Effect Of Butylphthalide Research Articles

Butylphthalide inhibits ferroptosis and ameliorates cerebral Ischaemia–Reperfusion injury in rats by activating the Nrf2/HO-1 signalling pathway

This study aims to investigate whether butylphthalide can inhibit ferroptosis and ameliorate cerebral ischaemia–reperfusion (I/R) injury in rats by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase-1 (HO-1) signalling pathway, known for its antioxidative and cytoprotective properties. Middle cerebral artery occlusion reperfusion (MCAO/R) rat models were established. Male rats were randomly divided into five groups: a sham-operated group (sham), MCAO/R group, MCAO/R ​+ ​ML385 (Nrf2-specific inhibitor) group, MCAO/R ​+ ​NBP (butylphthalide) group and MCAO/R ​+ ​ML385 ​+ ​NBP group. The effect of butylphthalide on cerebral I/R injury was evaluated using neurological deficit scores. The expression levels of Nrf2, HO-1, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and transferrin receptor 1 (TfR1) protein were detected using Western blot. Moreover, the expression levels of GPX4, HO-1 and TfR1 mRNA were determined through real-time fluorescence quantitative reverse transcription polymerase chain reaction. The distribution of Nrf2, HO-1, GPX4 and TfR1 was detected using immunohistochemical staining. The levels of iron and related lipid peroxidation indexes, such as reduced glutathione, reactive oxygen species, malondialdehyde and nitric oxide, were measured using a kit. The changes in mitochondria were observed through transmission electron microscopy. Butylphthalide treatment significantly improved neurological dysfunction, reduced cerebral infarction volume and mitigated histopathological damage in MCAO/R rats. It induced the nuclear translocation of Nrf2 and upregulated HO-1 expression, which was attenuated by ML385. Butylphthalide also attenuated lipid peroxidation, iron accumulation and mitochondrial damage induced by MCAO/R. The expression of GPX4, ACSL4 and TfR1 proteins, as well as their mRNA levels, was modulated through butylphthalide treatment, with improvements observed in mitochondrial morphology. Butylphthalide exerts neuroprotective effects by attenuating neurological dysfunction and ferroptosis in MCAO/R rats through the activation of the Nrf2/HO-1 pathway and inhibition of lipid peroxidation and iron accumulation.

Effect Of Butylphthalide Combined with Ozagrel Sodium on Cerebral Perfusion and Oxidative Stress Indexes in Patients with Transient Ischemic Attack

Background The pathogenesis of transient ischemic attack is not clear. Microthrombosis theory is a theory with high clinical recognition. Microthrombosis of carotid artery and vertebral basilar artery wall occurs shedding and vasospasm, resulting in transient cerebral insufficiency. Microembolic decomposition or distal movement, cerebrovascular dilatation, local collateral circulation after the establishment of symptoms relieved or disappeared. Most patients can be relieved in a short time, but recurrent attacks can gradually damage the structure and function of brain tissue, and increase the risk of acute cerebral infarction. The clinical treatment of this disease is mainly based on the comprehensive control of risk factors, anti thrombosis, and anti-platelet aggregation. Objective To observe the effect of butylphthalide combined with ozagrel sodium on cerebral perfusion and oxidative stress indexes in patients with transient ischemic attack. Methods A total of 116 patients diagnosed as transient ischemic attack in our hospital (February 2018 - February 2020) were selected and divided into two groups according to the treatment methods. 58 cases in the control group were treated with ozagrel sodium, 58 cases in the observation group were treated with butylphthalide combined with ozagrel sodium. The CT perfusion imaging parameters, oxidative stress indexes, plaque area, and the levels of platelet activating factor ( PAF ), α-granule membrane protein-140 ( GMP-140 ), fibrinogen ( FIB ), platelet aggregation rate (PAgT), neuron-specific enolase (NSE), oxygend-inducible factor-1α (HIF-1α), and matrix metalloproteinases 9 (MMP-9) in the two groups were recorded, and the total effective rate and adverse reaction rate were counted. Results The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (χ2=4.640, P = 0.031). Compared with before treatment, the average time (MTT) required for the two groups of contrast agents to pass through the local brain tissue and the time (TTP) required to start the injection of contrast agents to reach the peak concentration decreased compared with before treatment. After treatment, the MTT and TTP of the observation group were shorter than those of the control group (P < 0.05). Compared with before treatment, superoxide dismutase ( SOD ) in the two groups was higher than that in the control group, PAF, GMP-140, FIB, PAgT, NSE, HIF-la, MMP-9, malondialdehyde (MDA) and plaque area decreased. After treatment, the levels of related factors in the observation group were better than those in the control group, and the plaque area was less than that in the control group (P < 0.05). There was no significant difference in the adverse reaction rate between the observation group and the control group (χ2 = 0.438, P=0.508). Conclusion Butylphthalide combined with ozagrel sodium in the treatment of transient ischemic attack can improve cerebral perfusion, reduce oxidative stress injury, reduce plaque and improve curative effect.

