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ObjectiveTo explore the mechanism of Shenxiong glucose injection （SGI） in inhibiting hydrogen peroxide （H2O2）-induced oxidative damage in H9c2 cells by tandem mass tags （TMT）-labeled quantitative proteomics. MethodH9c2 cells cultured in vitro were exposed to H2O2 for inducing oxidative damage. The cell viability was measured by cell proliferation and cytotoxicity assay （MTS）， followed by peptide fractionation by high performance liquid chromatography （HPLC） and protein expression detection in H9c2 cells by ultrahigh performance liquid chromatography-mass spectrometry. MaxQuant （v1.5.2.8） was utilized for data retrieval， and the high-resolution mass spectrometry was conducted to screen out differentially expressed proteins， which were then subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The protein expression levels of perilipin 2 （Plin2） and tropomyosin 1 （Tpm1） in cells were measured by Western blot. ResultThe spectral analysis yielded 48 608 specific peptide fragments and 5 903 quantifiable proteins. Compared with the model group，the SGI group exhibited 82 differentially expressed proteins，of which 22 were up-regulated and 60 were down-regulated. GO analysis results showed that the differentially expressed proteins were mainly involved in biological processes such as programmed cell death regulation，regulation of cell proliferation，cardiovascular system development， and cell migration. As revealed by KEGG analysis， these proteins were mainly related to peroxisome proliferator-activated receptor （PPAR），focal adhesion，phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt），and Ras-related protein 1 （Rap1） pathways. Western blot results demonstrated that compared with the model group，SGI significantly increased the Plin2 protein expression and decreased the Tpm1 protein expression （P<0.01），consistent with the proteomics results. ConclusionSGI may inhibit cell apoptosis and antagonize H2O2-induced cell oxidative damage by regulating PPAR，focal adhesion，PI3K/Akt and Rap1 pathways，which should be further verified by subsequent experiments.
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OBJECTIVE To compare the phar macokinetics o f ligustrazine hydrochlori de，salvianic acid and rosemarinic acid from Shenxiong glucose injection （SGI）in normal and acute myocardial ischemia （AMI）rats. METHODS Male SD rats were randomly divided into normal group and model group ，with 9 rats in each group. AMI model was established by isoproterenol hydrochloride modeling method. Three rats in each group were selected for model verification. The remaining 6 rats in each group were given SGI （1.2 mL/kg）or equal volum of normal saline via tail vein ；0.3 mL blood was collected through orbital venous bush 0.083，0.167，0.333，0.5，0.75，1，1.5，2，3，5 h after administration. Using luteoloside as internal standard ，the plasma concentrations of ligustrazine hydrochloride ，salvianic acid and rosemarinic acid were determined by ultra performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were fitted by WinNonlin 8.1 software，and statistical analysis was performed by SPSS 18.0 software. RESULTS The linear ranges of ligustrazine hydrochloride ，salvianic acid and rosmarinic acid were 0.06-29.96，0.01-5.15 and 0.006-3.09 μ g/mL（all r＞0.99），respectively. The results of methodological investigation were all in line with the requirements of Chinese Pharmacopoeia （2020 edition）. Compared with normal rats ，CLz of ligustrazine hydrochloride in AMI model rats was significantly increased （P＜0.05）；t1/2 and Vz of salvianic acid were significantly prolonged or increased （P＜0.05）；but the cmax and AUC 0－5 h were significantly decreased （P＜0.05）；AUC0－5 h of rosmarinic acid was significantly decreased （P＜0.05）. CONCLUSIONS The exposure levels of salvianic acid and rosmarinic acid in SGI are lower in AMI model rats than in normal rats ，and the elimination of ligustrazine hydrochloride in AMI model rats is stronger than that in normal rats.
