Danhong Injection Research Articles

Comparative study of the effects of Danhong injection with different doses on ischemic stroke: A substudy of hospital-based Danhong injection registry

OBJECTIVETo compare the effects of Danhong injection (DHI) with different doses on ischemic stroke. METHODSChinese hospital registered DHI study is a perspective observational study, in which a total of 1292 patients with ischemic stroke were treated with DHI. Two different doses of DHI were used in the present study. The patients were matched by acute phase of ischemic stroke (within 2 weeks after onset), partial anterior circulation infraction, sex, age, and National Institute of Health Stroke Scale (NIHSS) score. Finally 148 patients were grouped into the 20 or 40 mL DHI group with 74 in each. The primary endpoint was the improvement of NIHSS score at 14-day after treatment. RESULTSOf the 148 patients with ischemic stroke, the 74 in the 40 mL DHI group had clinically important improvements in the NIHSS score. The baseline and 14-day NIHSS score for the 40 mL DHI group were 6.6 ± 4.3 and 2.4 ± 2.5 respectively, versus 6.3 ± 5.7 and 3.6 ± 4.2, for the 20 mL DHI group (change from baseline in the 40 mL DHI group vs change from baseline in the 20 mL DHI group, −1.49 points; P = 0.029). Improvements were maintained after the baseline characteristics and other drugs were controlled (P = 0.012). No adverse events were observed. CONCLUSIONEffects of DHI on partial anterior circulation infarction in patients with acute phase of ischemic stroke is dose-dependent; however, further studies with larger sample sizes are needed to validate our findings (Chinese Clinical Trial Register, Number: ChiCTR-ONC-13003230).

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential.

Cardiovascular and cerebrovascular diseases are the main cause of mortality worldwide, currently with less than optimum therapeutic options. Danhong injection (DHI) is a medicinal preparation based on two eminent Chinese herbal medicines, Salviae Miltiorrhizae (Dan Shen; family: Lamiaceae) and Flos Carthami (Hong Hua; family: Compositae/Asteraceae). DHI has been mainly used in the clinical therapy of cardiovascular (such as acute coronary syndrome and angina pectoris) and cerebrovascular diseases (such as stroke) in China for many years. The pharmacological properties of DHI include anti-inflammatory, anti-oxidant, anti-coagulatory, hypolipidemic, anti-apoptotic, vasodilatory, and angiogenesis-promoting actions. DHI offers a safe and effective therapeutic agent against cardiovascular and cerebrovascular diseases by modulating multiple disease-relevant signaling pathways and molecular targets. Herein, we provide a comprehensive review of the phytochemistry, therapeutic effects, molecular mechanisms, and adverse reactions of DHI in cardiovascular and cerebrovascular diseases. We also highlight the latest pharmacological advances and therapeutic potential of this promising herb-derived cardiovascular drug preparation.

Retrospective analysis and discussion on 74 cases of adverse reactions of traditional Chinese medicine injection

As a modern dosage form drug with rapid effect, traditional Chinese medicine (TCM) injection has been more and more used in clinical practice. Meanwhile the safety of TCM injection has attracted more and more attention. The retrospective analysis on 74 cases of adverse reaction of TCM injections collected from 2007 to 2016 in the Third Affiliated Hospital of Beijing University of Chinese Medicine showed that the proportion of men and women with adverse reactions was 0.54:1; the average age was 62.5 years old; 21 kinds of TCM injections were involved. Among them, the most reported were blood-regulating agents. The top four kinds of TCM injections with highest adverse drug reactions (ADRs) were Tanreqing injection, Danhong Injection, Shuxuening Injection and Xuesaitong for injection. The top three clinical manifestations of adverse reactions were lesions of skin and its appendages, damage of circulatory system and damage of nervous system. The potential causes of the adverse reactions of TCM injections were analyzed, and it was believed that individual difference, medicine, pharmaceutical excipients, solvent and TCM syndrome differentiation may be the main five causes for the adverse reactions of TCM injections. In order to reduce the adverse reactions of TCM injections, it is suggested that the clinical pharmacists should participate in the application management of TCM injections in the hospital; the production enterprises shall strengthen the whole life cycle management of the drugs; and at the same time, the drug control and administration authorities should improve the drug management methods constantly and encourage the development of TCM injections to the high quality level.

