Xueshuantong injection alleviates cerebral microcirculation disorder in middle cerebral artery occlusion/reperfusion rats by suppressing inflammation via JNK mediated JAK2/STAT3 and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: In the long history of traditional Chinese medicine, Panax notoginseng has been used as a key herb for the treatment of blood diseases. Brain microvessels support adequate blood circulation to maintain normal physiological function, therefore, brain microcirculation disorder is an important therapeutic target for various brain diseases. However, the role of Xueshuantong (XST) injection composed of saponins from P. Notoginseng (PNS) in the amelioration of cerebral microcirculation disorder is unclear. AIMS OF THE STUDY: Cerebral microcirculation disorder and inflammation play a vital role in stroke. Capillary endothelial cells and adjacent tight junctions are fundamental to the structure and function of cerebrovascule. XST injection has been used clinically in the treatment of stroke, but no studies have reported its indication in cerebral microcirculation disorder. This study is to explore the action and mechanism of XST injection in the alleviation of cerebral microcirculation disorder in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. MATERIALS AND METHODS: MCAO/R rats and LPS-induced bEnd.3 cells were employed for the investigation of effect and mechanism of XST injection. Brain damages were evaluated by neurobehavioral assessment, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin staining (H&E), and Nissl staining. Morphology and density changes of cerebral microvessels were monitored by immunohistochemistry. Cell permeability was detected by measurement of trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage. The mRNA and protein expressions of inflammatory cytokines, tight junction proteins, adhesion molecules, Janus kinase 2 (JAK2), signal transducer and activator of transcription-3 (STAT3), inhibitor of NF-κB (IκB), nuclear factor-κB (NF-κB) and c-jun N-terminal kinase (JNK) in brain microvessels and lipopolysaccharide (LPS)-induced bEnd.3 cells were measured by real-time PCR and Western blot, respectively. RESULTS: XST injection at 48 mg/kg significantly improved the neurological damage, inflammatory infiltration, and microvessel morphology, and increased microvessel density in brain of MCAO/R rats. The endothelial permeability was significantly mitigated by XST injection in LPS-induced bEnd.3 cells. Meanwhile, the tight junction proteins such as zona occludens 1 (ZO-1) and occludin were elevated remarkably in brain microvessel of MCAO/R rats and LPS-induced bEnd.3 cells. Moreover, the expression of inflammatory mediators including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), cycloocygenases 2 (COX-2), vascular cellular adhesion molecule-1 (VCAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 were inhibited by XST injection. In addition, XST injection suppressed the phosphorylation of JAK2, STAT3, IκB, NF-κB and JNK, which could be abolished by anisomycin, the JNK agonist. CONCLUSION: XST injection improved cerebral microvescular structure damage and dysfunction in MCAO/R rats through inhibiting inflammation activated by JNK mediated JAK2/STAT3 and NF-κB signaling pathways. The novel findings may provide theoretical basis for the clinical application in the treatment of cerebral microcirculation disorder.

Proteomic analysis revealed the pharmacological mechanism of Xueshuantong injection in preventing early acute myocardial infarction injury.

Background: Acute myocardial infarction (AMI) is a common and life-threatening cardiovascular disease. However, there is a lack of pathology and drug studies on AMI within 20 min. Xueshuantong injection (XST) is mainly composed of Panax notoginseng saponins, which can dilate blood vessels and improve blood circulation, and is clinically used in the treatment of cardiovascular and cerebrovascular diseases. Purpose: The study aimed to investigate the protective mechanism of Xueshuantong injection against acute myocardial infarction within 20 min in rats by proteomic methods and molecular docking. Method: The male Sprague-Dawley rat acute myocardial infarction model was established by LAD ligation, and Xueshuantong injection (38 mg/kg) was injected into the caudal vein 15 min before surgery. Cardiac function evaluation, morphological observation, label-free quantitative proteomics, Western blotting analysis, molecular docking, and affinity measurement were applied in this study. Results: In a span of 20 min after acute myocardial infarction, the model group showed significant cardiac function impairment. Xueshuantong injection can significantly improve cardiac function and prevent pathological injury of myocardial tissue. A total of 117 vital differentially expressed proteins were identified by proteomic analysis, including 80 differentially expressed proteins (DEPs) in the sham group compared with model rats (Sham: model) and 43 DEPs in model rats compared with the Xueshuantong injection group (Model: XST). The treatment of Xueshuantong injection mainly involves "poly(A) RNA binding" and "cadherin binding involved in cell-cell adhesion." The differentially expressed levels of the pathways related to proteins Echdc2, Gcdh, Dlst, and Nampt, as well as 14-3-3 family proteins Ywhaz and Ywhab, could be quantitatively confirmed by WB. Molecular docking analysis and SPR analysis revealed that Ywhaz has a generally stable binding with five Xueshuantong injection components. Conclusion: Xueshuantong injection (XST) could protect rat myocardial function injury against AMI in 20 min. Echdc2, Ywhaz, Gcdh, Ywhab, Nampt, and Dlst play an essential role in this protective effect. In particular, Ywhaz might be the core target of Xueshuantong injection when treating acute myocardial infarction in the early stage. This study promoted the understanding of the protective mechanism of Xueshuantong injection in 20 min injury of acute myocardial infarction and contributed to the identification of possible targets of Xueshuantong injection.

