Danhong Injection Research Articles

Rapid separation and identification of multiple constituents in Danhong Injection by ultra-high performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry

To characterize and identify multiple constituents in Danhong injection (DHI), a fast ultra-high performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-QTOF/MS) method was established and validated in the present study. A total of 63 compounds, including 33 phenolic acids, 2 C-glycosyl quinochalcones, 6 flavonoid O-glycosides, 4 iridoid glycosides, 6 organic acids, 5 amino acids, and 3 nucleosides, were identified or tentatively characterized. In conclusion, the UHPLC-ESI-QTOF/MS method is useful and efficient for in-depth structural elucidation of chemical compounds in complex matrices of herbal medicines such as DHI.

An Overview of Systematic Reviews of Danhong Injection for Ischemic Stroke

Objective. This overview is to evaluate the current evidence from systematic reviews (SRs) of Danhong injection (DHI) for ischemic stroke (IS). Methods. SRs of randomized controlled trials (RCTs) concerning DHI and IS were searched in six databases without language restrictions until September 2015. Assessment of multiple systematic reviews (AMSTAR) was used to evaluate the methodological quality of all included SRs. Result. A total of 8 articles were included. After the administration of DHI, clinical efficiency and neurological deficits score have marked advantages over those of the control group. However, the overall poor quality of meta-analysis and original studies affected the reliability of the results. Evaluation of methodological quality found that no one paper meets the requirements of all 11 items. The main flaws of the methodology quality included the following: not providing “a priori” design and reasonable objectives, duplicate study selection not given enough attention, performing an incomprehensive literature search, not paying attention to publication bias and other bias reports, characteristics of included studies not provided in detail, and ignoring clinical heterogeneity when performing meta-analyses. Conclusion. The current published SRs suggest DHI appears to be a safe and effective way for IS treatment in general. However, it lacks a high quality systematic evaluation and analysis. The quality of SRs should be improved. Further large sample-size and well-designed RCTs are needed.

A novel and improved UHPLC-QTOF/MS method for the rapid analysis of the chemical constituents of Danhong injection

Danhong injection (DHI), one of the best-selling traditional Chinese medicine injections (TCMIs), is used extensively for treating myocardial infarction, atherosclerosis, coronary heart disease, and traumatic intracranial hematoma in clinics.

Evaluating the effects of Danhong injection in treatment of acute ischemic stroke: study protocol for a multicenter randomized controlled trial.

BackgroundDanhong injection (DHI) has been widely prescribed to patients with acute ischemic stroke (AIS). However, due to methodological deficiencies, previous research has not yet provided rigorous evidence to support the use of DHI in the treatment of AIS. Therefore, we designed this multicenter, randomized, controlled, and double-blind trial to evaluate the efficacy and safety of DHI for AIS.Methods/DesignIt is a randomized, multicenter, double-blind, placebo-controlled, adaptive clinical trial. A total of 864 eligible patients will be randomized into either the DHI or placebo group in a 2:1 ratio. All patients will be given the standard medical care as recommended by guidelines. Participants will undergo a 2-week treatment regimen and 76-day follow-up period. The primary outcome is the proportion of patients with a favorable outcome, defined as a score of 0–1 on the modified Rankin scale at day 90. Secondary outcomes include a change in the total score of the Chinese medicine symptom scales of “Xueyu Zheng” (blood stasis syndrome), the proportion of patients with a Barthel Index score of ≥90, the proportion of patients with an improvement in NIHSS score of ≥4 or NIHSS score of 0–1, quality of life measured by the EQ-5D scale, etc. Safety outcomes such as global disability (mRS ≥3) at day 90 will also be assessed. The changes in mRNA and microRNA profiles in 96 patients selected from certain centers will also be assessed. As this is an adaptive design, two interim analyses are prospectively planned, which will be carried out after one-third and two-thirds of patients have completed the trial, respectively. Based on the results of the interim analyses, the Data Monitoring Committee (DMC) will decide how to modify the study.DiscussionThis trial will provide high-quality evidence for DHI in treatment of AIS.Trial registrationClinical Trials.gov NCT01677208 (Date of registration 22 December 2012).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1076-4) contains supplementary material, which is available to authorized users.