Monitoring unbound warfarin in drug combination therapy by pharmacokinetics and fluorospectrometry

ObjectiveMonitoring the unbound drug concentration in blood in combination therapy is necessary, because its concentration determines the efficacy of drug therapy. This study was designed to explore the effect of Dan Hong Injection (DHI) on the unbound warfarin using two approaches including an in vivo pharmacokinetic and in vitro fluorescence studies. MethodsThe effect of DHI on the pharmacokinetic properties of the unbound warfarin was investigated by a microdialysis sampling method coupled with LC–MS/MS. The effect of DHI and salvianolic acid B (SaB) on warfarin binding with bovine serum albumin (BSA) was conducted by fluorescence spectrometry. ResultsThe AUC0-tn of warfarin with DHI group was higher than that of warfarin alone group. The result showed that DHI could increase the concentration of unbound warfarin in rat blood, which may be due to the competition between warfarin and DHI as well as its components binding to serum albumin. The competition process was demonstrated by fluorescence study. ConclusionCombination therapy of DHI with warfarin could enhance the release profile of warfarin from serum protein.

Clinical characteristics of five traditional Chinese medicine injections in treating heart failure based on Meta-analysis literature

In this article, we analyze the clinical characteristics of five kinds of traditional Chinese medicine injections in treating heart failure based on Meta-analysis. A total of 24 Meta-analysis papers were included, which involved Shenfu Injection, Shenmai Injection, Shengmai Injection, Danhong Injection and Huangqi Injection. The numbers of literatures of Shenfu Injection, Shenmai Injection and Shengmai Injection are high than the other two injections. The efficiencies of these injections combined with Western medicine are higher than the Western medicine used alone. They can improve 6 minute walk test result, ejection fraction, the level of brain peptide sodium and so on. Shenfu Injection can also improve the living quality of patients' life, heart rate and other indicators. Shenfu Injection can be used for patients with Yin deficiency, while Shenmai Injection can be used for patients with Yin deficiency and Shengmai Injection can be used for patients with Qi and Yin deficiency. From this information, we can see that Western medicine combined with traditional Chinese medicine injections can significantly improve the clinical efficiency. These injections need to be used according to patients' symptom. In the present, as the quality of clinical research literature of traditional Chinese medicine injections is low, the efficiency and safety evaluation of Chinese medicine injections still requires higher level of clinical evidence.

GW29-e0502 Danhong Injection Enhances Angiogenesis after Myocardial Infarction by Activating MiR-126/ERK/VEGF Pathway

Danhong Injection (DHI) is a widely used Chinese patent drug for relieving cardiovascular diseases. The present study aimed to identify the effect and mechanism of DHI on post-infarct angiogenesis, with particularly focusing on the epigenetic regulation of angiogenic pathways and factors. We

GW29-e1665 Effects of advanced glycation end products on function and angiogenesis of adipose tissue-derived stem cells and protective effects of Danhong injection.

GW29-e1665 Effects of advanced glycation end products on function and angiogenesis of adipose tissue-derived stem cells and protective effects of Danhong injection.

Danhong Injection Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells in Myocardial Infarction by Promoting Angiogenesis

Stem cell-based therapies have the potential to dramatically transform the treatment and prognosis of myocardial infarction (MI), and mesenchymal stem cells (MSCs) have been suggested as a promising cell population to ameliorate the heart remodeling in post-MI. However, poor implantation and survival in ischemic myocardium restrict its efficacy and application. In this study, we sought to use the unique mode of action of Chinese medicine to improve this situation. Surrounding the myocardial infarct area, we performed a multi-point MSC transplantation and administered in conjunction with Danhong injection, which is mainly used for the treatment of MI. Our results showed that the MSC survival rate and cardiac function were improved significantly through the small animal imaging system and echocardiography, respectively. Moreover, histological analysis showed that MSC combined with DHI intervention significantly reduced myocardial infarct size in myocardial infarcted mice and significantly increased MSC resident. To investigate the mechanism of DHI promoting MSC survival and cell migration, PCR and WB experiments were performed. Our results showed that DHI could promote the expression of CXC chemokine receptor 4 in MSC and enhance the expression of stromal cell–derived factor-1 in myocardium, and this effect can be inhibited by AMD3100 (an SDF1/CXCR4 antagonist). Additionally, MSC in combination with DHI interfered with MI in mice and this signifies that when combined, the duo could the expression of vascular endothelial growth factor (VEGF) in the marginal zone of infarction compared with when either MSC or DHI are used individually. Based on these results, we conclude that DHI enhances the residence of MSCs in cardiac tissue by modulating the SDF1/CXCR4 signaling pathway. These findings have important therapeutic implications for Chinese medicine-assisted cell-based therapy strategies.

