Astragalus injection inhibits c-Jun N terminal kinase mRNA expression following oxygen-glucose deprivation and reintroduction in rat hippocampal neurons

BACKGROUND： In studies concerning cell injury induced by cerebral ischemia-reperfusion, current experiments have primarily focused on altered protein levels. In addition, the apoptotic proteins Bax and Bcl-2 have been thoroughly studied with regard to initiating neuronal apoptosis. OBJECTIVE： To establish an in vitro model of oxygen-glucose deprivation and reintroduction in the rat hippocampus to simulate cerebral ischemia-reperfusion injury; to observe c-Jun N-terminal kinase 3 （JNK3） mRNA expression in hippocampal neurons following Astragalus injection; and thus to determine changes in the signaling and downstream pathways of neuronal apoptosis at the cellular and molecular level. DESIGN, TIME AND SETTING： A randomized, controlled, cellular and molecular experiment was performed at the Department of Central Laboratory, Chengde Medical College from February to June 2008. MATERIALS： Astragalus injection, the main ingredient of astragaloside, was purchased from Chengdu Di＇ao Jiuhong Pharmaceutical Manufactory, China. JNK3 mRNA probe and in situ hybridization kit were purchased from Tianjin Haoyang Biological Technology, China, and JNK3 RT-PCR primers were designed by Shanghai Bio-engineering, China. METHODS： Primary cultures of hippocampal neurons derived from Sprague Dawley rats, aged 1 2 days, were established. After 8 days, the hippocampal neurons were assigned to the following interventions： model group, Astragalus group, and vehicle control group, cells were subjected to oxygen-glucose reintroduction after oxygen-glucose deprivation for 30 minutes in sugar-free Earle＇s solution and a hypoxia device, which contained high-purity nitrogen. The normal control group was subjected to primary culture techniques and was not treated using above-mentioned interventions. In addition, the Astragalus and vehicle control groups were treated with Astragalus injection （0.5 g/L raw drug） or sterile, deionized water at 2 hours prior to oxygen-glucose deprivation, respectively. MAIN OUTCOME MEASURES： JNK3 mRNA expression was measured by in situ hybridization and RT-PCR at 0, 0.5, 2, 6, 24, 72, and 120 hours after oxygen-glucose reintroduction. RESULTS： Hippocampal neuronal morphology was normal in the normal control group. Hippocampal neurons exhibited apparent apoptosis-like pathological changes in the model, as well as the vehicle control, groups. The apoptosis-like pathological changes in the hippocampal neurons were less in the Astragalus group. Results from in situ hybridization and RT-PCR showed that JNK3 mRNA expression significantly increased in hippocampal neurons from model group, as well as the vehicle control group, compared with the normal control group （P 〈 0.05）. In addition, JNK3 mRNA expression significantly decreased in hippocampal neurons of the Astragalus group, compared with the model group and vehicle control group （P 〈 0.05）. CONCLUSION： Astragalus injection inhibited apoptosis-related JNK3 mRNA expression following oxygen-glucose deprivation and reintroduction, and accordingly played a role in inhibiting hippocampal neuronal apoptosis.

Effect of Astragalus Injection on Plasma Levels of Apoptosis-related Factors in Aged Patients with Chronic Heart Failure

Objective： To investigate the effect of Astragalus injection （AI） on plasma levels of apoptosis-related factors in aged patients with chronic heart failure （CHF）. Methods： Seventy-two CHF patients were randomly divided into the AI group （36 cases） treated with AI and the control group （36 cases） treated with conventional treatment. Plasma levels of soluble Fas （sFas）, soluble Fas ligand （sFasL）, tumor necrosis factor alpha （TNF-α） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assays （ELISA） with monoclonal anti-human antibodies. Besides, New York Heart Association （NYHA） grading was assessed according to improved symptoms and left ventricular end-diastolic volume （LVEDV）, left ventricular end-systolic volume （LVESV） and left ventricular ejection fraction （LVEF） were assessed by echocardiogram after 4 weeks of treatment. Results： After 4 weeks of treatment, NYHA grading was markedly improved in the two groups, but it was significantly better in AI group than that in the control group （P〈0. 05）. As compared with the control group, sFas, sFasL,TNF-α and IL-6 in the AI group were obviously lower, the difference between the two groups and between before and after treatment were significant （ P〈0. 05 or P〈0. 01 ）. Moreover, in AI group, LVESV and LVEDV decreased, LVEF increased, which was significantly different than that before treatment （P〈0. 05）, respectively. Conclusion： Al could lower plasma levels of apoptosis- related factors, and is one of the effective drugs in improving cardiac function in the aged patients with CHF.

