Efficacy and Safety of Breviscapine Injection Combined with Routine Treatment of AECOPD ：A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate therapeutic efficacy and safety of Breviscapine injection combined with routine treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD），and to provide evidence-based reference for clinical drug use. METHODS ：Retrieved from Cochrane Library ，PubMed，Embase，CBMdisc，CNKI，VIP and Wanfang database ，randomized controlled trials （RCTs）about Breviscapine injection combined with routine treatment （trial group ） versus routine treatment （control group ）in the treatment of AECOPD were collected. After literature screening and data extraction ， the qualities of literatures were evaluated with modified Jadad scale ；Meta-analysis was performed by using Rev Man 5.2 statistical software. RESULTS ：A total of 19 RCTs were included ，involving 1 930 patients. Results of Meta-analysis showed that total response rate [OR ＝2.80，95％ CI （1.96，4.01），P＜0.000 01]，FEV1[MD＝0.65，95％ CI（0.57，0.72），P＜0.000 01]， FEV1％[MD＝5.33，95％CI（0.31，10.35），P＝0.04]，FVC[MD＝0.69，95％CI（0.23，1.16），P＝0.004]， FEV1/FVC [MD ＝ 4.83，95％CI（0.98，8.67），P＝0.01]，PEF [M D＝0.95，95％CI （0.57，1.33），P＜0.001]，PaO2 [MD＝4.70，95％CI（2.02， No.81402991） + 7.37），P＜0.001]，CD3 level [MD ＝5.11，95％ CI（3.04， 7.18），P＜0.001] and CD 4+ level [MD ＝2.62，95％CI（1.78， qq.com 3.47），P＜0.001] of trial group were significantly higher than those of control group ；PaCO2 [MD＝－3.33，95％CI（－5.02， －1.65），P＜0.001]，CD8+ level [MD ＝－2.55，95％CI（－4.28，－0.82），P＜0.004]，cough relief time [MD ＝－1.93，95％CI （－2.24，－1.63），P＜0.001]，sputum remission time [MD ＝－2.19，95％CI（－2.48，－1.89），P＜0.001]，wheezing remission time [MD ＝－1.59，95％CI（－1.86，－1.32），P＜0.001] and hospital stay [MD ＝－1.73，95％CI（－2.06，－1.39），P＜0.001] of trial groups were significantly lower or shorter than those of control group ；there was no statistical significance in CD 4+/CD8+ between 2 groups [MD ＝－0.11，95％CI（－0.23，0.01），P＝0.06]. In terms of safety ，3 studies reported the occurrence of ADR ， and no serious ADR occurred. CONCLUSIONS ：Breviscapine injection can improve clinical efficacy and lung function ，enhance immunity in patients with AECOPD with good safety.

Efficacy and safety of Breviscapine Injection in treatment of diabetic nephropathy: systematic review and Meta-analysis of randomized controlled trials / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of Breviscapine Injection in the treatment of diabetic nephropathy( DN). Eight electronic databases and Clinical Trials.gov were searched to collect randomized controlled trials on Breviscapine Injection in the treatment of DN. According to the Cochrane Handbook 5. 1,two independent reviewers screened out the literatures,extracted data and assessed the quality of the studies included. Rev Man5. 3 software was used for the data analysis. A total of 29 studies containing 37 trials were included,involving 2 097 patients,1 054 cases in test groups and 1 043 cases in control groups. The clinical studies included had a low overall quality. According to Meta-analysis: ①Conventional therapy plus breviscapine injection was superior to conventional therapy in total efficiency rate,24 h UTP,SCR,BUN,UEAR,ALB and m ALB during DN stage Ⅲ( RRtotal effective rate=1. 60,95%CI [1. 32,1. 93],P<0. 000 01; SMD24 h UTP=-1. 21,95%CI[-1. 56,-0. 87],P<0. 000 01; MDSCR=-6. 33,95%CI[-9. 20,-3. 46],P<0. 000 1; MDBUN=-6. 6,95%CI[-1. 10,-0. 22],P = 0. 003; MDUEAR=-20. 30,95%CI [-28. 14,-12. 46],P<0. 000 01; MDALB= 0. 47,95%CI[0. 42,0. 52],P<0. 000 01; MDmALB=-10. 03,95%CI[-10. 62,-9. 46],P<0. 000 01). ②Conventional therapy plus Breviscapine Injection was better than conventional therapy in total efficiency rate( only 1 study),24 h UTP,SCR and BUN during DN stage Ⅳ( RRtotal effective rate= 1. 57,95% CI[1. 10,2. 25],P = 0. 01; SMD24 h UTP=-0. 52,95% CI [-0. 71,-0. 33],P<0. 000 01; MDSCR=-35. 38,95%CI[-48. 57,-22. 19],P<0. 000 01; MDBUN=-1. 89,95%CI [-3. 01,-0. 77],P<0. 000 01). ③Conventional therapy plus Breviscapine Injection was better than conventional therapy in SCR( MD =-26. 35,95% CI[-47. 45,-5. 24],P= 0. 01),but with no significant difference in 24 h UTP,BUN and ALB during DN stageⅤ. ④It was impossible to obtain the specific judgment information on the adverse reactions of Breviscapine Injection in the treatment of the disease from the existing evidences. The current evidences suggest that the combination of Breviscapine Injection and conventional therapy had a certain curative effect in the treatment of DN,especially in stages Ⅲ and Ⅳ. The safety of Breviscapine Injection needs to be further explored.Because the low quality of the study impacted the accuracy of the result,more rigorous,high-quality,multi-center,randomized doubleblind controlled trials are required to increase the support of the evidences in the future.

