Butylphthalide Research Articles

Therapeutic effectiveness of Donepezil hydrochloride in combination with butylphthalide for post-stroke cognitive impairment.

To study the therapeutic effectiveness of donepezil hydrochloride (DPZ) in combination with butylphthalide (BP) for the treatment of post-stroke cognitive impairment (PSCI). In this retrospective study, the clinical data of 125 PSCI patients treated at the First Affiliated Hospital of Harbin Medical University from December 2019 to December 2023 were collected and analyzed. The patients were grouped into a joint group (n=75, receiving DPZ + BP) and a control group (n=50, receiving DPZ alone) according to their treatment regimen. Inter-group comparisons were then carried out from the perspectives of therapeutic effectiveness, safety (constipation, abdominal distension and pain, and gastrointestinal reactions), cognitive function (Montreal Cognitive Assessment Scale [MoCA], Chinese Stroke Scale [CSS]), Activities of Daily Living Scale (ADL), and serum biochemical indexes (neuron-specific enolase [NSE], high-sensitivity C-reactive protein [hs-CRP], nitric oxide [NO], and malondialdehyde [MDA]). In addition, a univariate analysis was carried out to identify factors affecting therapeutic effectiveness in PSCI patients. The joint group showed significantly better therapeutic effectiveness compared to the control group (P<0.05). There was a significant correlation between the type of stroke, treatment method, and therapeutic effectiveness in PSCI patients (P<0.05). There was no significant difference in the total incidence of adverse reactions (P>0.05). After the treatment, compared to the control group, the joint group demonstrated significant improvements in MoCA and ADL scores (all P<0.05) and reductions in CSS scores and levels of NSE, hs-CRP, NO, and MDA (all P<0.05). DPZ in combination with BP is highly effective for the treatment of PSCI. It positively affects cognitive function and ADL, alleviates neurological deficits, and reduces abnormal serum biochemical indices without increasing the risk of adverse reaction.

Danggui Shaoyao San: Chemical characterization and inhibition of oxidative stress and inflammation to treat CCl4-induced hepatic fibrosis

Ethnopharmacological relevanceDanggui Shaoyao San (DSS) has effective in treating hepatic ascites and liver disease. Aim of the studyTo explore the chemical characterization of DSS and protective effect on CCl4-induced hepatic fibrosis and its mechanism, especially its anti-oxidative stress and anti-inflammation. Materials and methodsThe chemical characterization of DSS was determined by HPLC-Q-Exactive Orbitrap MS. And the antioxidant activity of DSS in vitro was determined. The hepatic fibrosis model was established using intragastric administration of 40% CCl4/soybean oil (v/v) twice weekly for 13 weeks. From 6th week, the DSS group and the positive control group were given DSS (2, 4, 8 g/kg/d) and silymarin (50 mg/kg/d), respectively. The livers of rats were examined histologically by H&E. The ALT, AST, ALB and TBIL were determined, and hepatic fibrosis markers (HA, LN, CIV, PIIINP), oxidative stress (SOD, MDA, GST, GSH) and inflammatory factor (IL-6, TNF-α) were tested using ELISA kits. In addition, the levels of TAC, TOS, LOOH and AOPP in the liver were also determined. ResultsThe chemical characterization of DSS was determined by HPLC-Q-Exactive Orbitrap MS. The results show that DSS mainly includes triterpenoids, monoterpenes, phenols, sesquiterpenes, butyl phthalide, etc., and DSS has good antioxidant activity in vitro. In addition, the ALT, AST and TBIL of rats were remarkably reduced after treatment with DSS at three doses. Liver histopathological analysis showed that DSS alleviated the inflammatory infiltration, hepatocyte swelling, necrosis and hepatic fibrosis induced by CCl4. DSS significantly decreased HA, IV-C, PIIINP and LN. Further determination showed that DSS significantly increased TAC, OSI and decreased TOC, LOOH and MDA, indicating that DSS could regulate redox balance and reduce lipid peroxidation in vivo. DSS also increased the activity of GST, SOD and GSH concentration. In addition, DSS also reduced IL-6 and TNF-α. ConclusionsIn this study, we described the chemical characterization of DSS and found that it has good antioxidant activity. We proved that DSS has the functions of reducing oxidative stress, anti-inflammatory, protecting liver cells and reducing hepatic fibrosis.

Effect of DL-3-n-butylphthalide on cognitive function and the regulating role of Nrf2/SIRT3 signaling pathway in vascular dementia mice

