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This study aims to evaluate the efficacy and safety of Guanxinning Tablets+conventional western medicine in the treatment of angina pectoris of coronary heart disease, and provide evidence-based references for clinical medication. Retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, randomized controlled trial(RCT) about Guanxinning Tablets for the treatment of angina pectoris of coronary heart disease from the inception to April 2022 were collected. After literature screening and data extraction, the bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literature, and RevMan 5.3 and Stata 14.0 were used for Meta-analysis. Eighteen RCTs were finally included, involving 2 281 patients. Meta-analysis showed that, compared with conventional western medicine treatment alone, Guanxinning Tablets+conventional western medicine significantly improved angina pectoris efficacy(RR=1.33, 95%CI[1.13, 1.57], P=0.000 8), electrocardiogram efficacy(RR=1.32, 95%CI[1.02, 1.71], P=0.03), and exercise duration(MD=59.53, 95%CI[39.16, 79.90], P<0.000 01) and reduced the incidence of cardiovascular events(MACE)(RR=0.43, 95%CI[0.30, 0.61], P<0.000 01), high sensitivity C-reactive protein(hs-CRP)(MD=-2.75, 95%CI[-3.71,-1.79], P<0.000 01), and endothelin-1(ET-1) levels(MD=-9.34, 95%CI[-11.36,-7.32], P<0.000 01). There was no statistically significant difference in the incidence of adverse reactions between two groups(RR=0.91, 95%CI[0.68, 1.22], P=0.52). Subgroup analysis showed that Guanxinning Tablets may have better short-term efficacy(less than 6 months) in the treatment of heart-blood stasis syndrome. GRADE grading showed that angina pectoris efficacy, electrocardiogram efficacy, MACE, and ET-1 were in the medium grade, hs-CRP and adverse reactions were in the low grade, and exercise duration was in the extremely low grade. In conclusion, the efficacy of Guanxinning Tablets+conventional western medicine is better than conventional western medicine treatment alone, with good safety. Therefore, it is recommended for the short-term treatment of patients with heart-blood stasis syndrome. However, the evidence quality of some results is low, and more rigo-rous RCT is still needed to enhance the reliability of evidence.
Subject(s)
Humans , C-Reactive Protein , Reproducibility of Results , Drugs, Chinese Herbal/adverse effects , Angina Pectoris/drug therapy , Coronary Disease/drug therapy , TabletsABSTRACT
This study investigated the intervention effect of Guanxinning Tablet on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low density lipoprotein (ox-LDL), providing experimental basis for Guanxinning Tablet in the treatment of atherosclerosis-related diseases. Under the damage of HUVECs by ox-LDL, the cell viability was detected by CCK-8 (cell counting kit-8) assay; lactate dehydrogenase (LDH) in the cell culture supernatant was detected by the corresponding kit; the cell morphology of different groups was observed by common phase contrast microscope; reactive oxygen species (ROS) and NO levels in the cells were detected by DCFH-DA and DAF-FM DA probes, respectively; monocyte adhesion assay was used to detect the recruitment of THP-1 in HUVECs, and TMRM dye was used to detect the level of mitochondrial membrane potential; interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) secretion in the cells was detected by ELISA assay. The results showed that Guanxinning Tablet had a concentration-dependent proliferative effect on HUVECs. Under the stimulation of 100 μg·mL-1 ox-LDL, the morphology of endothelial cells was significantly changed. At this time, NO level was significantly decreased, ROS level was significantly increased and accompanied by a decrease in mitochondrial membrane potential. The recruitment of THP-1 cells by endothelial cells and IL-6, ICAM-1 and MCP-1 were also significantly increased, resulting in oxidative stress and inflammatory injury. Guanxinning Tablet and its composed extracts could significantly improve cell morphology, increase NO level, decrease ROS production, and also reduce the secretion of inflammation-related proteins IL-6 and MCP-1. Salvia miltiorrhiza and Ligusticum striatum DC. have significant synergistic effects on NO. Among them, salvianolic acid B and salvianic acid A exerted the main effects, and the combined efficacy of salvianic acid A and ferulic acid was superior to that of single administration. The above results showed that Guanxinning Tablet and their active substances had the effects of improving endothelial basal function, resisting oxidative stress, and alleviating inflammatory injury, and Salvia miltiorrhiza and Ligusticum striatum DC. synergized, which may be related to their regulation of oxidative stress and inflammation and have application prospects in the treatment of atherosclerosis-related diseases.