Efficacy and safety of breviscapine injection in treatment of unstable angina pectoris: systematic review and Meta-analysis / 中国中药杂志

To systematically evaluate the efficacy and safety of breviscapine injection in the treatment of unstable angina pectoris (UAP). Eight electronic databases and clinical trials registries were searched to collect randomized controlled trials on breviscapine injection in the treatment of UAP. According to the evaluation standards in Cochrane Handbook 5.1, two independent reviewers screened out the literature, extracted data and assessed the quality of the studies included. RevMan 5.3 software was used for Meta quantitative analysis and corresponding description analysis. A total of 36 studies involving 3 058 patients were included, 1 552 cases in the trial group, 1 506 cases in the control group, 1 846 males and 1 212 females. All the clinical studies showed a low quality. Meta-analysis results showed that the combination of breviscapine injection and conventional therapy was superior to conventional therapy in angina pectoris efficacy (RRangina pectoris efficacy=1.29, 95%CI[1.23,1.35],<0.000 01；RRECG1=1.25,95%CI[1.12,1.38],<0.000 1；RRECG2=1.38,95%CI[1.27,1.49],<0.000 01); descriptive analysis of a single study showed that the efficacy of combination of breviscapine injection and conventional therapy was superior to that of conventional therapy alone. In respect of hemorheology, the combination of breviscapine injection and conventional therapy was better than conventional therapy in lowering LBV and EAI (MDLBV=-1.27,95%CI[-1.55,-0.99],<0.000 01；MDEAI=-0.38,95%CI[-0.60,-0.16],=0.000 6), as well as in lowering WBV and HCT in the descriptive analysis of single study. In respect of blood lipid, the combination of breviscapine injection and conventional therapy was better than conventional therapy in lowering TC, TG and LDL-C (MDTC=-0.30,95%CI[-0.51,-0.10],=0.003；MDTG=-0.32,95%CI[-0.77,0.13],=0.16；MDLDL-C=-0.45,95%CI[-0.76,-0.14],=0.004). In reducing the frequency of angina attacks, heart rate, high sensitive C-reactive protein and improving exercise tolerance, the combination of breviscapine injection and conventional therapy was also superior to the conventional therapy alone (MDFAP=-3.30,95%CI[-4.06,-2.54],< 0.000 01；MDHR=-9.38,95%CI[-12.78,-5.98],=0.000 2；MDhs-CRP=-0.56,95%CI[-0.85,-0.27],=0.000 2；MDET=0.88,95%CI[0.41,1.35],=0.000 2). The main adverse reactions in the two groups included headache, dizziness, palpitations, nausea, abdominal distension, skin pruritus, flushes and allergic reactions in the study. The safety of breviscapine injection needs to be further studied and clarified because of the combination of drugs and the incomplete information reported in the original study. The current evidence suggested that the combination of breviscapine injection and conventional therapy had certain advantages in curative effect for the treatment of UAP. Due to the low quality of the study and its own shortcomings, it is necessary to design more rigorous, high-quality, multi-center randomized double-blind controlled trials to increase the strength of the evidence.

