Effect Of Danhong Injection Research Articles

Effect of Danhong injection on pharmacokinetics and pharmacodynamics of rivaroxaban in rats.

Rivaroxaban is often used in combination with DHI to treat thromboembolic disease. Whether the combination causing HDIs is still unknown. The purpose of this study was to evaluate effects of DHI on pharmacokinetics and pharmacodynamics of rivaroxaban in rats and effects on CYP3A2. Plasma concentration of rivaroxaban with or without DHI was determined by HPLC. Pharmacokinetics parameters were calculated. Effect of DHI on pharmacodynamics of rivaroxaban was investigated by APTT, PT, TT, FIB, INR, length of tail thrombosis, vWF, t-PA, PAI-1, IL-1β, TNF-α and histopathological sections. Effect of DHI on CYP3A2 in rats was investigated by probe drug method. Cmax and AUC of rivaroxaban increased significantly in combination group (P < 0.05). APTT, PT, INR and TT increased (P < 0.05), length of tail thrombosis, FIB, vWF, PAI-1, IL-1β and TNF-α of combination group decreased significantly (P < 0.05) compared with rivaroxaban or DHI alone. Histopathologic section of tail thrombus had significant improvement. Cmax and AUC of dapsone increased (P < 0.05) in DHI group. In summary, DHI is an inhibitor of CYP3A2 and could significantly affect pharmacokinetics and pharmacodynamic of rivaroxaban, enhance anticoagulant and antithrombotic efficacy in rats. However, the combination of rivaroxaban and DHI might lead to potential HDIs. The dosage of rivaroxaban should be adjusted in clinical.

Effect of Danhong injection on heart failure in rats evaluated by metabolomics.

Heart failure (HF) is characterized by reduced ventricular filling or ejection function due to organic or non-organic cardiovascular diseases. Danhong injection (DHI) is a medicinal material used clinically to treat HF for many years in China. Although prior research has shown that Danhong injection can improve cardiac function and structure, the biological mechanism has yet to be determined. Serum metabolic analysis was conducted via ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UHPLC-QE/MS) to explore underlying protective mechanisms of DHI in the transverse aortic constriction (TAC)-induced heart failure. Multivariate statistical techniques were used in the research, such as unsupervised principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). MetaboAnalyst and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to pinpoint pertinent metabolic pathways. After DHI treatment, cardiac morphology and function as well as the metabolism in model rats were improved. We identified 17 differential metabolites and six metabolic pathways. Two biomarkers, PC(18:3(6Z,9Z,12Z)/24:0) and L-Phenylalanine, were identified for the first time as strong indicators for the significant effect of DHI. This study revealed that DHI could regulate potential biomarkers and correlated metabolic pathway, which highlighted therapeutic potential of DHI in managing HF.

Danhong injection alleviates cerebral ischemia-reperfusion injury by inhibiting mitochondria-dependent apoptosis pathway and improving mitochondrial function in hyperlipidemia rats

Cerebral ischemia threatens human health and life. Hyperlipidemia is a risk of cerebral ischemia. Danhong injection (DHI) is a traditional Chinese medical preparation for the treatment of cerebrovascular diseases. However, the effects of DHI on mitochondria-dependent apoptosis and mitochondrial function following cerebral ischemia in hyperlipidemia rats are not clear. In this study, SD rats were fed by high-fat diet for six weeks to establish the hyperlipidemia model, except for the sham and ischemia-reperfusion (I/R) groups. Hyperlipidemia rats were assigned into I/R + high-fat diet (HFD) group, DHI 1 mL/kg group, and DHI 2 mL/kg group. DHI was administrated to the drug group via caudal vein for seven consecutive days (once per day). Subsequently, rats underwent middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. The results showed that DHI significantly reduced cerebral infarction volume, ameliorated neurological function, improved pathological changes, and inhibited apoptosis. DHI could significantly restore the levels of mitochondrial respiratory chain complexes I-IV, increase the ATP content and COX activity, and decrease the level of OFR in the ischemic brain mitochondria of hyperlipidemia rats after I/R. DHI significantly regulated the levels of cytochrome c (Cyt c), Apaf1, Bax, Bcl-2, Caspase-3, and Caspase-9 in brain tissue, and improved mitochondrial dynamics (Mfn1, Mfn2, OPA1, Drp1, and Fis1). The results indicate that DHI could alleviate ischemic brain injury in hyperlipidemia rats, and the mechanism may be to improve mitochondrial function by restoring the mitochondrial respiratory chain and changing the protein balance of mitochondrial fusion and fission, and inhibiting mitochondria-dependent apoptosis.