Pharmacokinetic Study on Protocatechuic Aldehyde and Hydroxysafflor Yellow A of Danhong Injection in Rats with Hyperlipidemia

Background: Protocatechuic aldehyde (PAL) and hydroxysafflor yellow A (HSYA) are 2 effective ingredients of Danhong Injection, which is extensively used for the clinical treatment of cardio-cerebrovascular diseases. This study aims to investigate the pharmacokinetic differences between single and combined medication of PAL and HSYA and analyze the interaction of the above effective components in hyperlipidemia rats. Methods: Thirty male SD rats were randomly divided into the control group (n = 6) and the model group (n = 24). The hyperlipidemia model was established by feeding with superfatted forage. The successful model rats were then randomly divided into the PAL group (16 mg/kg), the HSYA group (10 mg/kg), and the combination group (16 mg/kg + 10 mg/kg). Administration through tail-vein, and orbital blood was sampled at different time points. The mass concentration of PAL and HSYA was determined by high performance liquid chromatography (HPLC-DAD). Analysis of pharmacokinetic parameters was conducted by using DAS 3.2.6 software and SPSS 19.0 statistical analysis software. Results: According to the parameters of statistical moment of non-compartmental model, there was a significant difference in plasma clearance (CL) between the PAL group and the drug combination group (p < 0.01), as well as in the area under the first moment of the plasma concentration-time curve and the elimination half-life (t_1/2) between the HSYA group and the drug combination group (p < 0.01) but no obvious differences about the blood concentration time curve area, the average dwell time (MRT), and the peak concentration (C_max; p > 0.05). Conclusion: The combined medication of PAL and HSYA could increase the plasma CL significantly and have a great influence on the absorption of HSYA in rats with hyperlipidemia.

Dose-dependent target diversion of Danhong injection on the Glu-GLT-1/Gly-GlyRα dynamic balance module of cerebral ischemia.

Function-oriented modular structure analysis is a great challenge in module-based pharmacological studies. A strategy to uncover target-target interaction (TTI) and dynamic balance regularity (DBR) was established to discover the structural factors influencing modular functions and explore the mechanism of Danhong injection (DHI) in treating cerebral ischemia. The dose-related metabolic features of DHI intervention were investigated using metabolomics and modular pharmacology. The findings indicated that Glu/Gly was a biomarker and Glu-GLT-1/Gly-GlyRα was the core unit regulated by DHI. Gly and Glu displayed opposite patterns and functional roles, representing intra-modular balance. GlyRα was identified as the upstream target and GLT-1 as the downstream target by inhibiting or activating GlyRα, indicating that DHI has two dose-dependent regulatory modes. GlyRα was the major target at low doses, while GLT-1 was activated as the dominant target as doses accumulated. Our study reveals that target-target interaction and dynamic balance regularity are the key factors influencing modular functions, which is a promising breakthrough for module-based pharmacological studies.

Danhong Injection Reversed Cardiac Abnormality in Brain-Heart Syndrome via Local and Remote β-Adrenergic Receptor Signaling.