Breviscapine pretreatment attenuates ischemia reperfusion induced intestinal mucosal barrier damage via promoting eNOS/NO production / 实用医学杂志

Objective To investigate the effects of breviscapine injection on intestinal mucosal barrier damage induced by intestine ischemia-reperfusion (IIR). Methods 44 old SD rats were randomly divided into four groups:sham,intestine ischemia-reperfusion(IIR),EB+IIR,LN+IIR. Breviscapine injection 20 mg/(kg·d) was given intraperitoneally in EB+IIR group. L-NAME(100 mg/kg)was given intravenously 30 min before surgery in LN+IIR group. Rats were subjected to superior mesenteric artery occlusion consisting of 45 min of ischemia and 4 h of reperfusion;sham laparotomy served as controls. Intestine pathology was assayed by H&E staining. Concen-trations of SIgA,iNOS,eNOS and NO in intestinal mucosa,also endotoxine in plasma,were determined by ELI-SA. Results IIR induced serious intestinal mechanical and immune barrier damage ,evidenced as poor intestine pathology,depression of intestinal SIgA and eNOS levels,elevation of intestinal iNOS/NO levels. However,brevis-capine injection pretreatment could promote eNOS/NO production ,down-regulated iNOS expression ,leading to ele-vating SIgA concentration in intestine ,attenuate endotoxemia induced by IIR. The protection was canceled when application of L-NAME. Conclusion Breviscapine pretreatment attenuates ischemia-reperfusion-induced intestinal mucosal barrier damage via promoting eNOS/NO production.

Meta-analysis on the randomized controlled trials of breviscapine injection plus conventional therapy for unstable angina pectoris / 国际中医中药杂志

Objective To systematically evaluate the clinical effectiveness and safety of Breviscapine injection combined with conventional therapy in the treatment of unstable angina pectoris (UAP).Methods The literature were systematicly retrieved about the randomized controlled trials (RCTs) of Breviscapine injection for UAP. The Cochrane Risk of Bias Assessment Table was used to evaluate the methodological quality of the RCTs and then the data were extracted and meta-analysed by RevMan 5.3 software.Results A total of 15 RCTs with 1202 participants were included. In the meta-analysis, the combination of Breviscapine injection and conventional therapy in the treatment of UAP can achieve better angina pectoris curative effect (Z=7.74,P<0.01), theRR(95% CI) was 1.23 (1.17,1.30), and the electrocardiogram curative effect (Z=6.26,P<0.01), the RR(95% CI) was 1.32(1.21, 1.44). Furthermore, Breviscapine injection can improve hemorheologic parameters. And there was no major or serious adverse drug event.Conclusions The Breviscapine injection combined with conventional therapy shows good therapeutic effect on UAP.

Breviscapine reduces intestinal ischemia reperfusion via inhibiting IκB-α/NF-κB/ICAM-1 pathway in a rat model / 实用医学杂志

Objective To investigate the effects of breviscapine injection on intestinal injury induced by intestine ischemia-reperfusion(IIR). Methods 48 males SD rats with 8-week old were randomly divided into 4 groups:Sham,intestine ischemia-reperfusion(IIR),EB+IIR,TP+IIR. Breviscapine injection 20 mg/(kg·d) was given intraperitoneally in EB + IIR group. TPCA-1(12 mg/kg)was given intravenously 30 min before surgery in TP+IIR group. Rats were subjected to superior mesenteric artery occlusion consisting of 45 min of ischemia and 6 h of reperfusion;sham laparotomy served as controls. Intestine pathology was assayed by H&E staining. Con-centrations of TNF-α,IL-1β,and IL-6 in intestinal mucosa were determined by ELISA. The protein expressions of IκB-α,NF-κB ,ICAM-1of intestine tissue were assayed by western blot. Results IIR induced serious intesti-nal injury ,evidenced as poor intestine pathology ,elevation of TNF-α,IL-1β,and IL-6 levels in intestinal mu- cosa,accompanied with IκB-α/NF-κB/ICAM-1 pathway activation. However,breviscapine injection pretreatment could inhibit IκB-α/NF-κB/ICAM-1 pathway activation,leading to reduction of TNF-α,IL-1β,and IL-6 concen-trations in lung,finally attenuate ALI induced by IIR. Conclusion Breviscapine injection pretreatment could atten-uate inflammation in intestine after IIR injury via inhibiting IκB-α/NF-κB/ICAM-1signaling pathway.