Effect of Astragalus Injection on Serious Abdominal Traumatic Patients’ Cellular Immunity

Objective： To explore the change of serious abdominal traumatic patients＇ cellular immunity and the effect of Astragalus Injection （AI） on it. Methods： Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with Al20 ml was added into 250 ml of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored. Results： On the first day, in the conventional group and treated group, the levels of CD3^＋ , CD4^＋ , CD4^＋/CD8^＋ , 0D16^＋ , CD69^＋ and CD3^＋/homologous leucocytic antigen-DR （HLA-DR＋ ） were apparently lower than those in the healthy group （ P〈0.05）, while the CD8^＋ was significantly higher than that in the healthy group （P〈0.05）, and there was no significant difference between the conventional group and the treated group （P〉0.05） ; on the 14th days, the levels of CD3^＋, CD4^＋, CD4^＋/CD8^＋, CD16^＋, CD69^＋ and CD3^＋/HLA-DR^＋ of the treated group got closed to healthy subject value, and got even higher than those of conventional group （P〈0. 05）; CD8^＋ got close to that of healthy subjects, while obviously lower than that of conventional group （ P〈0. 05）. Conclusion： After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI was beneficial to the restoration of cellular immunity.

Effect of Astragalus Injection on Left Ventricular Remodeling in Aged Patients with Acute Early-stage Myocardial Infarction

Objective: To observe the effect of Astragalus Injection (AI) on left ventricular remodeling in aged patients with acute myocardial infarction (AMI). Methods: Patients with AMI were randomly divided into the AI group (46 cases) treated with AI and the control group (46 cases) treated conventionally. Left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), anterior endocardial segmental length (ASL) and posterior endocardial segmental length (PSL) were all assessed by echocardiogram after 1 week and 4 weeks treatment. The cardiac systolic and diastolic functions were detected by nuclide gating cardiac blood pool imaging at the 4th week. Results: After four weeks' treatment, no obvious change of LVEDVI, LVESVI and ASL in the AI group was found, but these indexes increased significantly in the control group, with significant difference shown between the two groups (P<0. 05). As compared with the control group, the left ventricular ejection fraction (LVEF), left ventricular peak ejecting rate (LVPER) and left ventricular peak filling rate (LVPFR) were heightened, the time for peak filling rate (LVTPFR) in the left ventricle was shortened in the AI group. Conclusion: AI is one of the effective drugs in reversing left ventricular remodeling in aged patients with AMI.

Effect of Astragalus Injection on Levels of Blood Selenium and Immunity Function in Children with Viral Myocarditis

Objective: To observe the effect of Astragalus Injection (AD on levels of blood selenium (Se) and cytokines, and T cellular immune function with viral myocarditis (VM) in children. Methods: Eighty children with VM were randomly divided into 2 groups. The control group consisted of 38 patients, to whom conventional therapy, including energy mixture, vitamin C and coenzyme Q10, etc. were given. The treated group (n = 42), to whom combination therapy of conventional therapy and Al were given. The levels of blood Se and cytokine, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and also evaluation of T lymphocyte subsets and cardiac function were observed. Results: The results showed that after treatment, the levels of blood Se were significantly higher (P<0.01), while IL-1,IL-6 and TNF-a were significantly lower (P<0.01) than those before treatment in the control group. The left ventricular end diameter (LVED) were significantly decreased (P<0.01), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly increased than those before treatment in the treated group(P<0.01, P<0.05). T lymphocyte subsets got normalized (P<0.01), and compared with the control group, the difference was significant (P<0.01). Conclusion: Astragalus membranaceus possesses anti-viral effect, adjusts the balance of cytokine and T cellular immunity, and improves the clinical manifestation and cardiac function. It is an effective approach in treating viral myocarditis.