Objective To investigate the effects of butylphthalide(NBP) on cognitive function and Nrf2 / SIRT3 signal pathway in vascular dementia (VD) mice. Methods Wild-type mice (Nrf2+ /+ ) were divided into sham group, model group (VD group), butylphthalide treatment group (Nrf2+ /+ NBP group), and Nrf2 gene knockout mice (Nrf2-/-) were divided into Nrf2-/-model group (Nrf2-/-VD group) and Nrf2-/-treatment group (Nrf2-/-NBP group). Both the model group and the treatment group were repeated.The bilateral common carotid arteries were ligated three times to establish a mouse model of cognitive dysfunction caused by cerebral ischemia-reperfusion.The sham group only isolated the bilateral common carotid arteries and threaded the wires, but did not block blood flow.Morris water maze experiment was used to analyze the cognitive function of mice.HE staining was used to observe the changes of neuron morphology and structure in CA1 region of hippocampus, and immunohistochemical analysis was used to analyze the positive expression of caspase 3 and caspase 9 in mouse CA1 region of hippocampus.Western blot was used to detect mouse hippocampus Nrf2, p62, LC3, SIRT3 protein expression. Results (1) In Morris water maze experiment: compared with VD group, the escape latency of Sham group and Nrf2+ /+ NBP group was significantly shorter on the 5th day ((20.69±8.91) s, (7.58±9.47)s, (8.41±12.20)s; q=3.58, 5.07, both P 0.05). (2) Pathological results showed that, compared with VD group, the damage of pyramidal neurons in CA1 area of hippocampus in Sham group and Nrf2+ /+ NBP group was lighter, and that in Nrf2-/- VD group was more serious, and the improvement of neuron morphology was not obvious after NBP treatment.(3) The expression of apoptosis: compared with VD group, the expression of caspase-3 and caspase-9 in the CA1 area of hippocampus in Sham group and Nrf2+ /+ NBP group were significantly lower, and those in Nrf2-/-VD group were significantly higher (t=3.48, 2.95, 3.46, 2.93, -2.99, -3.77, all P 0.05). (4) Expression of related proteins: compared with VD group, Nrf2, SIRT3, p62 protein expression increased, LC3II/I ratio decreased in Nrf2+ /+ NBP group(t=-3.24, -4.04, -4.03, 3.62, all P<0.01); Nrf2, LC3II/ I ratio decreased, SIRT3, p62 protein expression increased in Sham group(t=3.44, 4.72, -3.52, -4.19, all P<0.01); Nrf2, SIRT3, p62 protein expression decreased and LC3II/I ratio increased in Nrf2-/-VD group(t=9.14, 4.20, 4.30, -3.78, all P<0.01); Compared with Nrf2-/- NBP, the expression of Nrf2, SIRT3, p62 decreased, and LC3II/I ratio increased in Nrf2-/-VD group(t=2.40, 3.24, 1.21, -1.16, all P<0.01). The expression of Nrf2, SIRT3, p62 protein in Nrf2+ /+ NBP group increased, and the ratio of LC3II/ I decreased (t=-3.29, -5.00, 6.24, all P<0.01). Conclusion Butylphthalide can reduce the apoptotic damage in hippocampus of VD mice and improve cognitive dysfunction caused by repeated ischemia-reperfusion injury.Regulating Nrf2 / SIRT3 pathway to inhibit hippocampal neuronal apoptosis and autophagy may be its role mechanism. Key words: Butylphthalide(NBP); Vascular dementia; Nrf2; SIRT3; Apoptosis autophagy

Analysis of serum S-100 beta protein, NSE and neurological deficits in patients with cerebral infarction and reperfusion treated with butylphthalide

Objective To investigate the effects of butylphthalide on serum S-100 beta protein, NSE and neurological deficits in patients with cerebral infarction and reperfusion. Methods From January 2016 to January 2018, 104 patients with early cerebral infarction admitted to the People's Hospital of Feicheng were divided into two groups according to different treatment methods.The control group (n=52) was given routine treatment, while the observation group (n=52) was given butylphthalide treatment on the basis of the control group.The degree of neurological deficit, serum NSE and S-100 beta protein levels were compared between the two groups before and after thrombolysis. Results The NIHSS scores of the two groups before thrombolysis were (10.27±1.32)points and (10.28±1.30)points, respectively, the difference between the two groups was no statistically significant(t=0.038, P>0.05). The NIHSS scores of the two groups were decreased at 24h and 7d after thrombolysis, which of the observation group at 24h and 7d after thrombolysis were (8.32±1.37)points and (4.25±1.54)points, respectively, which were significantly lower than those of the control group [(9.24±1.40)points and (9.50±1.24)points], the differences were statistically significant (t=3.396, 19.147, all P 0.05). At 24h and 7d after thrombolysis, the serum NSE levels of the two groups were decreased.The serum NSE levels of the observation group at 24h and 7d after thrombolysis were (15.08±9.35)U/mL and (13.25±6.47)U/mL, respectively, which were significantly lower than those in the control group [(18.96±10.14)U/mL and (16.98±7.11) U/mL], the differences were statistically significant (t=2.028, 2.79, all P 0.05). At 24h and 7d after thrombolysis, the serum S-100β protein levels were decreased in both two groups, which in the observation group were (1.13±0.62 )μg/L and (0.53±0.48)μg/L, respectively, which were significantly lower than those in the control group [(1.40±0.64)μg/L, (0.87±0.32)μg/L], the differences were statistically significant (t=2.185, 4.25, all P<0.05). Conclusion Butylphthalide injection for patients with cerebral infarction and reperfusion can effectively promote the recovery of neurological function, improve the levels of serum NSE and S-100 beta protein, and help patients recover as soon as possible. Key words: Infarction, middle cerebral artery; Reperfusion; Serum S-100 beta protein; NSE; Neurological deficit; Butylphthalide

Effects of butylphthalide on hydrogen peroxide induced retinal pigment epithelial cells injury