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OBJECTIVE@#To investigate the effect and safety of Guanxinning Tablet (, GXN) for the treatment of stable angina pectoris patients with Xin (Heart)-blood stagnation syndrome (XBSS).@*METHODS@#One hundred and sixty stable angina pectoris patients with XBSS were randomly assigned to receive GXN (80 cases) or placebo (80 cases, Guanxinning simulation tablets, mainly composed of lactose), 4 tablets (0.38 g/tablet), thrice daily for 12 weeks. After treatment, an exercise stress test (treadmill protocol), Chinese medicine (CM) syndrome score, electrocardiogram (ECG), and nitroglycerin withdrawal rate were evaluated and compared in the patients between the two groups. Meanwhile, adverse events (AEs) were evaluated during the whole clinical trial.@*RESULTS@#Compared with the control group, the time extension of exercise duration in the GXN group increased 29.28 ±17.67 s after treatment (P>0.05); moreover, the change of exercise duration in the GXN group increased 63.10 ±96.96 s in subgroup analysis (P<0.05). The effective rates of angina pectoris, CM syndrome and ECG as well as nitroglycerin withdrawal rate were 81.33%, 90.67%, 45.76%, and 70.73%, respectively in the GXN group, which were all significantly higher than those in the control group (40.58%, 75.36%, 26.92%, 28.21%, respectively, P<0.05).@*CONCLUSION@#GXN was a safe and effective treatment for stable angina pectoris patients with XBSS at a dose of 4 tablets, thrice daily.
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Objective: To study network pharmacology mechanism of main ingredients of Guanxinning Injection treating cardiovascular diseases by computer simulation. Methods: Danshensu, salvianolic acid B, protocatechuic aldehyde, rosmarinic acid, tanshinone IIA, lithospermic acid, ferulic acid, senkyuno lide I, ligustrazine, butylphthalide, and ligustilide from Guanxinning Injection were used to predict and screen the targets by reverse molecular docking technology, and were used to study pharmacological mechanism of main ingredients of Guanxinning Injection treating cardiovascular diseases relying on protein-protein interaction network, GO biological processes enrichment, and KEGG signaling pathways enrichment. Results: There were total 11 active ingredients acting INS, Akt1, TNF, MAPK1, ESR1, F2, SERPINE1, and 142 cardiovascular diseases related targets in Guanxinning Injection. These targets were mainly involved in steroid hormone mediated signaling pathway, glutathione metabolic process, positive regulation of smooth muscle cell proliferation and other biological processes, and regulation of coagulation, inflammation and immune, endocrine, and 20 relevant pathways. Conclusion: Guanxinning Injection participated in the treatment of the cardiovascular diseases by anti-inflammatory, anti-oxidant, anticoagulation, promoting fibrinolysis, regulating hormones, and maintaining cardiovascular homeostasis.
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Objective To observe the repeat administration toxicity of Guanxinning Injection in rats.Methods Totally 120 rats (males and females) were randomly divided into vehicle control group and three Guanxinning Injection groups with different dosages (3.40,1.70,and 0.85 g/kg).Rats were administered with Guanxinning Injection by consecutive intravenous injection for 13 weeks.Besides the general conditions were observed,the related indexes were detected,such as body weight,the routine control of blood,hepatic function,renal function,the metabolism condition of lipids,the glycometabolism indexes,and histopathology analysis were determined at 13 weeks of treatments and 4 weeks after the withdrawal,respectively.Results Rats in the Guanxinning Injection group at 3.40,1.70 g/kg apperance shortness of breath,unsteady gait,lying motionless,and other symptoms.There was no obvious abnormal reaction in the 0.85 g/kg dose group.There were two male rats in the Guanxinning Injection group at 3.40 g/kg died at about week 4 of treatments,and there was no death in the 0.85 and 1.70 g/kg dose groups.Compared with vehicle control group,the related indexes of blood,blood biochemistry,organ relative quality,and histopathological showed no obvious abnormalities in Guanxinning Injection 0.85 and 1.70 g/kg group.The levels of urea nitrogen (BUN) and the relative weight of kidney in Guanxinning Injection 3.40 g/kg group were significantly higher than those in vehicle control group at 13 weeks.The change of these parameters regained to normal at 4 weeks after withdrawal and the rest of the detection index showed no obvious abnormality in 3.40 g/kg dase group.Conclusion Intravenous administration of Guanxinning Injection for 13 weeks at high dose could induce reversible damage to kidney.