Protective Effect of Butylphthalide on Neuronal Apoptosis in Parkinson Rats and Its Effect on miR-146a-5p Expression and Phosphatidylinositide 3-Kinases/Protein Kinase B Pathway

80 male Wistar rats were stochastically assigned to Sham + Vehicle group, Sham + BUT group, PD + Vehicle group and PD + BUT group. Rotenone PD model rats were prepared by subcutaneous injection of rotenone sunflower oil emulsion 2 mg/(kg · d) for 5 consecutive weeks. Butylphthalide 80 mg/(kg · d) were given to the rats in Sham + BUT group and PD + BUT group by gavage from the first day of rotenone injection for 5 weeks. Subsequently, the motor retardation ability and the morphological changes of the substantia nigra (SN) of each group were evaluated. Meanwhile, the levels of neuronal injury, apoptosis, inflammation and oxidative stress in each group of rats were assayed. The impact of BUT treatment on miR-146a-5p expression and PI3K/AKT signal pathway in rat brain tissue was assayed. Finally, by constructing a PD cell model of the neurotoxin 6-hydroxydopamine (6-OHDA)-treated human neuroblastoma cell line SH-SY5Y, the in vitro anti-PD pharmacological effect of BUT was further verified.

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

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

The clinical effect of butylphthalide in the treatment of acute cerebral infarction

Objective To investigate the clinical value of butylphthalide in patients with acute cerebral infarction. Methods 120 patients with acute cerebral infarction were randomly divided into study group and control group according to the method of random number table, 60 cases in each group.The study group used butylphthalide on the basis of routine treatment, while the control group only received routine treatment.Main outcome measures included the National Institutes of Health Stroke Scale (NIHSS) table, activities of daily living Barthel index, blood viscosity, clinical curative effect and health related quality of life (HRQL) score. Results There was no significant difference in NIHSS score, Barthel score, blood viscosity and HRQL between the two groups on admission (P>0.05). When compared with the control group after 3 months, NIHSS score of the study group decreased significantly[(948±3.84)points vs.(14.38±3.29)points, t=5.395, P=0.000], Barthel score increased significantly[(84.44±10.59)points vs.(75.89±8.39)points, t=3.854, P=0.015]; blood viscosity decreased significantly[(5.09±0.64)mPa.s vs.(648±0.71)mPa.s, t=7.493, P=0.000]; HRQL scores increased significantly [(80.47±15.39)points vs.(69.58±14.39)points, t=4.395, P=0.002]; clinical curative effect in the study group was significantly higher than control group (χ2=6.122, P=0.013). Conclusion Butylphthalide is helpful to improve the prognosis and quality of life in patients with acute cerebral infarction. Key words: Acute cerebral infarction; Butylphthalide; Clinical curative effect

Effect of butylphthalide on VEGF and Ang-1 levels of cerebra and serum in rats with middle cerebral artery ischemia-reperfusion

