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.

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.

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.

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.

Clinical Study on Effect of Astragalus Injection (黄芪注射液) and Its Immuno-regulation Action in Treating Chronic Aplastic Anemia

Objective： To observe the clinical effect of Astragalus Injection （黄芪注射液, Al） and its immuno-regulatory action in treating chronic aplastic anemia （CAA）. Methods： Sixty patients with CAA were randomly assigned to two groups equally, both were treated with Stanozolol three times a day, 2 mg each time through oral intake, but AI was given additionally to the patients in the treated group once a day via intravenous dripping. All were treated for 15 days as one therapeutic course and the whole medication lasted for more than 4 months totally, with follow-up adopted. The clinical efficacy was estimated and the changes of T-lymphocyte subsets in peripheral blood as well as the serum levels of tumor necrosis factor-α （TNF-α ） and interleukin-2 （IL-2） were observed. Results： The total effective rate in the treated group was 83.3% （25/30）, which was higher than that in the control group 66.7% （20/30）, showing significant difference between them （P〈0.05）. Levels of hemoglobin, WBC, reticular cell and platelet were elevated in both groups after treatment, but the improvement was significantly better in the treated group than that in the control group with respect to the former three indexes （P〈0.05）. The level of CD4^＋ increased and that of CD8^＋ decreased significantly after treatment in the treated group （P〈0.05）, which showed significant difference as compared with those in the control group （P〈0.05）. Levels of serum TNF-α and IL-2 lowered after treatment in both groups, but significance only showed in the treated group （P〈0.05）. The degree of proliferation in bone marrow got raised significantly and the percentage of non-hemopoietic cells reduced significantly in the treated group after treatment, also showing significant difference to those in the control group （P〈0.05）. Conclusion： AI could promote the recovery of hemopoietic function, which might be through improving T-lymphocyte subsets and reducing the release of negative regulatory factors such as TNF-α and IL-2 to alleviate the inhibition on hemopoietic function.

Effect of astragalus injection on plasma adiponectin concentration in patients with chronic heart failure

In recent years, astragalus made great progress in the treatment of heart failure, and become an important supplementary conventional treatment of heart failure drugs. The article will investigate the effect of astragalus injection on plasma adiponectin concentration and its possible mechanisms in patients with chronic heart failure. Methods sixty-two chronic heart failure （CHF） patients with NYHA functional class Ⅱ-Ⅲ grade were randomly divided into treatment group （treatment group of 31 cases） and conventional treatment group （control group of 31 cases）,blood samples were collected at 2 weeks before and after treatment in 62 CHF patients and in 30 healthy subjects. Plasma adiponectin and brain natriuretic peptide were measured in two groups before and after treatment. NYHA functional class and left ventricular function indexes were also assessed by echocardiography. Results The NYHA functional class were improved after treatment （P 〈 0.05）, and significantly in treatment group than in control group （P 〈 0.05）; There were significantly decreased in left ventricular end-systolic volume （LVESV） and left ventricular end-diastolic volume （LVEDV） and improved in left ventricular ejection fraction （LVEF） after treatment in treatment group （P 〈 0.05）. At the same time,plasma adiponectin and brain natriuretic peptide levels were significantly decreased after astragalus injection in treatment group （P 〈 0.05）. Conclusion These findings indicate that astragalus injection can improve cardiac remodeling, decrease the secretion of brain natriuretic peptide, which may exercise through the lipid effect to decrease plasma adiponectin concentration.

Effect of Astragalus membranaceus injection on the activity of the intestinal mucosal mast cells after hemorrhagic shock-reperfusion in rats

Background The mechanism of mucosal damage induced by ischemia-reperfusion （IR） after hemorrhagic shock is complex; mast cells （MC） degranulation is associated with the mucosal damage. Astragalus membranaceus can protect intestinal mucosa against intestinal oxidative damage after hemorrhagic shock, and some antioxidant agents could prevent MC against degranulation. This study aimed to observe the effects of astragalus membranaceus injection on the activity of intestinal mucosal mast cells （IMMC） after hemorrhage shock-reperfusion in rats Methods Thirty-two Wistar rats were randomly divided into the normal group, model group, low dosage group, （treated with Astragalus membranacaus injection, 10 g crude medication/kg） and high dosage group （treated with Astragalus membranacaus injection, 20 g crude medication/kg）. The rat model of hemorrhagic shock-reperfusion was induced by hemorrhage for 60 minutes followed by 90 minutes of reperfusion. The animals were administrated with 3 ml of the test drug solution before reperfusion. At the end of study, intestinal pathology, ultrastructure of IMMC, and expression of tryptase were assayed. The levels of malondisldehyde （MDA）, TNF-α, histamine, and superoxide dismutase （SOD） activity in intestine were detected, and the number of IMMC was counted. Results The Chiu＇s score of the rats in the model group was higher than in other groups （P〈0.01）. The Chiu＇s score in the high dosage group was higher than that in the low dosage group （P〈0.05）. Hemorrhage-reperfusion induced IMMC degranulation： Astragalus membranaceus injection attenuated this degranulation. Expression of tryptase and the number of IMMC in the model group increased compared with the other groups （P〈0.01） and was significantly reduced by the treatments of Astragalus membranaceus injection at both doses. There was no significant difference between the two treatment groups （P〉0.05）. MDA content and concentration of TNF-α in the model group were higher than that in the other three groups （P〈0.05）, and the concentration of TNF-α in the low dosage group was higher than that in the high dosage group （P〈0.05）. SOD activity and the concentration of histamine in the model group were lower than the other three groups （P〈0.05）. There was a negative correlation between the Chiu＇s score and the concentration of histamine and a positive correlation between the Chiu＇s score and the concentration of TNF-α and between the SOD activity and the concentration of histamine in the four groups （P〈0.05）. Conclusion Astragalus membranaceus injection may reduce the damage to small intestine mucosa by inhibiting the activated IMMC after hemorrhagic shock.

Astragalus Membranaceus Injection Combined with Conventional Treatment for Viral Myocarditis:A Systematic Review of Randomized Controlled Trials

Objective：To assess the efficacy and safety of Astragalus membranaceus Injection combined with conventional therapy in the treatment of viral myocarditis.Methods：Randomized controlled trials（RCTs） of A.membranaceus Injection combined with conventional treatment compared with conventional treatment alone were included.Study population characteristics and outcome results were extracted independently by two assessors.Meta-analysis was performed for data available.Results：Six RCTs,involving 639 participants,were included in this study.The methodological quality of the included trials was generally low,and there was high risk of publication bias in the included trials.The total effective rate of A.membranaceus Injection combined with conventional treatment was significantly higher than that of conventional treatment alone.Compared with conventional treatment,the cointervention treatment group showed significant recovery in myocardium enzyme levels and electrocardiography.Two RCTs reported there were no adverse effects from A.membranaceus Injection combined with conventional treatment.Conclusion：A.membranaceus Injection combined with conventional treatment appeared to be more efficacious compared with conventional treatment alone for treating viral myocarditis.However,this conclusion should be cautiously interpreted due to low methodological quality,small sample size,limited number of trials,and high risk of publication bias and other unidentified risks of bias.The safety of A.membranaceus Injection combined with conventional treatment remains uncertain.