Protective effect with vascular endothelium of Danhong injection on unstable angina after coronary intervention in patients

Objective To observe the protective effects with vascular endothelium of Danhong injection for unstable angina (UA) after percutaneous coronary intervention in patients. Methods 180 patients with UA were randomly divided into two groups, and patients undergoing percutaneous coronary intervention (PCI) therapy.In addition, 90 cases in the control group were treated with conventional western medicine treatment, 90 cases in the observation group were treated with conventional western medicine treatment and Danhong injection therapy.The serum superoxide dismutase (SOD), malondialdehyde (MDA) and brachial artery flow-mediated endothelium-dependent vasodilation (FMD), von Willebrand factor (vWF), plasma nitric oxide (NO), endothelin-1 (ET-1) levels and other indicators before and after treatment were detected. Results The total effective rate of the observation group was 96.67%, which was significantly higher than 75.56% of the control group (χ2=9.23, P<0.05). The endothelial function parameters NO(73.66±11.58)μmol/L, ET-1(64.75±6.83)ng/L, vWF(114.58±16.24)%, FMD (6.54±0.88)% of the observation group after treatment were significantly improved than before treatment (t=8.04, 7.90, 8.44, 7.67, all P<0.05), which of the control group were (62.78±10.42)μmol/L, (92.31±8.67)ng/L, (152.64±18.75)%, (4.18±0.72)%, there were significant differences(t=6.78, 7.34, 7.70, 6.56, all P<0.05). The serum SOD (154.62±21.37)U/mL and MDA (4.18±0.79)nmol/L levels of the observation group were significantly improved than before treatment(t=7.58, 8.67, all P<0.05), which of the control group were (132.45±26.89)U/mL, (5.27±1.16)nmol/L, there were significant differences (t=7.22, 7.81, all P<0.05). Conclusion Danhong injection for the treatment of UA stasis syndrome can be widely promoted by reducing oxidative stress on vascular endothelial damage, and improving endothelial function in patients after PCI, has great clinical value. Key words: Danhong injection; Unstable angina; Percutaneous coronary intervention; Vascular endothelial function

Danhong injection in the treatment of chronic stable angina: study protocol for a randomized controlled trial.

BackgroundChronic stable angina is a leading cause of death worldwide. Danhong injection, a complementary alternative medicine for chronic stable angina, has been demonstrated to be effective in numerous studies and is widely prescribed to patients. However, the methodological quality of most prior studies was found to be, in general, low. Therefore, we designed this randomized controlled trial to evaluate the efficacy and safety of using Danhong injection to treat chronic stable angina.Methods/designThis is a randomized multicentre, double-blind, placebo-controlled, adaptive clinical trial. A total of 870 patients meeting the eligibility criteria will be randomly assigned into either the Danhong injection or the placebo group in a 2:1 ratio. Participants will then undergo a 2-week treatment regimen and a 76-day follow-up period. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. Based on the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire, which will be administered on day 30. Other secondary efficacy and safety outcomes will also be assessed.DiscussionThis trial will provide high-quality evidence regarding the use of Danhong injection to treat chronic stable angina.Trial registrationClinicalTrials.gov: NCT01681316.

