Naoxintong dose effects on inflammatory factor expression in the rat brain following focal cerebral ischemia

BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B （ kB）, interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia. DESIGN, TIME AND SETTING： The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIALS： A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320g, were selected. Naoxintong powder （mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis） was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608. METHODS： The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 g/kg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage All rats were administered by gavage at 5 and 23 hours following surgery, and subsequently, once per day. MAIN OUTCOME MEASURES： At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor- α, and complement 3 was examined by immunohistochemistry. RESULTS： A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as well as the high-dose, moderate-dose, and low-dose Naoxintong groups at 24 hours, which reached a peak at 48 hours. At 6, 24, 48, 72 hours, and 7 days, brain water content was greater in the ischemic hemisphere of rats from the saline, as well as the high-dose, moderate-dose, and low-dose Naoxintong groups, compared with the sham operation group （P 〈 0.05）. At 24 and 48 hours, brain water content was reduced in the high-dose and moderate-dose Naoxintong groups, compared to the saline and low-dose Naoxintong groups （P 〈 0.05）. In the saline, as well as high-dose, moderate-dose, and low-dose Naoxintong groups, neuronal edema was observed at 6 hours surrounding the ischemic sites. Inflammatory cells appeared at 24 hours, reached a peak at 48 hours, and gradually diminished. A small amount of glial cell proliferation and neuronal degeneration were observed in the hippocampus at 72 hours following infarction. Microglial proliferation and aggregation were detected at 7 days after infarction. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor-α, and complement 3 was significantly less in the high-dose, moderate-dose, and low-dose Naoxintong groups, compared to the sham operation group （P 〈 0.05）. Expression of the above-mentioned inflammatory cytokines was lower in rat brain tissues of the high-dose Naoxintong group, compared to the low-dose Naoxintong group （P 〈 0.05）. CONCLUSION： High-dose Naoxintong and moderate-dose Naoxintong significantly alleviated rat brain edema and decreased expression of nuclear factor-kB, interleukin-6, tumor necrosis factor-α, and complement 3 in brain tissues. The protective effect of high-dose Naoxintong was most significant.

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.

The Effects of Naoxintong Capsule on the Vascular Endothelial Function and Inflammatory Factors in Spontaneously Hypertensive Rats

Objective:To investigate the effects of Naoxintong(NXT)capsule on vascular endothelial function and inflammatory mechanism in spontaneously hypertensive rats.Methods:A total of 100 spontaneously hypertensive rats were divided into model group,positive control group,NXT low-dose group,NXT medium-dose group and NXT high-dose group.Rats in the model group were given an equal dose of normal saline once a day;the positive control group was given telmisartan 50 mg/(kg·d)once a day;the low,middle and high dose groups were given the NTX 0.5,1.0,2.0 mg/(kg·d)once a day,respectively.Rats in each group were continuously intragastrically administered for 12 weeks.The vascular endothelial function index,inflammation index and blood pressure of each group were observed at the end of 8 weeks.Results:Endothelin(ET),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)and systolic blood pressure levels were lower in the positive control group and NXT group compared with model group.In the model group,the NO level was lower than the positive control group and NXT group;the levels of ET,IL-6,TNF-α,CRP and systolic blood pressure in the middle-dose group and the high-dose group were lower than those in the positive control group and NXT low-dose group.Furthermore,the level of NO was higher in positive control group and NXT middle and high dose group compared with model group.The levels of ET,IL-6,TNF-α,CRP and systolic pressure in NXT high dose group were lower than in NXT middle dose group,while the level of NO was higher in NXT high group than in NXT middle dose group and the difference was statistically significant(p<0.05).Conclusions:NXT has obviously antihypertensive effect on spontaneously hypertensive rats,and its mechanism may be related to the improvement of vascular endothelial function and inflammatory factors.

