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 expressi...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.展开更多
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 th...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.展开更多
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 endot...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.展开更多
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...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.展开更多
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 infarct...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.展开更多
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 medic...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.展开更多
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 cerebrovascul...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.展开更多
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 ...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.展开更多
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 a...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）展开更多
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 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
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 percutaneou...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.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
Background:Depression is a common clinical phenomenon in the patients with heart failure(HF).In traditional Chinese medicine(TCM),diseases in the brain and heart are thought to be correlated and interact.Naoxintong ca...Background:Depression is a common clinical phenomenon in the patients with heart failure(HF).In traditional Chinese medicine(TCM),diseases in the brain and heart are thought to be correlated and interact.Naoxintong capsules(NXT)has been used for treating cardio-cerebrovascular diseases,while its therapeutic effect on depression after HF remains unclear.Objective:The aim of the study is to evaluate the intervention effect of NXT on depression after HF.Methods:Sprague-Dawley rats were assigned into the following 5 groups:sham,model,NXT(250,1000 mg/kg),and valsartan(8mg/kg).Coronary artery occlusion was performed to induce HF and subsequent depression in rats.The cardiac function was evaluated by echocardiography,hematoxylin-eosin staining,and Masson trichrome staining.The sucrose preference test and Morris water maze test were carried out to assess the depressive behaviors in rats.The ultrastructure of hippocampal CA1 neurons was observed and the levels of corticotropin-releasing hormone in the hypothalamus,brain-derived neurotrophic factor in the cortex,and adrenocorticotropic hormone(ACTH)in the plasma were determined by enzyme-linked immunosorbent assay.The levels of dopamine,5-hydroxytryptamine,norepinephrine,andγ-aminobutyric acid in the hippocampus were measured by UPLC-QQQ-MS.Results:NXT reduced myocardial injury and pathological changes in the cardiac tissue and increased the left ventricular ejection fraction,left ventricular fractional shortening,and cardiac output.NXT increased the sugar preference rate and number of crossings and shortened the escape latency.Furthermore,the NXT treatment restored the levels of corticotropin-releasing hormone,adrenocorticotropic hormone,brain-derived neurotrophic factor,dopamine,andγ-aminobutyric acid to the baseline values.Conclusions:NXT not only demonstrates cardioprotective effect but also attenuates depression in the rats after HF.It may exert the antidepressant effect by inhibiting the hyperactivity of the hypothalamic-pituitary-adrenal axis and recovering the levels of neurotrophic factors and neurotransmitters.展开更多
Naoxintong Capsule（脑心通胶囊,NXTC）is derived from the classic formula Buyang Huanwu Decoction（补阳还五汤）by WANG Qing-ren of the Qing Dynasty.Based on the concept of＂concurrent treatment on Nao（Brain）and Xin（...Naoxintong Capsule（脑心通胶囊,NXTC）is derived from the classic formula Buyang Huanwu Decoction（补阳还五汤）by WANG Qing-ren of the Qing Dynasty.Based on the concept of＂concurrent treatment on Nao（Brain）and Xin（Heart）＂（Nao Xin Tong Zhi）proposed by Prof.ZHAO Bu-chang,activating blood circulation and dredging collaterals herbs were supplemented to the classic formula.NXTC is composed of Astragalus membranaceus（Fisch.）Bge.展开更多
基金Supported by: the Scientific Technology Research and Development Plan of Hebei Province, No. 06276103Dthe Natural Science Foundation of Hebei Province, No. C2006000915
文摘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.
文摘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.
基金Supported by grants from the National Natural Science Foundation of China(NSFC)81700405(a Study of FOXCUT/FOXC1 on Promoting the Occurrence and Development of Degenerative Aortic Stenosis via BMPER)。
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by the Grants of Fujian Province Health Education Union Scientific,Ministry of Health of the People's Republic of China(WKJ 2008-2-59)
文摘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.
基金Supported by the Ministry of Health of the People's Republic of China of Fujian Province Health Education Union Scientific(No.WKJ 2008-2-59)Provincial Natural Science Foundation of Fujian(No.2011J0133)National Natural Science Foundation of China(No.81373838)
文摘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）
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 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.
基金Supported by the Provincial Natural Science Foundation of Fujian(No.2011J0133)the National Natural Science Foundation of China(No.81373838)
文摘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.
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 Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021B017-07,CI2021A05208,CI2021A04202)National Natural Science Foundation of China(No.81973711).
文摘Background:Depression is a common clinical phenomenon in the patients with heart failure(HF).In traditional Chinese medicine(TCM),diseases in the brain and heart are thought to be correlated and interact.Naoxintong capsules(NXT)has been used for treating cardio-cerebrovascular diseases,while its therapeutic effect on depression after HF remains unclear.Objective:The aim of the study is to evaluate the intervention effect of NXT on depression after HF.Methods:Sprague-Dawley rats were assigned into the following 5 groups:sham,model,NXT(250,1000 mg/kg),and valsartan(8mg/kg).Coronary artery occlusion was performed to induce HF and subsequent depression in rats.The cardiac function was evaluated by echocardiography,hematoxylin-eosin staining,and Masson trichrome staining.The sucrose preference test and Morris water maze test were carried out to assess the depressive behaviors in rats.The ultrastructure of hippocampal CA1 neurons was observed and the levels of corticotropin-releasing hormone in the hypothalamus,brain-derived neurotrophic factor in the cortex,and adrenocorticotropic hormone(ACTH)in the plasma were determined by enzyme-linked immunosorbent assay.The levels of dopamine,5-hydroxytryptamine,norepinephrine,andγ-aminobutyric acid in the hippocampus were measured by UPLC-QQQ-MS.Results:NXT reduced myocardial injury and pathological changes in the cardiac tissue and increased the left ventricular ejection fraction,left ventricular fractional shortening,and cardiac output.NXT increased the sugar preference rate and number of crossings and shortened the escape latency.Furthermore,the NXT treatment restored the levels of corticotropin-releasing hormone,adrenocorticotropic hormone,brain-derived neurotrophic factor,dopamine,andγ-aminobutyric acid to the baseline values.Conclusions:NXT not only demonstrates cardioprotective effect but also attenuates depression in the rats after HF.It may exert the antidepressant effect by inhibiting the hyperactivity of the hypothalamic-pituitary-adrenal axis and recovering the levels of neurotrophic factors and neurotransmitters.
文摘Naoxintong Capsule（脑心通胶囊,NXTC）is derived from the classic formula Buyang Huanwu Decoction（补阳还五汤）by WANG Qing-ren of the Qing Dynasty.Based on the concept of＂concurrent treatment on Nao（Brain）and Xin（Heart）＂（Nao Xin Tong Zhi）proposed by Prof.ZHAO Bu-chang,activating blood circulation and dredging collaterals herbs were supplemented to the classic formula.NXTC is composed of Astragalus membranaceus（Fisch.）Bge.