Ischemic brain injury impacts cardiac dysfunction depending on the part of the brain affected, with a manifestation of irregular blood pressure, arrhythmia, and heart failure. Generally called brain–heart syndrome in traditional Chinese medicine, few mechanistic understanding and treatment options are available at present. We hypothesize that considering the established efficacy for both ischemic stroke and myocardial infarction (MI), Danhong injection (DHI), a multicomponent Chinese patent medicine, may have a dual pharmacological potential for treating the brain–heart syndrome caused by cerebral ischemic stroke through its multi-targeted mechanisms. We investigated the role of DHI in the setting of brain–heart syndrome and determined the mechanism by which it regulates this process. We induced Ischemia/Reperfusion in Wistar rats and administered intravenous dose of DHI twice daily for 14 days. We assessed the neurological state, infarct volume, CT scan, arterial blood pressure, heart rhythm, and the hemodynamics. We harvested the brain and heart tissues for immunohistochemistry and western blot analyses. Our data show that DHI exerts potent anti-stroke effects (infarct volume reduction: ∗∗p < 0.01 and ∗∗∗p < 0.001 vs. vehicle. Neurological deficit correction: ∗p < 0.05 and ∗∗∗p < 0.001 vs. vehicle), and effectively reversed the abnormal arterial pressure (∗p < 0.05 vs. vehicle) and heart rhythm (∗∗p < 0.01 vs. vehicle). The phenotype of this brain–heart syndrome is strikingly similar to those of MI model. Quantitative assessment of hemodynamic in cardiac functionality revealed a positive uniformity in the PV-loop after administration with DHI and valsartan in the latter. Immunohistochemistry and western blot results showed the inhibitory effect of DHI on the β-adrenergic pathway as well as protein kinase C epsilon (PKCε) (∗∗p < 0.01 vs. model). Our data showed the underlying mechanisms of the brain–heart interaction and offer the first evidence that DHI targets the adrenergic pathway to modulate cardiac function in the setting of brain–heart syndrome. This study has made a novel discovery for proper application of the multi-target DHI and could serve as a therapeutic option in the setting of brain–heart syndrome.

The Therapeutic Efficacy of Danhong Injection Combined With Percutaneous Coronary Intervention in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Background: Percutaneous coronary intervention (PCI) is widely used in treatment of acute coronary syndrome (ACS) clinically. It is believed that Danhong injection (DHI) extracted from salviae miltiorrhizae and flos carthami combined with PCI could increase the therapeutic efficacy on ACS. We provide an updated meta-analysis with detailed information on combination of DHI and PCI therapy.Materials and Methods: Electronic databases were searched for appropriate articles without language limitations on key words before October 22, 2017. All trails were screened according to certain criteria. Quality of eligible studies was also assessed. We made a detailed record of outcome measurements. RevMan 5.3 software was used to perform the meta-analysis.Results: 14 articles involving 1533 patients with ACS were selected. Compared to PCI treatment alone, total efficacy rate (TER) was enhanced and major adverse cardiovascular events (MACE) were reduced significantly for the combination of DHI and PCI (P < 0.00001). Vascular endothelial function was improved by significantly decreasing the contents of ET-1, vWF and increasing the levels of NO and FMD (P < 0.00001). The serum levels of IL-1, IL-6, IL-18, TNF-α, LpPLA2, MMP-9, and pentraxin-3 were significantly decreased (P < 0.00001), whereas IL-10 in serum was increased (P < 0.00001), indicating a stronger anti-inflammatory effect of the combination. The combination therapy decreased the serum levels of CD62P, PAGT, PADT, FIB-C significantly (P < 0.05), which was beneficial for preventing coagulation of platelets. Blood lipid was also affected by regulating TC, TG, LDL, and HDL, but the results were not statistically significant (P > 0.05). Cardiac function was improved by increasing LEVF (P = 0.006) but not LVED (P = 0.08). The combination treatment was associated with an improvement in antioxidant effect by decreasing MDA and increasing SOD significantly (P < 0.00001).Conclusion: Combination of DHI and PCI in treatment of ACS could improve TER and reduce incidence of MACE after PCI therapy. These effects may be mediated by combined actions of several mechanisms. However, these results of this study should be handled cautiously due to the limitations of this research. Several rigorous RCTs are in need to confirm these findings.

Inhibitory effects of Danhong Injection and its major constituents on human cytochrome P450 enzymes in vitro.

