The efficacy and safety of Shuxuening injection combined with western medicine in vascular dementia treatment:a meta-analysis

Background:To systematically evaluate the efficacy and safety of the Chinese patent medicine Shuxuening injection combined with western medicine in vascular dementia treatment.Methods:Randomized controlled trials of the Chinese patent medicine Shuxuening injection in vascular dementia treatment is searched in the databases of CNKI,Wanfang,VIP,CBM,PubMed,The Cochrane Library,Embase and Web of Science from the establishment time to December 2020.After screen the literature,extract the data and evaluate the bias risk of studies included;tRevMan5.3 was used for met-analysis.Results:Nine randomized controlled trials including 932 patients were included.The results of meta-analysis included:(1)the total effective rate(RR=1.27,95%CI(1.18,1.36),P<0.00001);(2)MMSE score(MD=4.78,95%CI(1.75,7.80),P=0.002);(3)ADL score(MD=8.87,95%CI(6.70,11.05),P<0.00001);(4)NIHSS score(MD=−6.60,95%CI(−7.04,−6.16).P<0.00001).The results of meta-analysis of the test group are better than those in the control group.Conclusion:The Chinese patent medicine Shuxuening injection combined with conventional western medicine has showed some advantages in the total effective rate,MMSE score,ADL score,NIHSS score than conventional western medicine without more side effects in vascular dementia treatment.More randomized,double-blind,large sample clinical studies are needed to confirm the above conclusions.

Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway

Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese Medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was closely related to SXNI treatment of MIRI. In vivo experiments showed that SXNI reduced the myocardial infarction area in the model group, improved rat heart pathological damage, and reduced the cardiomyocyte apoptosis rate(all P<0.01). After SXNI treatment, the p-PI3K/PI3K and p-AKT/AKT ratios as well as B-cell lymphoma-2(Bcl-2) protein expression in cardiomyocytes were increased, while the Bax and cleaved caspase 3 protein expression levels were decreased(all P<0.05). LY294002 partially reversed the protective effect of SXNI on MIRI. Conclusion: SXNI protects against MIRI by activating the PI3K/AKT signaling pathway.

Combined Common Femoral Artery Endarterectomy with Superficial Femoral Artery Stenting Plus Shuxuening Injection(舒血宁注射液) Infusion for Chronic Lower Extremity Ischemia:3-Year Results

Objective： To investigate the efficacy and safety of combined common femoral artery （CFA） endarterectomy with superficial femoral artery （SFA） stenting plus Shuxuening Injection （舒血宁注射液） infusion in patients with complex multifocal arterial steno-obstructive lesions of the lower extremities. Methods： From March 2006 to March 2011, 104 lower limbs in 96 patients with multilevel peripheral arterial steno-occlusive disease, involving SFA as well as CFA and deep femoral artery （DFA） orifice, were treated by combined surgical with endovascular therapy, such as SFA stenting as an adjunct to CFA endarterectomy and patch angioplasty with the great saphenous vein. Before the end of the operation, 20 mL of Shuxuening Injection was infused through the catheter located in the treated artery. Technical and hemodynamic success, as well as primary and primary-assisted patency, was determined according to the Society for Vascular Surgery Guidelines. During follow-up, clinical status assessment, ankle-brachial index （ABI） test, and duplex Doppler ultrasound were administered every 6 months, and computed tomography angiography or magnetic resonance angiography was performed at 12, 24, and 36 months after discharge. Results： All patients underwent successful combined CFA endarterectomy with SFA stenting treatment. The average ABI after the combination treatment increased from pretreatment of 0.32 ± 0.21 to 0.82±0.24 （P〈0.01）. No perioperative death and major limb amputations occurred. The mean duration of follow-up for 104 limbs from 96 patients was 1,180 days （range, 196-2,064 days）. During follow-up, 5 patients died due to myocardial infarction, cerebral infarction, or pneumonia, and 5 patients were lost to follow-up. There were 21 cases （21.4%） of restenosis, with 15 that occurred in-stent and 6 near the dJstal end of the stent. A total of 18 （18.3%） reinterventions were performed, including 6 balloon angioplasty, 8 restenting procedures, 2 bypass surgeries, and 2 major limb amputations： The primary patency rates were 92.2%, 76.8%, and 61.3% at 12, 24, and 36 months, respectively, while the primary-assisted patency rates were 94.4%, 83.2%, and 75.6% at 12, 24, and 36 months, respectively. Conclusion： The combined CFA endarterectomy with SFA stenting plus Shuxuening Injection infusion appears to offer a safe, less invasive, and effective treatment option to patients with chronic lower extremity ischemia due to complex multifocal peripheral artery disease.