Efficacy and Safety of Xueshuantong Injection on Acute Cerebral Infarction: Clinical Evidence and GRADE Assessment.

INTRODUCTION: Xueshuantong injection (XST), a Chinese Medicine, is clinically effective in treating acute cerebral infarction (ACI). However, the meta-analysis of XST combined with conventional treatments (CTs) on ACI remain unexplored. The purpose of this study is to investigate the efficacy and safety of XST combined with CTs on patients with ACI. METHODS: Randomized controlled trials (RCTs) were screened from the Cochrane Library, PubMed, Web of Science, EMBASE, and four Chinese medical databases. The meta-analysis was performed using RevMan 5.3 and STATA 16.0. The GRADE assessment was performed by the GRADEprofiler (GRADEpro version: 3.6). The aggregate 95% confidence intervals (CIs) and relative risk (RR) estimates were calculated. RESULTS: Forty studies were included, involving a total of 3,868 patients. XST combined with CTs performed significantly better than CTs alone on the overall response rate (ORR) after treatment (RR = 1.21, 95% CI = 1.17-1.25, P < 0.001). There was no statistical differences in the incidence of adverse reactions between the experimental group (XST plus CTs) and control group (CTs alone). Groups treated with XST substantially decreased the National Institutes of Health Stroke Scale (NIHSS) score compared to the groups without XST (WMD = -5.31, 95% CI = -6.40 to -4.22, P < 0.001). Activities of daily living (ADL) scores were significantly better in the group treated with XST than CTs alone (WMD = 12.51, 95% CI = 5.6-19.38, P < 0.001). Patients who received XST combined with CTs showed significantly higher improvements in high-sensitivity C-reactive protein (hs-CRP) (WMD = -2.47, 95% CI = -3.11 to -1.82, P < 0.001) and interleukin 6 (IL-6) (WMD = -13.66, 95% CI = -17.80 to -9.51, P < 0.001) than those who received CTs alone. The GRADE assessment indicates that the comprehensive quality of this evidence is low. CONCLUSIONS: This meta-analysis and GRADE assessment conditionally recommend that XST combined with CTs can increase the overall response rate, ameliorate neurological deficit, and improve activities of daily living function more than CTs alone. A significant reduction in the hs-CRP and IL-6 levels were observed when XST was combined with CTs.

[Effects of Xueshuantong Injection on thrombosis formation and blood flow in rats].

The aim of this paper was to explore the effect of Xueshuantong Injection(freeze-dried powder,XST) on κ-carrageenan-induced thrombosis and blood flow from the aspects of interactions among blood flow,vascular endothelium and platelets. Fifty male Sprague-Dawley rats(190-200 g) were randomized into five groups: control group, model group, heparin sodium(1 000 U·kg~(-1)) group, low-dose and high-dose(50, 150 mg·kg~(-1)) XST groups. Rats were intraperitoneally injected with corresponding drugs and normal saline(normal control and model groups) for 10 days. One hour after drugs were administered intraperitoneally on the 7 th day, each rat was injected with κ-carrageenan(Type Ⅰ, 1 mg·kg~(-1)) which was dissolved in physiological saline by intravenous administration in the tail to establish tail thrombus model. The lengths of black tails of the rats were measured at 2, 6, 24 and 48 h after modeling. Vevo®2100 small animal ultrasound imaging system was used to detect the internal diameter of rat common carotid artery, blood flow velocity and heart rate, and then the blood flow and shear rate were calculated. Meanwhile, the microcirculatory blood flow perfusion in the thigh surface and tail of rats were detected by laser speckle blood flow imaging system. Platelet aggregometry was used to detect the max platelet aggregation rate in rats. Pathological changes in tail were observed through hematoxylin-eosin staining, and Western blot was used to detect the protein content of platelet piezo1. According to the results, XST could inhibit the rat tail arterial thrombosis and significantly reduce the length of black tail(P<0.05). The blood flow of common carotid artery in XST low dose group was significantly higher than that in the model group(P<0.05). XST high dose group could significantly increase the microcirculatory blood flow perfusion of the tail in rats as compared with the model group(P<0.05). XST high dose group could significantly inhibit platelet aggregation rate(P<0.05) and XST low dose group could significantly inhibit platelet piezo1 protein expression(P<0.01). In summary, XST could play an effect in fighting against thrombosis induced by κ-carrageenan in rats, which may be related to significantly inhibiting platelet aggregation, improving body's blood flow state, maintaining normal hemodynamic environment and affecting mechanical ion channel protein piezo1.