GW26-e2420 Danhong Injection Prevents Nitroglycerin-induced Tolerance in Rat

Danhong Injection (DHI) is a traditional Chinese medicine consisted by two herbal medicines, Radix et Rhizoma Salviae Miltiorrhizae and Rhizoma Flos Carthami, which is used in clinic as a remedy for cardiovascular diseases. The early studies indicated that DHI has protective effect on endothelial

GW26-e3856 Danhong Injection (A Traditional Chinese Patent Medicine) for Acute Myocardial Infarction: A Systematic Review and Meta-analysis

GW26-e3856 Danhong Injection (A Traditional Chinese Patent Medicine) for Acute Myocardial Infarction: A Systematic Review and Meta-analysis

Danhong injection protects cardiomyocytes against hypoxia/reoxygenation- and H2O2-induced injury by inhibiting mitochondrial permeability transition pore opening

Ethnopharmacological relevanceDanhong injection (DHI), a Chinese medical product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been widely used for the treatment of ischemic heart disease, and clinical and experimental studies have demonstrated the protective effects against myocardial ischemia/reperfusion injury. Nevertheless, the underlying cellular mechanisms responsible for this protective effect are poorly understood. Aim of the studyThe present study aimed to examine the mechanism of DHI in regulating hypoxia/reoxygenation- and H2O2-induced cardiomyocytes injury. Materials and methodsNeonatal rat cardiomyocytes were subjected to hypoxia (9h)-reoxygenation (2h) or H2O2 (100μM) in the presence or absence of DHI (2.5, 5, 10μg/mL). Intracellular reactive oxygen species (ROS), cytosolic and mitochondrial Ca2+ concentrations, mitochondrial membrane potential (ΔΨm) and mitochondrial permeability transition pore (mPTP) opening were monitored using CMH2DCFDA, Fluo-4 and rhod-2, JC-1 and calcein, respectively. Cell survival was evaluated using the 2-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide (MTT) assay and apoptosis was detected by Annexin V/propidium iodide (PI) staining. ResultsDHI improved cell survival following H/R and H2O2 injury and reduced H/R-induced cytochrome c release and apoptosis when compared with non-DHI treated cells. In addition, DHI attenuated H/R-induced ROS generation, H2O2-induced cytosolic and mitochondrial Ca2+ overload, and cellular ROS generation when compared with H/R- and H2O2-only groups. Moreover, DHI significantly inhibited both mPTP opening and ΔΨm depolarization. ConclusionThese data demonstrate that the protective mechanism of DHI against H/R- and H2O2-induced injury is mediated by the inhibition of mPTP opening via mitigating Ca2+ overload and ROS generation.

Bioactivity-integrated UPLC/Q-TOF–MS of Danhong injection to identify NF-κB inhibitors and anti-inflammatory targets based on endothelial cell culture and network pharmacology

Ethnopharmacological relevanceDanhong injection (DHI) is a traditional Chinese medicine injection that has been widely used in therapy for cardiovascular diseases. However, neither its mechanism nor its active constituents are clearly understood. Aim of the studyOur research aimed at identifying the anti-inflammatory ingredients and mechanism of DHI by combining high-throughput screening (HTS) with network pharmacology analysis. Materials and methodsThe human endothelial cell line EAhy926 was cultured in vitro. Methyl thiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays were performed to detect cell viability. The expression of Bcl-2 and Bax, interleukin-6 (IL-6), inhibitor of nuclear factor kappa-B kinase (IKK), phosphorylated IKK, phosphorylated NF-κB and phosphorylated IκB-α from the supernatant were determined. Then, we constructed an assay system combining ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF–MS) with an NF-κB activity luciferase reporter to screen DHI for essential anti-inflammatory components, and the results were verified using network pharmacology. ResultsDHI could significantly suppress inflammatory responses, and the mechanism may be via an NF-κB-dependent pathway. We found nine potential anti-inflammatory ingredients: danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, hydroxysafflor yellow A, safflor yellow A, salvianolic acid A salvianolic acid B and salvianolic acid C. Among these compounds, the NF-κB inhibitory activity of SAC is reported here for the first time. ConclusionsDHI plays an important role in suppressing inflammatory responses through inhibiting the NF-κB signaling pathway. The potential NF-κB inhibitors in DHI contribute to the cross-talk of multiple targets in anti-inflammation.

