Tongqiao Huoxue Decoction combined with butylphthalide in the treatment of acute ischemic stroke and its effect on VEGF

Objective:To study the effect of Tongqiao Huoxue Decoction combined with butylphthalide soft capsules on acute ischemic stroke and its effect on serum vascular endothelial growth factor(VEGF).Methods:There are 76 patients with acute ischemic stroke(Acute Ischemic Stroke,AIS),including 38 cases in the control group and the observation group.All patients were treated with conventional treatment methods for this disease.On this basis,the control group was given butylphthalide soft capsules orally,0.2g/time,3 times a day,and the observation group was given Tongqiaohuoxue Decoction on the basis of oral butylphthalide soft capsules.One dose a day,two times in the morning and evening.All patients were treated for 20 days as a course of treatment.The clinical efficacy of the two groups of patients were compared,the collateral circulation rate before and after treatment,NIHSS,MoCA and MMSE,hemorheology(plasma viscosity,fibrinogen,whole blood high and low shear viscosity),VEGF levels and the occurrence of adverse reactions.Results:The effective rate of the two groups was 92.1%in the observation group and 73.7%in the control group,which was significantly different(P<0.05).The collateral circulation patency rate was 86.8%in the observation group and 57.9%in the control group,which was significantly different(P<0.05).After treatment,the MoCA,MMSE scores and VEGF levels of the observation group were significantly higher than those before the treatment and the control group,with significant differences(P<0.05).The NIHSS score and hemorheology were improved compared with those before the treatment and the control group.There are significant differences(P<0.05).Conclusion:Tongqiao Huoxue Decoction combined with butylphthalide soft capsules can significantly improve collateral circulation,hemorheology,neurological and cognitive functions in patients with acute ischemic stroke.The mechanism may be related to the increase of VEGF levels and the promotion of neovascularization.

Effect of Butylphthalide combined with Urinary Kallidinogenase on the pathological course of nerve damage in patients with massive cerebral infarction

Objective: To study the effect of Butylphthalide combined with Urinary Kallidinogenase on the pathological course of nerve damage in patients with massive cerebral infarction. Methods:The patients with massive cerebral infarction who received treatment in our hospital between January 2016 and December 2017 were selected and randomly divided into the group A receiving Butylphthalide treatment, the group B receiving Urinary Kallidinogenase treatment and the group C receiving Butylphthalide combined with Urinary Kallidinogenase treatment on the basis of conventional treatment. 14 d after treatment, serum levels of nerve markers, coagulation indexes, growth factors and oxidative stress indexes were determined. Results:After treatment, visinin-like protein-1 (VILIP-1), neuron-specific enolase (NSE), S100B protein (S100B), thromboxane A2 (TXA2), lysophosphatidic acid (LPA), D-dimer (D-D), 8-isoprostanes F2α (8-iso-PGF2α) and malondialdehyde (MDA) levels of 3 groups significantly decreased whereas nitric oxide (NO), nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels significantly increased, and VILIP-1, NSE, S100B, TXA2, LPA, D-D, 8-iso-PGF2α and MDA levels of the group C after treatment were significantly lower than those of the group A and group B whereas NO, NOS, VEGF, BDNF, IGF-I, SOD and T-AOC levels were significantly higher than those of the group A and group B. Conclusion: Butylphthalide combined with Urinary Kallidinogenase is better than monotherapy in improving the pathological course of nerve damage in patients with massive cerebral infarction.

Effect of butylphthalide soft capsule on the anti-inflammatory effect and plaque stability in patients with ischemic cerebrovascular disease and carotid atherosclerosis