Effects of Xueshuantong Injection on thrombosis formation and blood flow in rats / 中国中药杂志

The aim of this paper was to explore the effect of Xueshuantong Injection(freeze-dried powder,XST) on κ-carrageenan-induced thrombosis and blood flow from the aspects of interactions among blood flow,vascular endothelium and platelets. Fifty male Sprague-Dawley rats(190-200 g) were randomized into five groups: control group, model group, heparin sodium(1 000 U·kg~(-1)) group, low-dose and high-dose(50, 150 mg·kg~(-1)) XST groups. Rats were intraperitoneally injected with corresponding drugs and normal saline(normal control and model groups) for 10 days. One hour after drugs were administered intraperitoneally on the 7 th day, each rat was injected with κ-carrageenan(Type Ⅰ, 1 mg·kg~(-1)) which was dissolved in physiological saline by intravenous administration in the tail to establish tail thrombus model. The lengths of black tails of the rats were measured at 2, 6, 24 and 48 h after modeling. Vevo®2100 small animal ultrasound imaging system was used to detect the internal diameter of rat common carotid artery, blood flow velocity and heart rate, and then the blood flow and shear rate were calculated. Meanwhile, the microcirculatory blood flow perfusion in the thigh surface and tail of rats were detected by laser speckle blood flow imaging system. Platelet aggregometry was used to detect the max platelet aggregation rate in rats. Pathological changes in tail were observed through hematoxylin-eosin staining, and Western blot was used to detect the protein content of platelet piezo1. According to the results, XST could inhibit the rat tail arterial thrombosis and significantly reduce the length of black tail(P<0.05). The blood flow of common carotid artery in XST low dose group was significantly higher than that in the model group(P<0.05). XST high dose group could significantly increase the microcirculatory blood flow perfusion of the tail in rats as compared with the model group(P<0.05). XST high dose group could significantly inhibit platelet aggregation rate(P<0.05) and XST low dose group could significantly inhibit platelet piezo1 protein expression(P<0.01). In summary, XST could play an effect in fighting against thrombosis induced by κ-carrageenan in rats, which may be related to significantly inhibiting platelet aggregation, improving body's blood flow state, maintaining normal hemodynamic environment and affecting mechanical ion channel protein piezo1.

Effect of Salvianolate Lyophilized Injection and Xueshuantong Injection (Lyophilized) on Permeability of Blood-brain Barrier via Inhibition of MMPs in Cerebral Ischemia/Reperfusion Injury Rats / 中国实验方剂学杂志

Objective:To investigate the effect of salvianolate lyophilized injection and Xueshuantong injection (lyophilized) on the permeability of blood-brain barrier (BBB) via inhibition of metallomatrix protease（MMPs） in cerebral ischemia/reperfusion injury rats. Method:The focal cerebral ischemia/reperfusion model in rats was built by middle cerebral artery occlusion/reperfusion (MCAO/R) technique. Male Wistar rats were randomly divided into sham operation group, ischemia/reperfusion (I/R) group, edaravone (Eda, 6 mg·kg-1) group, salvianolate lyophilized injection (SLI, 21 mg·kg-1) group, Xueshuantong (XST, 100 mg·kg-1) group and SLI combined with XST (SLI+XST, 21 mg·kg-1+100 mg·kg-1) group. Drugs were injected via tail vein for 2 d, while sham group and I/R group were injected with the same amount of normal saline. Neurological deficit score, hematoxylin-eosin (HE) staining and Nissl staining were assessed 2 d after MCAO/R. The permeability of BBB was observed by the leakage of IgG/CD31. The expressions of Claudin-5，Occludin，collagen-Ⅳ（Col- Ⅳ），Laminin，Fibronectin were observed by immunofluorescence staining，and MMP-2 and MMP-9 were observed by Western blot. Result:Compared with the I/R group, SLI group, XST group and SLI+XST group showed improvements in neurological deficit score, HE staining and Nissl staining. The leakage of IgG was alleviated; The positive expressions of Claudin-5，Occludin，Col-Ⅳ，Laminin，Fibronectin in ischemic penumbra were significantly up-regulated, while the expressions of MMP-2 and MMP-9 were down-regulated. The effect in improving SLI combined with XST was much better than a single factor. Conclusion:Salvianolate lyophilized injection and Xueshuantong injection (lyophilized) can alleviate cerebral ischemia/reperfusion injury and exert the synergistic effect when they are used in combination. The mechanisms might be associated with the improvement in the permeability of blood-brain barrier by inhibiting MMPs in cerebral ischemia/reperfusion injury rats.