Effect of adjuvant Naoxintong capsule therapy on nerve function and inflammatory stress response in patients in convalescence of cerebral infarction

Objective: To explore the effect of adjuvant Naoxintong capsule therapy on nerve function and inflammatory stress response in patients in convalescence of cerebral infarction. Methods:91 patients with cerebral infarction who were treated in our hospital between September 2015 and October 2017 were selected as the research subjects, and the medication during convalescence was reviewed and used to divide all patients into the control group (n=50) who received conventional western medicine treatment and the Naoxintong capsule group (n=41) who received western medicine combined with Naoxintong capsule treatment. The differences in serum levels of nerve function indexes, inflammatory mediators and oxidative stress indexes were compared between the two groups before convalescence medication (T1) and after 1 month of convalescence treatment (T2). Results: At T1, serum levels of nerve function indexes, inflammatory mediators and oxidative stress indexes were not significantly different between the two groups. At T2, serum nerve function indexes Copeptin and α-HBDH levels of Naoxintong capsule group were lower than those of control group whereas BDNF and IGF-1 levels were higher than those of control group;serum inflammatory mediators hs-CRP, YKL-40, IL-6 and IL-18 levels were lower than those of control group;serum oxidative stress index SOD level was higher than that of control group whereas 8-OHdG and MDA levels were lower than those of control group. Conclusion: Adjuvant Naoxintong capsule therapy can be further optimize the nerve function and relieve the inflammatory stress response in patients in convalescence of cerebral infarction.

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.

奥氮平联合脑心通胶囊治疗精神分裂症的效果及对血清α-突触核蛋白和褪黑素水平的作用

目的:探究奥氮平联合脑心通胶囊治疗精神分裂症的疗效及对血清α-突触核蛋白和褪黑素水平的影响。方法:选取2021年3月至2023年5月该院收治的精神分裂症患者124例,采用随机数字表法分为对照组和观察组,每组62例。对照组患者接受奥氮平治疗,观察组患者在对照组的基础上加用脑心通胶囊治疗,两组患者均连续治疗8周。比较两组患者的临床疗效、精神状态、生活质量、认知功能、糖代谢、血清α-突触核蛋白和褪黑素水平。结果:观察组患者的总有效率明显高于对照组[85.48%(53/62)vs.69.35%(43/62)],差异有统计学意义(P<0.05)。治疗后,观察组患者的阳性症状、阴性症状、精神病理表现以及阳性和阴性症状量表总分明显低于对照组,心理社会评分、症状和副作用评分、运动和精力评分低于对照组,神经心理状态量表评分明显高于对照组,差异均有统计学意义(P<0.05)。观察组患者治疗后的空腹血糖和餐后2 h血糖水平较对照组更低,α-突触核蛋白和褪黑素水平较对照组更高,差异均有统计学意义(P<0.05)。观察组、对照组患者的不良反应发生率分别为4.84%(3/62)、6.45%(4/62),差异无统计学意义(P>0.05)。结论:奥氮平联合脑心通胶囊治疗精神分裂症患者能显著提高疗效,恢复患者精神状态、生活质量、认知功能和糖代谢水平,提高血清α-突触核蛋白和褪黑素水平,且不良反应小。

1例脑心通胶囊致迟发性腹型过敏性紫癜用药分析

目的促进脑心通胶囊的临床合理应用。方法回顾性分析山东省千佛山医院收治的1例脑心通胶囊致迟发性腹型过敏性紫癜患者的治疗经过,结合世界卫生组织药品不良反应数据库及文献报道,采用诺氏评估量表判断用药与药品不良反应的相关性,并探讨其临床特点。结果患者使用脑心通胶囊后,出现阵发性腹痛伴消化道出血症状,后经甲泼尼龙片、地衣芽孢杆菌活菌胶囊、复方谷氨酰胺肠溶胶囊等对症治疗,患者皮疹明显改善,且未再出现腹痛、腹泻。患者出现严重的腹型过敏性紫癜与服用脑心通胶囊“很可能有关”(诺氏评估量表评分为6分)。结论脑心通胶囊可引起过敏性紫癜,但其药品说明书未予记载和警示。临床药师和医师应加强用药监护,同时建议药品生产厂家和广大医务工作人员应加强药物警戒,有关部门必要时修订药品说明书。

