Intervention effect and mechanism of breviscapine on hepatic fibrosis in rats / 中国药房

OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Expert consensus on Injection of Breviscapine in clinical practice / 中国中药杂志

With the advancement of the aging process, cerebrovascular disease has become China's first cause of death. Injection of Breviscapine is a type of traditional Chinese medicine injections published in the Chinese Pharmacopoeia of 2015 Edition and the National Basic Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drug Catalogue, and used to treat ischemic cerebrovascular disease in clinic. In order to further improve clinicians' understanding of the drug and guidance of its rational clinical use, we gave full consideration of clinical research evidences and expert experience, followed the procedures developed based on expert consensus of Chinese Academy of Traditional Chinese Medicine, and then offered recommendations for clinical problems summarized by clinical first-line investigations and evidence-based clinical problems according to internationally accepted evidence grading and recommendation standards, i.e. Grade. As for clinical problems without evidence, we reached through nominal group method, and formed consensus recommendations. Safety issues of Injection of Breviscapine, such as indication, syndrome, dosage, course of treatment, precautions, suggestions and contraindications, were defined to improve clinical efficacy, promote rational drug use and reduce drug risks. This consensus needs to be revised in the future based on emerging clinical issues and evidence-based updates in practical applications.

Preparation and Quality Evaluation of Breviscapine Nanocrystals / 中国药房

OBJECTIVE：To prepare Brevisc apine（BRE） nanocrystals，and to evaluate its quality. METHODS ：BRE nanocrystal suspensions were prepared by media milling method. The diameter and amount of grinding beads ，grinding time ，type and ratio of stabilizer ，BRE ratio were investigated to screen the optimal technology and formulation with particle size and polydispersity index （PDI） as evaluation indexes. Using morphology ，color，particle size and PDI of BRE nanocrystals as evaluation index ，different lyoprotectants （50％ mannitol，5％ glucose，5％ lactose）and without lyoprotectant were investigated to screen the optimal lyoprotectant. Particle size analyzer ，scanning electron microscope （SEM），X-Ray diffraction （XRPD）， differential scanning calorimeter （DSC）were used to evaluate the quality of BRE nanocrystals which was prepared with the optimal technology and formulation. RESULTS ：The optimal technology and formulation of BRE nanocrystals included that particle size of 0.6 mm zirconia beads with the amount of 450 g，grinding time of 1 h，stabilizer of 15％ Tween-80，BRE ratio of 25％，without lyoprotectant. Prepared BRE nanocrystals were yellow powder with loose texture and uniform color. The average particle size of BRE nanocrystals was （283.10±3.08）nm，average PDI was （0.212±0.021）and average Zeta potential was （－38.48±0.39）mV. BRE nanocrystals were rod-like crystals ，uniform in distribution and had no change in crystalline state. Accumulative dissolution of BRE nanocrystals were （90.37±1.22）％ within 20 min. Under the condition of （40±2）℃ temperature and （75±5）％ relative humidity，BRE nanocrystals remained stable after being kept away from light for 3 months. CONCLUSIONS ：Established preparation method of BRE nanocrystals is simple and feasible. Prepared BRE nanocrystals show good stablility and dissolution.

Preparation and Quality Evaluation of Breviscapine Gastric Adhesive Tablets / 中国药房

OBJECTIVE：To prepar e Breviscapine gastric adhesive tablets ，to optimize the formulation and to evaluate the quality. METHODS ：HPMC K 100M and carbomer 934P were used as bioadhesives and skeleton materials ，and lactose was used as filler，and magnesium stearate was used as glidant and lubricant to prepare Breviscapine gastric adhesive tablets by direct powder pressing method. The comprehensive scores of scores of accumulative release rate of Breviscapine gastric adhesive tablets in pH 6.8 PBS at 2，6，12 h（Q2 h，Q6 h，Q12 h，with scutellarin meter ，by HPLC method ）and in vitro adhesion force of gastric tissue were evaluated by weighting method. Taking this scores as indexes，L9（34）orthogonal test design was used to optimize the amount of HPMC K 100M，carbomer 934P and lactose in Breviscapine gastric adhesive tablets and validation tests were conducted. The properties，identification，weight difference ，fragility，release and the content of scutellarin of the gastric adhesive tablets were determined. RESULTS ：The optimal prescription of Breviscapine gastric adhesive tablets were 42％ breviscapine，10％ HPMC K100M，3％ carbomer 934P and 45％ lactose. The verification test results show that the Q2 h，Q6 h，Q12 h of 3 batches of Breviscapine gastric adhesive tablets were 20.36％，48.55％，and 87.00％ ；the average in vitro adhesion force of gastric tissue was 31.36 g/cm2；the average comprehensive score was 70.23（RSD＝1.84％，n＝3）. The gastric adhesive tablets were light yellow，tasteless or slightly salty ；the peak time was consistent with that of scutellarin control ；its weight difference were ±6％， the fragility was 0.54％，and the Q12 h was 83.51％（RSD＝2.14％，n＝6）. The content of scutellarin was 288.47 mg/g（RSD＝ 0.70％，n＝3）. CONCLUSIONS ：Breviscapine gastric adhesive tablets is prepared successfully ，and its quality evaluation conforms to the requirements of Chinese Pharmacopoeia （2015 edition）.