[Effictiveness and safety of Xueshuantong Injection in treatment of unstable angina pectoris: a systematic review and Meta-analysis of randomized controlled trials].

To assess the effectiveness and safety of Xueshuantong Injection in the treatment of unstable angina pectoris. Literatures were retrieved in PubMed,the Cochrane Library,EMbase,the China National Knowledge Infrastructure Database( CNKI),the Chongqing VIP Chinese Science Database( VIP),the Chinese Biomedical Literature Database( Sino Med) and Wanfang Data. The time limitation ranged from the commencement of each database to April 28,2019. The assessment of ethodological quality was based on the Cochrane Handbook 5.1,and the data were analyzed by using Rev Man 5.3 software. A total of 38 RCTs involving 4 074 patients were included. The included trials were all of low quality. Xueshuantong Injection combined with routine basic treatment( RBT) was superior to RBT alone in alleviating clinical symptoms,with statistically significant differences between the groups( RR = 1. 19,95% CI[1. 15,1. 24]). Xueshuantong Injection combined with RBT was better than RBT alone in the efficiency of anginal symptom( RR = 1.23,95%CI[1.18,1.29]). Xueshuantong Injection combined with RBT reduced the consumption of nitroglycerin,which was more effectively than RBT alone,with statistically significant differences between the groups( RR = 1.64,95%CI[1.23,2.19]). Xueshuantong Injection combined with RBT decreased hs-CRP levels,which was more effectively than RBT alone,with statistically significant differences between the groups( MD =-0.48,95%CI[-0.57,-0.40]). However,there was no statistical difference between groups in the incidence of myocardial infarction. The reported adverse effects of Xueshuantong Injection were mainly dizziness,headache,itchy skin and gastrointestinal symptoms. Xueshuantong Injection combined with RBT can alleviate unstable angina pectoris. However,due to the low quality of included studies,further well-designed multicenter and large-scale RCTs are still needed to evaluate the efficacy of Xueshuantong Injection.

Effictiveness and safety of Xueshuantong Injection in treatment of unstable angina pectoris: a systematic review and Meta-analysis of randomized controlled trials / 中国中药杂志

To assess the effectiveness and safety of Xueshuantong Injection in the treatment of unstable angina pectoris. Literatures were retrieved in PubMed,the Cochrane Library,EMbase,the China National Knowledge Infrastructure Database( CNKI),the Chongqing VIP Chinese Science Database( VIP),the Chinese Biomedical Literature Database( Sino Med) and Wanfang Data. The time limitation ranged from the commencement of each database to April 28,2019. The assessment of ethodological quality was based on the Cochrane Handbook 5.1,and the data were analyzed by using Rev Man 5.3 software. A total of 38 RCTs involving 4 074 patients were included. The included trials were all of low quality. Xueshuantong Injection combined with routine basic treatment( RBT) was superior to RBT alone in alleviating clinical symptoms,with statistically significant differences between the groups( RR = 1. 19,95% CI[1. 15,1. 24]). Xueshuantong Injection combined with RBT was better than RBT alone in the efficiency of anginal symptom( RR = 1.23,95%CI[1.18,1.29]). Xueshuantong Injection combined with RBT reduced the consumption of nitroglycerin,which was more effectively than RBT alone,with statistically significant differences between the groups( RR = 1.64,95%CI[1.23,2.19]). Xueshuantong Injection combined with RBT decreased hs-CRP levels,which was more effectively than RBT alone,with statistically significant differences between the groups( MD =-0.48,95%CI[-0.57,-0.40]). However,there was no statistical difference between groups in the incidence of myocardial infarction. The reported adverse effects of Xueshuantong Injection were mainly dizziness,headache,itchy skin and gastrointestinal symptoms. Xueshuantong Injection combined with RBT can alleviate unstable angina pectoris. However,due to the low quality of included studies,further well-designed multicenter and large-scale RCTs are still needed to evaluate the efficacy of Xueshuantong Injection.

Post-marketing safety surveillance and re-evaluation of Xueshuantong injection.