A metabolomics strategy to explore urinary biomarkers and metabolic pathways for assessment of interaction between Danhong injection and low-dose aspirin during their synergistic treatment.

The drug combination of Danhong injection (DHI) and low-dose aspirin (ASA) was frequently applied for the treatment of cardiovascular and cerebrovascular diseases. Due to the drug interactions, a lot of potential benefits and risks might exist side by side in the course of combination therapy. However, there had been no studies of interaction between DHI and ASA. Metabolomics was a powerful tool to explore endogenous biomarkers and metabolic pathways. In present study, metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis was performed to provide insight into understanding the interaction between DHI and low-dose ASA. Eleven potential biomarkers of three types were identified and seven metabolic pathways were constructed. The results showed that the interaction between DHI and low-dose ASA during synergistic treatment indeed affected some key endogenous biomarkers and metabolic pathways, which could not happen when DHI or low-dose ASA was used alone. The quality and quantity of endogenous metabolite were both influenced by interaction between DHI and low-dose ASA. In details, the amount of flavin mononucleotide, L-2, 4-diaminobutyric acid (DABA) and 4-aminohippuric acid were significantly increased. On the contrary, the amount of 3-methyluridine, 4, 6-dihydroxyquinoline, cortolone-3-glucuronide, and serotonin were significantly decreased. Furthermore, O-phosphotyrosine, 3-methyl-2-butenal, indoxyl sulfate and dolichyl diphosphate were disappeared in urine. As to metabolic pathways, riboflavin metabolism, pentose and glucuronate interconversions, and tryptophan metabolism were all significantly influenced. The emerging alterations of biomarkers and metabolic pathways were associated with a lot of drugs and diseases based on literature researches, which might influence the co-administration of other drugs or the treatments of relevant diseases. Our paper presented some hints to uncover the mechanism of interaction between DHI and low-dose ASA, which would provide some references for application of DHI and low-dose ASA combination.

Effect of Danhong Injection Combined with Naoxintong Tablets on Prognosis and Inflammatory Factor Expression in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention.

Danhong is a Chinese medical component that has been broadly used to treat various cerebrovascular diseases. This work aimed to investigate the effect of Danhong injection combined with Naoxintong tablets on the short-term prognosis and expression of inflammatory factor-soluble CD40 ligand (sCD40L) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). A total of 100 ACS patients with PCI were randomly divided equally into treatment and control groups. The control group was treated with conventional secondary prevention of coronary heart disease. Based on secondary prevention, Danhong injection combined with Naoxintong tablets was administered in the treatment group. The incidences of major adverse cardiovascular events and cardiac functions, including ejection fraction (EF) and six-minute walk test distance, during hospital discharge and at the third postoperative month were observed. The serum sCD40 levels at different times were also noted. There were 2 patients in the treatment group and 7 in the control group that were lost during follow-up, so the collected data were from only 48 patients in the treatment and 43 in the control group. During hospital discharge and at the third postoperative month, no significant difference in death, myocardial infarction, stroke, angina pectoris and readmission were observed between the two groups (p > 0.05). Upon hospital discharge, EF, six-minute walk test distance and serum sCD40L level in the two groups were not significantly different (p > 0.05). At the third postoperative month, EF and six-minute walk test distance in treatment group were significantly higher than those in the control group (p < 0.05), and the serum sCD40L level in the treatment group was significantly lower than that in the control group (p < 0.01). In addition, serum sCD40L levels in the two groups at the third postoperative month were significantly lower than those during hospital discharge (p < 0.01). Danhong injection combined with Naoxintong tablets decreased serum sCD40L level and improved cardiac functions in ACS patients undergoing PCI at 3 months following discharge, but not at discharge. Acute coronary syndrome; Danhong injection; Naoxintong tablets; sCD40.

Administration of Danhong Injection to diabetic db/db mice inhibits the development of diabetic retinopathy and nephropathy.