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.

Progress in Prevention and Treatment of Diabetic Complications with Breviscapine / 中国实验方剂学杂志

Erigeron breviscapus, a species within the genus of Erigeron, is mainly distributed in Southwest China. It is cold in property, slightly bitter in taste, and has the effect of dispersing cold table, removing wind and dehumidification, promoting blood circulation and removing blood stasis, relieving pain and inflammation. Breviscapine is the extract of E. breviscapus. It is mainly consisted of flavonoids, lignans, coumarins, terpenes, phytosterols, etc. As the major components of breviscapine, the content of breviscapine b (4′-hydroxybaicalin-7-O-glucuronide) and breviscapine a (apigenin-7-O-glucuronide) is greater than 90%. Modern pharmacological studies have shown that breviscapine has a wide range of pharmacological effects, including anti-oxidation, anti-fibrosis, anti-inflammation, anti-aging, anti-platelet aggregation, lowering blood lipid, increasing blood flow, improving microcirculation, preventing and treating tumors, and resisting brain injury. In clinical, breviscapine has been widely used in the treatment of diabetes, cerebral insufficiency, sequelae caused by cerebral hemorrhage, hypermucolipemia, cerebral thrombosis, kidney disease, liver disease, Alzheimer's disease, and some other complex diseases. Specially, in the treatment of diabetes and its chronic complications, such as diabetic nephropathy, diabetic cardiomyopathy, diabetic foot, diabetic retinopathy, breviscapine has showed significant efficacy. In addition, studies have demonstrated that the combined application of breviscapine, mecobalamine, and micopol can improve the therapeutic effect. In this work, the application of breviscapine in the treatment of chronic complications of diabetes mellitus and its related combination drugs were reviewed, by which we attempted to provide some valuable clues for the clinical application of breviscapine in the treatment of diabetes mellitus and its chronic complications.

Breviscapine induced the apoptosis of non-small cell lung cancer A549 cells / 中国临床药理学与治疗学

AIM: To analyze the apoptosis promoting effect of breviscapine on NSCLC cells and the growth of transplanted tumor and investigate the mechanism. METHODS: The apoptosis, Caspase-3 activity, Bax and Bcl-2 expression of A549 cells treated with 25, 50 and 100 μmol/L breviscapine were detected. The subcutaneous transplanted tumor model was constructed with A549 cells. The mice were intraperitoneally injected with 10 mg/kg and 20 mg/kg breviscapine every day. The size and weight of the tumor were observed every week. On the 21st day, the mice were killed and the tumor was obtained. The expression of Bax and Bcl-2 was detected by Western blot. Bax/Bcl-2 ratio was analyzed. Caspase-3 expression was detected by immunohistochemistry and apoptosis in the tumor was detected by TUNEL staining. RESULTS: Breviscapine increased the apoptosis rate of A549 cells. The results of enzyme labeling showed that Caspase-3 activity increased significantly after breviscapine treatment compared with the control group. Western blot showed that breviscapine could significantly inhibit the expression of anti-apoptosis protein Bcl-2, increase the expression of pro-apoptosis protein Bax, and increase the ratio of Bax/Bcl-2. In vivo, on the 14th and 21st day, the tumor size of the treatment group was significantly smaller than that of the control group, while the weight of nude mice was not significantly reduced. Western blot showed that breviscapine could upregulate the expression of Bax and down regulate the expression of Bcl-2 in the transplanted tumor, while the expression of Caspase-3 was significantly increased. TUNEL staining showed that the proportion of apoptosis increased significantly compared with the control after breviscapine treatment. CONCLUSION: Breviscapine can induce the apoptosis of A549 cells in vitro and in vivo. The mechanism may be that breviscapine upregulates Bax expression and downregulates Bcl-2 expression, increases Bax/Bcl-2 ratio, activates Caspase-3, resulting in A549 cell apoptosis.