BACKGROUND: Traditional Chinese medicine injections (TCMIs) have been widely used to treat severe and acute diseases due to their high bioavailability, accurate curative effect, and rapid effect. However, incidence rates of adverse drug reactions (ADRs) of TCMIs have also increased in recent years. Xueshuantong injection (XSTI) is a commonly-used TCMI comprised of Panax notoginseng total sapiens for the treatment of stroke hemiplegia, chest pain, and central retinal vein occlusion. Its safety remains uncelar. Therefore, post-marketing safety of XSTI was studied in this research. METHODS: In present study, post-marketing safety surveillance and re-evaluation of XSTI were reported. Thirty thousand eight hundred eighty-four patients in 33 hospitals from 7 provinces participated in this study. Incidence rate, most common clinical manifestations, types, severity, occurrence time, and disposal of ADRs were calculated. RESULTS: Incidence rate of ADR of XSTI was 4.14‰ and the most common clinical manifestations were skin and its appendages damage. Type A accounts for 95.49% of ADRs of XSTI and most of them (41.41%) were occurred within 24 h after receiving XSTI treatment. Severities of most ADRs of XSTI were moderate reactions (86.72%). Main disposition of ADRs of XSTI was drug withdrawal and symptomatic treatment (54.69%). CONCLUSIONS: Our data provide basis for improvement of instructions of XSTI and clinical safety of XSTI. Post-marketing surveillance of TCMIs in this study is a powerful tool to identify types and manifestations of ADRs to improve safety and effectiveness of drugs in clinical applications. TRIAL REGISTRATION: This protocol has international registration in China clinical trial registration center ( ChiCTR~OPC~ 14,005,718 ) at December 22, 2014.

Protection of Salvianolate Lyophilized Injection combined with Xueshuantong Injection (Lyophilized) against focal cerebral ischemia/reperfusion injury in rats through suppression of inflammatory response / 中草药·英文版

Objective: Inflammatory reactions induced by microglia in the brain play an important part in the pathogenesis of focal cerebral ischemia/reperfusion (I/R) injury, resulting in neuronal death. Salvianolate Lyophilized Injection (SLI) and Xueshuantong Injection (Lyophilized) (XST), which have been widely used in the treatment of acutely cerebral infarction clinically in China, exhibit various biological activities. In this study, the neuroprotective properties of SLI combined with XST in a rat model of middle cerebral artery occlusion- reperfusion (MCAO/R) were investigated. Methods: In this study, male Wistar rats were subjected to 1.5 h of middle cerebral artery occlusion followed by reperfusion for 24 h. The rats were randomly divided into the following six groups: normal group (NOR), model group (MOD), SLI group (21 mg/kg, SLI), XST group (100 mg/kg, XST), SLI combined with XST (XST 100 mg/kg + SLI 21 mg/kg, 1X1S), and Edaravone (as a positive control drug, 6 mL/kg, EDI), once a day for 3 d. The neuronal injury, the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), and the changes of pro-inflammatory mediators interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and anti-inflammatory mediator interleukin-10 (IL-10) were observed. Results: 1X1S treatment significantly increased the number of neuron, compared with the MOD group, SLI group and XST group. Gliosis (GFAP and IBA-1) and expression of pro-inflammatory mediators IL-6 and TNF-α were significantly reduced. Meanwhile, 1X1S significantly increased the expression of anti-inflammatory mediator IL-10 in the brains of MCAO/R rats, compared with the MOD group, SLI and XST groups. SLI and XST also remarkably down-regulated the expression of IL-6 and TNF-α compared with the MOD group. Conclusions: This study shows that SLI combined with XST (1X1S) can protect cerebral ischemia-reperfusion injury due to its anti-inflammatory property, and may provide a potential promising new therapeutic strategy for acute ischemic stroke.

Analysis on Clinical Rational Application of Xueshuantong Injection in Gansu Provincial Hospital of Traditional Chinese Medicine / 中国中医药信息杂志

Objective To investigate the influence of TCM Xueshuantong Injection on the clinical benefit and risk factors; To promote rational medication. Methods HIS system of Gansu Province Hospital of Traditional Chinese Medicine was used, and the medical records and information of patients who used Xueshuantong Injection from August 1st,2015 to August 1st,2016 were selected,including patient information, medicine information, and medicine application information. SPSS19.0 software statistics was used for rational analysis on the clinical application of Xueshuantong;two-class Logistic regression analysis was used to look for adverse reactions related factors. Results Totally 1229 patients with 10 974 medical records were included in the study. Irrational use of medicine was mainly for inappropriate indications (accounted for 21.11%), time of unreasonable administration (accounted for 1.87%), and too large dosage (accounted for 0.9%). Regression analysis showed: 1. Patients with history of allergies to food, medicine, and other substances, increased the risk of adverse reactions 8.725 times after application of Xueshuantong Injection; 2. The medicine combination increased the risk of adverse reaction of Xueshuantong Injection 1.799 times; 3. Medicine combination with Xiaozhong Zhitong Mixture, Jianwei Xiaoshi Mixture, ossotide injection, cobamamide, dextran injection, polyene lipid phosphoryl acid choline injection, and glucosamine hydrochloride tablets, may have potential risk factors for adverse reaction of Xueshuantong Injection. Conclusion Clinical irrational medicine use factors of Xueshuantong Injection mainly manifest in the indications are not suitable, the dosage of the drug medicine is too large and the course of treatment is too long. Adverse reactions occur mainly in patients with allergic history,combination of medication and large dosage.