Efficacy of Xuebijing injection for the treatment of coronavirus disease 2019 via network pharmacology

Background:To evaluate the mechanism of Chinese patent drug Xuebijing(XBJ)injection in the treatment of a new coronavirus disease 2019(COVID-19)based on network pharmacology and molecular docking technology.Methods:The TCMSP database was employed to collect and screen the active ingredients of the Chinese herb contained in the XBJ injection.The GeneCards database and STRING database were applied to collect and expand the targets of COVID-19 and compare and screen the related targets of COVID-19 by XBJ injection.Cytoscape was employed to build a network connecting Chinese medicine,compounds,targets,disease,and topology analysis was performed via the Network Analyzer to screen the key ingredients and targets.The software of Schrödinger molecular docking was used to verify the binding activity of the key ingredients of XBJ injection and the key targets of COVID-19.Metascape platform and DAVID database were utilized to conduct Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the key targets of COVID-19 treated by XBJ injection.Results:Eight key compounds and 15 key targets were screened and verified by molecular docking;these key compounds included luteolin,quercetin,baicalein,and kaempferol.The key targets included DPP4,AR,ESR1,CALM1,and protein kinase 1.Gene Ontology analysis involved an apoptosis and hypoxia reaction and the changes in blood vessel morphology.Kyoto Encyclopedia of Genes and Genomes analysis involved signaling pathways of hypoxia inducible factor-1,VEGF,and PI3K/AKT/NF-κB.Conclusion:The mechanism of XBJ injection when used to treat COVID-19 should be further investigated as the key compounds in XBJ regulated the expression of key targets such as protein kinase 1,VEGF-A,B-cell lymphoma-2,and TNF,which affected the COVID-19 receptors such as angiotensin-converting enzyme 2 and signaling pathways like hypoxia inducible factor-1,PI3K-Akt,and NF-κB,which alleviated the inflammation,respiratory distress,and hypoxia caused by COVID-19 infection.

Predict the anti-cancer mechanism of astragalus membranaceus based on network pharmacology

Objective: To explore the anti-cancer mechanism of active ingredients of Astragalus membranaceus (AM) through network pharmacology. Methods: TCMSP, PubChem, STICTH and GeneCards databases were used to predict and screen the main active ingredients and anti-cancer targets of AM. Active ingredient-target-disease network was constructed by Cytoscape 3.7.0 software, and protein interaction network was constructed by STRING platform. KEGG signaling pathway and GO biological process of targets were analyzed by Bioconductor database. Results: Twenty-four active ingredients were screened from AM, which acted on 106 cancer targets such as PTGS, NCOA2, ADRB2, PRSS1, NOS2, NOS3, GABRA1. Through these targets, the anti-cancer effect of AM mainly acts on small cell lung cancer, colorectal cancer, thyroid cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma, pancreatic cancer, gastric cancer, endometrial cancer, enriched in chemical carcinogenesis, Platinum drug resistance, Epstein-Barr virus infection, TNF signaling pathway, Toll-like receptor signaling pathway, p53 signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, and PI3K - Akt signaling pathway. Conclusion: This study found that the main anti-cancer compounds of AM are kaempferol, quercetin, 7-O-methylisomucronulatol, formononetin, isorhamnetin, Calycosin, 3,9-di-O-methylnissolin. The main targets include PTGS, PTGS1, NCOA2, ADRB2, PRSS1, NOS2, NOS3, GABRA1, F2. The mechanisms involved in anticancer could be summarized as following: blocking the chemical carcinogenesis, reversing the platinum drug resistance, anti - Epstein - Barrvirus infection, and inhibiting cell proliferation related signaling pathways, such as TNF signaling pathway, Tolllike receptor signaling pathway, p53 signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, PI3K - AKT signaling pathway.

Effects of Astragalus injection on chemokines, renal function and humoral immunity in patients with pulmonary tuberculosis

Objective:To investigate the effects of Astragalus Injection on inflammatory factors, chemokines, renal function and humoral immunity in patients with pulmonary tuberculosis. Methods:80 patients with pulmonary tuberculosis who were treated in the department of respiratory medicine in our hospital from October 2015 to October 2017 were randomly divided into control group and observation group, 40 cases in each group. Patients in the control group were given levofloxacin treatment;and patients in the observation group were given astragalus injection combined with levofloxacin treatment. Before and after treatment, procalcitonin (PCT), interferon-γ (INF-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1 ), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA) and immunoglobulin (IgA, IgM, IgG) levels were measured and compared between the patients in the two groups.Result: After treatment, the levels of PCT, INF-γ, MCP-1 and MIP-1 in serum of the patients in the two groups were significantly decreased, and the levels of IgA, IgM and IgG were significantly increased. The changes of the PCT, INF-γ, MCP-1, MIP-1 , IgA, IgM and IgG of patients in the observation group were significantly stronger than those in the control group (P<0.05). After treatment, the levels of BUN, SCr and UA in serum of patients in the two groups increased significantly. The serum levels of above indexes of patients in the observation group were significantly lower than those in the control group (P<0.05).Conclusion: Astragalus injection can significantly relieve the inflammatory state of patients with pulmonary tuberculosis, reduce the level of chemokines, enhance the renal function and immune function of patients. It has good clinical efficacy.