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Objective: To establish a method for determining arabinose, mannose, fructopyranose and amylaceum in Shenxiong glucose injection by UPLC-MS/MS, so as to provide the basis for the scientific evaluation of the quality of Shenxiong glucose injection, and lay a foundation for the safe use of drugs in clinic. Method: Domestic GDX-403 solid-phase extraction column was used to purify Waters ACQUITY UPLC BEH Xbridge Amide column (2.1 mm×100 mm, 1.7 μm)at the column temperature of 35℃, and the mobile phase was 0.1% ammonia, 0.1% acetonitrile-0.1% ammonia water and water 85:15. The contents of arabinose, mannose, fructose and glucose in Shenxiong glucose injection were determined by UPLC-MS/MS with a flow rate of 0.3 mL·min-1. Result: A method was established to determine arabinose, mannose, fructopyranose and amylaceum in Shenxiong glucose injection. The concentration range of arabinose, mannose, fructopyranose and amylaceum showed a good linear relationship with the peak area, with a good repeatability and precision. Recoveries were 98.43%, 102.13%, 100.72%, 101.75%, and RSD were 2.4%, 1.3%, 3.1%, 2.7%. Arabinose and mannose content were stable in five batches of Shenxiong glucose injection. Conclusion: The method is simple and specific. Compared with the determination of total sugar, the method is more scientific and stable, and can be used for the quality control of Shenxiong glucose injection.
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To systematically evaluate the efficacy and safety of Shenxiong Glucose Injection in the treatment of cerebral thrombosis.Randomized controlled trials( RCTs) of Shenxiong Glucose Injection for cerebral thrombosis were screened out by searching CNKI,Wan Fang,VIP,Sino Med,Cochrane Library,PubMed,EMbase,and Web of Science in a systematic way,and the Meta-analysis on finally included studies was conducted by using Handbook 5. 1 evaluation criteria and tools and Rev Man 5. 3 software. GRADE system( GRADE pro 3. 6. 1) was used to grade the evidence quality of key outcome indicators. A total of 25 studies were included,with a total sample size of 2 286 cases,1 144 in the experimental group and 1 142 in the control group. The results of Meta-analysis showed that the total effective rate of Shenxiong Glucose Injection combined with ozagrel in the treatment of cerebral thrombosis was better than that of ozagrel alone( RR = 1. 26,95%CI [1. 20,1. 32],P<0. 000 01); the total effective rate of conventional treatment plus Shenxiong Glucose Injection and ozagrel for cerebral thrombosis was better than that of conventional treatment combined with ozagrel( RR = 1. 26,95%CI [1. 09,1. 46],P = 0. 002). In addition,Shenxiong Glucose Injection combined with ozagrel could reduce the incidence of adverse reactions( RR = 0. 38,95%CI [0. 24,0. 60],P < 0. 000 1),improve the neurological impairment( MD14 d=-7. 19,95% CI[-9. 16,-5. 22],P< 0. 000 1; MD30 d=-5. 34,95% CI [-5. 85,-4. 83],P < 0. 000 1; MD42 d=-7. 03,95% CI [-7. 79,-6. 28],P<0. 000 01; MD60 d=-6. 18,95%CI [-6. 55,-5. 81],P< 0. 000 01; MD90 d=-4. 90,95% CI [-5. 74,-4. 06],P<0. 000 01),and improve activities of daily living( ADL)( MD = 15. 00,95%CI [12. 20,17. 80],P<0. 000 01). The mortality was only included in one study,and the sample size was small,requiring to be further verified by a large sample size. The adverse reactions mainly included lung infection,skin pruritus,gastrointestinal reaction and so on,all of which could be tolerated or disappeared without affecting the treatment. Based on the available data and methods,Shenxiong Glucose Injection combined with ozagrel for cerebral thrombosis could improve the total effective rate,neurological impairment,and ability of daily living,with no serious adverse reactions. The evidence quality level of GRADE system was low in the evaluation of total effective rate,mortality and incidence of adverse reactions.However,the quality of the included researches was not high,requiring rigorously designed and internationally standardized clinical trials with a large sample size to improve the quality of evidence.
