Cerebral edema is characterized by fluid accumulation,and the glymphatic system(GS)plays a pivotal role in regulating fluid transport.Using the Tenecteplase system,magnesium salt of salvianolic acid B/ginsenoside Rg1(...Cerebral edema is characterized by fluid accumulation,and the glymphatic system(GS)plays a pivotal role in regulating fluid transport.Using the Tenecteplase system,magnesium salt of salvianolic acid B/ginsenoside Rg1(SalB/Rg1)was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h.GS function was assessed by Evans blue imaging,near-infrared fluorescence region II(NIR-II)imaging,and magnetic resonance imaging(MRI).SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score,improving neurobehavioral function,and protecting tissue structure,especially inhibiting cerebral edema.Meanwhile,the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI.SalB/Rg1 inhibited matrix metalloproteinase-9(MMP-9)activity,reduced cleavedβ-dystroglycan(β-DG),and stabilized aquaporin-4(AQP4)polarity,which was verified by colocalization with CD31.Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema,accompanying the regulation of the MMP9/β-DG/AQP4 pathway.展开更多
The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand Whit...The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand White(NZW)rabbits,compared with those of SalB immediate-release pellets(SalB-IRPs).The SalB plasma concentrations and Superoxide dismutase levels(PD index)were recorded continuously at predetermined time interval after administration,and the related parameters were calculated by using Win-Nonlin software.The release profile of MPOPs was more sustained than that of IRPs.PK results indicated that the mean C_(max)was significantly lower,the SalB plasma concentrations were steadier,both area under concentration-time curve from 0 to 24 h(AUC_(0-24 h))and from 0 to infinity(AUC_(0-∞))were presented larger,and both the peak concentration time(T_(max))and mean residence time(MRT)were prolonged for MPOPs,as compared with those of IRPs.PD results suggested that peak drug effect(E_(max))was lower and the equilibration rate constant(k_(e0))between the central compartment and the effect compartment was higher of MPOPs vs.those of IRPs.PKePD relationships demonstrated that the effectconcentration-time(ECT)course of MPOPs was clockwise hysteresis loop,and that of IRPs was counter-clockwise hysteresis loop.Collectively,those results demonstrated that MPOPs were potential formulations in treating angina pectoris induced by atherosclerosis.展开更多
OBJECTIVE:To investigate the influence and mechanism of salvianolic acid B(SalB) on apoptosis inhibition in rat bone marrow-derived mesenchymal stem cells(BMSCs) induced by hypoxia and serum deprivation(hypoxia/SD).ME...OBJECTIVE:To investigate the influence and mechanism of salvianolic acid B(SalB) on apoptosis inhibition in rat bone marrow-derived mesenchymal stem cells(BMSCs) induced by hypoxia and serum deprivation(hypoxia/SD).METHODS:SalB concentration of 0.1,1,10 or 100 mg/L(drug groups) were investigated for their ability to inhibit apoptosis in rat BMSCs.BMSCs in both the apoptosis model and drug groups were cultured under hypoxic conditions for 6 h,after which cell apoptosis and change in mitochondrial membrane potential(MMP) were detected using flow cytometry.Activation of caspase-3 was detected using western blot analysis.RESULTS:Hypoxia/SD induced apoptosis in rat BMSCs.The early apoptosis rate was lower in the drug groups compared to the apoptosis model group(P<0.05).SalB was found to inhibit the reduction in MMP and decrease the activation of caspase-3.CONCLUSION:0.1,1 and 10 mg/L of SalB inhibits activation of caspase-3 and early apoptosis of rat BMSCs induced by hypoxia/SD and could therefore enhance the survival rate of grafted stem cells.展开更多
基金supported by Zhao Guoping Academician Workstation(Hangzhou Academician Workstation)of Zhejiang Chinese Medical University,Chinese Academy of Sciences-the Alliance of National and International Science Organizations for the Belt and Road Regions Fellowship(CAS-ANSO-FP-2024-06)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1060000)the Science and Technology Commission of Shanghai Municipality(No.YDZX20233100004032001,China).
文摘Cerebral edema is characterized by fluid accumulation,and the glymphatic system(GS)plays a pivotal role in regulating fluid transport.Using the Tenecteplase system,magnesium salt of salvianolic acid B/ginsenoside Rg1(SalB/Rg1)was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h.GS function was assessed by Evans blue imaging,near-infrared fluorescence region II(NIR-II)imaging,and magnetic resonance imaging(MRI).SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score,improving neurobehavioral function,and protecting tissue structure,especially inhibiting cerebral edema.Meanwhile,the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI.SalB/Rg1 inhibited matrix metalloproteinase-9(MMP-9)activity,reduced cleavedβ-dystroglycan(β-DG),and stabilized aquaporin-4(AQP4)polarity,which was verified by colocalization with CD31.Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema,accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
基金This study is financially supported by the major project of National Science and Technology of China for new drugs development(No.2009ZX09310-004)Jiangsu Province Ordinary College and University innovative research programs(No.CX10B-374Z).
文摘The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand White(NZW)rabbits,compared with those of SalB immediate-release pellets(SalB-IRPs).The SalB plasma concentrations and Superoxide dismutase levels(PD index)were recorded continuously at predetermined time interval after administration,and the related parameters were calculated by using Win-Nonlin software.The release profile of MPOPs was more sustained than that of IRPs.PK results indicated that the mean C_(max)was significantly lower,the SalB plasma concentrations were steadier,both area under concentration-time curve from 0 to 24 h(AUC_(0-24 h))and from 0 to infinity(AUC_(0-∞))were presented larger,and both the peak concentration time(T_(max))and mean residence time(MRT)were prolonged for MPOPs,as compared with those of IRPs.PD results suggested that peak drug effect(E_(max))was lower and the equilibration rate constant(k_(e0))between the central compartment and the effect compartment was higher of MPOPs vs.those of IRPs.PKePD relationships demonstrated that the effectconcentration-time(ECT)course of MPOPs was clockwise hysteresis loop,and that of IRPs was counter-clockwise hysteresis loop.Collectively,those results demonstrated that MPOPs were potential formulations in treating angina pectoris induced by atherosclerosis.
基金Supported by China Post-doctoral Scientific Fund (20090450542)
文摘OBJECTIVE:To investigate the influence and mechanism of salvianolic acid B(SalB) on apoptosis inhibition in rat bone marrow-derived mesenchymal stem cells(BMSCs) induced by hypoxia and serum deprivation(hypoxia/SD).METHODS:SalB concentration of 0.1,1,10 or 100 mg/L(drug groups) were investigated for their ability to inhibit apoptosis in rat BMSCs.BMSCs in both the apoptosis model and drug groups were cultured under hypoxic conditions for 6 h,after which cell apoptosis and change in mitochondrial membrane potential(MMP) were detected using flow cytometry.Activation of caspase-3 was detected using western blot analysis.RESULTS:Hypoxia/SD induced apoptosis in rat BMSCs.The early apoptosis rate was lower in the drug groups compared to the apoptosis model group(P<0.05).SalB was found to inhibit the reduction in MMP and decrease the activation of caspase-3.CONCLUSION:0.1,1 and 10 mg/L of SalB inhibits activation of caspase-3 and early apoptosis of rat BMSCs induced by hypoxia/SD and could therefore enhance the survival rate of grafted stem cells.