Study on the multi-targets mechanism of YiQiFuMai powder injection on cardio-cerebral ischemic diseases based on network pharmacology

Aim YiQiFuMai Powder Injection is a well-known traditional Chinese medicine formula that has been used extensively in clinical treatment of cardio-cerebral ischemic diseases in China. However, the mechanisms under-lying its clinical efficacy remain unknown. In this study, a network pharmacology approach was employed to identify the YiQiFuMai Powder Injection＇s potential pathways and targets against cardio-cerebral ischemia. The target-path- way interaction network clustered the signaling pathways based on high degree nodes of the drug-target network. The potential protein targets presented in the highly scored clustered pathways were the key network hubs and concentrated on one or limited functional signaling pathways amenable to experimental verification. Twelve main functional annota- tion clusters and main signaling pathways for YiQiFuMai Powder Injection were established by Biocarta analysis, in- eluding the NF-KB signaling pathway, the MAPKinase signaling pathway and the mTOR-signaling pathway and so on. YiQiFuMai Powder Injection is hypothesized to target multiple proteins with a high degree and betweenness of net- work. In addition, the most related pathways were also confirmed in tumor necrosis factor-alpha （TNF-oL） induced human vascular endothelial cell line EA. hy926 by Western blot. This study elucidates the systematic network and pathway analysis of multi-targets in YiQiFuMai Powder Injection. The results provide the possible mechanisms for its mode of action against cardio-cerebral ischemic diseases and may also reveal new clues for its potential application in the inflammatory diseases or tumors.

Astragalus injection as an adjuvant treatment for colorectal cancer:a meta-analysis

Background:The combination of Chinese patent medicine Astragalus injection and Western medicine has achieved a certain clinical effect in colorectal cancer patients.However,due to the uneven basic conditions and research indicators of these clinical trials,it is difficult to comprehensively evaluate the effect of Astragalus injection in the adjuvant treatment of colorectal cancer.This study aimed to systematically evaluate the efficacy and safety of Astragalus injection as an adjuvant treatment for colorectal cancer.Methods:The Cochrane Library,VIP database,Wanfang database,and Chinese Academic Journal Full Text database were searched for potentially eligible articles from inception to December 15,2018.Randomized controlled trials in which patients were diagnosed with colorectal cancer were included.Patients in the control group received chemotherapy alone or combined with other drugs,or chemotherapy combined with radiotherapy.Patients in the experimental group were treated with Astragalus injection combined with interventions in the control group.Results:A total of 8 articles were included.Compared with Western medicine alone,the Astragalus injection could improve the therapeutic effect(RR=1.18,95%CI(1.01,1.38),P=0.03),improved the quality of life of colorectal cancer patients(SMD=1.18,95%CI(0.86,1.50),P<0.001),inhibited leukopenia(RR=0.55,95%CI(0.42,0.71),P<0.001),reduced neurotoxicity(RR=0.43,95%CI(0.34,0.56),P<0.001),and reduced the incidence of nausea and vomiting(RR=0.67,95%CI(0.55,0.80),P<0.001).Conclusion:Astragalus injection can reduce the toxicity and improve the efficiency of the conventional Western medicine in the treatment of colorectal cancer.

The mechanism of Astragalus-Prunella vulgaris in the treatment of diabetic cardiomyopathy based on network pharmacology and molecular docking