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Humans , Activities of Daily Living , Drugs, Chinese Herbal , Therapeutic Uses , Glucose , Therapeutic Uses , Intracranial Thrombosis , Drug Therapy , Randomized Controlled Trials as TopicABSTRACT
The aim of this paper was to explore the mechanism of Shenxiong Glucose Injection antagonizing apoptosis of H9 c2 cells induced by H_2O_2. H9 c2 cells were pretreated with 1. 7%,3. 4% and 6. 8% Shenxiong Glucose Injection,and then H_2O_2 was introduced to induce apoptosis in vitro. Cell viability was detected by MTS assay,morphological changes of apoptosis were observed by AO/EB fluorescence staining,apoptosis rate was detected by Annexin/PI method,cell expression profile was detected by gene chip technology,the mRNA of PIK3 CA,Bcl-2,Bax,caspase-3 and GAPDH were detected by qRT-PCR,the protein expression levels of PIK3 CA,AKT,P-AKT,Bcl-2,Bax and caspase-3 were detected by Western blot,and the contents of LDH and MDA were detected by kit. The results showed that Shenxiong Glucose Injection of different concentrations significantly increased the viability of H9 c2 cells treated with H_2O_2( P<0. 01),and reversed H_2O_2-induced apoptosis( P< 0. 01). The microarray experiments showed that 138 genes were altered in H9 c2 cells after treatment with Shenxiong Glucose Injection. The differential expression fold of PIK3 CA associated with PI3 K/AKT pathway was 3. 59. The results of qRT-PCR and Western blot showed that Shenxiong Glucose Injection could down-regulate the mRNA and protein expression levels of caspase-3( P<0. 01),up-regulate the mRNA and protein expression level of PIK3 CA and Bcl-2( P<0. 01),and up-regulate the phosphorylation levels of AKT( P<0. 01) in H_2O_2-treated H9 c2 cells. The protective effect of Shenxiong Glucose Injection on H_2O_2 cells injury was significantly inhibited by LY294002,a PI3 K/AKT pathway inhibitor. The results suggested that Shenxiong Glucose Injection may inhibit H_2O_2-induced H9 c2 cells apoptosis by regulating PI3 K/AKT signaling pathway.
Subject(s)
Animals , Rats , Apoptosis , Cell Line , Chromones , Drugs, Chinese Herbal , Pharmacology , Glucose , Morpholines , Phosphatidylinositol 3-Kinases , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Signal TransductionABSTRACT
OBJECTIVE: To evaluate the effectiveness and economics of Danshen ligustrazine injection and Shenxiong glucose injection in the treatment of cerebral infarction, and to provide reference for clinical treatment decisions. METHODS: Retrieved from CNKI, VIP, WANFANG DATA and CBM, RCTs about Danshen ligustrazine injection or Shenxiong glucose injection vs. Compound danshen injection in the treatment of cerebral infarction were collected. Clinical efficacies of two drugs were compared indirectly by using Meta-analysis, and the costs were obtained through domestic routine treatment plan and cost level. Based on it, pharmacoeconomic cost-effectiveness analysis was conducted. RESULTS: A total of 14 literatures were included, involving 1 305 patients. Average total response rates of Danshen ligustrazine group and Shenxiong glucose injection group were 89. 63％ and94. 11％, and the costs were 3 855. 29 and 4 198. 68 yuan, respectively; cost-effectiveness ratio were 43. 01 and 44. 61. The incremental cost-effectiveness ratio was 76. 65, i. e. Shenqiong glucose injection group needed extra cost of 76. 65 yuan for each additional 1％ of the average total response rate, which was higher than the daily disposable income of 60. 18 yuan in China. Meanwhile, the results of cost-effectiveness analysis were supported by sensitivity analysis. CONCLUSIONS: Compared to Shenxiong glucose injection, Danshen ligustrazine injection is probably more cost-effective for cerebral infarction. Furthermore, the conclusion need to be confirmed by pharmacoeconomics evaluation based on RCTs.
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Objective To investigate the effect of Shenxiong glucose injection on platelet reactivity during aspirin treatment in patients with acute ischemic stroke.Methods A total of 263 patients with acute ischemic stroke admitted to 12 hospitals from January 2014 to December 2016 were enrolled prospectively.They were randomly divided into aspirin group and aspirin + Shenxiong glucose injection group.The changes of platelet maximum aggregation rate induced by 4 platelet aggregating agents (arachidonic acid,adenosine diphosphate,collagen and platelet activating factor) were detected before and after the treatment.Results There were no significant differences in the demographic data and baseline clinical characteristics between the aspirin group (n =132) and the Shenxiong glucose injection + aspirin group (n =131).At baseline,the maximum aggregation rate of platelet induced by arachidonic acid and platelet activating factor in Shenxiong glucose injection + aspirin group was significantly higher than that in the aspirin group (all P ＜0.05).On the 6th day after treatment,the maximum aggregation rate of platelets induced by the 4 aggregating agents in the Shenxiong glucose injection + aspirin group was significantly lower than that in the aspirin group (all P ＜ 0.001).Conclusion Shenxiong glucose injection had a significant inhibitory effect on platelet reactivity during aspkin treatment in patients with acute ischemic stroke.
