Efficacy of Dual Antiplatelet Therapy Combined with Naoxintong Capsules(脑心通胶囊) Following Coronary Microembolization Induced by Homologous Microthrombi in Rats

Objective： To evaluate the efficacy of dual antiplatelet therapy combined with Naoxintong Capsule （脑心通胶囊, NXTC） in a rat model of coronary microembolization （CME）. Methods： A total of 95 rats were randomly divided into 6 groups： control, sham-operation, CME model, NXTC, dual antiplatelet （clopidogrel and aspirin） intervention （DA）, and NXTC combined with DA （NDA） groups. The complete data in 69 rats were obtained. The number of CME, myocardial apoptosis rate, bleeding time, clotting time, and adensosine diphosphate （ADP）-induced platelet aggregation were assessed. Results： Compared with the CME group, the number of CME and myocardial apoptosis rates were significantly decreased in the NXTC, DA, and NDA groups （P〈0.01）. Compared with other intervention groups, the number of CME and myocardial apoptosis rates were the least in the NDA group （P〈0.01）, and the incidence of surgical bleeding was the highest in the DA group （P〈0.01）. Compared with the CME group, ADP-induced maximum platelet aggregation rate was significantly inhibited in the NXTC, DA, and NDA groups （P〈0.01）, both bleeding time and clotting time were significantly increased in the NXTC, DA, and NDA groups （P〈0.01）, while the above parameters were the highest in the DA group （P〈0.05）. Conclusion： The combination therapy of NXTC and DA enhanced the anti-CME effect of either therapy alone and reduced the risk of the DA therapy-associated bleeding, demonstrating an improved benefit/ risk ratio in the rat model of CME.

Curative Effect of Naoxintong Capsule in Treating Senile Cerebral Arteriosclerosis

Objective： To observe the curative effect of Naoxintong capsule in treating senile cerebral arteriosclerosis. Methods：60 cases of senile cerebral arteriosclerosis were randomly divided into the contrast group and the treatment group with 30 cases each group. Same medicine was used in two groups. The treatment group was added with Naoxintong capsule. The cerebrovascular hemodynamics index （CVDI） of fight carotid was compared before and after therapy. Results： CVDI of the treatment group after therapy was significantly different from that before therapy （ P 〈 0.05 ～ 0.01 ）. Conclusion： Naoxintong capsule has certain curative effect in treating senile cerebral arteriosclerosis.

A review on function of the Naoxintong Capsule in anti atherosclerosis and protection of vascular endothelium

Atherosclerosis(As) is the common pathological basis of cardiovascular and cerebrovascular diseases, it starts with the injury of vascular endothelial. The Naoxintong Capsule, a modern patent traditional Chinese medicine, is composed of Huangqi, Danshen, Quanxie, Shuizhi and other sixteen herbs. It is extensively used to treat coronary heart disease, stroke and other cardiovascular and cerebrovascular diseases, with the activity of anti-coagulation, anti-inflammatory, protecting endothelial cells, anti-atherogenic and plaque stabilization.

Pharmacokinetic Comparison of Four Major Bio-Active Components of Naoxintong Capsule in Normal and Acute Blood Stasis Rats Using Ultra-Performance Liquid Chromatography Coupled with Triple-Quadrupole Mass Spectrometry

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.

Protective Effect of Naoxintong Capsule(脑心通胶嚢)Combined with Guhong Injection(谷红注射液)on Rat Brain Microvascular Endothelial Cells during Cerebral Ischemia-Reperfusion Injury

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.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke:A Multicenter,Randomized,and Placebo-Controlled Trial

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.

A Randomized Controlled Trial of Adjunctive Bunchang Naoxintong Capsule (步长脑心通胶囊) Versus Maintenance Dose Clopidogrel in Patients with CYP2C19*2 Polymorphism

Objective：To determine the impact of adjunctive Buchang Naoxintong Capsule（步心脑心通胶囊,NXT） on dual antiplatelet therapy in patients with cytochrome P450 2C19＊2（CYP2C19＊2） polymorphism undergoing percutaneous coronary intervention（PCI）.Methods：Ninety patients with CYP2C19＊2 polymorphism were enrolled,and their genotypes were confirmed by polymerase chain reaction（PCR）.The patients were randomly assigned to receive either adjunctive NXT（triple group,45 cases） or dual antiplatelet therapy（dual group,45 cases） using a computer-generated randomization sequence and sealed envelopes.Platelet function was assessed at baseline and 7 days after treatment with conventional aggregometry.Subsequent major adverse cardiovascular events（MACE,including sudden cardiac arrest and acute coronary syndrome） were recorded during a 12-month followup.Results：Baseline platelet function measurements were similar in both groups.After 7 days,percent inhibitions of maximum platelet aggregation and late platelet aggregation were significantly greater in the triple versus dual group（42.3%±16.0%vs.20.8%±15.2%,P〈0.01,and 54.7%±18.3%vs.21.5%±29.2%,P〈0.01,respectively）.During the 12-month follow-up,the rate of subsequent MACE（6/45） was significantly lower in the triple group compared with the dual group（14/45;P〈0.05）.Conclusion：Adjunctive NXT to maintenance dose clopidogrel（75 g） could enhance the antiplatelet effect and decrease subsequent MACE in patients with the CYP2C19＇2polymorphism undergoing PCI.