Objective To analyze the methodological quality of clinical trails on butylphthalide for cerebral ischemic stroke. Methods We collected all of the published clinical studies on butylphthalide for cerebral ischemic stroke in the world, and evaluated the methodological quality of the included studies according to clinical epidemiologic standard. The search time was from the establishment of each database to December, 2009. Results A total of 62 studies involving 5 762 patients were included. In all included studies, there were 56 randomized controlled trials (RCTs). A total of 8 studies described the method of random assignments. There were 4 multi-center randomized double-blind placebo-control trials. A total of 55 reported diagnosis criteria, 40 reported included criteria, 28 reported excluded criteria; 36 reported the curative efficacy at the end of the treatment, 51 assessed the neurological deficit score of patients before and after the treatment, 27 evaluated the ADL scores; 32 studies reported the side effects; 6 trials did not conduct intention-to-treat analysis even though some people withdrew the treatment because of the side effects or poor tolerance, etc. Conclusion Except for several high quality RCTs, current quality of some clinical trials on butylphthalide for ischemic stroke should be improved. We recommend that researchers should use internationally accepted consolidate standards of reporting trials (CONSORT) in future studies.
ObjectiveTo observe the protective effect of dl-3-n-Butylphthalide (NBP) on apoptosis of retinal Müller cells induced by hydrogen peroxide (H2O2).MethodsHuman retinal Müller 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. Müller 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 Müller 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.ResultsHE 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.ConclusionNBP alleviates H2O2-induced apoptosis of human retinal Müller cells by inhibiting ROS production.
ObjectiveTo investigate the protective effect of butylphenyphthalein (NBP) on RPE apoptosis induced by H2O2.MethodsThe 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.ResultsThe 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).ConclusionsOxidative 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.
ObjectivesTo systematically review the efficacy and safety of butylphthalide soft capsule with routine treatment for Alzheimer’s disease (AD).MethodsDatabases including CNKI, WanFang Data, VIP, CBM, PubMed, EMbase, and The Cochrane Library were electronically searched from September 2002 to July 2018 to collect randomized controlled trials of butylphthalide soft capsule with routine treatment for Alzheimer’s disease. The trial was screened based on inclusion and exclusion criteria, and the methodological quality of the included trial was assessed. Meta-analysis was then performed by Revman 5.3 software.ResultsA total of 8 studies involving 576 patients were included. The butylphthalide soft capsule group included 283 patients and the control group included 293 patients. The result of meta-analysis showed that butylphthalide soft capsule with routine treatment (Donepezil hydrochloride or Memantine or EGb761) significantly improved the score of mini-mental state examination (MMSE) (MD=3.19, 95% CI 2.69 to 3.69, P<0.001) and clinical efficacy (RR=1.36, 95%CI 1.21 to 1.53, P<0.001). There was no significant difference in number of adverse events between the butylphthalide group and the control group (RR=1.13, 95%CI 0.77 to 1.67, P=0.52).ConclusionsBased on the routine treatment, combining with butylphthalide soft capsule can further facilitate cognitive function of AD and improve clinical efficacy. At the same time, no increase in adverse reactions has been found. However, due to the low quality of the included studies, more high quality randomized controlled trials are required to verify the results.
ObjectivesTo systematically evaluate the efficacy and safety of butylphthalide soft capsule in the treatment of vascular dementia (VaD).MethodsDatabases including CNKI, WanFang Data, VIP, CBM, PubMed, EMbase, The Cochrane Library were electronically searched to collect randomized controlled trials of butylphthalide soft capsule in the treatment of vascular dementia published from September 2002 to July 2018. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software.ResultsA total of 15 studies involving 1 149 patients were included. The butylphthalide soft capsule treatment group included 578 patients and the control group included 571 patients. The results of meta-analysis showed that compared with the control group (donepezil hydrochloride tablets or memantine hydrochloride tablets or EGb761 or negative control), the butylphthalide soft capsule treatment group improved the MMSE score of patients with VaD (MD=3.52, 95%CI 2.59 to 4.46, P<0.01), CDR score (MD=−0.72, 95%CI −0.80 to −0.65, P<0.01), and treatment efficiency (RR=1.31, 95%CI 1.20 to 1.43, P<0.01). However, there was no statistical difference in the number of adverse reactions between the treatment and control groups.ConclusionsButylphthalide soft capsule can be used in the treatment of patients with mild to moderate VaD. It can improve the cognitive function, raking of clinical dementia, and increase the effect rate of treatment. It can also work in conjunction with other drugs that improve cognitive function and no increase in adverse reactions has been found. However, due to the low quality of the included studies and small sample size, the actual efficacy strength is uncertain and the above conclusions are still required to be verified by more high-quality randomized controlled trials.