The combination of danhong injection plus tissue plasminogen activator ameliorates mouse tail thrombosis-induced by κ-carrageenan

BackgroundAfter thrombosis, t-PA thrombolysis is the first choice, but the use of t-PA can easily lead to hemorrhagic injury and neurotoxicity. The combination of Danhong injection (DHI) and tissue plasminogen activator (t-PA) therapy may be a new strategy to find high-efficiency anti-thrombosis and low bleeding risk. However, nothing is about the effect of DHI plus t-PA on platelet activation. PurposeThe present research was to explore the optimal dose of DHI and t-PA in vivo and mechanisms involved with the treatment of combining DHI and t-PA for thrombotic disease and determined whether DHI plus t-PA affects thrombotic processes related to platelet activation. MethodsMice were induced by administering κ-carrageenan intraperitoneally, the ratio of different doses of DHI and t-PA in vivo, and the optimal dose effects on platelet aggregation, platelet adhesion, thrombosis formation, and platelet activation were determined. The effects of the αIIbβ3 signaling pathway were analyzed in mice. ResultsIn vitro, DHI (62% v/v), t-PA (1 mg/ml), and DHI + t-PA (62% v/v + 1 mg/ml) decreased rat platelet aggregation and adhesion, with a stronger effect from the combination as compared to t-PA monotherapy. In vivo, injections of κ-carrageenan were used to induce BALB/c mice. The optimal dose of DHI, t-PA, and DHI + t-PA is 12 ml/kg, 10 mg/kg, and 12 ml/kg + 7.5 mg/kg. The administration of DHI (12 ml/kg), t-PA (10 mg/kg), and DHI + t-PA (12 ml/kg + 7.5 mg/kg) decreased thrombi in mouse tissue vessels. Furthermore, the reduction of thrombosis formation by DHI, t-PA, and DHI + t-PA was related to lower collagen deposition, and lowered expressions of collagen I, matrix metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9) in mouse tails, with increased efficacy in combination as compared to t-PA alone. The anti-thrombosis actions of DHI, t-PA, and their combination regulated the expression of CD41, purinergic receptor (P2Y12), guanine nucleotide-binding protein G (q) subunit alpha (GNAQ), phosphatidylinositol phospholipase c beta (PLCβ), Ras-related protein 1 (Rap1), RIAM, talin1, fibrinogen alpha chain (FG), kindlin-3, and RAS guany1-releasing protein 1 (RasGRP1). ConclusionsBased on expression, the mechanism responsible for thrombosis may be attributed to platelet activation via the αIIbβ3 signaling pathway. Combination therapy with DHI and t-PA exerted potent thrombolytic effects. Thus, our data can be used as a foundation for further clinical studies examining the efficacy of traditional Chinese medicines for the treatment of thrombosis.

Effect of Danhong Injection on platelet metabolites based on metabonomics technology

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.

Curative Effect of Danhong Injection Combined with Trimetazidine on Angina Pectoris Patients

Curative Effect of Danhong Injection Combined with Trimetazidine on Angina Pectoris Patients

Effects of Danhong injection on dyslipidemia and cholesterol metabolism in high-fat diets fed rats