Objective:To study the main chemical components and mechanism of Astragalus and Prunella vulgaris in the treatment of diabetes cardiomyopathy(DCM)based on network pharmacology and in vitro experiments.Methods:The main active components and prediction targets of Astragalus membranaceus and Prunella vulgaris herbal pairs were obtained by TCM Pharmacology database and analysis platform(TCMSP),and the disease genes were retrieved by genecards,OMIM,PharmGKB and drugbank databases.The disease and drug prediction targets were intersected to screen out common potential therapeutic targets.Cytoscape3.7.2 software was used to construct"drug component disease target"interaction network diagram;The PPI network of protein-protein interaction was constructed by using string database.R software was used to analyze the function enrichment of GO and KEGG for drug disease common targets,and autodock Vina 1.1.2 for molecular docking.Finally,the specific mechanism of Astragalus and Prunella vulgaris medicated serum on high glucose stimulated cardiomyocytes was verified in vitro.H9c2 cardiomyocytes were divided into five groups:normal group:low glucose(5.5 mmol/L)culture group,model group:high glucose(33 mmol/L)culture group,5%serum group:high glucose+5%Astragalus membranaceus Prunella vulgaris herb serum culture group,10%serum group:high glucose+10%Astragalus membranaceus Prunella vulgaris herb serum culture group,15%serum group:Hg high glucose+15%Astragalus membranaceus Prunella vulgaris herb serum culture group.MTT assay was used to detect the cell survival rate,and Western blot was used to detect the effect of Astragalus and Prunella vulgaris medicated serum on the expression of AKT1,p-AKT1,MAPK14 and p-MAPK14 proteins.Results:In this study,31 active components of Astragalus and Prunella vulgaris were screened,involving 157 targets of diabetes cardiomyopathy and 178 related signal pathways.The results of network analysis showed that Astragalus and Prunella vulgaris herbs may play a role in the treatment of DCM by acting on key targets such as AKT1,FOS,MAPK1,MAPK8,MAPK14,Jun and key pathways such as PI3K-AKT.Molecular docking showed that Astragalus membranaceus and Prunella vulgaris medicine had good binding between the active components luteolin,quercetin,pistil isoflavone,kaempferol and key targets such as AKT1,MAPK14,MAPK1,FOS,mapk8 and Jun,and the Vina score of luteolin and AKT1 was the lowest.The results in vitro showed that Astragalus and Prunella vulgaris medicated serum significantly improved the inhibition of H9c2 cardiomyocyte proliferation induced by high glucose,and increased the phosphorylation levels of AKT1 and MAPK14 proteins to play a role in the treatment of DCM.Conclusion:Astragalus and Prunella vulgaris have the characteristics of multi-target and multi-channel in the treatment of DCM.Its mechanism may be related to the regulation of the protein expression of p-AKT1 and p-MAPK14.These findings provide a new idea and basis for further experimental study on the mechanism of Astragalus and Prunella vulgaris in the treatment of diabetes cardiomyopathy.

Astragalus injection for asthma:A meta-analysis and systematic review

Objective:To evaluate the efficacy of Astragalus Injection on asthma.Methods:CNKI,VIP,Wan Fang Database,Medline,Embase,Web of Science and Cochrane Library were searched for published researches up to November,2020.Randomized controlled trials that focused on Astragalus Injection for asthma were included.We managed the data analysis with RevMan 5.3 software.Results:A total of 17 RCTs with 1648 patients were involved in the meta-analysis which indicated that Astragalus Injection could improve clinical efficacy[OR=4.72,95%CI(3.08,7.24),P<0.00001]and improve FEV1[MD=0.48,95%CI(0.32,0.64),P<0.00001],while reduce IL-4[MD=-6.29,95%CI(-8.91,-3.66),P<0.00001],IL-6[MD=-18.46,95%CI(-23.17,-13.75),P<0.00001]and IL-17[MD=-3.14,95%CI(-5.51,-0.76),P<0.00001]and decrease adverse events[OR=0.18,95%CI(0.08,0.43),P=0.0001].Conclusion:Astragalus Injection is more effective and of safety,but more RCTs are needed.

Study on the mechanism of Astragalus in the treatment of diabetic cardiomyopathy based on network pharmacology and its preliminary verification study