Danhong Injection (DHI) as a Chinese patent medicine is mainly used to treat ischemic encephalopathy and coronary heart disease in combination with other chemotherapy. However, the information on DHI's potential drug interactions is limited. The goal of this work was to examine the potential P450-mediated metabolism drug interaction arising from DHI and its active components. The results showed that DHI inhibited CYP2C19, CYP2D6, CYP3A4, CYP2E1 and CYP2C9 with IC50 values of 1.26, 1.42, 1.63, 1.10 and 1.67% (v/v), respectively. Danshensu and rosmarinic acid inhibited CYP2E1 and CYP2C9 with IC50 values of 36.63 and 75.76 μm, and 34.42 and 76.89 μm, respectively. Salvianolic acid A and B inhibited CYP2D6, CYP2E1 and CYP2C9 with IC50 values of 33.79, 21.64 and 31.94 μm, and 45.47, 13.52 and 24.15 μm, respectively. The study provides some useful information for safe and effective use of DHI in clinical practice.

The lipid-lowering effects of Danhong and Huangqi injections: a meta-analysis of clinical controlled trials

BackgroundDyslipidaemia is a major risk factor for coronary heart disease (CHD). Danhong and Huangqi injections, two traditional Chinese medicine prescriptions, have been widely studied regarding their lipid-lowering properties. However, the results were inconsistent and inconclusive. Thus, we conducted this meta-analysis of clinical controlled trials to clarify the lipid-lowering effects of Danhong and Huangqi injections.MethodsThe databases including PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang Database, CNKI and VIP were searched. The following information was obtained from each study: first author, age, gender, ethnicity, health condition, treatment dose, treatment duration, sample size, mean and standard deviation or standard error of lipid variables before and after treatment. The changes in lipid levels from pre- to post-treatment were calculated and compared between the control groups and the treatment groups in this meta-analysis.ResultsForty-four studies (5021 subjects) and 7 studies (542 subjects) were respectively identified for Danhong and Huangqi injections. Compared with the control groups, Danhong injection yielded a significant reduction in triglycerides (TG) [standardized mean difference (SMD) = − 0.76, 95% confidence interval (CI) = (− 0.91, − 0.61), P < 0.001], total cholesterol (TC) [SMD = − 1.29, 95% CI = (− 1.56, − 1.03), P < 0.001] and low-density lipoprotein cholesterol (LDL-C) [SMD = − 0.76, 95% CI = (− 0.93, − 0.59), P < 0.001], and a significant elevation in high-density lipoprotein cholesterol (HDL-C) [SMD = 0.70, 95% CI = (0.41, 0.98), P < 0.001]. Regarding Huangqi injection, it yielded a significant reduction in TC [SMD = − 1.13, 95% CI = (− 2.09, − 0.16), P = 0.02] and marginally in TG [SMD = − 1.27, 95% CI = (− 2.53, 0.00), P = 0.05] comparing with the control groups.ConclusionsDanhong injection can effectively decrease the plasma levels of TG, TC and LDL-C, and increase HDL-C levels. Huangqi injection also has significant effects on TG and TC reduction, but not as powerful as Danhong injection.

Analysis of serious adverse drug reactions in 2016 from Qingdao of Shandong province

Objective To analyze characteristics of serious adverse drug reaction from Qingdao and provide reference for clinical applications. Methods 1 130 reports collected by Qingdao Center for ADR Monitoring in 2016 were analyzed using retrospective study method. Results The antibiotics, traditional Chinese medicine injection and antitumor drug caused the higher proportion of serious adverse drug reaction.Injection was the main way for administration, which induced 73.45% of serious adverse drug reaction.65.00% cases with allergic shock occurred within 10min.Levofloxacin lactate injection caused the highest proportion of serious adverse drug reaction, Danhong injection caused the highest proportion of allergic shock reaction, Reduning injection caused the highest proportion of serious adverse drug reaction in children. Conclusion Safety monitoring for antibiotics, traditional Chinese medicine injection and antitumor drug should be further strengthened, including children adverse reactions. Key words: Adverse drug reaction reporting systems; Shock; Analysis

Detection of antioxidant activity of Danhong injection and its intermediate with a paper-based analytical device