Effect and mechanism of Salvianolate Lyophilized Injection combined with Xueshuantong Injection on expression of astrocytes and microglia on focal cerebral ischemia-reperfusion injury in rats / 中草药

To investigate the effect of Salvianolate Lyophilized Injection (SLI) combined with Xueshuantong Injection (XST) on expression of astrocytes and microglia in cerebral ischemia-reperfusion injury rats. Methods The Wistar rats (250-300 g, male) were randomly divided into six groups: control group, model group, Edaravone group (6 mg/kg, EDI), SLI group (21 mg/kg), XST group (100 mg/kg), and SLI+XST group (1X1S, 21 mg/kg and 100 mg/kg). Rat model of cerebral ischemia-reperfusion injury was created by the middle cerebral artery occlusion (MCAO) by longa method. Drugs were administered tail intravenous injection once a day for 3 d starting from 24 h after reperfusion. The body weight, neurological deficit scores and survival percentage were observed in 3 d after the cerebral ischemia. The expression of GFAP and IBA-1 was determined at 3 d by immunofluorescence. The complicated compound-target-stroke network of SLI and XST was constructed and analyzed by IPA. Results Compared with the model group, 1X1S could significantly improve the neurological dysfunction, increase the body weight, and inhibit the expression of GFAP and IBA-1 in ischemic penumbra (P < 0.01), IPA reveals the molecular mechanism of SLI and XST in the active ingredient and related targets. Conclusion 1X1S has significant protection on cerebral ischemia reperfusion injury in rats, which may be related to the inhibition of the expression of GFAP and IBA-1 and high mobility group box-1 signaling and Interleukine-8 signaling.

Clinical observation on treatment of diabetic peripheral neuropathy bytraditional Chinese medicine foot bath combined with Xueshuantong / 中国生化药物杂志

Objective To observe the clinical efficacy of traditional Chinese medicine foot bath combined with Xueshuantong injection in the treatment of diabetic peripheral neuropathy.Methods Sixty patients with diabetic peripheral neuropathy(DPN)were randomly divided into two groups.According to the patients' condition,oral hypoglycemic drugs or insulin were used to control blood glucose.The control group was treated with Xueshuantong injection on routine nutrition nerve program.In the conventional nutrition nerve program based on the use of traditional Chinese medicine foot bath combined with Xueshuantong injection treatment,2 groups were treated after 10 days to evaluate the efficacy.Results The total effective rate of the observation group and the control group was 90％and 66.7％respectively.The sensory and motor function of the observation group were significantly improved after the treatment group,and the blood rheology and serum endothelin level were significantly decreased.Conclusion Chinese medicine foot bath combined with Xueshuantong injection for the treatment of diabetic peripheral neuropathy.

Therapeutic effect of Xueshuantong Injection combined with Sodium Monosialotetrahexosylganglioside Injection on cerebral infarction / 药物评价研究

Objective To investigate the clinical effect of Xueshuantong Injection combined with Sodium Monosialotetrahexosylganglioside Injection on cerebral infarction.Methods Selected 100 cases of patients with cerebral infarction who were treated in Occupational Disease Hospital of Xinjiang Uygur Autonomous Region from January 2013 to December 2015,divided into two groups randomly.The observation group was treated with Xueshuantong Injection combined with Sodium Monosialotetrahexosylganglioside Injection,control group was treated with Xueshuantong Injection.The therapeutic effect,IL-6,C reactive protein level,NIHSS score,Barthel index and hemorheology were compared.Results The effective rate of observation group was 92.00％,significantly higher than the control group 70.00％,the difference was statistically significant (P ＜ 0.05).The level of serum IL-6 and C reactive protein were significantly decreased (P ＜ 0.05),and the observation group decreased more obviously,the difference was statistically significant (P ＜ 0.05).After treatment,NIHSS score of two groups decreased significantly,and Barthel index increased significantly (P ＜ 0.05),and the study group was significantly better than the control group,the difference was statistically significant (P ＜ 0.05).After treatment,platelet aggregation and blood viscosity were decreased significantly (P ＜ 0.05),and the observation group decreased more obviously,the difference was statistically significant (P ＜ 0.05).Conclusion Xueshuantong Injection combined with Sodium Monosialotetrahexosylganglioside Injection has significant therapeutic effect,can significantly improve the level of inflammatory factors,neural function,ability of daily life and blood rheology in patients with cerebral infarction.

