It appeared that WSTC had no influence on coagulation function in rats.Incubation with WSTC decreased FIB binding to GP IIb/IIIa by 17.47%and 32.29%at the concentrations of 0.6 and 6 g/L,respectively.WSTC at 0.6 and 6 g/L markedly downregulated PI3 K110β,PDI,and PECAM-1 in platelets,and upregulatedβ1-Tubulin,in a concentration-dependent manner.Conclusion:WSTC inhibits platelet activation through modulation of platelet skeletal stability and suppresses GP IIb/IIIa receptor-mediated platelet aggregation,likely via the PI3 K signaling pathway and PDI inhibition.