The paper-based analytical device (PAD) was applied in this study to analyze the antioxidant activity of Danhong injection and its intermediates. First polycaprolactone was printed on the surface of a filter paper with a 3D printing device. The modified filter paper was then prepared using polycaprolactone and solid paraffin as the modifiers. The PAD was prepared after adding DPPH ethanol solution to the modified filter paper. Ascorbic acid solutions with different concentrations were used as the positive drug on PAD. After the occurrence of color reactions, the PAD was dried, and the data of color were collected by a cell phone. The color component G and grayscale were selected as the potential indices for measurement according to the values of determination coefficients, detection limits, and effective number of digits. Qualitative and quantitative analysis of Danhong injection and the concentrate of aqueous extract were realized with the PAD. Because no significant differences were observed between the results obtained using the two potential indices, the average values of these two were used for analysis, and the antioxidant activity of Danhong injection and the concentrate of aqueous extract was equivalent to ascorbic acid solutions of 3.7, 46 g·L⁻¹, respectively. The PAD method presented in this work can be a simple method to determine biological activities of Chinese medicines and their intermediates.

Efficacy of Danhong Injection on Serum Concentration of TNF-α, IL-6 and NF-κB in Rats with Intracerebral Hemorrhage.

ObjectiveTo investigate the efficacy of Danhong injection on the serum concentration of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) in rats with intracerebral hemorrhage (ICH) and evaluate its therapeutic effects on inflammation and cerebral edema.MethodsSixty male Wistar rats were randomly divided into control, model and Danhong groups with 25 rats in each group. Intracerebral injection of autologous arterial blood was performed on model and Danhong groups in order to establish intracerebral hemorrhage model. Rats in the control group were given the same operation procedure without blood injection. After successfully establishing the intracerebral hemorrhage model, the rats were given Danhong (2ml/kg/d) through intraperitoneal injection. Rats in the control and model groups were given the same amount of normal saline respectively. The brain water content (BWC) and serum level of TNF-α, IL-6 and NF-κB were measured in all groups at the time points of day 1, 3, 5, 7 and 9.ResultsThe neurological deficit score (NDS) were not statistical different in days 1, 3 and 5 between the model and Danhong group (P>0.05); However, on day 7 and 9 after modeling, the NDS in the Danhong group was significant lower than that of the Model group (P<0.05). The brain water content in the model and Danhong groups were significantly elevated compared to control group (P<0.05). The brain water content was significant elevated after modeling in the model and Danhong groups on day 3 and gradually decreased over the next 6 days.The brain water content was significantly higher in the model group for days 3 to 9 compared to the Danhong group (P<0.05). Compared to the model group, the serum NF-κb was significantly lower in the Danhong group for the time point of day 3 and 5 (P<0.05); However, compared to the model group, the serum TNF-α and IL-6 levels in the Danhong group were significantly lower for each time point (P<0.05). Conclusion Danhong injection can reduce cerebral edema in rats with cerebral hemorrhage, and protect the brain nerve function. These effects may be related to its function of regulating serum TNF-α, NF-κB and IL-6 expression.

Danhong Injection Combined With t-PA Improves Thrombolytic Therapy in Focal Embolic Stroke.

Background: Hemorrhagic transformation, neurotoxicity, short treatment time windows, and other defects are considered as the major limitations for the thrombolytic therapy. This study is devoted to figure out whether Danhong injection (DHI) combined with tissue-plasminogen activator (t-PA) could extend the treatment time windows and ameliorate brain injury, hemorrhagic complication and BBB disruption after focal embolic stroke.Methods: In vitro, the combined concentrations of DHI and t-PA were added to wells reacted with plasminogen and D-Val-Leu-Lys-AMC. The optimum ratio of the combination of DHI plus t-PA was explored by detecting relative fluorescent. In vivo experiments, we firstly investigated the optimal dose of t-PA and Danhong injection for focal embolic stroke. The neurological deficit score, infarct volume and brain edema were assessed. Secondly, we proved that the combination group extended the thrombolytic window for treatment of focal embolic stroke. The neurological deficit score, infarct volume, brain edema and hemorrhagic complication were assessed, while levels of BAX, Bcl-2 and caspase-3 in brain tissue were analyzed by real-time polymerase chain reaction. Finally, to ask whether combination therapy with DHI plus t-PA protected the blood–brain barrier in a rat model of focal embolic stroke, neurological deficit score, ELISA, RT-PCR, western blot and fluorescence were used to detect the indicators of blood–brain barrier, such as tight junction protein, blood–brain barrier permeability and related gene expression.Results: In vitro, plasmin activity assays showed that the combination of t-PA with DHI at about 1:1.6 w/v ratio increased by almost 1.4-fold the plasmin-generating capability of t-PA. In vivo experiments, the results showed that the combination of Danhong injection (4 mL/kg) and t-PA (2.5 mg/kg) could extend the t-PA treatment time windows to 4.5 h. And the combination t-PA (2.5 mg/kg) with DHI (4 mL/kg) ameliorated neurological score, cerebral infarction, brain edema, brain hemorrhage, and BBB disruption.Conclusion: Combination therapy with Danhong injection (4 mL/kg) plus t-PA (2.5 mg/kg) could extend the t-PA treatment time windows to 4.5 h, ameliorate BBB disruption, reduce infarction, brain swelling and hemorrhage after ischemic stroke.