Objective:To explore the potential active ingredients and targets of Astragalus,and also to predict the targets and mechanisms of Astragalus in the treatment of diabetic cardiomyopathy.Based on the predicted results,the key signaling pathways were validated in a diabetic cardiomyopathy model mouse.Methods:Compounds and targets in Astragalus were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The protein names to corresponding"Gene Symbol ID"was convert by STRING database.We obtained targets of diabetic cardiomyopathy data from DisGeNET datasets.The protein-protein interaction network(PPI network)was established using STRING database.Cytoscape 3.6.0 was used to construct a disease-drug-target gene network map and to screen the 10 closest target genes by Cytohuba plug-in.The overlapping genes were then subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)-based enrichment analysis.Finally,the key molecules of the MAPK signaling pathway were validated by in vitro experiments.Animal experiments were performed using 21 Kunming mice randomly divided into normal group,model group,and Chinese herbal medicine Astragalus group,with seven mice in each group.The myocardium of mice in each group was stained with HE to compare the pathological morphological changes,and Western Blot was also used to compare the key molecules of MAPK signaling pathway,ERK1 and p-p38.Results:Astragalus contained 20 active ingredients with 188 corresponding targets,220 targets related to diabetic cardiomyopathy and 37 targets acting in conjunction with Astragalus.The common targets were imported into the STRING database to obtain a PPI network graph of overlapping genes,with 37 nodes and 391 edges.The PPI network map was imported into Cytoscape 3.6.0 software,and the most significant top 10 hub genes were obtained using the MCC algorithm in the cytoHubba plugin,namely AKT1,TP53,CASP3,MMP9,EGF,IL-10,CXCL8,IL-1β,VEGFA,PPARG.GO functional enrichment analysis yielded 40 entries for biological process(BP),23 entries for cellular component(CC),22 entries for molecular function(MF)and 94 entries for KEGG pathway enrichment screening,mainly involving PI3K-AKT,MAPK,HIF-1,FOXO,TNP pathway and other inflammation or apoptosis regulatory pathways.Animal experiments showed that Astragalus can improve the inflammatory state of myocardial tissue in mice with diabetic cardiomyopathy,and the expression of ERK1 and p-p38 protein in myocardial tissue of mice in the model group was higher than that in the normal group(P<0.05,P<0.01),and after the intervention with Astragalus,the expression of ERK1 and p-p38 protein was significantly lower than that in the model group,and the difference was statistically significant(P<0.05,P<0.01).Conclusion:Astragalus has multi-target,multi-component and multi-pathway action characteristics in the treatment of diabetic cardiomyopathy,which can exert anti-inflammatory and anti-oxidative stress effects by regulating protein expression of MAPK signaling pathway ERK1,p-p38.

Mechanism of Aidi injection on hepatocellular carcinoma based on network pharmacology

Objective:To explore the active ingredients and potential mechanism of Aidi injection in the treatment of hepatocellular carcinoma by network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID)were used to screen the active ingredients of four traditional Chinese medicines of Renshen,Huangqi,Ciwujia,and Banmao and corresponding potential targets.Screening of hepatocellular carcinoma-related targets through the Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database platforms.The drug and disease targets are merged to obtain the intersection,and the information is imported into Cytoscape 3.7.2 to construct a network diagram of the active ingredients of Aidi injection and related targets of hepatocellular carcinoma,and the topology analysis is performed.A protein-protein interaction(PPI)network was constructed and analyzed using the STRING online analysis platform.Uses the Database for Annotation,Visualization and Integrated Discovery(DAVID)to perform GO function enrichment analysis of targets and enrichment of KEGG pathways analysis.Results:A total of 33 potential active ingredients were screened from Aidi injection for treating hepatocellular carcinoma,including quercetin,kaempferol,beta-sitosterol,isorhamnetin and other important active ingredients.There are 106 potential targets for active ingredient action,6,677 disease-related targets,and 89 drug-disease common targets.Through the network diagram,it was found that the highest degree of target is PTGS1.In the PPI graph,a total of 87 nodes.Among them,the higher degree values include IL6,CASP3,VEGFA,MAPK8,JUN,EGFR,MYC,PTGS2 and FOS.A total of 60 related signal pathways were obtained by GO enrichment analysis.It mainly involves biological processes such as inhibiting abnormal proliferation and differentiation of hepatocellular carcinoma cells,inhibiting angiogenesis of hepatocellular carcinoma,regulating cell cycle and promoting apoptosis.KEGG pathway enrichment analysis screened a total of eight significantly different signal pathways.Among them,P53,VEGF,MAPK,Toll-like receptor,ErbB signaling pathways play an important role in treatment.Conclusion:This study initially revealed the potential mechanism of multi-component,multi-target and multi-pathway treatment of Aidi injection for hepatocellular carcinoma,and provided ideas for the subsequent verification of the molecular mechanism of Aidi injection for hepatocellular carcinoma.