Objective To investigate the protective effect of butylphenyphthalein (NBP) on RPE apoptosis induced by H2O2. Methods The human RPE cell line (human ARPE-19 cell line) were used as the experimental cells and were divided as control group, model group, NBP group. Complete medium was used in control group. The model group was stimulated with 200 μmol/L H2O2 for 2 h, and the cells were cultured in complete medium. The NBP group was cultured with 200 μmol/L H2O2 and 1 μmol/L NBP for 2 h. After changing the medium, complete medium was combined with 1 μmol/L NBP to continue the culture of the cells. Cell viability were detected by MTT assay while the morphology of RPE were observed by HE staining. Moreover, Hoechst 33258 was used to detect RPE cell apoptosis. Mitochondrial membrane potential (JC-1) staining were performed to monitor changes in cell membrane potential and the characteristic change of apoptosis in RPE cells. Furthermore, 2′,7′-Dichlorofluorescin diacetate (DCFH-DA) staining were used to analyze the effect of NBP treatment on the expression of ROS. The effect of NBP on the expression of Heme oxygenase-1(HO-1) was analyzed by cellular immunofluorescence and western blotting. Results The results of MTT assay showed that the cells were cultured for 24 and 48 hours, cell viability of control group (t=17.710, 13.760; P<0.000 1, <0.000 1) and treatment group (t=4.857, 9.225; P=0.000 7, <0.000 1) were stronger than that of model group, and the difference was statistically significant. HE staining and Hoechst33258 staining showed that compared with the control group, the number of cells in the model group was significantly less, and the cell morphology was incomplete. Compared with the model group, the number of cells in the treatment group was significantly increased, and the cell morphology was better. The results of JC-1 assay showed that the number of apoptotic cells in the model group was significantly higher than that in the control group, and the number of apoptotic cells in the treatment group was significantly lower than that in the model group. DCFH-DA staining showed that the ROS accumulation in the model group was more than that in the control group, and the ROS accumulation in the treatment group was less than that in the model group. Immunostaining observation showed that the HO-1 fluorescence intensity of the cells in the treatment group was significantly higher than that of the control group, and the difference was statistically significant (t=10.270, P=0.000 5). Western blot analysis showed that NBP up-regulated the expression level of HO-1 in a time-dependent manner. The relative expression of HO-1 at 4, 8, and 12 h of NBP showed a clear increase trend compared with 0 h, and the difference was statistically significant (F=164.91, P<0.05). Conclusions Oxidative stress injury can down-regulate the viability of RPE cells and induce apoptosis. NBP can increase the antioxidant capacity of RPE cells, reduce cell damage and inhibit cell apoptosis by up-regulating HO-1 expression. Key words: Retinal pigment epithelium; Apoptosis; Butylphthalide; Oxidative stress

Effect of butylphthalide injection to mitochondrial function of porcine cerebral neuron after cardiopulmonary resuscitation

Objective To investigate the mechanism of cerebral protection by treatment of butylphthalide (NBP) and its effect to mitochondria in a porcine model of cardiac arrest (CA) after cardiopulmonary resuscitation (CPR). Methods Healthy Wuzhishan pigs weighting (30±2) kg were divide into three groups randomly(random number): The sham group (n=6), the control group (n=12) and the NBP group (n=12). Operation was performed in the sham group. Cardiac arrest of ventricular fibrillation was induced by programed electrical stimulation in the control and NBP group. After CPR, asynchronous defibrillation of 150J was performed to achieve the restoration of spontaneous circulation. NBP was injected at the rate of 2.5 mg•kg-1 in the NBP group. Hemodynamics were recorded at baseline, 1 hr, 2 hr, 3 hr and 4 hr after CPR. The number of injured neurons, apoptosis index and evaluation of mitochondrial injury were calculated under light and electrical microscope respectively. Mitochondria were separated by differential centrifugation. Mitochondrial respiratory function was measured with oxygen consumption of R3 and R4, respiratory control rate (RCR), ADP/oxygen. Mitochondrial permeability transition pore (MPTP) open was tested by colorimetric. Results After CPR, the mean artery pressure, coronary perfusion pressure and cardiac output decreased significantly, whereas no significant differences were found between the control and NBP group (P>0.05). Significant cerebral injury was found after CPR. The number of injured neurons, apoptosis index and evaluation of mitochondrial injury were improved significantly by the NBP treatment (P<0.05). Compared with the sham group, oxygen consumption of R3 and R4, R3/R4 and ADP/O decreased significantly in the cerebral frontal cortex mitochondria of the control group (P<0.01), whereas they were increased in the NBP group (P<0.01). MPTP increased in the control group, which could be improved by the NBP treatment. Conclusions NBP can improve the neurologic outcome after CPR and decrease the apoptosis of neurons by improving the respiratory function of mitochondria and inhibiting the MPTP opening. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Butylphthalide injection; Neurologic outcome; Mitochondrial function

Clinical trial of nimodipine combine with butylphthalide in the treatment of patients with mild to moderate vascular cognitive impairment