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To explore the real world clinical medication and combination characteristics of Shenxiong glucose injection. The basic information of patients with Shenxiong glucose injection, traditional Chinese and western medicine diagnosis information, doctor advice information and laboratory test information from the hospital information system(HIS) of 19 tertiary hospitals in China. Apriori algorithm was adopted to establish the models, and Clementine 12.0 was used for correlation analysis to analyze the real world clinical medication and combination characteristics of Shenxiong glucose injection. Among 8 316 patients in the study, 523 kinds of western medicine and 148 kinds of traditional Chinese medicine(TCM) were used. In combined application, the single western medicine with highest use frequency was aspirin(1 908 cases, 22.94%), and single Chinese medicine with highest use frequency was Shuxuetong injection (771 cases, 9.27%); the most common TCM pair was Xianling Gubao capsule+Lugua Duotai injection(rules support degree was 2.55%), and the most common western medicine pair was aspirin+atorvastatin(degree of association rules was 10.15%). They were often used in combination with antibiotics, blood-activating and stasis-dissolving prescription, and adrenal cortical hormone drugs. Shenxiong glucose injection was often used in combination with antiplatelet drugs and blood-activating and stasis-dissolving prescription in clinical application to enhance the effects of anti-platelet aggregation and blood-activating and stasis-dissolving; it was often used in combination with antibiotics to treat cor pulmonale, and incompatibility shall be noticed to ensure efficacy enhancement under the premise of clinical medication safety.
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To analyze the clinical drug use characteristics of Shenxiong glucose injection in the treatment of ischemic cerebrovascular disease. From hospital information system (HIS) of 19 hospitals over China, the basic information of patients with Shenxiong glucose injection for ischemic cerebrovascular disease, traditional Chinese medicine and Western medicine diagnosis information, order information, and laboratory examination information were extracted. Then Apriori algorithm was used to construct the model, and the association analysis was performed by using Clementine 12 to analyze the clinical drug use characteristics of Shenxiong glucose injection in the real world. A total of 411 kinds of Western medicines and 110 kinds of traditional Chinese medicines were included in 784 cases of drug combination. In the drug combination, aspirin had the highest frequency in Western medicine, which was used in 515 cases (65.69%); Ginkgo biloba extract had the highest frequency in Chinese medicine, which was used in 121 cases (15.43%). Atorvastatin+aspirin (association rules of 10.15%) was the most common Western medicine pairs; atorvastatin+clopidogrel+aspirin (association support 5.56%) was the most common triple Western medicine therapy, often combined with antibiotics and blood stasis drugs in use. Results showed that Shenxiong glucose injection was often combined with antiplatelet drugs and blood stasis drugs in the treatment of ischemic cerebrovascular disease clinically, contributing to the enhancement of platelet aggregation and blood stasis. The incompatibility of combined application of drugs shall be noted to ensure the clinical medication safety and efficacy of the combined drug use.
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In order to analyze Shenxiong glucose injection in combined use with other medicines for cerebral infarction in real world, the basic information, Chinese and western medicine diagnosis information, doctors'advice information, and laboratory checking information for the patients with Shenxiong glucose injection in treatment of cerebral infarction were extracted from the hospital information system (HIS) of sixteen 3A hospitals. Apriori Algorithm was used to establish models, and Clementine 12.0 was used for correlation analysis. Then complex network was established to analyze the combined drug use and visualize the results. A total of 635 patients were included in the study, among which 599 patients (94.33%) showed superior effect. Shenxiong glucose injection was often used with platelet suppressant drug, neuroprotective agent, lipid regulating agents, free radical scavenger, vitamins and Chinese medicine blood activating and stasis eliminating agent in the treatment of cerebral infarction. In the patients with superior effect, neuroprotective agent and free radical scavengers were also used based on the combined use with Aspirin, hypolipidemic drugs and blood activating and stasis removing agents, highlighting the rain protection strategies. Shenxiong glucose injection in combined use with Chinese and western medicines for cerebral infarction complied with the latest clinical practice guideline on the treatment of cerebral infarction, and the application of neuroprotective agent was propitious to improve the therapeutic effect.