Analysis and structural identification of relevant substances in Breviscapine for Injection / 中国中药杂志

To define the composition of relevant substances in Breviscapine for Injection, in order to improve the quality control of impurity, and ensure the clinical safety. The analysis and structural identification of relevant substances in different specifications and batches of Breviscapine for Injection powders were carried out by HPLC and UPLC-QTOF-MS. Three primary relevant substances, namely 5,6,7,3',4'-pentahydroxyflavone-7-O-glucuronide(3), 3,5,6,7,4'-pentahydroxyflavone-3-O-glucuronide(4) and scutellarein(10), as well as three minor impurities, namely 6-hydroxyapigenin-6-O-glucosyl-7-O-glucuronide(1), methoxylscutellarin(6) and apigenin-7-O-glucuronide(7) were structurally identified by matching retention time, UV spectra, and mass spectra with authentic compounds and MS fragmentation rules. The main relevant substances(3) and(4) were separated and purified by semi-preparative HPLC, and their structures were further confirmed by NMR data. The study defined relevant substances of Breviscapine for Injection, and provided reference for improving the quality control level of single impurity in breviscapine preparation.

Role of scutellarin in human cancer—A review

Scutellarin is a flavone glycoside isolated from Erigeron breviscapus, a perennial herb of the daisy family Asteraceae.The scutellarin-rich extract of E. breviscapus, known as breviscapine, has been used as a traditional Chinese medicineto improve blood circulation and cerebral blood supply. There is increasing scientific evidence affirming that scutellarinpossesses pharmacological properties, notably, anti-cancer properties. This review is focused on scutellarin, itschemistry, and anti-cancer properties. Scutellarin induces apoptosis and cell cycle arrest and inhibits proliferation andprogression of a wide spectrum of human cancer cells. Of particular interest are the multiple molecular targets andpathways of scutellarin, structure-activity relationships of its cytotoxicity, and future research. Sources of informationwere from ScienceDirect, Google Scholar, and PubMed.

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.

Structural identification of related substances in Breviscapine by UPLC-QTOF-MS / 中国中药杂志

To systematically identify the related substances in the original materials of breviscapine injection, 18 batches of samples collected from different pharmaceutical companies, its ethanol extract and breviscapine mother liquor concentrate were analyzed by high performance liquid chromatography (HPLC), and their structures were identified by ultra performance liquid chromatography and quadruple/time-of-flight mass spectrometry (UPLC-QTOF-MS). Under the selected chromatographic conditions, scutellarin and related substances have good resolution and 13 related substances were observed. Based on the molecular weight and fragmentation patterns obtained by UPLC-QTOF-MS as well as reference substances, their structures were elucidated as 6-hydroxyapigenin-6--glucosyl-7--glucuronide (1), 5,7,8,3',4',5'-hexahydroxyflavone-7--glucuronide (2), 5,6,7,3',4'-pentahydroxyflavone-7--glucuronide（3）and its isomer (4), patuletin-3--glucuronide (5), methoxylscutellarin (6), apigenin 7--glucuronide (7), isorhamnetin 7--glucuronide (8), diosmetin 7--glucuronide (9), scutellarein (10), scutellarin methyl ester (11), scutellarin ethyl ester (12), and apigenin (13). This study has clarified related substances in the original materials of breviscapine injection, providing references for the improvement of quality control for breviscapine drug material and its preparations.

Preparation of galangin molecular imprinted polymers on silica gel surface and its adsorption properties / 中草药

Objective To prepare surface molecular imprinted polymers (MIP) of galangin by using surface molecular imprinting technique. Methods Galangin MIP was prepared by surface polymerization method at the surface of silica gel, which was modified with (3-aminopropyl) trimethoxysilane, by using galangin as the template molecule, methacrylic acid (MAA) as the functional monomer, and N,N′-methylenebisacrylamide (MBA) as crosslinking agent. The polymer was characterized by infrared spectroscopy and scanning electron microscopy. And its adsorption properties were studied by static and competitive adsorption method. Results The experimental research showed that the optimal preparation condition was that the molar ration of galangin to MAA was 1∶4, with molar ration of MAA to MBA 1∶7, reaction temperature 40 ℃ and reaction time 12 h. Infrared spectrum and scanning electron microscopy showed that MIP was successfully grafted on the surface of silica gel, and recognition holes and sites selectively appeared for galangin molecules. Adsorption experiments exhibited that MIP had specific recognition and good affinity for galangin molecules. Compared to the controls of breviscapine and luteolin, the selectivity coefficients of MIP to galangin were 11.2 and 5.3, respectively. Conclusion MIP has good recognition and high selectivity for galangin, which provides a new method for the separation and extraction of flavonoids from Chinese medicine.

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.

Preparation of Breviscapine Microemulsion for Parenteral Injection / 医药导报

Objective To study the prescription and preparation technology of breviscapine microemulsion for parenteral injection,and to evaluate its quality.Methods The prescription was selected and optimized through single-factor test and the pseudo-ternary phase diagram method.The preparation technology was investigated,and the particle diameter,drug content,encapsulation efficiency and haemolyticus were evaluated.Results The prescription composition of breviscapine microemulsion was soybean oil:phospholipid:HS15:PEG400:water=1:0.1:0.55:0.55:6.64 (m/m),with the drug content of 4.01 mg·mL-1,the acquired breviscapine microemulsion exhibited light yellow,uniform and transparent,with average particle diameter of 92.1 nm and encapsulation efficiency of 96.8%.The compatibility test showed no drug precipitation and the preparation was no hemolytic crisis.Conclusion The preparation of breviscapine microemulsion injection is correspond to the main index of parenteral injection.