Analysis of adverse reactions' factors to Danhong injection--nested case control study by using hospital centralized monitoring data

To study the adverse reactions' factors to Danhong injection in the real world. A multi-center, large sample and prospective hospital centralized monitoring method was adopted, and 30 888 cases of Danhong injection from 37 national 3A hospitals were collected to carry out a nested case control design study. These cases were divided into adverse reaction group and non-adverse group. Single factor logistic regression and multiple factor logistic regression were used to analyze data, and investigate the correlation between adverse reaction and gender, allergy history, methods of administration, and combined drug use. One hundred and eight cases of adverse reactions in 30 888 patients were determined, with an incidence of 0.35%. The results showed that Danhong injection combined with other medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol) with history of adverse reactions including scephalosporin allergy and proprietary Chinese medicine allergies had more adverse reactions than the control group(P<0.05, estimated coefficient>0), indicating that these six factors were the risk factors for the adverse reaction of Danhong injection. The adverse reaction of Danhong injection combined with the aspirin was less than that in the control group(P<0.05, estimated coefficient<0), indicating that the aspirin was a non-risk factor for the adverse reaction of Danhong injection. All the above results indicate that the adverse factors to Danhong injection include scephalosporin allergy, patent Chinese medicine allergy, Danhong injection combined with medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol), suggesting special attention shall be paid in clinical application.

Transcriptomic Study Reveals Recovery of Impaired Astrocytes Contribute to Neuroprotective Effects of Danhong Injection Against Cerebral Ischemia/Reperfusion-Induced Injury.

Danhong Injection (DHI) is widely used in clinics for treating cardiovascular and cerebrovascular diseases in China. However, the mode of action of DHI for neuroprotection remains unclear. In the present study, we deemed to investigate the effects of DHI on a rat model of cerebral ischemia/reperfusion injury (IRI) with an emphasis on its regulated gene profile obtained from microarray assays. Firstly, we showed that a 14-day DHI treatment effectively ameliorated severity of neurological deficits, reduced size of ischemic damage, improved status of oxidation stress, as well as systemic inflammation for IRI rats, along with which was a pronounced reduced cell infiltration in the area of periaqueductal gray matter. Secondly, bioinformatic analyses for the 429 differentially expressed genes (DEGs) regulated by DHI treatment pointed out ECM–receptor interaction, neuroactive ligand–receptor interaction, and endocytosis as the top three biological processes, while Toll-like recptor 4 (TLR4) as the most relavant singaling molecule. Lastly, we provided evidences showing that DHI might directly protect primary astrocytes from oxygen and glucose deprivation/re-oxygenation (OGD/Re) injury, the effects of which was associated with LAMC2 and ADRB3, two DEGs related to the top three biological processes according to transcriptomic analysis. In conlusion, we reported that DHI might work through maintaining the integrity for brain–blood barrier and to regulate TLR4-related signaling pathway to diminish the inflammation, therefore, effectively improved the outcomes of IRI. Our findings suggested that the attenuated astrocytic dysfunction could be a novel mechanism contributing to the neuroprotective effects of DHI against cerebral ischemia/reperfusion-induced damage.