Meta-analysis of Effectiveness and Safety of Butylphthalide Capsules Combined with Xueshuantong Injec-tion in the Treatment of Acute Cerebral Infarction / 中国药师

Objective:To evaluate the effectiveness and safety of butyl phthalide capsules combined with Xueshuantong injection in the treatment of acute cerebral infarction (ACI). Methods: Cochrane Library, Medline, Embase, SCI, CBM, CNKI, VIP and Wanfang databases were searched from the building time to May 2016. The enrolled randomized controlled trails were studied by using Cochrane system evaluation methods to perform methodological quality assessment, and RevMan 5. 2 software was used to carry out Me-ta-analysis. Results:A total of 7 randomized controlled trails including 640 patients were enrolled. The results of Meta-analysis dem-onstrated that the effective rate of butylphthalide capsules combined with Xueshuantong injection was superior to that of Xueshuantong injection (RR=1. 33, 95%CI:1. 16-1. 52, P<0. 0001), butylphthalide (RR=1. 45, 95%CI:1. 15-1. 83, P=0. 002) and blank control (RR=1. 31, 95%CI:1. 08-1. 57, P=0. 005). NHISS of butylphthalide capsules combined with Xueshuantong injection was higher than that of Xueshuantong injection (MD=4. 63, 95%CI:3. 38-5. 87, P<0. 00001) and blank control (MD=6. 85, 95%CI:4. 90-8. 80, P<0. 00001). There was no significant difference in adverse drug reactions. Conclusion: Butylphthalide capsules combined with Xueshuantong injection is effective for the therapy of ACI. However, due to the limited quantity and quality of the in-cluded studies, larger scale trials are needed.

Therapeutic Efficacy and Safety of Fibrinolytic Combined with Xueshuantong Injection in the Treatment of Acute Ischemic Stroke: A Meta-analysis / 中国药房

OBJECTIVE:To systematically evaluate the therapeutic efficacy and safety of fibrinolytic combined Xueshuantong injection in the treatment of acute ischemic stroke,and to provide evidence-based reference.METHODS:Retrieved from CJFD,Wanfang database,ScienceDirect and ELSEVIER,RCTs about fibrinolytic combined Xueshuantong injection (trial group) vs.fibrinolytic alone (control group) in the treatment of acute ischemic stroke were collected.After data extraction and quality evaluation according to modified Jadad evaluation,Meta-analysis was conducted by using Rev Man 5.2 and Stata 12.0 statistical software.RESULTS:A total of 14 RCTs were included,involving 1 342 patients.The results of Meta-analysis showed that,total response rate [RR =1.24,95 ％ CI (1.18,1.31),P ＜ 0.001],cure rate [RR=1.59,95 ％ CI (1.23,2.06),P ＜ 0.001] and efficiency rate [RR =1.41,95 ％ CI(1.24,1.60),P＜0.001] of trial group were significantly higher than those of control group.There was no significant difference in the response rate [RR=0.93,95％CI(0.79,1.10),P=0.40] and the incidence of ADR [RR=0.63,95％ CI (0.17,2.36),P=0.49] between 2 groups.CONCLUSIONS:Fibrinolytic combined Xueshuantong injection shows good therapeutic efficacy and safety for acute ischemic stroke.

Therapeutic Efficacy and Safety of Fibrinolytic Combined with Xueshuantong Injection in the Treatment of Acute Ischemic Stroke: A Meta-analysis / 中国药房

OBJECTIVE:To systematically evaluate the therapeutic efficacy and safety of fibrinolytic combined Xueshuantong injection in the treatment of acute ischemic stroke,and to provide evidence-based reference.METHODS:Retrieved from CJFD,Wanfang database,ScienceDirect and ELSEVIER,RCTs about fibrinolytic combined Xueshuantong injection (trial group) vs.fibrinolytic alone (control group) in the treatment of acute ischemic stroke were collected.After data extraction and quality evaluation according to modified Jadad evaluation,Meta-analysis was conducted by using Rev Man 5.2 and Stata 12.0 statistical software.RESULTS:A total of 14 RCTs were included,involving 1 342 patients.The results of Meta-analysis showed that,total response rate [RR =1.24,95 ％ CI (1.18,1.31),P ＜ 0.001],cure rate [RR=1.59,95 ％ CI (1.23,2.06),P ＜ 0.001] and efficiency rate [RR =1.41,95 ％ CI(1.24,1.60),P＜0.001] of trial group were significantly higher than those of control group.There was no significant difference in the response rate [RR=0.93,95％CI(0.79,1.10),P=0.40] and the incidence of ADR [RR=0.63,95％ CI (0.17,2.36),P=0.49] between 2 groups.CONCLUSIONS:Fibrinolytic combined Xueshuantong injection shows good therapeutic efficacy and safety for acute ischemic stroke.