Establishment of safety evidence for Xingxue~ Shuxuening injection

OBJECTIVE: To systematically investigate the safety of Xingxue~ Shuxuening injection(SXN) in preand post-marketing, and to ensure clinical drug safety.METHODS: Strict quality control in raw herb selection and production processes was adopted and pharmacology research on SXN was performed by the drug manufacturing company, Heilongjiang ZBD Pharmaceutical Co., Ltd. We systematically reviewed the safety literature of Xingxue~ SXN. Adverse drug reaction(ADR) data of the drug, extracted from Spontaneous Reporting System(SRS), and clinical characters based on 20 hospital information systems(HIS) in China, were analyzed. Large-scale prospective safety monitoring and Risk Minimization Action Plans(Risk MAPs) of Xingxue~SXN were carried out.RESULTS: The quality of SXN was stable and controllable when it was produced. Drug toxicology studies found no effect on rabbits with hemolytic or condensed, local stimulation and muscle stimulation, and no allergic reactions in guinea pigs. The ADRs of Xingxue~ SXN were dizziness, phlebitis,and vomiting based on SRS data. The injection did not conform to instructions in clinical practice when we analyzed HIS database, and patient’s abnormal blood urea nitrogen levels may be related to the drug, when analyzed using the propensity score method. A nested case-control study was designed and performed to analyze the influencing factors of suspected allergic reactions to SXN. The study showed that patients with an allergy history were more prone to allergic reactions(P<0.001),and some medicine combinations could cause allergic reactions.CONCLUSION: These studies have established a body of evidence on Xingxue~ SXN safety, and provide a good model for Chinese medicine injection for clinical safety. The Xingxue~ SXN production process and toxicology research indicate the safety of the injection. However, the use of the injection is not consistent with instructed clinical practice.Xingxue~ SXN causes ADRs perhaps from inappropriate usage or its pharmacological action. This injection needs better Risk MAPs to ensure its clinical safety.

Comprehensive Quality Evaluation of ShuXueNing Injection Employing Quantitative High-Performance Liquid Chromatography Fingerprint and Chemometrics

Objective:In this study,a comprehensive and effective quality method for evaluating the efficacy of ShuXueNing injection(SXNI)was developed.Materials and Methods:Quantitative high-performance liquid chromatography fingerprint,the quantitative analysis of multicomponents by a single marker(QAMS)method,hierarchical cluster analysis(HCA),and orthogonal partial least squares discrimination analysis(OPLS-DA)were used to distinguish 53 batches of SXNI samples from 7 manufacturers.Results:A total of 53 batches of samples were analyzed to establish antithesis fingerprint of SXNI,and 12 peaks of the common model were collected and used for the similarity analysis.Meanwhile,six index flavonoid components were determined by the QAMS method,using rutin as internal reference substance.The accuracy of the QAMS method was confirmed by investigating the relative deviation between the QAMS method and the traditional external standard method.The results demonstrated that there was no significant difference(RE<1%),suggesting that QAMS was a reliable and convenient method for the content determination of multiple components.The HCA and OPLS-DA methods drew a similar conclusion.The 53 batches of SXNI samples from 7 manufacturers were categorized into five groups,indicating that chemometrics could reveal the quality differences of SXNI between the manufacturers.Conclusions:The method established herein was efficient and successful in assessing the quality of SXNI,and that it may be potentially employed in the quality control of related products composed of Ginkgo biloba extract.