Danhong Injection (DHI), a Chinese medicine for treatment of patients with coronary heart disease, inhibits primary abdominal aortic aneurysms in apoE deficient (apoE−/−) mice. Formation of microaneurysms plays an important role in the development of diabetic retinopathy and nephropathy. It remains unknown if DHI can reduce these diabetic complications. In this study, diabetic db/db mice in two groups were injected with saline and DHI, respectively, for 14 weeks. Blood and tissue samples were collected to determine serum glucose, lipids and tissue structure. DHI reduced diabetes-induced body weight gain, serum cholesterol and glucose levels. In retinas, DHI blocked the shrink of whole retina and retinal sub-layers by inhibiting expression of caspase 3, matrix metalloproteinase 2 (MMP-2) and MMP-9, accumulation of carbohydrate macromolecules and formation of acellular capillaries. DHI improved renal functions by inhibiting mesangial matrix expansion, expression of vascular endothelial growth factor A, fibronectin and advanced glycation end products in kidneys. Mechanistically, DHI induced expression of glucokinase, AMPKα/phosphorylated AMPKα, insulin receptor substrate 1, fibroblast growth factor 21 and peroxisome proliferator-activated γ. Expression of genes responsible for energy expenditure was also activated by DHI. Therefore, DHI inhibits diabetic retinopathy and nephropathy by ameliorating glucose metabolism and demonstrates a potential application in clinics.

Interaction between the Natural Components in Danhong Injection (DHI) with Serum Albumin (SA) and the Influence of the Coexisting Multi-Components on the SaB-BSA Binding System: Fluorescence and Molecular Docking Studies.

Danhong injection (DHI) is a widely used Chinese Materia Medica standardized product for the clinical treatment of ischemic encephalopathy and coronary heart disease. The bindings of eight natural components in DHI between bovine serum albumin (BSA) were studied by fluorescence spectroscopy technology and molecular docking. According to the results, the quenching process of salvianolic acid B and hydroxysafflor yellow A was a static quenching procedure through the analysis of quenching data by the Stern-Volmer equation, the modified Stern-Volmer equation, and the modified Scatchard equation. Meanwhile, syringin (Syr) enhanced the fluorescence of BSA, and the data were analyzed using the Lineweaver-Burk equation. Molecular docking suggested that all of these natural components bind to serum albumin at the site I location. Further competitive experiments of SaB confirmed the result of molecular docking studies duo to the displacement of warfarin by SaB. Base on these studies, we selected SaB as a research target because it presented the strongest binding ability to BSA and investigated the influence of the multi-components coexisting in DHI on the interaction between the components of the SaB-BSA binding system. The participation of these natural components in DHI affected the interaction between the components of the SaB-BSA system. Therefore, when DHI is used in mammals, SaB is released from serum albumin more quickly than it is used alone. This work would provide a new experiment basis for revealing the scientific principle of compatibility for Traditional Chinese Medicine.

Design space development for the extraction process of Danhong injection using a Monte Carlo simulation method.

A design space approach was applied to optimize the extraction process of Danhong injection. Dry matter yield and the yields of five active ingredients were selected as process critical quality attributes (CQAs). Extraction number, extraction time, and the mass ratio of water and material (W/M ratio) were selected as critical process parameters (CPPs). Quadratic models between CPPs and CQAs were developed with determination coefficients higher than 0.94. Active ingredient yields and dry matter yield increased as the extraction number increased. Monte-Carlo simulation with models established using a stepwise regression method was applied to calculate the probability-based design space. Step length showed little effect on the calculation results. Higher simulation number led to results with lower dispersion. Data generated in a Monte Carlo simulation following a normal distribution led to a design space with a smaller size. An optimized calculation condition was obtained with 10000 simulation times, 0.01 calculation step length, a significance level value of 0.35 for adding or removing terms in a stepwise regression, and a normal distribution for data generation. The design space with a probability higher than 0.95 to attain the CQA criteria was calculated and verified successfully. Normal operating ranges of 8.2-10 g/g of W/M ratio, 1.25-1.63 h of extraction time, and two extractions were recommended. The optimized calculation conditions can conveniently be used in design space development for other pharmaceutical processes.

DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia.

To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection (DHI). Adult male rats underwent middle cerebral artery occlusion (MCAO), and were injected with DHI (DH-1: 1 mL/kg; DH-2: 2.5 mL/kg; DH-3: 5 mL/kg, and DH-4: 10 mL/kg, iv) daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods (PCA and PLS-DA) and web-based metabolomics tools (MetPa and MetaboAnalyst) were used to analyze the biological data sets for the amino acids. Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups. Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.

Systemic exposure to and disposition of catechols derived from Salvia miltiorrhiza roots (Danshen) after intravenous dosing DanHong injection in human subjects, rats, and dogs.

DanHong injection is a Danshen (Salvia miltiorrhiza roots)-based injectable solution for treatment of coronary artery disease and ischemic stroke. Danshen catechols are believed to be responsible for the injection's therapeutic effects. This study aimed to characterize systemic exposure to and elimination of Danshen catechols in human subjects, rats, and dogs receiving intravenous DanHong injection. A total of 28 catechols were detected, with content levels of 0.002-7.066 mM in the injection, and the major compounds included tanshinol, protocatechuic aldehyde, salvianolic acid B, rosmarinic acid, salvianolic acids A and D, and lithospermic acid with their daily doses ≥10 μmol/subject. After dosing, tanshinol, salvianolic acid D, and lithospermic acid exhibited considerable exposure in human subjects and rats. However, only tanshinol had considerable exposure in dogs. The considerable exposure to tanshinol was due to its having the highest dose, whereas that to salvianolic acid D and lithospermic acid was due to their relatively long elimination half-lives in the human subjects and rats. Protocatechuic aldehyde and rosmarinic acid circulated in the bloodstream predominantly as metabolites; salvianolic acids A and B exhibited low plasma levels with their human plasma metabolites little or not detected. Tanshinol and salvianolic acid D were eliminated mainly via renal excretion. Elimination of other catechols involved hepatobiliary and/or renal excretion of their metabolites. Methylation was found to be the primary metabolism for most Danshen catechols and showed intercompound and interspecies differences in rate and degree in vitro. The information gained here is relevant to pharmacological and toxicological research on DanHong injection.

Study on action mechanism of Danhong injection based on computational system biology approach

Danhong injection is a compound preparation of traditional Chinese medicine Salvia miltiorrhiza and Carthamus tinctorius, and has been widely applied in treating coronary heart diseases and ischemic encephalopathy in clinic. Despite the complexity of its chemical compounds and the diversity of targets, especially in system biology, there have not a report for its action mechanism as a whole regulatory biological network. In this study, protein data of S. miltiorrhiza and C. tinctorius were searched in TCMGeneDIT database and agilent literature search (ALS) system to establish the multi-component protein network of S. miltiorrhiza, C. tinctorius and Danhong injection. Besides, the protein interaction network was built based on the protein-protein interaction in Genecards, BIND, BioGRID, IntAct, MINT and other databases. According to the findings, 10 compounds of S. miltiorrhiza and 14 compounds of C. tinctorius were correlated with proteins. The 24 common compounds had interactions with 81 proteins, and formed a protein interaction network with 60 none-isolated nodes. The Cluster ONE module was applied to make an enrichment analysis on the protein interaction network and extract one sub-network with significant difference P <0.05. The sub-network contains 23 key proteins, which involved five signaling pathways, namely Nod-like receptor signaling pathway, epithelial cell signaling in helicobacter pylori infection, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway and neurotrophin signaling pathway through KEGG signaling pathway mapping. In this study, the computational system biology approach was adopted to preliminarily explain the molecular mechanism of main compounds of Danhong injection in preventing and treating diseases and provide reference for systematic studies on traditional Chinese medicine compounds.