Objective To evaluate the clinical efficacy and safety of nimodipine combine with butylphthalide in the treatment of patients with mild to moderate vascular cognitive impairment(VCI). Methods From January 2012 to December 2016, 100 patients with mild to moderate VCI in Jinhua Municipal Central Hospital were randomly divided into control group(n=50) and treatment group(n=50) according to the random number table method.The control group received butylphthalide capsule, 200 mg po tid.The treatment group received nimodipine tablets, 40mg po tid, on the basis of the control group.The two groups of patients were treated for 24 weeks.Montreal cognitive assessment(MoCA), activities of daily living(ADL), serum hs-CRP, IL-6, TNF-α, clinical efficacy and adverse drug reactions were compared after treatment. Results After treatment, the scores of MoCA and ADL in the treatment group were (24.32±2.87)points, (59.22±6.17)points, respectively, which were significantly higher than those in the control group[(22.76±2.67)points, (55.63±6.3)points, t=2.814, 2.870, all P 0.05). Conclusion Nimodipine combined with butylphthalide in the treatment of mild to moderate VCI is effective and has high safety. Key words: Cognition disorders, vasculogenic; Drug therapy, combination; C-reaction protein; Interleukins 6; Tumor necrosis factorα; Comparative effectiveness research; Nimodipine; Butylphthalide

The role and mechanism of dl-3-n-butylphthalide in inflammatory response after traumatic brain injury in mice

Objective To investigate whether butylphthalide (NBP) can protect neurons by inhibiting microglial activation and inflammation after traumatic brain injury in mice. Methods One hundred and forty-four mice were randomly assigned to four experimental groups: sham, traumatic brain injury (TBI), TBI+ vehicle (V) and TBI+ NBP. Neurological score, Nissl staining were performed in each group of mice, immunofluorescence staining was used to localize the distribution of ionized calcium binding adapter molecule 1 (IBA-1) in the cerebral cortex of mice, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the contusion and laceration brain tissue of mice. Statisticalanalysis of data using the statistical product and service solutions 22.0 software. Results NBP could improve the neurological function score, relieve neurodegeneration after brain injury in mice (t=6.320, 5.440, P<0.05). NBP can inhibit the expression of IBA-1 protein and the inflammatory factors TNF-α [(7.21±1.21) pg/mg] and IL-1β [(3.52±1.13) pg/mg] after brain injury in mice (t=3.370, 3.420, 3.350, 3.400, P<0.05). Conclusion NBP can inhibit the activation of microglia in mice after TBI, which is related to the decrease of the release of pro-inflammatory cytokines. Key words: Traumatic brain injury; Butylphthalide; Neuroprotection; Inflammatory factors

Effect of butylphthalide combined with edaravone on cerebral hemodynamics, vascular endothelial function and cytokines in elderly patients with acute cerebral infarction

Objective To investigate the effects of butylphthalide combined with edaravone on cerebral hemodynamics, vascular endothelial function and cytokines in elderly patients with acute cerebral infarction. Methods From May 2017 to May 2018, 82 elderly patients with acute cerebral infarction admitted to the First People's Hospital of Wenling were selected and randomly divided into two groups according to the digital table, with 41 cases in each group.The patients in the control group were treated with edaravone, while the patients in the treatment group were treated with butylphthalide on the basis of the control group.The two groups were treated for 2 weeks.The neurological deficit scale (NIHSS), cerebral hemodynamics, vascular endothelial function and cytokines were compared between the two groups before and after treatment. Results The NIHSS score of the treatment group was (18.49±1.87)points, which was lower than (22.17±1.32)points of the control group at 2 weeks after treatment (t=10.294, P<0.05). The mean flow velocity [(31.70±3.25)cm/s], vascular resistance index (0.79±0.12) and maximum peak flow velocity [(54.21±2.65)cm/s] in the treatment group were higher than those in the control group [(26.91±4.39)cm/s, (0.61±0.05) and (43.76±3.10)cm/s] (t=5.615, 8.866, 16.407, all P<0.05). The contents of NO [(71.27±6.58)μmol/L] and eNOS [(66.37±3.65)U/mL] in the treatment group were higher than those in the control group [(62.30±2.71)μmol/L and (57.89±4.08)U/mL] (t=8.071, 9.919, all P<0.05). After 2 weeks of treatment, the contents of IL-6 [(27.36±2.71)pg/mL], CRP [(2.87±0.76)mg/L] and TNF- α[(98.24±10.48)ng/mL] in the treatment group were lower than those in the control group [(43.25±4.10)pg/mL, (4.59±0.91)mg/L and (160.27±15.42)ng/mL] (t=20.702, 9.289, 21.303, all P<0.05). The total effective rate of treatment group (90.24%) was higher than that of control group (68.29%) (χ2=6.011, P<0.05). Conclusion Butylphthalide combined with edaravone can improve cerebral hemodynamics, vascular endothelial function and alleviate cellular inflammatory reaction in elderly patients with acute cerebral infarction, and the curative effect is significant, which is worthy of clinical study. Key words: Infarction, middle cerebral artery; Vascular resistance; Blood flow velocity; Nitric oxide; Nitric oxide synthase; Interleukin-6; Tumor necrosis factor-alpha; Butylphthalide; Edaravone; Aged

Effects of butylphthalide soft capsules on cognitive function and daily living ability in patients with Parkinson's disease dementia