Ethnopharmacological relevanceDanhong injection (DHI) is a Chinese medical injection applied to the clinical treatment of cardiovascular diseases that has anti-inflammatory, antiplatelet aggregation and antithrombotic effects. This study aimed to explore the effects of DHI on dyslipidemia and cholesterol metabolism in high-fat diet-fed rats. MethodsSprague Dawley (SD) rats were randomly divided into six groups: normal group (Normal); hyperlipidemia model group (Model); DHI-treated groups at doses of 1.0 mL/kg, 2.0 mL/kg, 4.0 mL/kg; and simvastatin positive control group (2.0 mg/kg). The hypolipidemic effects of DHI were evaluated by measuring serum lipid levels, hepatic function and oxidative stress, respectively. And pathological changes in liver tissues were determined using hematoxylin-eosin (H&E) and oil red O staining. Moreover, the mRNA and protein expression levels of cholesterol metabolism related genes were detected by real-time PCR (RT-PCR) and Western blot. ResultsCompared with the Model group, DHI treatment markedly decreased the liver index and improved the pathological morphology of liver tissues. DHI treatment dose-dependently decreased the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and free fatty acids (FFA) in serum or liver tissues (P < 0.01 or P < 0.05), and increased the high-density lipoprotein cholesterol (HDL-C) and tripeptide glutathione (GSH) (P < 0.01 or P < 0.05). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in the DHI-treated groups (P < 0.01 or P < 0.05), while the alanine transaminase (ALT) and aspartate transaminase (AST) were decreased (P < 0.01 or P < 0.05). Furthermore, the expression levels of LDL receptor (LDLR), cholesterol 7-α-hydroxylase (CYP7A1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor α (PPARα) were dose-dependently upregulated in the DHI-treated groups, whereas the expression of sterol regulatory element-binding protein-2 (SREBP-2) was downregulated. ConclusionsOur study demonstrated that DHI markedly ameliorated hyperlipidemia rats by regulating serum lipid levels, inhibiting hepatic lipid accumulation and steatosis, improving hepatic dysfunction, and reducing oxidative stress. The potential mechanism was also tentatively investigated and may be related to the promotion of bile acid synthesis via activation of the PPARα-LXRα-CYP7A1 pathway. Therefore, DHI could be regarded as a potential hypolipidemic drug for the treatment of hyperlipidemia.

Effect of Danhong Injection () on Improving Coronary Microcirculation Injury after Percutaneous Coronary Intervention.

To explore the effectiveness of Danhong Injection () on improving microcirculatory injury after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). A randomized controlled trial was conducted and 90 patients were enrolled. A random sequence was generated using statistical analysis software. Patients with microcirculatory injuries after PCI were randomly divided into 3 groups for treatment (30 subjects in each group): Danhong Injection group: after PCI, Danghong Injections were given with intravenous administration with 40 mL twice a day for a week; statins intensive group: after PCI, atorvastatin calcium tablets were given oral medication with 80 mg once, and then atorvastatin 40 mg daily for 1 week; the control group: after PCI, atorvastatin calcium tablets were given oral medication with 10-20 mg daily for 1 week. The index of microcirculation resistance (IMR) was used to assess microcirculatory injury during PCI. The IMR of the target vessel was reexamined after 1 week of drug treatment. After one week's drug treatment, IMR was significantly decreased in both statins intensive group and Danhong Injection group compared with the control group (P<0.01), but no difference was found between statins intensive group and Danhong injection group (14.03 ± 2.54 vs. 16.03 ± 5.72 U, P=0.080). The efficacy of Danhong Injection is non-inferior to statin. Early use of Danhong Injection after PCI can effectively improve coronary microcirculation injury after PCI.

Effect of Danhong injection combined with edaravone in the treatment of patients with acute cerebral infarction and its influence on cytokines, cerebral hemodynamics and vascular endothelial function

Objective To investigate the effect of Danhong injection combined with edaravone in the treatment of patients with acute cerebral infarction, and its influence on cytokines, cerebral hemodynamics and vascular endothelial function. Methods From March 2018 to March 2019, 142 patients with acute cerebral infarction treated in the People's Hospital of Yuhuan were randomly divided into treatment group and control group according to the digital table, with 71 cases in each group.The treatment group was treated with Danhong injection combined with edaravone, while the control group was only treated with edaravone.Both two groups were treated for 2 weeks.The therapeutic effects, changes of cytokines, cerebral hemodynamics, vascular endothelial function, activity of daily living index(Barthel index) and neurological deficit score(NIHSS score) before and after treatment were compared between the two groups. Results The total effective rate of the treatment group was 90.14%(64/71), which was higher than 74.65%(53/71) of the control group, the difference was statistically significant(χ2=5.874, P<0.05). After treatment, the serum levels of CRP[(5.43±1.20)mg/L] and IL-6[(32.15±7.39)ng/L] in the treatment group were lower than those in the control group[(9.38±1.74)mg/L and (67.43±10.29)ng/L](t=15.747, 23.465, all P<0.05). After treatment, the Vp[(69.83±3.24)v·-1·s-1] and Vm[(35.24±2.10)v·-1·s-1] in the treatment group were higher than those in the control group[(63.81±2.68)v·-1·s-1 and (32.18±1.73)v·-1·s-1], while the PI in the treatment group[(0.72±0.04)] was lower than that in the control group[(0.83±0.07)], the differences were statistically significant(t=12.064, 9.477, 11.497, all P<0.05). After treatment, the serum level of ET-1[(60.17±5.46)mg/L] in the treatment group was lower than that in the control group[(73.21±6.78)mg/L], while the NO level in the treatment group[(72.15±7.39)ng/L] was higher than that in the control group[(61.43±10.29)ng/L], the differences were statistically significant(t=12.622, 7.130, all P<0.05). After treatment, the Barthel index score of the treatment group[(68.93±7.83)points] was higher than that of the control group[(54.57±7.38)points], while the NIHSS score of the treatment group[(9.34±1.97)points] was lower than that of the control group[(14.54±2.89)points], the differences were statistically significant(t=11.246, 12.528, all P<0.05). Conclusion Danhong injection combined with edaravone in the treatment of acute cerebral infarction is effective, which can alleviate inflammation and improve cerebral hemodynamics and vascular endothelial dysfunction. Key words: Infarction, middle cerebral artery; Cytokines; Hemodynamics; Endothelium, vascular; Quality of life; Danhong needle; Edaravone