Objective:To explore the effect of butylphthalide soft capsule on the serum hs-CRP, MMP-9, and TNF-α in patients with ischemic cerebrovascular disease in order to evaluate the the therapeutic effect in the treatment of carotid atherosclerosis.Methods:According to the carotid ultrasound results, the patients were divided into the stable plaque group (control group) and the vulnerable plaque group. The patients in the vulnerable plaque group were randomized into the intervention 1 group and intervention 2 group. The patients in the two subgroups were given bayaspirin and atorvastatin. On this basis, the patients in the intervention 1 group were given butylphthalide soft capsules. The serum hs-CRP, MMP-9, and TNF-αbefore treatment and 6 months after treatment in each group were detected. The color Doppler ultrasound was used to measure and evaluate IMT, Crouse score, and plaque echo change. Results: The serum hs-CRP, MMP-9, and TNF-α levels before treatment between the two subgroups were significantly higher than those in the control group, but the comparison between intervention 1 group and intervention 2 group was not statistically significant. The serum hs-CRP, MMP-9, and TNF-α levels 6 months after treatment in the two subgroups were significantly reduced when compared with before treatment. The serum hs-CRP, MMP-9, and TNF-α levels after treatment in the intervention 1 group were significantly lower than those in the intervention 2 group. IMT 6 months after treatment in the two subgroups was significantly reduced when compared with before treatment. The reduced degree of IMT after treatment in the intervention 1 group was significantly greater than that in the intervention 2 group. Crouse score after treatment in the two subgroups was significantly reduced when compared with before treatment, but the comparison between the two groups was not statistically significant. The unstable plaque number after treatment in the two subgroups was significantly reduced when compared with before treatment. The unstable plaque number after treatment in the intervention 1 group was significantly lower than that in the intervention 2 group.Conclusions:Butylphthalide soft capsule can resist the inflammation, reverse the prolieration of carotid intima, stabilize the vulnerable plaque, and remove the non-atherosclerotic plaque.

THE STUDY ON IN VITRO METABOLISM OF BUTYLPHTHALIDE BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY

The in vitro metabolism o. butylphthalide (HBP) by rat liver microsomes was studied in this paper. Capillary GC/MS and BSTFA/1%TMCS derivatization were used for the separation and structure identification of the six metabolites. 3-Hydroxylation and r-hydroxylation have been proved to be the main metabolism pathways of HBP by rat liver microsomes.

Effect of dl-3-n-butylphthalide on infarction volume in animal models of ischemic stroke:A meta-analysis

BACKGROUND Ischemic stroke is a frequently-occurring disease in the elderly and characterized by high morbidity and mortality.Dl-3-n-butylphthalide(NBP),a synthetic compound based on natural celery seeds,has potential therapeutic effects on cerebral ischemia,brain trauma,memory impairment,and epilepsy.AIM To evaluated the effect of NBP on infarct volume in experimental ischemic stroke.METHODS Twenty one relevant literatures were included from the PubMed,EMBASE,Web of Science,Chinese National Knowledge Infrastructure,VIP information database,and Wanfang database,and data on the effect of dl-3-n-butylphthalide on infarction volume in the middle cerebral artery occlusion model were extracted.Statistical analysis was performed using standard mean difference with random effects model of Revman 5.3.RESULTS The data of meta-analysis of the 21 studies had suggested that NBP reduced the cerebral infarction volume of middle cerebral artery occlusion model animals compared to the control group significantly[SMD:-3.97,95%CI:-4.71 to-3.23,P<0.01;heterogeneity:χ2=59.09,df=20(P<0.01);I2=66%].CONCLUSION NBP was effective in experimental ischemic stroke.

To investigate the effects of butylphthalide on reducing neuronal apoptosis in rats with cerebral infarction by inhibiting the JNK/P38 MAPK signaling pathway

Objective:To investigate the effects of butylphthalide on reducing neuronal apoptosis in rats with cerebral infarction by inhibiting the JNK/P38 MAPK signaling pathway.Methods:Forty-eight SD male rats were divided into DZ group(control group),CI group(model group)and NBP group(butylphthalide group).Rats in CI group and NBP group were used to establish cerebral infarction models.NBP group used NBP.The solution(80 mg/(kg?d))was administered orally,and the remaining two groups were administered with the same volume of peanut oil.After 14 consecutive days of treatment,the Zea Longa score was used to evaluate the neurological function of DZ,CI and NBP rats.Scoring,TTC staining was used to observe the cerebral infarction volume of rats in DZ group,CI group and NBP group,HE staining was used to observe the pathological morphology of brain tissue in DZ group,CI group and NBP group.Neuronal apoptosis,Western blot was used to detect the expression of p-JNK and p-p38MAPK in brain tissues of DZ group,CI group and NBP group.Results:The neurological function of the rats in the CI group was higher than that in the DZ group,and the difference was statistically significant(P<0.05).The neurological function score of the rats in the NBP group was reduced compared with the CI group,and the difference was statistically significant(P<0.05).The cerebral infarction volume in the group was 35.56%higher than that in the DZ group,and the difference was statistically significant(P<0.05).The minor infarct volume in the NBP group was 21.59%,which was less than that in the CI group,and the difference was statistically significant(P<0.05).Nerve cells are neatly sorted,with a large number.The gap between blood vessels and interstitial tissue in the CI group is enlarged,the cells are severely contracted,and the neuron structure is incomplete.Compared with the CI group,the NBP group has reduced neuron contraction and increased number;The dead nerve cells were brown.The apoptosis rate of nerve cells in the CI group was 79.65%higher than that in the DZ group was 5.82%.The difference was statistically significant(P<0.05).The nerve cell apoptosis rate in the NBP group was 30.23%.Compared with CI group,the difference was statistically significant(P<0.05);Western blot results showed that p-JNK and p-p38MAPK protein expression in CI group was higher than that in DZ group,and the difference was statistically significant(P<0.05).The levels of p-JNK and p-p38MAPK proteins in the NBP group were lower than those in the CI group.There was statistically significant(P<0.05).Conclusion:Butylphthalide can improve neurological damage,reduce apoptotic nerve cells,and reduce infarct volume in rats with cerebral infarction,which is related to the inhibition of JNK/P38 MAPK pathway expression.