Objective To investigate the effects of butylphthalide soft capsules on cognitive function and daily living ability in patients with Parkinson's disease dementia(PDD). Methods From January 2016 to January 2017, 90 patients with PDD in the First People's Hospital of Wenling were divided into control group and study group by random number table method, with 45 cases in each group.The patients in the two groups were treated with conventional symptomatic treatment, and the control group was treated with donepezil, the study group was treated with butylphthalide soft capsules on this basis.The treatment time was 12 weeks.The clinical efficacies of the two groups were compared.Before treatment and 12 weeks after treatment, the cognitive functions of patients were assessed by Montreal cognitive assessment scale (MoCA) and mini-mental state examination (MMSE), and the daily living abilities of patients were assessed by Barthel index scale. Results The total effective rate of the study group was 93.33%, which was higher than 75.56% of the control group (χ2=5.414, P 0.05). Conclusion Butylphthalide soft capsules can significantly improve the cognitive function and daily living ability of patients with PDD, which is suitable for clinical application and promotion. Key words: Parkinson disease; Dementia; Cognitive; Activitise of daily living; Butylphthalide soft capsules

The effect of butylphthalide on cell necroptosis in cerebral ischemia reperfusion injury model mice

Objective To explore the protective effect and mechanism of butylphthalide on cerebral ischemia reperfusion injury in mice. Methods The cerebral ischemia reperfusion injury model was established by middle cerebral ischemia occlusion(MCAO). Thirty mice were divided into sham group, ischemia reperfusion group(I/R group) and butylphthalide group(NBP group) with 10 in each group.Neurological defect score and brain infarction volume were detected by TTC to evaluate the treatment effects of butylphthalide.Western blot was used to detect expression of RIP, RIP3 and AIF.Immunocoprecipitation(IP) was used to detect the interaction of AIF and RIP3.Immunofluorescence(IF) was used to detect the nuclear translocation and co-localization of AIF and RIP3. Results Compared with the I/R group, NBP treatment reduced the neurological defect score(I/R: (2.60±0.22), NBP: (1.90±0.23), t=2.18, P<0.05) and brain infarction volume(I/R: (38.32±2.22)%, NBP: (25.23±2.70)%, t=3.74, P<0.01) .I/R elevated the expression of RIP1 and RIP3 whereas NBP significantly inhibited the expression of these two proteins (RIP1(I/R: 0.99±0.24, NBP: 0.47±0.10, t=2.71, P<0.05); RIP3(I/R: 0.52±0.17, NBP: 0.15±0.04, t=2.87, P<0.05)). I/R and NBP had no significant effects on the expression of AIF, but the IP results showed that I/R increased the interaction between AIF and RIP3 compared with the sham group.NBP alleviated the interaction between AIF and RIP3.IF results showed that the colocalization and nuclear expression of AIF and RIP3 increased after I/R whereas NBP treatment decreased the effect induced by I/R. Conclusion Butylphthalide alleviated cerebral ischemia reperfusion injury in mice through inhibiting the cell necroptosis.The mechanisms may correlate with decreasing the expression of RIP1 and RIP3 and alleviating the interaction and nuclear translocation of AIF and RIP3. Key words: Butylphthalide; Ischemia reperfusion; Necroptosis; Apoptosis inducing factor; Mice

Effect of dl-3-n-Butylphthalide on apoptosis of retinal müller cells induced by hydrogen peroxide

Objective To observe the protective effect of dl-3-n-Butylphthalide (NBP) on apoptosis of retinal Muller cells induced by hydrogen peroxide (H2O2). Methods Human retinal Muller cells cultured in vitro were divided into normal control group, model group (H2O2 group) and experimental group (H2O2+NBP group). The cells in the H2O2 group and H2O2+NBP group were cultured with 200 μmol/L H2O2 for 2 h. Then the culture solution of the H2O2 group replace with complete medium and the H2O2+NBP group replace with complete medium containing 1 μmol/L NBP. The normal control group was a conventional cultured cells. Muller cells were identified by immunofluorescence staining. Hematoxylin-eosin (HE) staining was used to observe the apoptosis morphological changes. MTT assay was used to detect the activity of of retinal Muller cells after after 24 h and 48 h of NBP intervention. Hoechst33258 staining was used to observe the apoptosis. LIVE/DEAD ® cell activity/cytotoxicity kit was used to detect cell viability. Dichlorofluorescein diacetate (DCFH-DA) + endoplasmic reticulum (ER) red fluorescent probe (ER-Tracker Red) double staining was used to observe the expression level of reactive oxygen species (ROS) in ER of cells. One-way ANOVA combined with Dunnett statistical method were used for data analysis. Results HE staining showed that the number of cells in H2O2+NBP group was higher than that in H2O2 group. MTT assay showed that after 24 h and 48 h of NBP intervention, the differences in cell viability between the normal control group and the H2O2 group, the H2O2 group and the H2O2+NBP group were statistically significant (t=28.96, 3.658, 47.58, 20.33; P<0.001, 0.022). The results of Hoechst33258 showed that the nuclear nucleus of a few cells in the H2O2+NBP group was crescent-shaped and the nuclear fragmentation was reduced, and the blue fluorescence of the remaining cells was uniform. The LIVE/DEAD ® cell activity/cytotoxicity kit showed that the number of dead cells with red fluorescence in the H2O2 group increased significantly, and the number of viable cells with green fluorescence decreased significantly. In the H2O2+NBP group, the number of viable cells with green fluorescence increased, and the number of dead cells with red fluorescence decreased. The double staining results of DCFH-DA+ER-Tracker Red showed that the green fluorescence intensity of H2O2 group was significantly enhanced; the green fluorescence intensity of H2O2+NBP group was lower than that of H2O2 group. Conclusion NBP alleviates H2O2-induced apoptosis of human retinal Muller cells by inhibiting ROS production. Key words: Butylphthalide; Oxidative stress; Apoptosis; Hydrogen peroxide; Muller cells