Objective To explore the effect of butylphthalide on the vascular endothelia growth factor(VEGF) and amgiopoietin-1(Ang-1) levels in cerebra and serum of rats with middle cerebral artery ischemia-reperfusion. Methods 39 male SD rats were randomly divided into sham operation group, ischemia-reperfusion group and butylphthalide- pretreated group with 13 rats in each group. The cerebral ischemia-reperfusion rat model was established in ischemia-reperfusion group and butylphthalide-pretreated group. 24 hours after reperfusion, the brain and serum were collected to detect VEGF and Ang-1 levels using ELISA and immunohistochemistry. The cerebral capillary endothelial morphology was observed with the electron microscope. Results The cell edema and impaired ultrastructure of cerebral capillary endothelial in butylphthalide-pretreated group were reduced compared with ischemia-reperfusion group. The VEGF and Ang-1 levels of cerebra(VEGF: (0.119±0.017) vs (0.100±0.016), Ang-1: (0.120±0.023) vs (0.097±0.018)) and serum (VEGF: (45.51±22.4) pg/ml vs (20.45±6.14) pg/ml, Ang-1: (126.32±61.89) ng/ml vs (70.02±20.80) ng/ml) were higher in ischemia-reperfusion group compared with sham operation group (P<0.05), while butylphthalide-pretreated rats displayed the higher VEGF (Cerebra: (0.137±0.022) vs (0.119±0.017), Serum: (80.46±13.65) pg/ml vs (45.51±22.4)pg/ml) and Ang-1 (Cerebra: (0.142±0.020) vs (0.120±0.023), Serum: (181.49±49.45) ng/ml vs (126.32±61.89) ng/ml) expression compared with ischemia-reperfusion rats (P<0.05). Conclusion Butylphthalide can protect the brain capillary endothelial cells in rats with middle cerebral artery ischemia-reperfusion, and upregulate production of VEGF and Ang-1. Key words: Butylphthalide; Cerebral ischemia reperfusion; Endothelium; VEGF; Ang-1

Effect of butylphthalide on VCAM-1 and ICAM-1 in rats with middle cerebral artery ischemia-reperfusion

Objective To explore the effect of butylphthalide on vascular cell adhesion molecule-1(VCAM-1) and intercellular adhesion molecule-1(ICAM-1) in rats with middle cerebral artery ischemia-reperfusion. Methods 30 male SD rats were randomly divided into sham operation group(n=10), the model group(n=10) and butylphthalide pretreated group(n=10). Rat model of cerebral ischemia and reperfusion was established using the cerebral artery occlusion method.The brain expression of VCAM-1 and ICAM-1 was detected by immunohistochemistry. The serum VCAM-1 and ICAM-1 levels were detected using Enzyme-linked immunosorbent assay (ELISA). Results The VCAM-1 and ICAM-1 levels of brain and serum in the model group were higher than those of sham operation group (P 0.05), while VCAM-1 expression was higher in butylphthalide pretreatment group compared with the model group (brain: (0.127±0.017)ng/ml vs(0.164±0.025)ng/ml; serum: (160.22±53.95)ng/ml vs (270.89±76.49)ng/ml, all P<0.05). Conclusion Butylphthalide can inhibit the VCAM-1 level of brain and serum in rat with middle cerebral artery ischemia-reperfusion. Key words: Butylphthalide; Middle cerebral artery ischemia-reperfusion; Vascular cell adhesion molecule-1; Intercellular adhesion molecule-1

The effect of butylphthalide combined with edaravone in the treatment of progressive cerebral infarction and its impact on neurological deficits and hemorheology

Objective To investigate the clinical effect of butylphthalide combined with edaravone in the treatment of progressive cerebral infarction and its impact on neurological deficits and hemorheology .Methods 78 patients with progressive cerebral infarction were divided into the control group and observation group according to the random number table ,39 cases in each group .The two groups were given conventional treatment ,the control group was given edaravone on the basis of the conventional treatment ,while the observation group was given butylphthalide soft capsules and edaravone .All of the patients were given continuous medication for 12d.The degree of neurological deficit score,clinical assessment efficacy and adverse reactions were compared between the two groups .Results The total effective rate of the observation group was 89.74%,which was significantly higher than 66.67% of the control group（χ2 =11.672,P〈0.05）.After treatment,the NIHSS scores were decreased significantly （t=11.04,12.88,all P〈0.05）,that in the observation group was declined more significantly ,compared with the control group ,the differ-ence was statistically significant （t=10.93,P〈0.05）.After treatment,the fibrin level,blood viscosity and platelet aggregation of the observation group were significantly lower than those of the control group （ t=6.69,6.22,7.30,all P〈0.05）.Conclusion Butylphthalide combined with edaravone in the treatment of progressive cerebral infarction can significantly improve the patients＇neurological symptoms ,reduce fibrin level ,blood viscosity and platelet aggrega-tion,and its security is good ,which is worth to be applied in clinical . Key words: Brain infarction; Butylphenol; Edaravone

