| Background:Zhongfeng disease in traditional Chinese medicine is similarly to stroke including ischemic stroke and hemorrhagic stroke,with high incidence rate,high disability rate,high mortality rate and high recurrence rate.It is the most common neurological emergency and disease in clinic.Intravenous alteplase and mechanical thrombectomy developed in recent years can open the occluded vessels early and improve the clinical outcome of patients.Patients may fail to receive these effective treatments due to contraindications or other reasons,therefore we need to find more effective treatments.Traditional Chinese medicine has a long history in the treatment of zhongfeng disease.Since the reform and opening up,the standard of diagnosis and treatment of stroke has been formed.With the deepening of the understanding of the disease,Academician Wang Yongyan emphasized the role of toxic pathogens in the pathogenesis of zhongfeng disease,and suggested that add detoxification drugs in the treatment of zhongfeng disease.Tanreqing injection is composed of lonicerae japonicae flos,scutellariae radix,forsythiae fructus,bubali cornu and bear bile.It is good at clearing heat and detoxifying,and is widely used in the treatment of respiratory diseases.Researchers found that tanreqing injection not only relieved the respiratory symptoms of stroke patients with pulmonary infection,but also improved the neurological function.Several clinical studies also found that tanreqing injection can promote the recovery of neurological function in patients with ischemic stroke or hemorrhagic stroke.Therefore,it can be speculated that tanreqing injection may be a potential effective drug in the treatment of stroke.Objectives:To explore the therapeutic effect and mechanism of tanreqing injection for stroke.Methods:1.we used the methods of systematic review and meta-analysis to screen and analyze the published clinical literatures on tanreqing injection for stroke.We searched Wanfang database,CNKI,CBM and PubMed for randomized controlled trials of tanreqing injection in the treatment of stroke up to January 1,2021.According to the inclusion and exclusion criteria,the eligible literatures were selected for meta-analysis,and the quality of the literatures was evaluated.2.We used network pharmacology to explore the mechanism of tanreqing injection for stroke.According to the published literature,we collected the detected compounds in tanreqing injection,calculated the QED scores of these compounds,and selected the compounds' score greater than 0.18 as the potential effective components.Online search for drug targets of these active ingredients in PubChem.The targets of tanreqing injection for stroke can be obtained by crossing these targets with the targets for stroke retrieved from the database.The protein-protein interactions between these targets were analyzed and annotated.We used the middle cerebral artery occlusion rat model to evaluate the effect of different doses of tanreqing injection on the volume of cerebral infarction in rats by 2,3,5-triphenyltetrazolium chloride staining.Hematoxylin-Eosin staining and Nissl staining were used to evaluate the pathological characteristics of the infarction area.Western bloting and immunofluorescence were used to detect the important proteins in apelin signaling pathway and its downstream apoptosis and autophagy.Results:1.a total of 11 articles involving 955 patients were included.The results of meta-analysis showed that tanreqing injection could reduce the score of National Institutes of Health Stroke Scale in patients with stroke or stroke complicated with pulmonary infection,and there were significant differences compared with the control group(MD=-5.45,95%CI:-10.82?-0.09.MD=-2.37,95%CI:-3.49?-1.26,P<0.05).It was helpful to improve the functional independence score(MD=14.90,95%CI:8.84?20.96,P<0.05)and Fugl-Meyer scale(MD=7.39,95%CI:2.74?12.04,P<0.05),and had significant differences compared with the control group.It was helpful for the improvement of Activity of Daily Living Scale,but there was no significant difference between the two groups(MD=12.95,95%CI:-1.02?26.92,P<0.05).However,the risk of bias included articles were high and there were high heterogeneity in included articles.2.We found 663 targets in 81 effective components of tanreqing injection.In the effective components targets network,chlorogenic acid were the most effective component with the highest degree,and nuclear factor E2 related factor 2 were the most effective target with the highest degree.There were 116 drug targets for stroke.Among the 116 drug targets,albumin,p53 and interleukin-8 were the most important.The results of biological function annotation showed that these targets involved 227 pathways such as bile secretion,drug metabolism,chemical carcinogenesis,liver disease and apelin signaling pathway;3258 biological processes such as fatty acid metabolic and biosynthetic process,response to xenobiotic stimulus and cellular response to drug;442 molecular functions such as nuclear receptor activity,heme binding reaction and serine-type peptidase activity;222 cellular components such as nucleotide-activated protein kinase complex,membrane raft and postsynaptic membrane.The pathological result showed that edema,vacuole formation and cell death were found in the infarct site.However,intraperitoneal injection of low dose tanreqing injection(2.5ml/kg,once every 6 hours)can significantly reduce the infarct volume 24 hours after infarction.Western bloting results showed that the protein content of APJ/PI3K/AKT/mTOR signaling pathway increased,BCL2/BAX ratio increased,caspase 8 decreased,LC3 ?/LC3 ? ratio decreased,NeuN increased,and GFAP decreased after using tanreqing injection.Conclusion:Tanreqing injection has a potential effect on stroke,especially ischemic stroke in meta-anaylsis and animal models.The mechanism may be related to activation of apelin signaling pathway and inhibition of apoptosis and autophagy.However,these research results are superficial,and higher quality clinical and basic researches are needed to certify the clinical efficacy and pharmacological mechanism of tanreqing injection on stroke. |
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