益气活血类方对心肌梗死恢复期病人心功能、中医证候的影响

目的:观察益气活血类方对心肌梗死恢复期病人心功能、中医证候的影响。方法:选取2021年5月—2022年12月首都医科大学附属北京中医医院及北京中医医院平谷医院门诊及住院治疗的心肌梗死恢复期病人144例作为研究对象,采用随机数字法将病人分为补阳还五颗粒组(31例)、脑心通胶囊组(49例)、养阴通脑颗粒组(31例)、对照组(33例)。补阳还五颗粒组给予标准化治疗+补阳还五颗粒+胶囊模拟剂,脑心通胶囊组给予标准化治疗+脑心通胶囊+颗粒模拟剂,养阴通脑颗粒组给予标准化治疗+养阴通脑颗粒+胶囊模拟剂,对照组给予标准化治疗+颗粒模拟剂+胶囊模拟剂。连续治疗3个月。比较各组左室射血分数(LVEF)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、N末端B型利钠肽原(NT-proBNP)水平、NT-proBNP变化率、中医证候积分及中医证候疗效。结果:治疗后,补阳还五颗粒组、脑心通胶囊组及养阴通脑颗粒组LVEF水平较治疗前升高,且优于对照组(P<0.05)。补阳还五颗粒组、脑心通胶囊组及养阴通脑颗粒组治疗前后LVEDD、LVESD水平比较差异无统计学意义(P>0.05)。治疗后,补阳还五颗粒组、脑心通胶囊组NT-proBNP水平均较治疗前下降(P<0.05)。以NT-proBNP下降30%为标准,补阳还五颗粒组NT-proBNP下降≥30%的病人较其他3组多(P<0.05)。治疗后,脑心通胶囊组及养阴通脑颗粒组胸痛积分均优于对照组(P<0.05);脑心通胶囊组出汗积分较治疗前下降(P<0.05);脑心通胶囊组面色紫暗积分及总分均优于对照组(P<0.05)。补阳还五颗粒能缓解病人神疲乏力的症状,脑心通胶囊能缓解病人胸闷、气短的症状且能更加全面地减轻病人临床症状。结论:补阳还五颗粒、脑心通胶囊、养阴通脑颗粒能够提高心肌梗死恢复期病人心功能水平,改善临床症状。

Effects of Naoxintong on atherosclerosis and inducible nitric oxide synthase expression in atherosclerotic rabbit

Background High levels of nitric oxide （NO） produced by inducible NO synthase （iNOS） have been associated with atherosclerosis processes. Naoxintong is a traditional Chinese medicine for treatment of cerebrovascular and cardiovascular disease. The aim of the present study was to detect and quantify changes of iNOS mRNA and NO levels in the vessel wall after the administration of Naoxintong in an atherosclerotic rabbit model. Methods Forty New Zealand white rabbits were randomly divided into five groups （n=8）. Rabbits were fed a standard diet （group A）, an atherogenic diet consisting of 79% standard feed＋l% cholesterol＋5% lard＋15% egg yolk powder （group B）, an atherogenic diet with Naoxintong 0.25 mg.kg^-l.d^-1 （group C）, an atherogenic diet with Naoxintong 0.5 mg.kg^-l.d^-1 （group D）, or atherogenic diet with Naoxintong 1.0mg.kg^-l.d^-1 （group E） for 12 weeks. Results Supplemented administration of Naoxintong led to a down-regulation of cholesterol （CHOL） （P 〈0.001） and low-density lipoprotein （LDL） （P 〈0.001）. The trend became more notable as the dose of Naoxintong increased; group C vs. group B （CHOL, P=0.568; LDL-cholesterol （LDL-C）, P=0.119）, group D vs. group B （CHOL, P=0.264; LDL-C, P=0.027）, group E vs. group B （CHOL, P=0.028; LDL-C, P=0.002）. Atherosclerotic lesions in aorta were reduced in Naoxintong groups （groups C, D, E） compared to group B. Group B had higher iNOS mRNA （P=0.001） and NO level （P 〈0.001） than group A. Compared with the atherogenic diet fed-rabbits, Naoxintong supplements decreased the expression of iNOS mRNA （P 〈0.001） and the NO level （P 〈0.001） in the vessel wall. Groups given a higher Naoxintong dose exhibited greater benefits, iNOS mRNA and NO levels seemed to be reduced in group C, although the difference did not quite reach statistical significance （iNOS mRNA, P=0.130; NO, P=0.038）. iNOS mRNA and NO levels significantly decreased in group D （iNOS mRNA, P=0.019; NO, P=0.018） and group E （iNOS mRNA, P=0.004; NO, P 〈0.001）. Conclusion Naoxintong has beneficial effects on atherosclerosis treatment by reducing expression of iNOS mRNA and the NO level in the vessel wall.