Effect of butylphthalide and sodium chloride injection combined with salvia miltiorrhiza injection in the treatment of acute ischemic stroke

Objective To investigate the value of butylphthalide and sodium chloride injectio combined with compound salvia miltiorrhiza injection in the treatment of acute ischemic stroke. Methods From January 2016 to December 2017, 104 patients with acute ischemic stroke in Tongji Huangzhou Hospital Affiliated to Huazhong University of Science and Technology were randomly divided into observation group(52 cases) and control group(52 cases) according to the digital table.The control group was given butylphthalide and sodium chloride injectio, and the observation group was combined with the compound salvia miltiorrhiza injection on the basis of the control group.The courses of the treatment in the two groups were 14 d. The effects of the two groups were compared. Results The total effective rate of the observation group(90.38%, 47/52) was higher than that of the control group(73.08%, 38/52)(χ2=5.216, P<0.05). After treatment, the daily living activity(ADL) score of the observation group was (60.49±5.46)points, which was higher than (44.54±4.10)points of the control group(t=16.845, P<0.05). After treatment, endothelin-1(ET-1), C reactive protein(CRP), homocysteine(Hcy) in the observation group were (37.42±5.47)ng/L, (6.51±1.89)mg/L, (7.42±1.27)μmol/L, respectively, which in the control group were (58.98±7.89)ng/L, (12.34±2.65)mg/L, (15.39±2.06)μmol/L, respectively, the levels of ET-1, CRP and Hcy in the observation group were lower than those in the control group(t=16.194, 12.916, 23.749, all P<0.05). After treatment, the plasma viscosity, fibrinogen, whole blood viscosity at high shear and low shear whole blood viscosity of the observation group were (1.20±0.23)mPa/s, (2.54±0.37)g/L, (2.54±0.37)mPa/s and (8.19±0.68)mPa/s, respectively, which of the control group were (2.09±0.32)mPa/s, (3.47±0.58)g/L, (3.46±0.59)mPa/s and (9.81±0.82)mPa/s, respectively, the plasma viscosity, fibrinogen, whole blood viscosity at high shear and low shear whole blood viscosity of water of the observation group after treatment were lower than those of the control group(t=16.286, 9.748, 10.994, 10.966, all P<0.05). Conclusion The effect of butylphthalide and sodium chloride injectio combined with compound salvia miltiorrhiza injection in the treatment of acute ischemic stroke is significant, which is worth studying. Key words: Stroke; Brain ischemia; Drug therapy, combination; Butylphthalide and sodium chloride injection; Compound salvia miltiorrhiza injection

Effect of vinpocetine combined with butylphthalide in the treatment of atherosclerotic cerebral infarction

Objective To observe the effect of vinpocetine combined with butylphthalide in the treatment of large artery atherosclerotic infarction. Methods From October 2014 to October 2016, Ninety patients with large artery atherosclerotic cerebral infarction in Datong Coal Mine Group Three Hospital were selected and randomly divided into two groups, with 45 cases in each group.The treatment group was given vinpocetine injection, and the observation group was given vinpocetine injection combined with butylphthalide soft capsules.The ability of daily life (Barthel) score, neurological deficit score(NIHSS), hemodynamics indicators[ high blood viscosity (HSV), plasma viscosity index(PSV)] and adverse reactions were compared between the two groups. Results After treatment, the Barthel score, NIHSS score of the observation group were (79.84±18.57)points, (9.54±3.22)points, respectively, which of the control group were (62.67±16.48)points, (13.69±3.47)points, respectively, there were statistically significant differences between the two groups(t=4.64, 5.88, all P<0.05). The HSV, PSV of the observation group were (3.96±2.14)mPa/s, (1.12±0.74)mPa/s, respectively, which of the control group were (5.77±2.69)mPa/s, (3.10±1.02)mPa/s, respectively, there were statistically significant differences between the two groups(t=3.53, 10.54, all P<0.05). The incidence rate of adverse reactions of the observation group was 4.44%, which was lower than 17.78% of the control group, the difference was statistically significant (χ2=4.05, P=0.04). Conclusion Vinpocetine injection combined with butylphthalide soft capsules in the treatment of large artery atherosclerotic infarction can improve neurological function and hemodynamics, the effect is superior to single vinpocetine treatment. Key words: Infarction, middle cerebral artery; Vinpocetine; Butylphthalide

Effects of n-butylphthalide on mitochondria in hippocampus and learning and memory abilities in rats with chronic alcoholism