Breviscapine reduces intestinal ischemia reperfusion via inhibiting IκB-α/NF-κB/ICAM-1 pathway in a rat model / 实用医学杂志

Objective To investigate the effects of breviscapine injection on intestinal injury induced by intestine ischemia-reperfusion(IIR). Methods 48 males SD rats with 8-week old were randomly divided into 4 groups:Sham,intestine ischemia-reperfusion(IIR),EB+IIR,TP+IIR. Breviscapine injection 20 mg/(kg·d) was given intraperitoneally in EB + IIR group. TPCA-1(12 mg/kg)was given intravenously 30 min before surgery in TP+IIR group. Rats were subjected to superior mesenteric artery occlusion consisting of 45 min of ischemia and 6 h of reperfusion;sham laparotomy served as controls. Intestine pathology was assayed by H&E staining. Con-centrations of TNF-α,IL-1β,and IL-6 in intestinal mucosa were determined by ELISA. The protein expressions of IκB-α,NF-κB ,ICAM-1of intestine tissue were assayed by western blot. Results IIR induced serious intesti-nal injury ,evidenced as poor intestine pathology ,elevation of TNF-α,IL-1β,and IL-6 levels in intestinal mu- cosa,accompanied with IκB-α/NF-κB/ICAM-1 pathway activation. However,breviscapine injection pretreatment could inhibit IκB-α/NF-κB/ICAM-1 pathway activation,leading to reduction of TNF-α,IL-1β,and IL-6 concen-trations in lung,finally attenuate ALI induced by IIR. Conclusion Breviscapine injection pretreatment could atten-uate inflammation in intestine after IIR injury via inhibiting IκB-α/NF-κB/ICAM-1signaling pathway.

Effects of Breviscapine Injection on Blood Biochemical Indexes and Hemorheology Indexes in Patients with Acute Cerebral Infarction / 中国药房

OBJECTIVE:To observe the effects of Breviscapine injection on serum copeptin,NT-proBNP and ischemia modi-fied albumin (IMA) level and hemorheology indexes in patients with acute cerebral infarction. METHODS:Data of 132 patients with acute cerebral infarction were selected and randomly divided into observation group(66 cases)and control group(66 cases). Control group received 1 Aspirin enteric-coated tablet,qd + 20 ml Muscular amino acids and nucleosides injection adding into 500 ml 0.9% Sodium chloride solution,intravenous infusion,qd + 4 ml Ozagrel injection adding into 250 ml Sodium chloride solution, intravenous infusion,qd. Observation group was additionally given 5 ml Breviscapine injection adding into 250 ml 0.9% Sodium chloride solution,intravenous infusion,qd. 7 d ag was regarded as 1 treatment course,it lasted for 2 courses. Copeptin,NT-proB-NP,IMA levels (showed by serum ACB value) and changes of related hemorheology indexes before and after treatment in 2 groups were observed. RESULTS:Before treatment,there was no significant difference in Copeptin,NT-proBNP,serum ACB val-ue,whole blood viscosity,plasma viscosity,hematocrit,ESR and fibrinogen levels in 2 groups(P>0.05);after treatment,Co-peptin,NT-proBNP,whole blood viscosity,plasma viscosity,hematocrit,ESR and fibrinogen levels in 2 groups were significant-ly lower than before,and observation group was lower than control group,while serum ACB value was significantly higher than be-fore,and observation group was significantly higher than control group,the differences were statistically significant(P<0.05). CONCLUSIONS:Based on conventional treatment,Breviscapine injection can significantly improve the copeptin,NT-proBNp and IMA levels,and improve hemorrheology.

Comparison of methods for active systemic anaphylactic reaction of guinea pigs induced by breviscapine injection / 中国药理学与毒理学杂志