Method development and application of offline two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry-fast data directed analysis for comprehensive characterization of the saponins from Xueshuantong Injection.

Xueshuantong Injection (XSTI), derived from Notoginseng total saponins, is a popular traditional Chinese medicine injection for the treatment of thrombus-resultant diseases. Current knowledge on its therapeutic basis is limited to five major saponins, whereas those minor ones are rarely investigated. We herein develop an offline two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry-fast data directed analysis (offline 2D LC/QTOF-Fast DDA) approach to systematically characterize the saponins contained in XSTI. Key parameters affecting chromatographic separation in 2D LC (including stationary phase, mobile phase, column temperature, and gradient elution program) and the detection by QTOF MS (involving spray voltage, cone voltage, and ramp collision energy) were optimized in sequence. The configured offline 2D LC system showed an orthogonality of 0.84 and a theoretical peak capacity of 8976. Total saponins in XSTI were fractionated into eleven samples by the first-dimensional hydrophilic interaction chromatography, which were further analyzed by reversed-phase UHPLC/QTOF-Fast DDA in negative ion mode. The fragmentation features evidenced from 36 saponin reference standards, high-accuracy MS and Fast-DDA-MS(2) data, elemental composition (C<80, H<120, O<50), double-bond equivalent (DBE 5-15), and searching an in-house library of Panax notoginseng, were simultaneously utilized for structural elucidation. Ultimately, 148 saponins were separated and characterized, and 80 have not been isolated from P. notoginseng. An in-depth depiction of the chemical composition of XSTI was achieved. The results obtained would benefit better understanding of the therapeutic basis and significant promotion on the quality standard of XSTI as well as other homologous products.

Effect of Xueshuantong combined with butylphthalide on clinical curative effect, cerebral vascular reserve capacity and serum hs-CRP on acute cerebral infarction / 中国生化药物杂志

Objective To observe the efficacy and effect on cerebral vascular reserve and serum hs-CRP of Xueshuantong combined with butylphthalide in patients with acute cerebral infarction.Methods A total of 140 cases with ACI in Huzhou Central Hospital from August 2015 to July 2016 were divided into the observation group and the control group with 70 cases in each group, according to the order of single and double number.The control group was treated with routine western medicine while giving butylphthalide , and the observation group was given Xueshuantong on the basis of the control group.After two weeks of treatment, the efficacy and CVR, BHI and hs-CRP levels were observed.Results After treatment, the total effective rate of the observation group was 92.86%, and the control group was 81.43%, the difference was statistically significant (χ2 =4.080, P<0.05), there was significant differences of CVR, BHI between two groups (Fgroup =5.534, 4.608, P<0.05), the CVR and BHI increased gradually with time (Ftime =11.325, 9.432, P<0.05), the rised amplitude in observation group was higher than the control group (Finteraction =5.742, 5.016, P<0.05), there were significant differences in the levels of hs-CRP between two groups (Fgroup =7.421, P<0.05), and hs-CRP decreased gradually with time (Ftime =10.185, P<0.05), the decrease of observation group was larger than that of control group(Finteraction =4.824, P<0.05).Conclusion Xueshitong combined with butylphthalide in the treatment of ACI is effective , can better improve cerebral vascular reserve capacity and inhibition of inflammatory response, better than the single use of butylphthalide.

Clinical observation on Xueshuantong Injection in treatment of acute cerebral infarction patients with Clopidogrel resistance / 中草药

Objective: To observe the effect of Xueshuantong Injection on platelet aggregation in acute cerebral infarction patients with Clopidogrel resistance (CR). Methods: This study selected acute cerebral infarction patients with CR from March 2012 to August 2014 in Tianjin Hospital. Patients (104 cases) were randomly divided into two groups (n = 52). The patients in the control group were treated with Western Medicine and Clopidogrel 75 mg/d, and the patients in treatment group were treated with Western Medicine and Clopidogrel 75 mg/d and given Xueshuantong Injection (5 mL dissolved in 0.9% saline 250 mL, iv drip). The two groups were treated for 14 d. Results: The platelet aggregation in the two groups was reduced significantly after treatment (P < 0.05), and after treatment the platelet aggregation in the treatment group was lower than that in the control group (P < 0.05). Conclusion: Xueshuantong Injection can reduce platelet aggregation in acute cerebral infarction patients with CR, and is a beneficial supplement therapy for CR.