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.

Comparison of Aspirin and Naoxintong Capsule(脑心通胶囊)with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase

Objective： To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule（脑心通胶囊, NXT） and aspirin with adjusted-dose warfarin in Chinese elderly patients（over 65 years） with nonvalvular atrial fibrillation（NVAF） and genetic variants of vitamin K epoxide reductase（VKORC1）, who are at high-risk of thromboembolism. Methods： A total of 151 patients, with NVAF and AA genotype of VKORC1-1639（a sensitive genotype to warfarin） and a CHA2 DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin（100 mg/day） and NXT（1.6 g thrice a day） or adjusted-dose warfarin [international normalized ratio 2.0–3.0）. The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. Results： Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding（secondary event） in the combination therapy group was lower than that in the adjusted-dose warfarin group（0% vs. 7.9%, odds ratio： 0.921, 95% confidence interval： 0.862–0.984, P=0.028）. Conclusions： Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin.（No. ChiC TR-TRC-13003596）

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.

脑心通胶囊对缺血性脑卒中二级预防作用的meta分析

目的 系统评价脑心通胶囊对缺血性脑卒中二级预防作用。方法 选取中国生物医学文献数据库、中国知网、万方数据知识服务平台、维普网、PubMed、Cochrane Library、Embase、Web of Science核心合集数据库及Clinical Trials.gov关于脑心通胶囊对缺血性脑卒中二级预防的随机对照试验(对照组用西医常规治疗,试验组加用脑心通胶囊治疗),检索时间为建库至2023年7月。2名研究人员根据纳入及排除标准独立筛选文献,提取相关数据并进行质量评价,使用Rev Man 5.3软件进行meta分析。结果 本研究共纳入11篇文献,5 081例患者。meta分析结果显示,试验组脑卒中复发率[RR=0.59,95%CI(0.48,0.73),P<0.000 01]、纤维蛋白原[MD=-0.78,95%CI(-0.92,-0.65),P<0.000 01]、低密度脂蛋白胆固醇[MD=-0.14,95%CI(-0.23,-0.06),P=0.001]、不良反应发生率[RR=0.57,95%CI(0.40,0.81),P=0.002]均低于对照组。结论 脑心通胶囊联合常规药物治疗对缺血性脑卒中的二级预防有较好效果,且安全性较高,临床值得推广。

脑心通胶囊联合盐酸多奈哌齐治疗多发性梗死性痴呆的疗效和安全性

目的:探讨脑心通胶囊联合盐酸多奈哌齐治疗多发性梗死性痴呆(MID)的临床效果和安全性。方法:选取2020年7月至2022年6月海安市人民医院急诊科收治的MID患者85例,采用抽签法分为观察组(n=44)和对照组(n=41)。两组患者均给予生活干预和常规治疗措施,对照组患者采用盐酸多奈哌齐口服,观察组患者采用脑心通胶囊联合盐酸多奈哌齐口服。观察两组患者炎症和氧化应激、血液流变学、脑血流动力学和神经功能指标的变化,以及药品不良反应发生情况。结果:治疗8周后,观察组患者的可溶性细胞间黏附分子、白细胞介素18、丙二醛、全血高切黏度、全血低切黏度和纤维蛋白原水平明显低于对照组,超氧化物歧化酶水平、大脑中动脉峰值流速和平均血流速度明显高于对照组,差异均有统计学意义(P<0.05)。观察组患者的蒙特利尔认知评测量表和长谷川简易智能评定量表评分明显高于对照组,差异均有统计学意义(P<0.05)。观察组、对照组患者的不良反应发生率分别为9.09%(4/44)、7.32%(3/41),差异无统计学意义(P>0.05)。结论:在盐酸多奈哌齐的基础上加用脑心通胶囊,可减轻MID患者的炎症反应、氧化反应,改善血液流变学异常,提高脑血液灌注量,促进神经功能恢复,安全性高。

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.