Effect of Ginkgo Biloba extract combined with butylphthalide on serum biochemical indexes of patients with mild to moderate Alzheimer's disease

Objective: To study the effect of Ginkgo Biloba extract combined with butylphthalide on serum biochemical indexes of patients with mild to moderate Alzheimer's disease. Methods:The patients who were diagnosed with mild to moderate Alzheimer's disease for the first time in Weinan Central Hospital between March 2015 and December 2017 were selected as the research subjects and randomly divided into two groups, observation group received Donepezil Hydrochloride Tablets + Ginkgo Biloba Extract Tablets + Butylphthalide Soft Capsules treatment, and control group received Donepezil Hydrochloride Tablets treatment. The serum levels of metabolites, cytokines, oxidative stress mediators and other biochemical indicators were measured before treatment and 3 months after treatment. Results: 3 months after treatment, serum Hcy, IL-1β, TNF-α, HMGB1, MCP-1, MDA and Tau levels of both groups of patients were significantly lower than those before treatment whereas UA, VitB12, FA, VEGF, BDNF, GPX3, CAT and SOD levels were significantly higher than those before treatment, and serum Hcy, IL-1β, TNF-α, HMGB1, MCP-1, MDA and Tau levels of observation group after treatment were significantly lower than those of control group whereas UA, VitB12, FA, VEGF, BDNF, GPX3, CAT and SOD levels were significantly higher than those of control group. Conclusion: Ginkgo Biloba extract combined with butylphthalide treatment of mild to moderate Alzheimer's disease can significantly improve the substance metabolism and reduce the inflammatory stress response.

Effect of butylphthalide injection on inflammatory factors, neurological factors and hemorheology in patients with acute cerebral infarction

Objective: To investigate the effects of butylphthalide injection on inflammatory factors, neurological factors and hemorheology in patients with acute cerebral infarction. Methods:The patients in the observation group were treated with intravenous infusion of butyphthalide on the basis of the control group, 120 cases of acute cerebral infarction patients are randomly divided into control group (n=60) and observation group (n=60), patients in the control group were given conventional thraphy, on the basis of the thraphy of the control group, the observation group were treated with intravenous infusion of butyphthalide. Both groups were given sustainable treatment for 14 d, the levels of inflammatory factors, neurological factors and hemorheologywere compared before and after the treatment. Results: The levels of serum hs-CRP, TNF-α, NSE, MBP, S100B, whole blood viscosity, plasma specific viscosity, hematocrit and platelet aggregation rate in the two groups before treatment were no significant difference. After treatment, the levels of hs-CRP, TNF-α in the observation group and observation group were (4.98±1.14) mg/L, (5.54±1.29) ng/L and (7.54±0.93) mg/L, (8.32±1.31) ng/L, which were significantly lower than those in the same group before treatment, and the level of hs-CRP, TNF-α in the observation group were significantly lower than those in the control group;the levels of NSE, MBP, S100B in the observation group and observation group were (6.38±2.39) μg/L, (10.19±3.28) μg/L, (0.96±0.09) ng/L and (11.73±2.43) μg/L, (17.43±4.51) μg/L, (1.65±0.12) ng/L, which were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of whole blood viscosity, plasma specific viscosity, hematocrit and platelet aggregation rate in the observation group and observation group were(5.17±0.89) mPa?s,(1.32±0.22) mPa?s, (0.35±0.13)%, (0.32±0.08)% and (5.68±0.91) mPa?s, (1.63±0.24) mPa?s, (0.41±0.14)%, (0.40±0.11)%, which were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group. Conclusion: On the basis of conventional treatment, the addition of butyphthalide can effectively reduce the level of serum inflammatory factors, promote the repair of nerve function, improve the level of hemorheology, which has important clinical value.