Effects of breviscapine combined with aspirin on aspirin resistance in elderly patients with coronary heart disease / 中国生化药物杂志

Objective To investigate the effect of breviscapine combined with aspirin on aspirin resistance and clinical effect in elderly patients with coronary heart disease.Methods A total of 178 patients with angina pectoris treated in our hospital from January 2014 to December 2015 were randomly divided into two groups,with 89 cases in each group.The control group received 100 mg oral administration of aspirin.The study group was given breviscapine tablets oral on the basis of the control group.After six months of treatment, aspirin resistance, hemorheology, serum lipid peroxides(LPO), superoxide dismutase(SOD), homocysteine(Hcy), hypersensitivity C-reactive protein(hs-CRP) and interleukin-6(IL-6) were measured.The incidence of clinical efficacy and end points was statistically analyzed.Results The rates of aspirin resistance, whole blood high shear viscosity, whole blood low shear viscosity, plasma viscosity, erythrocyte aggregation index, fibrinogen, LPO, Hcy, hs-CRP, IL-6 levels and end point events in the study group were lower than the control group(P<0.05).The level of SOD and the clinical efficiency were higher than those of the control group(P<0.05).Conclusion Breviscapine combined with aspirin in the treatment of senile coronary heart disease can reduce aspirin resistance, improve clinical effect, reduce the incidence of end points, with clinical value.

Effects of Compound Preparation of Milkvetch Root and Breviscapine on Memory Ability and SOD, MDA and LDH in Blood and Brain of Alzheimer's Disease Rats / 中国药师

Objective: To observe the effect of compound preparation of milkvetch root and breviscapine (HDs) on the activity of superoxide dismutase (SOD) and lactate dehydrogenase(LDH), the concentration of malondialdehyde (MDA) in blood and brain and memory impairment in Alzheimer's disease rats.Methods: The rats were randomly divided into 5 groups (10 rats /group): the normal control group, Alzheimer's disease (AD) model group induced by AlCl3(5 mg·kg -1·d-1,ig) and D-gal (40 mg·kg-1·d-1,ip), and 3 AD groups respectively treated with different drugs including piracetam (0.15 g·kg-1·d-1,ig), HDs1(1.5 ml·kg-1·d-1,ip) and HDs2 (3 ml·kg-1·d-1,ip).After 90-day treatment, the step-down test was used to detect the learning and memory ability, and SOD and LDH activity and MDA concentration in blood and brain were examined as well.Results: Compared with that in AD model group, the ability of learning and memory was improved, the activity of SOD and LDH increased significantly, the concentration of MDA decreased significantly in blood and brain in HDs treated groups.The differences were statistically significant (P<0.05 or P<0.01), but they were not restored to normal levels.Some indexes of HDs2 group were better than those of piracetam positive control group and HDs1 group (P<0.05 or P<0.01).Conclusion: HDs can effectively reduce MDA concentration, increase SOD and LDH activity in blood and brain, and improve the ability of learning and memory of AD rats.

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.

Clinical Observation of Breviscapine Combined with Vinpocetine in the Treatment of Acute Cerebral In-farction / 中国药房

OBJECTIVE:To investigate clinical efficacy and safety of breviscapine combined with vinpocetine in the treatment of acute cerebral infraction. METHODS:A total of 80 patients with acute cerebral infraction were selected from our hospital during Jan. 2014-Dec. 2015,and then divided into observation group and control group according to random number table,with 40 cases in each group. Control group was given Vinpocetine injection 20 mL+0.9％ Sodium chloride injection 250 mL,ivgtt,qd. Observa-tion group was additionally given Breviscapine injection 20 mL+5％ Glucose injection 250 mL,ivgtt,qd,at intervals of 2-3 h on the basis of control group. Both groups were treated for 2 weeks. Clinical efficacies as well as serum copeptin,NT-proBNP,albu-min cobalt binding(ACB)value,European stroke scale(ESS)and functional independence measurement(FIM)score before and after treatment were observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:Total response rate of observation group(90.0％)was significantly higher than that of control group(67.5％),with statistical significance(P0.05). After treatment,serum copeptin and NT-proBNP levels of 2 groups were decreased significantly,while ACB value,ESS and FIM score were increased significantly;the improvement of observation group was significantly better than that of control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Breviscapine combined with vinpocetine can improve neurological function of acute cerebral infraction patients and show good therapeutic efficacy with good safety.

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.