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.

Naoxintong capsules(脑心通胶囊)modulates tumor necrosis factor-α-induced endothelial senescence through silent information regulator 1 signaling

OBJECTIVE:To investigate the protective effects of Naoxintong capsules(脑心通胶囊,NXT)on tumor necrosis factor-α(TNF-α)-induced senescence inendothelial cells and its mechanism.METHODS:Human umbilical vascular endothelial cells(HUVECs)were treated with TNF-α±NXT and assessed for silent information regulator 1(SIRT1)expression and signaling.Cells were stained with beta-galactosidase to assess the levels of cellular senescence.SIRT1 was silenced through siRNA transfection.RESULTS:TNF-αtreatment led to the downregulation of SIRT1,resulting in forkhead box O1(FoxO-1)acetylation,p53 acetylation and enhanced p21 expression.Following TNF-αtreatment,higher SAβ-Gal activity improved.TNF-αenhanced the migration of HUVECs and increased SIRT1 expression,both of which were attenuated by NXT treatment.The downstream targets of SIRT1 including FoxO-1/p53/p21 were also modulated,and HUVECs were protected from TNF-α-induced senescence.In contrast,the NXT-mediated protection was prevented by SIRT1 silencing.CONCLUSIONS:These findings suggest that sustained endothelial senescence can be induced by TNF-αstimulation via the SIRT1/FoxO-1/p53/p21 pathway.The protection of NXT against TNF-αwas partially mediated through its effects on SIRT1.This highlights the promise of NXT as a therapeutic for atherosclerosis.

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.

脑心通胶囊联合丁苯酞氯化钠注射液治疗轻中度脑梗死患者的效果

目的:观察脑心通胶囊联合丁苯酞氯化钠注射液治疗轻中度脑梗死患者的效果。方法:回顾性分析2021年1月至2023年11月该院收治的65例轻中度脑梗死患者的临床资料,按照治疗方法不同将其分为观察组32例和对照组33例。两组入院后均采用注射用阿替普酶进行静脉溶栓,在此基础上,对照组采用丁苯酞氯化钠注射液治疗,观察组在对照组基础上口服脑心通胶囊治疗。比较两组治疗前后神经功能[美国国立卫生院卒中量表(NIHSS)]评分、认知功能[蒙特利尔认知评估量表(MoCA)]评分、凝血指标[凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)]水平及不良反应发生率。结果:治疗后,观察组NIHSS评分、FIB水平均低于对照组,PT、APTT均大于对照组,MoCA评分均高于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:脑心通胶囊联合丁苯酞氯化钠注射液治疗轻中度脑梗死患者效果确切,可改善神经功能、认知功能及凝血功能,效果优于单用丁苯酞氯化钠注射液治疗。

脑心通胶囊联合多奈哌齐治疗老年血管性痴呆患者的效果

目的:观察脑心通胶囊联合多奈哌齐治疗老年血管性痴呆患者的效果。方法:选取2021年1—12月该院收治的100例老年血管性痴呆患者进行前瞻性研究,按照随机数字表法将其分为对照组和观察组各50例。对照组给予多奈哌齐治疗,观察组在对照组基础上联合脑心通胶囊治疗,比较两组治疗前后认知功能[蒙特利尔认知评估量表(MoCA)]评分、血液流变学指标(纤维蛋白原、血浆黏度、全血黏度、血细胞比容)水平、神经功能指标[同型半胱氨酸(Hcy)、神经元特异性烯醇化酶(NSE)、中枢神经特异性蛋白β(S100β)]水平及不良反应发生率。结果:治疗后,两组MoCA评分均高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05);两组纤维蛋白原、血浆黏度、全血黏度、血细胞比容水平均低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05);两组Hcy、NSE及S100β水平均低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:脑心通胶囊联合多奈哌齐治疗老年血管性痴呆患者,可提高其认知功能,改善血液流变学指标水平,提高神经功能,效果优于单纯多奈哌齐治疗。