OBJECTIVE To compare the difference of methods for active systemic anaphylactic reaction induced by breviscapine injection between ″Pharmacopoeia″ 2010 edition, an Attached ⅫG in Traditional Chinese Medicine lnjection Safety Test Application Guidelines ″ Anaphylactic Reaction Test″(thereafter referred to as the method of ″Pharmacopoeia″) and the Traditional Chinese Medicine, Natural Medicine lmmune Toxicity (Anaphylaxis, Anaphylactic Reaction of Light) Technology Guiding Principles in the 2005 Version (thereafter referred to as the method of ″Guiding Principle″) and provide reference for non-clinical safety evaluation of drugs. METHODS According to the methods of ″Pharmacopoeia″and ″Guiding Principle″, respectively, the effect of breviscapine injection on active systemic anaphylactic reaction of guinea pigs was investigated. The guinea pigs were divided into four groups, negative control group, positive control group, breviscapine injection 5 and 50 mg.kg-1 groups. ln the sensitization phase, the guinea pigs were ip administrered with breviscapine injection 0.5 mL each every other day for 3 times. The dose was 5 and 50 mg.kg-1 , respectively. For the method of ″Pharmacopoeia″, on the 14th and 21st days after the first sensitization, the guinea pigs were iv administrered with breviscapine injec-tion 1 mL. For the method of ″Guiding Principle″, the guinea pigs were provocated on the 12th day after the first sensitization. Each group was studied by observing the symptom of anaphylactic reaction and immune time. RESULTS For the method of ″Pharmacopoeia″, on the 14th day after the first sensitization, there was 1 guinea pig with sneezing and (or) the nose-scratching at different time in the 5 mg.kg-1 group. ln the 50 mg.kg-1 group, there was one or two cases of sneezing and (or) 1 case of nose-scratc-hing. The 5 and 50 mg.kg-1 dose groups conformed to the regulations. On the 21st day after the first sensitization, trembling occurred in the 5 mg.kg-1 group, with 1 or 2 guinea pigs sneezing and ( or) scratching the nose. There were 4 guinea pigs (4/ 4) with sneezing 1 and 3 times, cough once or twice, 1 scratching nose and urination at different time, and 1 guinea pigs (1/ 4) appeared 3 times consecutive sneezing and shivering in 50 mg.kg-1 group. The 5 mg.kg-1 group conformed to the regulations, while the 50 mg.kg-1 group did not. For the method of ″Guiding Principle″, the 5 mg.kg-1 group was weak positive or positive, with different degrees of symptoms of an anaphylactic reaction, including 3 guinea pigs scratched nasal symptoms. And the 50 mg.kg-1 group of anaphylactic symptoms including scratc-hing nose, sneezing, coughing and (or) urination, showed positive. CONCLUSION During the active systemic anaphylactic reaction of drugs non-clinical safety evaluation of drugs the advantage of either method should be brought into play. The method of ″ Pharmacopoeia″ may be used for preliminary screening of test samples. ln case pf suspected reactions, the method of ″Guiding Principle″ should be used for more detailed observations.

Influence of Breviscapine Injection on IGF of Pregnant Rats and Growth of Fetus Rats / 国际中医中药杂志

Objective To discuss the influence of Breviscapine Injection on concentration of serum IGF-Ⅱ in pregnant rats and changes of fetus rat body weight, body length, and body-mass index. Methods Radio-immunity was used to determine the concentration of serum IGF- Ⅱ in mother rats and fetus rats. Body weight and body length were surveyed,the IGF- Ⅱ concentration of fetus rats in the FGR group was lower than the control group (P＜0.05) and IGF- Ⅱ concentration control group＞the FGR+intervention group＞ the FGR group, and the difference between each group was significant (P＜0.05).Breviscapine can treat fetal growth retardation effectively.

Clinical Observation on Therapeutic Effect of Breviscapine Injection on Migraine / 中国药房

OBJECTIVE:To observe the therapeutic effect of Breviscapine injection in treating migraine. METHODS: 81 patients with migraine were randomly divided into two groups: 42 in treatment group were treated with Breviscapine injection 20 mL added to 5% Glucose injection 300 mL iv gtt q.d, and 39 in control group with Flunarizine 10 mg po quaque nocte. The treatment lasted for 2 courses (1 course of treatment lasted 14 days) with an interval of 15 days between the two courses. The patients were followed for more than 6 months. The curative effects between the 2 groups were compared, and the variations in hemorheological indexes of the 2 groups before and after treatment were observed. RESULTS:The efficacy in the treatment was signficantly higher than in the control gorup(P

Determination of scutellarin in BREVISCAPINE INJECTION by HPLC / 中成药

Objective:To study the determination method of scutellarin in BREVISCAPINE INJECTION using HPLC.Methods:The waters ODS C 18 column (5?m,3.9?150mm) was used. The methanol water glacial acetic acid (40∶60∶1) was used as a mobile phase. The detection wavelength of scutellarin was set at 335nm and internal standard baicalin at 280nm. The resolution of scutellarin's and baicalin peaks was at least 5. Number of theoretical plates of column is no less than 1000 to scutellarin. Results:The recovery of additive sample is 99.8%. RSD is no more 2.0%.Conclusion: It is generally in agreement with external standard method.