Mechanism of Xuebijing injection on hepatic ischemia-reperfusion injury based on network pharmacology

Objective:Using network pharmacology to predict the main active ingredients,targets and signaling pathways of Xuebijing injection in the treatment of hepatic ischemia-reperfusion injury and explore its potential mechanism of action.Methods:Screen the active ingredients and their targets of Danshen,Honghua,Chishao,Chuanxiong,and Danggui in Xuebijing injection through Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and the Hepatic ischemia-reperfusion injury related targets through Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database.And acquire drug-disease intersection targets at the same time.The STRING database was used to construct a protein-protein interaction(PPI)network and topologically screen the central targets.Use the R language online search Bioconductor platform to perform GO function enrichment on the target;Database for Annotation,Visualization and Integrated Discovery(DAVID)database was used to perform KEGG channel enrichment analysis on the target.Use Cytoscape 3.7.2 to construct a"ingredient-target-pathway"network diagram and perform a topology analysis.Results:A total of 115 active ingredients were selected from Xuebijing injection,including Quercetin,Luteolin,Kaempferol,Beta-carotene,and Tanshinone IIa,etc.It corresponds to 217 targets.There are 1057 disease-related targets,and 114 drug-disease common targets.PPI topologically screened out 17 target proteins.Topological analysis of the network graph obtained 15 target genes.Thire intersection contains key targets such as JUN,PPARG,PTGS2,AKT1 and MAPK1.A total of 137 related signaling pathways were obtained by GO enrichment analysis.A total of 8 signaling pathways were obtained through KEGG enrichment(P<0.05,FDR<0.05),among which signaling pathways such as Toll-like receptors,T cell receptors,NOD-like receptors,VEGF,and ErbB played an important role in immune regulation,anti-apoptosis,anti-inflammatory,anti-oxidation,and promoting angiogenesis in the treatment.Conclusion:Xuebijing injection can treat hepatic ischemia-reperfusion injury through multiple components,multiple targets and multiple pathways.

Network pharmacology-based elucidation of molecular biological mechanisms of Kanglaite injection for treatment of non-small cell lung cancer

Objective: To investigate the effective compounds, potential targets and molecular mechanism of Kanglaite injection (KLTi) in the treatment of Non-Small Cell Lung Cancer (NSCLC) based on network pharmacology. Methods: The active compounds and targets of KLTi which extracted and isolated from Coix Seed were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The related genes of NSCLC were obtained by searching the Human Gene Database (GeneCards) and Online Mendelian Inheritance in Man (OMIM). The candidate targets of KLTi in the treatment of NSCLC were obtained after extracting the intersection network. The "drug-component-target-disease" network was constructed with the help of Cytoscape 3.7.2. The Protein- Protein Interaction networks were constructed on the STRING platform and core network modules were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of candidate genes were performed using Metascape platform, and a "pathway-target- compounds" network was constructed to further screen key genes and active compounds. Results: A total of 11 compounds, 22 candidate targets, 206 GO functions and 12 KEGG pathways were obtained. Conclusion: The active compounds of KLTi in the treatment of NSCLC are stigmasterol, stigmasterol α1 and ergosterol. The key targets are PGR, NCOA2, PTGS2, NR3C2, and PTGS1. The core GO functions included receptor activity and binding, neuronal signal transmission and hormone stimulation;KEGG mainly involves cancer pathways, neuroactive ligand-receptor interactions and calcium signaling pathways. This study reveals the molecular biological mechanism of KLTi in the treatment of NSCLC, which is speculated to be related to neuroendocrine, providing a new basis and therapeutic direction for subsequent clinical application and experimental research.

Effect of Astragalus Injection Combined with Chemotherapy on Qual ity of Life in Patients with Advanced Non-small Cell Lung Cancer

Objective: To observe the effect of Astragalus injection (AI) combined with chemotherapy on quality of life (QOF) in patients with advanced non-small cell lung caner (NSCLC). Methods: Sixty NSCLC patients were randomly divided into the treated group (n=30,treated with AI combined with chemotherapy) and the control group (n=30, treated with chemotherapy alone). Chemotherapy of MVP protocol was applied to both groups. AI was supplemented to the treated group by intravenous dripping 60 ml per day. Treatment of 21-28 days consisted one treatment cycle, and 2-3 cycles were applied. WResults: The effective rate in the treated group was 40.0% and in the control group was 36.7%, the mean remission rate in them being 5.4 month s and 3.3 months, the median survival period 11 month and 7 month and the 1-year survival rate 46.75% and 30.0%, respectively, the difference of these indexes between the two groups were all significant (P<0 05). Moreover, the clinical improving rate and QOF elevation rate in the treated group was 80.4% and 43.3%, as compared with those in the control group (50.0% and 23.3% respectively), the different was also significant (P<0 01). Conclusion: AI combined with chemotherapy can significantly improve the QOF in NSCLC patients of advanced stage.