Objective To explore the effects of n-butylphthalide (NBP) on mitochondria in hippocampus and learning and memory abilities in rats with chronic alcoholism. Methods 60 male SD rats were randomly divided into three groups on average, including normal group, model group and treatment group, with 20 rats in each group.Rats of model group and treatment group are given 6% (V/V) alcohol solution continuously for 28 d to establish the model of chronic alcoholism.Rats in the treatment group were given butylphthalide for 14 days from the fourteenth day after giving alcohol solution.The Y type electric maze was used to test the learning and memory ability of rats, the content of H2S in the hippocampus and the activity of mitochondrial ATP enzyme were measured by spectrophotometry, and the protein expression of F-actin was detected by Western blot. Results Compared with the normal group, the learning and memory ability of the rats in the model group were decreased, the content of H2S in the hippocampus were increased, and the activity of mitochondrial ATP enzyme and the expression of F-actin protein were decreased, and most of the mitochondria were damaged under the electron microscope.The training times of the rats in treatment group(61.88±3.61)was lower than that of the model group(82.19±4.87), the ability of learning and memory was improved(P<0.05). Compared with the model group ((1.50±0.07)U/mgprot, (0.08±0.01)), the activity of the mitochondrial ATP enzyme((1.84±0.11)U/mgprot) and the level of F-actin protein(0.12±0.01)in rat hippocampus of treatment group were increased, the difference was statistically significant(both P<0.05). The level of H2S in rat hippocampus of the treatment group ((34.56±2.47) nmol/g) was lower than that of the model group ((44.55±3.71) nmol/g), the difference was statistically significant(P<0.05). Compared with model group, the mitochondrial damage of the hippocampus in the treatment group was improved under electron microscope. Conclusion NBP can abate mitochondrial damage and improve learning and memory abilities in chronic alcoholism rats. Key words: N-butylphthalide; Chronic alcoholism rats; H2S; Mitochondria; F-actin

Effects of butylphthalide combined with clopidogrel on the blood viscosity and parameters of transcranial Doppler in patients with cerebral infarction

Objective To explore the effects of the combination of butylphthalide and clopidogrel on the blood viscosity and parameters of transcranial Doppler in patients with cerebral infarction. Methods Ninety patients with cerebral infarction were selected, and they were divided into control group and observation group according to the digital table, with 45 cases in each group.The control group was orally given clopidogrel, the observation group was given clopidogrel combined with butylphthalide.The clinical curative effect, blood viscosity changes and transcranial Doppler changes were compared between the two groups. Results The total effective rate of the observation group was 93.33%, which was significantly higher than 73.33% of the control group (χ2=5.67, P<0.05). After treatment, the HSV and PSV of the two groups were lower than those before treatment(t=4.34, 4.56, 7.89, 7.23, all P<0.05), and the decrease of HSV and PSV in the observation group was more significant than those in the control group after treatment(t=6.55, 6.67, all P<0.05). Compared with those before treatment, the Vm of ACA and MCA in the two groups after treatment significantly increased(t=4.34, 4.90, 7.33, 6.92, all P<0.05), the PI of ACA and MCA significantly decreased(t=4.77, 4.66, 7.12, 7.29, all P<0.05), and the above indicators in the observation group after treatment improved more significantly compared with those in the control group(t=6.31, 5.50, 6.54, 6.28, all P<0.05). Conclusion The effect of the early combination of butylphthalide and clopidogrel in the treatment of patients with cerebral infarction is significant, and it can effectively improve the change of blood viscosity. Key words: Brain Infarction; Clopidogrel; Ultrasonography, doppler; Hemorheology; Diphthalein

Low Dose of Anisodine Hydrobromide Induced Neuroprotective Effects in Chronic Cerebral Hypoperfusion Rats.

Chronic cerebral hypoperfusion is a common pathophysiological state in various cerebrovascular diseases. Anisodine has been reported to exert neuroprotective effects in cerebral ischemia/reperfusion (I/R) animal model. However, it is unclear whether anisodine hydrobromide, the hydrobromide format of anisodine, one of the tropic alkanes alkaloids, exhibits the same neuroprotective effect on chronic cerebral hypoperfusion(CCH) rats. Herein, we tried to unravel these issues. CCH model in adult male Sprague-Dawley rats was established by permanent ligation of the bilateral common carotid arteries [two-vessel occlusion (2-VO)] surgery. Rats were randomly divided into six groups: sham, 2-VO, 2-VO + Butyl phthalide and sodium chloride injection (NBP, as positive control group), 2-VO + anisodine hydrobromide (AH)1.2mg/kg, 2-VO +AH0.6mg/kg, 2-VO +AH0.3mg/kg. Cognitive behavior was examined by Morris Water Maze Test. Neuronal survival and apoptosis were evaluated by Nissl staining and Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL staining). The relative monoamine neurotransmitter (5-hydroxytryptamine (5-HT), norepinephrine (NA)), the content of Ach, the activity of acetylcholin esterase (AchE) were measured in cholinergic system, and the protein expressions of Bcl-2, Bax, p-Akt and p-GSK-3βwere detected by Western blot assay. The results showed that there is significant memory impairment and a remarkable neuron necrosis and apoptosis, along with the dysfunction of the neurotransmitter systems and central cholinergic system in CCH rats. AH treatment could significantly improve cognitive deficits, while reducing neuron necrosis and apoptosis, apart from increasing the content of 5-HT and decreasing the activity of AchE markedly. Further study revealed that AH could promote the protein expression of Bcl-2, phosphorylation of Akt and GSK-3β, and downregulate the protein of Bax. AH was demonstrated to ameliorate memory deficits by revising the imbalance of the monoamine neurotransmitter and cholinergic dysfunction. Moreover, AH can attenuate neuronal cell death and apoptosis by activating the Akt/GSK-3βsignaling pathway.