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Objective To observe the clinical efficacy and safety of Shenxiong glucose injection and lipo PGE1 injection in treating the lower extremity arteriosclerotic occlusive disease (LEAOD).Methods 80 patients with LEAOD were randomly divided into control group and treatment group. Both groups were given conventional therapy, including reducing blood pressure, blood sugar, blood lipid and anti-infection therapy.Control group was additonally given intra-femoral arterial infusion with urokinase 150000 units plus 15mL 0.9% sodium chloride and 10 mg anisodamine alternately every other day, 5 days for one course, stopping 3 days after another course.Treatment group was treated with intravenous injection Lipo PGE1 injection plus 10 mL 0.9% sodium chloride and intravenous Shenxiong glucose injection per day for 14 days.Clinical efficacy, changes in clinical symptoms, whole blood viscosity, high sensitivity C-reactive protein(hs-CRP), fibrinogen, ankle-brachial index(ABI), the inner diameter of the dorsalis pedis and the peak systolic velocity( PSV) of dorsalis pedis were compared and analyzed pre and post-treatment.Adverse drug reactions were recorded during the treatment.ResuIts The efficiency for the patients in the treatment group (90.0%) was higher than that in control groups(72.5%) (P<0.05).The symptoms of numbness and cold limbs, whole blood viscosity, ABI, hs-CRP improved more significantly in the treatment group (P<0.05).No adverse event occurred in the treatment group and 2 patients in control group had mild dry mouth.ConcIusion Shenxiong glucose injection combined with lipo PGE1 injection for the treatment of LEAOD is effective and safe and should be introduced in clinical practice.
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Objective To explore the action mechanism of shenxiong glucose injection in treatment of acute spinal cord injury(SCI) through observing its effects on the recovery of motor function and the expression of aquaporin-4(AQP-4) in SCI rats.Methods Totally 90 healthy,aduh,Sprague-Dawley rats were randomly divided into a sham operation group (n=30),aSCI group (n=30) and a drug group (n=30).The SCI rat models in both the SCI group and the drup group were established aecording to the modified Allen's method,while the sham operation group was only given laminectomy.After the operation,the drug group was given intraperitoneal shenxiong glucose injection of 30 rnl/kg a day,while the other two groups were injected in the same way with normal saline.The neural function recovery,the pathological changes after SCI and the expressions of AQP-4 were observed 1,3,7,14 and 21 d after the operation using the Tarlov score,the hematoxylin and eosin staining,as well as immunofluorescence techniques and Western blotting.And the correlation of Tarlov scores with AQP-4 expressions was analyzed.Results No significant changes in Tarlov scores were observed in the sham operation group (P ＞ 0.05),while in the SCI group and the drug group,postoperative Tarlov scores decreased significantly.The hindlimb nerve function recovered to some degree with time in the SCI group and drug group.At 3,7,14 and 21 days after the operation,the Tarlov scores in the drug group were significantly higher than the SCI group (P ＜ 0.05).The drug group showed less severe pathological changes,with more residual neurons still visible of nucleoli than the SCI group 21 days after the operation.Compared with the sham operation group,the expression levels of AQP-4 were significantly higher in the SCI group and drug group at all the time points (P ＜ 0.05).However,the expression levels of AQP-4 in the drug group were significantly lower than the SCI group accordingly (P ＜ 0.05).The Tarlov scores were found to be significantly and negatively related to the AQP-4 protein expression levels 3 days(r =-0.523,P =0.003),7 days(r =-0.437,P=0.016),14 days(r=-0.417,P=0.022) and 21 days(r=-0.377,P=0.040)after the operation.Conclusion Injecting shenxiong with glucose can effectively promote the recovery of motor function after SCI,at least in rats.And its mechanism may be that the development of spinal cord edema is prevented and the secondary spinal cord injury alleviated by restraining the expressions of AQ P-4 in the injured areas.
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Objective:To evaluate the clinical efficacy of shenxiong glucose injection in the treatment of chronic re- nal failure(CRF).Method:78 patients with CRF were divided into a treatment group(n=40)and a controlled gronp(n= 38).The treatment group received shenxiong glucose injection 200ml daily,14 days for one course of treatment.The con- trolled group received ligustrazine injection 80mg with 5% glucose.The changes of serum BUN and SCr were observed.Re- sult:The serum BUN and SCr were significantly decreased in the two groups after the treatment(P