Observation of the effect of butylphthalide combined with nimodipine in the treatment of vascular cognitive impairment

Objective To investigate the effect of butylphthalide combined with nimodipine in the treatment of vascular cognitive impairment.Methods 160 patients with vascular cognitive impairment were divided into the control group and the observation group according to treatment methods,80 cases in each group.The control group was treated with nimodipine,and the observation group was given butylphthalide combined with nimodipine treatment.The therapeutic effect and cognitive function were compared.Results The obvious effective rate of the observation group was 58.75 ％ (47/80),which was significantly higher than that of control group 45 ％ (36/80) (P =0.03).After treatment,MoCA score of the observation group was (24.83 ± 9.48),which was significantly higher than that of the control group(21.64 ±9.52) (P =0.04).ADL score of the observation group was(58.31 ± 11.27),which was significantly higher than(53.28 ± 10.32) of the control group (P =0.04).After treatment,directional force,visual spatial and executive function,delayed memory and attention of the observation group were higher than those of the control group (P =0.03,0.02,0.04,0.02).Conclusion Butylphthalide combined with nimodipine in the treatment of patients with vascular cognitive impairment has good effect. Key words: Cognitive function impairment ; Butylphthalide; Nimodipine

The Effect of Butylphthalide on the Brain Edema, Blood–Brain Barrier of Rats After Focal Cerebral Infarction and the Expression of Rho A

The aim of this study was to explore the effect of butylphthalide on the brain edema, blood-brain barrier of rats of rats after focal cerebral infarction and the expression of Rho A. A total of 195 sprague-dawley male rats were randomly divided into control group, model group, and butylphthalide group (40 mg/kg, once a day, by gavage). The model was made by photochemical method. After surgery 3, 12, 24, 72, and 144 h, brain water content was done to see the effect of butylphthalide for the cerebral edema. Evans blue extravasation method was done to see the changes in blood-brain barrier immunohistochemistry, and Western blot was done to see the expression of Rho A around the infarction. Compared with the control group, the brain water content of model group and butylphthalide group rats was increased, the permeability of blood-brain barrier of model group and butylphthalide group rats was increased, and the Rho A protein of model group and butylphthalide group rats was increased. Compared with the model group, the brain water content of butylphthalide group rats was induced (73.67 ± 0.67 vs 74.14 ± 0.46; 74.89 ± 0.57 vs 75.61 ± 0.52; 77.49 ± 0.34 vs 79.33 ± 0.49; 76.31 ± 0.56 vs 78.01 ± 0.48; 72.36 ± 0.44 vs 73.12 ± 0.73; P < 0.05), the permeability of blood-brain barrier of butylphthalide group rats was induced (319.20 ± 8.11 vs 394.60 ± 6.19; 210.40 ± 9.56 vs 266.40 ± 7.99; 188.00 ± 9.22 vs 232.40 ± 7.89; 288.40 ± 7.86 vs 336.00 ± 6.71; 166.60 ± 6.23 vs 213.60 ± 13.79; P < 0.05), and the Rho A protein of butylphthalide group rats was decreased (western blot result: 1.2230 ± 0.0254 vs 1.3970 ± 0.0276; 1.5985 ± 0.0206 vs 2.0368 ± 0.0179; 1.4229 ± 0.0167 vs 1.7930 ± 0.0158;1.3126 ± 0.0236 vs 1.5471 ± 0.0158; P < 0.05). The butylphthalide could reduce the brain edema, protect the blood-brain barrier, and decrease the expression of Rho A around the infarction.