Protective effect ofSalvia miltiorrhizaandCarthamus tinctoriusextract against lipopolysaccharide-induced liver injury

To investigate the hepatoprotective effects and mechanisms of an extract of Salvia miltiorrhiza and Carthamus tinctorius in vivo. C57BL/6J mice were randomly assigned to five groups and intraperitoneally administered 0.9% saline, Salvia miltiorrhiza and Carthamus tinctorius extract [Danhong injection (DHI), 0.75 and 3 g/kg mixed extract] or reduced glutathione for injection (RGI, 300 mg/kg) for 30 min before exposure to lipopolysaccharide (LPS, 16 mg/kg). After intraperitoneal LPS stimulation for 90 min or 6 h, the mice were sacrificed by ether anaesthesia, and serum and liver samples were collected. Histological analysis (H&E) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining were performed. Alanine transferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), glutathione-S-transferase (GST), malondialdehyde (MDA), tumour necrosis factor (TNF)-α, interleukin (IL)-6, and caspase-3 levels were measured. Bax, Bcl-2, P-IκBα, IκBα, P-NF-κB p65, and NF-κB p65 protein levels were determined by Western blot. TNF-α, IL-6, caspase-3, Bax and Bcl-2 mRNA expression was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and TUNEL results suggested that DHI (3 g/kg) treatment alleviated inflammatory and apoptotic (P < 0.01) injury in the liver of mice. DHI treatment dose-dependently blunted the abnormal changes in biochemical parameters such as ALT (72.53 ± 2.83 for 3 g/kg, P < 0.01), AST (76.97 ± 5.00 for 3 g/kg, P < 0.01), TBil (1.17 ± 0.10 for 3 g/kg, P < 0.01), MDA (0.81 ± 0.36 for 3 g/kg, P < 0.01), and GST (358.86 ± 12.09 for 3 g/kg, P < 0.01). Moreover, DHI (3 g/kg) remarkably decreased LPS-induced protein expression of TNF-α (340.55 ± 10.18 for 3 g/kg, P < 0.01), IL-6 (261.34 ± 10.18 for 3 g/kg, P < 0.01), and enzyme activity of caspase-3 (0.93 ± 0.029 for 3 g/kg, P < 0.01). The LPS-induced mRNA expression of TNF-α, IL-6 and caspase-3 was also decreased by DHI. Western blot analysis revealed that DHI antagonised LPS-stimulated decrease of Bcl-2 and increase of Bax protein expression. Furthermore, DHI inhibited LPS-induced IκBα and NF-κB p65 phosphorylation. DHI may be a multi-function protectant against acute hepatic injury in mice through its anti-inflammatory, anti-oxidative and anti-apoptotic activities.

Danhong Injection (a Traditional Chinese Patent Medicine) for Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

Objective. We aimed to systematically assess the efficacy and safety of Danhong injection (DHI) for acute myocardial infarction (AMI) patients. Methods. We searched several electrical databases and hand searched several Chinese medical journals. Randomized controlled trials (RCTs) comparing DHI plus conventional western medicine with conventional western medicine plus placebo and RCTs comparing DHI plus conventional western medicine with conventional western medicine were retrieved. Study screening, data extraction, quality assessment, and data analysis were conducted in accordance with the Cochrane standards. Results. 13 RCTs enrolling 979 patients were included. Danhong injection could significantly reduce the risk of mortality, recurrent angina, arrhythmia, and heart failure. In addition, DHI was associated with improvement of left ventricular ejection fraction (LVEF) and reperfusion. No significant difference of DHI was found on recurrent acute myocardial infarction. However, the safety of DHI remained unknown for limited data. Conclusion. DHI might be a potentially efficacious treatment for AMI patients. Nevertheless, the safety of DHI remained uncertain for limited information. Due to the fact that the overall quality of all included studies is generally low, more high quality RCTs are expected to validate the efficacy and safety of DHI for AMI patients.