Clinical Efficacy and Safety of Joint Butylphthalide and Human Albumin Treatment of PTCI

Objective:To observe the clinical efficacy and safety of butylphthalide joint human albumin in the treatment of the progress of type in acute cerebral infarction(PTCI).Methods:120 patients with PTCI in Department of Neurology of Shuyang People's Hospital were used to observe the efficacy.These patients were all treated by routine medicine including anti-platelet,statins,edaravone,ginkgo leaf extract and dipyridamole after admission.According to whether used butylphthalide and(or)human albumin in the treatment of PTCI,the patients were divided into A group 30 cases,B group 45 cases,and C group 45 cases.Patients of group C were given conventional treatment.Group B were given conventional treatment and human albumin injection(5 g,ivgtt,qd,3 days in a course);Group A were treated with butylphthalide(first,with butylphthalide and sodium chloride injection 100 ml,ivgtt,for 7 d,then with butylphthalide soft capsules 0.2 g,tid,for 21 d),human albumin(5 g,ivgtt,qd,for 3 d)and routine medicine.The change of NIHSS score,Barthel Index,and mRS of three groups respectively during progress,1 week,2 weeks and 90 days after progress were observed and analyzed.Results:NIHSS score,Barthel Index,and mRS of group A,group B and group C all showed no statistically significant(all p>0.05)on 1 week after treatment;NIHSS score and mRS of group A were both lower than group B and group C on 2 weeks and 90 days after treatment,and both of them showed statistically significant(p<0.05);Barthel Index of group A was higher than group B and group C on 90 days after treatment,it showed statistically significant(p<0.05);The total effective rate of group A(96.7%)>group B(88.9%)>group C(77.8%),showed statistically significant(p<0.05).Conclusions:Butylphthalide joint human albumin treatment of PTCI has good therapeutic effect and safety,it is useful to clinical promotion and further research.

dl-3-n-butylphthalide reduces brain damage in mice with closed head injury

To investigate the protective effect of dl 3 n butylphthalide (NBP) as an anti cerebral ischemic drug on brain damage 24?h after closed head injury in mice Methods Closed head injury was induced by dropping a 50 g weight from a height of 18?cm on a metal impounder resting on the parietal bone in mice Results The neurotraumatic model induced impair^ment of memory function, significant cerebral edema, and disruption of the blood brain barrier dl 3 n butylphthalide (50?mg·kg 1 ) given intraperitoneally 5 minutes and 60 minutes after the onset of closed head injury was found to attenuate the impairment of memory function ( P <0 05), alleviate brain edema in the injured cerebral cortex ( P <0 05), and reduce extravasation of plasma protein bound to Evans blue dye by 63 5% ( P <0 01) NBP was also shown to increase the activity of choline acetyltransferase in the injured cortex to 0 83±0 21?ng·min 1 ·mg 1 ( P <0 01, compared with 0 48±0 14?ng·min 1 ·mg 1 of vehicle group) Conclusion NBP provides therapeutic response in experimental closed head injury

Effects of Ateplase combined with routine therapy on antioxidant capacity, coagulation function and related factors in patients with cerebral infarction

Objective:To investigate the effects of Ateprase combined with Butylphthalide on antioxidant capacity, coagulation function and related factors in patients with cerebral infarction.Methods:A total of 80 patients with cerebral infarction who were treated in department of Neurology of our hospital from June 2015 to June 2018 were randomly divided into control group and observation group, with 40 cases in each group. Patients in the control group were treated with Butylphthalidel, while patients in the observation group were treated with Ateprase combined with Butylphthalide. The levels of superoxide dismutase (SOD), serum malondialdehyde (MDA), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), vascular endothelial growth factor (VEGF), nitric oxide (NO), endothelin (ET-1), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured and compared before and after treatment.Results: After treatment: the levels of SOD, APTT, PT, TT, VEGF and NO in the serum of the control group and the observation group were significantly increased (P<0.05), and the levels of MDA, FIB, TNF- , CRP and ET-1 were significantly decreased (P<0.05);the trend of the above indicators was significantly higher than that of the control group (P<0.05).Conclusions: Ateplase combined with Butylphthalide in the treatment of cerebral infarction can significantly enhance the antioxidant capacity, improve blood coagulation and endothelial function, alleviate inflammation, and it has a good clinical effect.