Clinical efficacy of combination therapy with Butylphthalide and fibrinolytic enzyme for acute cerebral infarction

Objective To evaluate the clinical efficacy of Butylphthalide combined with fibrinolytic enzyme in the treatment of acute cerebral infarction. Methods A total of 60 elderly patients with acute cerebral infarction who had missed the opportunity of thrombolytic therapy were enrolled in this study from January 2014 to December 2016 at Zhengzhou University Second Affiliated Hospital.Patients were randomly divided into an observation group(n=30)and a control group(n=30). Patients in the control group were treated with fibrinolytic enzyme alone, and those in the observation group received Butylphthalide combined with fibrinolytic enzyme.Peak flow velocity and mean flow velocity of the middle cerebral artery were analyzed and compared between the two groups before and after treatment.Data on clinical safety, efficacy, the national institutes of health stroke scale(NIHSS)and the Barthel score were also compared between the two groups. Results After treatment, the peak velocity 〔(74.60±4.31)cm/s vs.(69.19±3.36)cm/s〕 and average velocity 〔(38.71±2.29)cm/s vs.(34.01±2.01)cm/s〕 of the middle cerebral artery were significantly increased in the treatment group compared with those in the observation group(both P<0.05). Meanwhile, the clinical efficacy was significantly higher in the observation group(96.7% vs.73.3%, P<0.05). Moreover, NIHSS scores 〔(5.91±3.51)vs.(8.31±3.09)〕and Barthel scores 〔(71.29±3.81)vs.(53.60±4.33)〕 were significantly improved in the treatment group compared with those in the observation group(both P<0.05). In addition, there were no obvious adverse reactions during treatment in the two groups. Conclusions Butylphthalide combined with plasmin can safely and effectively improve cerebral hemodynamics and prognosis in patients with acute cerebral infarction. Key words: Brain infarction; Plasmin

Impact of butylphthalide soft capsules on the related factors and quality of life of Parkinson patients with dementia

Objective To explore the impact of butylphthalide soft capsules on the related factors and quality of life of Parkinson patients with dementia. Methods 90 Parkinson patients with dementia were selected, and they were divided into the study group and the control group by the random number table method, 45 cases in each group.The control group was treated with donepezil hydrochloride combined with routine nursing method, and the study group was treated with butylphthalide soft capsules based on the treatment of the control group.Before and after treatment, the serum C-reactive protein(CRP), recombinant human Parkinson disease protein 7(PARK7), neurotrophic factor-3(NT-3) levels of all patients were detected.And the quality of life of patients at admission and discharge were evaluated by the scale of disease self management efficiency and quality of life scale WHO(WHO QOL-BREF), quality of life of the two groups was compared before and after treatment.The Parkinson's Disease Rating Scale(UPDRS) scores was compared between the two groups before and after treatment. Results Before treatment, the dementia related factors and quality of life score, UPDRS score of the two groups had no statistically significant differences(all P>0.05). After treatment, the dementia related factors of the two groups were all improved, which of the study group improved significantly[CRP: (3.24±0.78)mg/L vs.(6.02±0.95)mg/L, PARK7: (13.15±1.51)μg/L vs.(24.93±2.02)μg/L, NT-3: (34.16±3.47)μg/L vs.(26.23±2.97)μg/L, all P<0.05]. After treatment, the quality of life(QOL) and UPDRS score of the study group were significantly higher than those of the control group[(80.5±12.5)points vs.(66.0±10.3)points, (33.28±2.18)points vs.(41.26±2.54)points, all P<0.05]. Conclusion Butylphthalide soft capsules can effectively improve the dementia related factor of Parkinson patients with dementia, and enhance the quality of life with good effect. Key words: Dementia; Parkinson disease; Risk factors; Quality of life; Butylphthalide

Observation of effect of sequential therapy of butylphthalide for acute cerebral infarction and its influence on plasma lipoprotein phospholipase A2

Objective To observe the effect of sequential therapy of butylphthalide injection and soft capsules for acute cerebral infarction and its influence on plasma lipoprotein phospholipase A2. Methods 120 patients with cerebral infarction were selected in the study, and they were divided into observation group(64 cases) and control group(56 cases) according to the digital table.The control group received conventional therapy plus placebo, the observation group received the sequential administration of butylphthalide injection and butylphthalide soft capsule treatment based on the conventional treatment.Before and after treatment, the plasma lipoprotein phospholipase A2 of the two groups was detected, and the National Institutes of Health Stroke Scale(NIHSS) was evaluated, compared neurological deficit improvement between the two groups and recorded adverse drug reactions of the two groups. Results There were no significant differences in NIHSS score and plasma lipoprotein phospholipase A2 level between the two groups before treatment(all P>0.05). After treatment, the NIHSS score of neurological impairment, plasma lipoprotein phospholipase A2 level in the observation group were (6.40±5.22)points, (203.26±29.33)ng/mL, those in the control group were (8.59±6.22)points, (253.10±52.99)ng/mL, the differences were statistically significant(t=-1.36, -2.089, P=0.039, 0.000). The total effective rate of the observation group was 90.6%, which was higher than 67.9% of the control group, the difference was statistically significant(χ2=9.676, P=0.002). The incidence rate of adverse reactions was similar in the two groups(P>0.05). Conclusion Sequential therapy of butylphthalide for acute cerebral infarction can improve the neurological function, decrease the level of plasma lipoprotein phospholipase A2, inhibit the inflammation of blood vessels, improve the prognosis of patients. Key words: Butylphthalide; Cerebral infarction; Nerve function defect; Plasma lipoprotein phospholipase A2