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Objective To observe the effect of Guanxinning Tablet (GXNT) on myocardial infarction and cardiac autonomic nervous function in rats with myocardial ischemia reperfusion injury (MI/RI).Methods Seventy SD rats were divided into 7 groups randomly (n=10);the sham group, the MI/RI group, 75 mg/kg, 150 mg/kg, 300 mg/kg and 600 mg/kg GXNT groups and 300 mg/kg Compound Danshen Tablets (DST) group.All rats were administered orally for 7 days, and then the MI/RI model was made by ligating the left anterior descending branch of coronary artery in rats.The changes of electrocardiogram were recorded and the electrocardiogram of J points and heart rate variability (HRV) parameters were analyzed.At the end of reperfusion, the myocardial infarct size was measured by using Evans blue and tetrazolium chloride (TTC) double staining, and pathological changes of myocardium were observed by HE staining.The changes of serum lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA) and nitric oxide (NO) levels were also detected.Results Compared with MI/RI group, GXNT and DST groups were significantly reduced myocardial infarct size and inhibited the rising of serum LDH and CK activities (P < 0.05, P < 0.01), and also reduced the total or average value of J point during reperfusion (P < 0.05, P < 0.01).Meanwhile, GXNT and DST groups were markedly increased HRV and serum NO level as well as decreased serum MDA content (P < 0.05, P < 0.01), and improved myocardial tissue pathology.Conclusions GXNT can reduce the myocardial infarction in rats with MI/RI, and also improve the cardiac autonomic nervous function.
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Objective To establish a zebrafish model of thrombosis induced by three kinds of inducers and observe the anti?thrombotic effect of a Chinese traditional medicine, Guanxinning tablet ( GXN) . Methods The zebrafish models of thrombosis was induced by using 1?5μmol/L phenyl hydrazine, 80μmol/L arachidonic acid and 5 mg/L ponatinib, re?spectively, and were treated with various concentration of GXN, clopidogrel or asprin. The thrombus in the tail vein was observed under microscope, Erythrocytes in the zebrafish heart were stained with o?dianisidine and the erythrocyte staining intensity was assessed with a NIS?Elements DTM image analyzer, and the anti?thrombolic effect of GXN was calculated. Results Venous thrombus was significantly increased and the staining intensities of erythrocytes in the heart were signifi?cantly decreased after induction by phenyl hydrazine, arachidonic acid or Ponatinib ( P <0?001 ) , respectively. At the same time, GXN showed an incresing anti?thrombolic effect in the zebrafish models (P<0?001) in a dose?effect manner, with a IC50 of GXN of 44?32 mg/L,138?5 mg/L and 459?5 mg/L, respectively. Conclusions The zebrafish models of thrombosis are successfully established by phenyl hydrazine, arachidonic acid or Ponatinib, respectively, by different for?mation mechanisms. GXN has been shown to have an anti?thrombosis effect, probably, by multiple target effects.
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Objective: To investigate the chemical constituents from Guanxinning Injection. Methods: The chemical constituents were repeatedly isolated by column chromatographic techniques including silica gel, ODS, Sephadex LH-20, and macroporous resin, and were purified by preparation HPLC chromatography and recrystallization, and their structures were identified by physicochemical properties and spectroscopic data. Results: Nineteen compounds were isolated and identified as protocatechuic aldehyde (1), vanillin (2), ferulic acid (3), 2-furoic acid (4), senkyunolide I (5), caffeic acid (6), salvianolic acid A (7), isosalvianolic acid A (8), salvianolic acid B (9), isosalvianolic acid C (10), rosmarinic acid (11), 1, 3-dicaffeoylquinic acid (12), senkyunolide H (13), 4-hydroxybenzoic acid (14), m-hydroxybenzoic acid (15), o-hydroxybenzoic acid (16), 4-hydroxycinnamic acid (17), methyl rosmarinate (18), and salvianolic acid N methyl ester (19). Conclusion: Nineteen compounds are isolated from the Guanxinning Injection for the first time, and all HPLC analyses and literature data show that compounds 2, 3, 5, 13-16 are originated from Ligusticum chuanxiong, compounds 7-11, and 18-19 from Salvia miltiorrhiza, and compounds 1, 4, 6, 12, and 17 from L. chuanxiong and S. miltiorrhiza.
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AIM:To study the purified factors of Guanxinning for Injection(Radix et Rhizoma salviae miltiorrhizae,Rhizoma Chuanxiong,etc). METHODS: The total of salvianolic acid B、protocatchuci aldehyde and ferulic acid were used to evaluate for the study of type of macroporous adsorption resin,sample volume,the ratio of diameter to height,pH value and sample consistency etc. RESULTS: pH value Guanxinning extract was adjusted to 3.0,through D101 resin finally reached the ratio of diameter to height 1∶2,4 times of water was applied to elution and then 3 times of 70% ethanol for re-elution and collected. CONCLUSION: These factors are approprite for purifying Guanxinning for Injection.
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AIM: To identify an unknown peak in Guanxinning Injection(Radix et Rhizome Salviae Miltiorrhizae,Rhizoma Chuanxiong) chromatographic fingerprint. METHODS: The elution(44-46 min) separated and collected by HPLC was analyzed by GC-MS and HPLC-PDA-MS-MS. RESULTS: The unknown peak was corresponding to senkyunolidel I. CONCLUSION: It is quick method to identify the reported chemical in herbal medicine based on a small quantity of sample by GC-MS and HPLC-PDA-MS-MS.