Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divid...Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divided into 6 groups:control group,oxygen and glucose deprivation(OGD)group,nimodipine group(9.375 mg/kg),NXTC group(0.5 g/kg),GHI group(5 mL/kg)and NXTC+GHI group(0.5 g/kg NXTC+5 mL/kg GHI),after the onset of reperfusion and once per day for the following 7 days.Blood was collected 1 h after final administration,and the sera were collected.Cultured primary rat brain microvascular endothelial cells(rBMECs)were subjected to OGD to establish a cell injury model.Untreated rBMECs were used as blank control.The cell counting kit-8 assay was used to assess cell viability using the sera.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels were assessed using an enzyme-linked immunosorbent assay.Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry.JC-1 staining was performed to assess changes in mitochondrial membrane potential.Results:Statistical analysis indicated that more than 95%of the cells were rBMECs.Compared with the OGD group,the cellular morphology of the all drug delivery groups improved.In particular,the combined drug group had the most significant effect.Compared with the OGD group,all drug intervention groups induced a decrease in the apoptotic rate of rBMECs,increased the SOD levels,and decreased the MDA levels(all P<0.01).Compared with the mono-therapy groups,the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs(P<0.01).All drug intervention groups showed different degrees of increase in membrane potential,and the NXTC+GHI group was higher than the NXTC or GHI group(P<0.01).Conclusion:The combinationa application of NXTC and GHI on cerebral l/R injury clearly resulted in protective benefits.展开更多
Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline ...Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice;during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix Win Nonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in C_(max) of ferulic acid and formononetin, AUC_(all) of caffeic acid and ferulic acid, and AUC_(INF_obs) of ferulic acid. Conversely, an increase in the Vz_F_obs and MRT_(last) of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.展开更多
Objective:To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding.Methods:A total of 23 Chinese...Objective:To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding.Methods:A total of 23 Chinese medical centers participated in this trial.Adult patients with a history of ischemic stroke were randomlyassigned ina 1:1ratiousing a blockdesign toreceive eitherNaoxintong Capsule(1.2gorally,twice a day)or placebo in addition to standard care.The primary endpoint was recurrence of ischemic stroke within 2 years.Secondary outcomes included myocardial infarction,death due to recurrent ischemic stroke,and all-cause mortality.The safety of drugs was monitored.Results were analyzed using the intention-to-treat principle.展开更多
基金the National Natural Science Foundation of China(No.81630105,81973560)Zhejiang Provincial Natural Science Foundation of China(Nos.LZ17H270001,LZ18H270001)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents。
文摘Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divided into 6 groups:control group,oxygen and glucose deprivation(OGD)group,nimodipine group(9.375 mg/kg),NXTC group(0.5 g/kg),GHI group(5 mL/kg)and NXTC+GHI group(0.5 g/kg NXTC+5 mL/kg GHI),after the onset of reperfusion and once per day for the following 7 days.Blood was collected 1 h after final administration,and the sera were collected.Cultured primary rat brain microvascular endothelial cells(rBMECs)were subjected to OGD to establish a cell injury model.Untreated rBMECs were used as blank control.The cell counting kit-8 assay was used to assess cell viability using the sera.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels were assessed using an enzyme-linked immunosorbent assay.Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry.JC-1 staining was performed to assess changes in mitochondrial membrane potential.Results:Statistical analysis indicated that more than 95%of the cells were rBMECs.Compared with the OGD group,the cellular morphology of the all drug delivery groups improved.In particular,the combined drug group had the most significant effect.Compared with the OGD group,all drug intervention groups induced a decrease in the apoptotic rate of rBMECs,increased the SOD levels,and decreased the MDA levels(all P<0.01).Compared with the mono-therapy groups,the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs(P<0.01).All drug intervention groups showed different degrees of increase in membrane potential,and the NXTC+GHI group was higher than the NXTC or GHI group(P<0.01).Conclusion:The combinationa application of NXTC and GHI on cerebral l/R injury clearly resulted in protective benefits.
基金supported by the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” 2015ZX09501004-001-007National Natural Science Foundation of China 82004082Top talent training project of TCM in Henan Province。
文摘Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice;during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix Win Nonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in C_(max) of ferulic acid and formononetin, AUC_(all) of caffeic acid and ferulic acid, and AUC_(INF_obs) of ferulic acid. Conversely, an increase in the Vz_F_obs and MRT_(last) of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.
基金Supported by the Shanghai Municipal Commission of Science and Technology,China(No.STCSM 14401970300)。
文摘Objective:To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding.Methods:A total of 23 Chinese medical centers participated in this trial.Adult patients with a history of ischemic stroke were randomlyassigned ina 1:1ratiousing a blockdesign toreceive eitherNaoxintong Capsule(1.2gorally,twice a day)or placebo in addition to standard care.The primary endpoint was recurrence of ischemic stroke within 2 years.Secondary outcomes included myocardial infarction,death due to recurrent ischemic stroke,and all-cause mortality.The safety of drugs was monitored.Results were analyzed using the intention-to-treat principle.