A review on the Pharmacology and Adverse Drug Reaction of Chaihu Herbal Injection

The Chaihu herbal injection was the first herbal injection to be developed and used in China,which has been used in clinic for more than 70 years.This injection is widely used to treat fever caused by influenza or common cold and malaria.However,there is an ongoing debate about the safety of the clinical use of Chaihu herbal injection in view of the large number of adverse drug reaction reports and literature in China.On May 29,2018,the China Food and Drug Administration issued a notice requiring to revise the instruction manual of Chaihu herbal injection,list"prohibit for children"under the taboo item,and add the warning"adverse reactions of this product include anaphylactic shock".The purpose of this review is to provide updated,comprehensive information on the pharmacology and adverse drug reaction of Chaihu herbal injection based on scientific literatures in the past few decades.

Network pharmacology studies on Reduning injection in treatment of COVID-19

Background:Network pharmacology was used to explore the mechanism of the Chinese patent medicine Reduning injection in the treatment of corona virus disease 2019.Methods:The chemical constituents and targets of Qinghao(Artemisiae annuae herba),Jinyinhua(Lonicerae japonicae flos),Zhizi(Gardeniae fructus)in the Chinese patent medicine Reduning injection were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the target related to corona virus disease 2019 was searched in GeneCards database,then perform Venn analysis on the targets of corona virus disease 2019 and the Chinese patent medicine Reduning injection,to screen the compounds and targets of the Chinese patent medicine Reduning injection in the treatment of corona virus disease 2019.The String platform was used to construct the protein-protein interaction network,and key targets were screened.Cytoscape 3.5.1 was used to construct the active traditional Chinese medicine-chemical composition-target-disease network to screen the key active components,and the gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the common target through DAVID(6.8)online analysis data tool to predict the mechanism of action.Results:Fifty-two active ingredients and 232 targets were selected from the Chinese patent medicine Reduning injection,including 44 targets related to corona virus disease 2019.A total of 310 gene ontology biological processes and 94 Kyoto Encyclopedia of Genes and Genomes signaling pathways were obtained,which were mainly involved in inflammation,viral infection,bacterial infection,immune response and substance metabolism,et al.Conclusion:The mechanism of the Chinese patent medicine Reduning injection in the treatment of corona virus disease 2019 may be related to antivirus,bacteriostasis,anti-inflammatory and antifebrile,immune regulation and metabolism regulation,et al.

Effects of astragalus injection on the skin lesion degree and Caspase-14,SOCS1 and STAT3 levels of psoriasis model in Balb/c nude mice

Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divided into groups A, B and C with 20 mice in each group. Group A mice were used as blank control, group B mice as model group and group C mice as treatment group. The PASI score of psoriasis, skin thickness, inflammatory factors, serum levels of Caspase-14, SOCS1 and STAT3 in three groups of mice were analyzed after 2 weeks of treatment. Result: After treatment, the P ASI score of group B was significantly higher than that of group C, with statistical significance (P < 0.05);there was statistical significance in the measurements of lesion skin of three groups of mice after treatment (P <0.05). Compared with the blank control group, the thickness of lesion skin in group B and C was significantly higher, and the thickness of lesion skin in treatment group was significantly lower than that in control group (P < 0.05). Compared with the blank control group, the inflammatory factors IL-17, IL-22 and IL-23 in the B and C groups were significantly increased, and the inflammatory factors IL-17, IL-22 and IL-23 in the treatment group were significantly lower than those in the model group. The levels of serum C aspase-14, SOCS1 and STAT3 in three groups of mice were significantly different after treatment (P < 0.05). Compared with the blank control group, the levels of serum C aspase-14 and SOCS1 in B and C groups were significantly lower and the levels of STAT3 were significantly higher, and the levels of inflammatory factors aspase-14 and SO in treatment group were significantly higher than those in control group. The level of CS1 was significantly lower than that of model group, and the level of STAT3 was significantly higher than that of model group (P <0.05). Conclusion: Astragalus membranaceus injection can effectively improve the degree of psoriasis in Balb/c nude mice. Its possible mechanism is that it can decrease the expression of Caspase-14 and SOCS1, reduce the degree of keratosis in the lesion site of mice, improve the local surface hyperplasia, increase the level of STAT3 and enhance the level of local cell proliferation, which is of positive significance for the rehabilitation of psoriasis.