Initiate Danhong Injection before or after percutaneous coronary intervention for microvascular obstruction in ST-elevation myocardial infarction (DIRECTION): study protocol for a randomized controlled trial

BackgroundNo treatment has convincingly been proven to be beneficial for microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI). Several studies have described the effects of Danhong Injection. However, evidence of a rigorously designed verification study is still lacking, and the intervention timing of Danhong Injection is uncertain.MethodsThe DIRECTION study is a multicenter, prospective, randomized, evaluator-blind study. A total of 336 patients with STEMI receiving percutaneous coronary intervention (PCI) will be randomly assigned to conventional treatment, the preoperative Danhong Injection, or the postoperative Danhong Injection. The primary outcome is rate of ST-segment resolution (STR) ≥ 70% at 90 min after PCI. The secondary outcomes are the degree of STR, Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI myocardial perfusion grade, left ventricular ejection fraction, N-terminal prohormone brain natriuretic peptide, high-sensitivity C-reactive protein, and infarct size expressed as area under the curve for cardiac troponin I (cTnI) and for creatine kinase MB. The major adverse cardiovascular events and hospital readmission events will be recorded. Health quality will be assessed with the 12-item Short Form Health Survey. The safety outcomes include bleeding events, adverse events, and abnormal changes in routine blood tests. Psychological status and dietary patterns will be evaluated using Hamilton Depression Rating Scale and Food Frequency Questionnaire as the relevant indicators.DiscussionThis trial will evaluate the efficacy and safety of Danhong Injection, as well as its optimal timing of intervention to prevent MVO in patients with STEMI.Trial registrationChinese Clinical Trial Registry, ChiCTR1900021440. Registered on February 21, 2019.

Effect of Danhong injection on expression of nephrin and podocin in podocyte of renal tissue in rats with membranous nephropathy

Objective To observe the effect of Danhong injection on the expression of nephrin podocin protein and gene in the kidney of membranous nephropathy rats. Methods A total of 34 male clean level SD rats were divided at random into the normal control group (8 rats), model group (26 rates). The model group were injected the C-BSA into caudal vein to establish the model of the membranous nephropathy. After four week of succession of the models, two model rats were taken to confirm the success of the model. Another 24 models divided at random into model group, Losartan potassium treatment group and Danhong injection treatment group, 8 in each group. In the losartan group, the losartan 40 mg/kg was administered, and the Danhong group was injected with 4 ml/kg of Danhong injection in the tail vein for 4 weeks. The rat urine was collected after the last administration, and 24 h urine protein was determined by spectrophotometer. The serum total protein, albumin, TC and TG levels were determined by automatic biochemical analyzer. The renal pathological changes were observed by HE staining. The expressions of nephrin, podocin and WT1 labeled podocytes were detected by immunohistochemical staining. The expressions of nephrin and podocin in renal tissue were detected by real-time quantitative PCR and Western blot, and the results were correlated. Results Compared with the model group, the content of serum albumin increased in the Danhong group (P<0.01), 24 h urine protein quantitation, TC, TG significantly decreased (P<0.01). The expression of nephrin protein (1.12 ± 0.03 vs. 0.57 ± 0.09), podocin protein (0.99 ± 0.04 vs. 0.53 ± 0.08), nephrin mRNA (0.49 ± 0.08 vs. 0.14 ± 0.02), podocin mRNA (0.50 ± 0.11 vs. 1.18 ± 0.05) in Danhong group significantly increased (P<0.01), and the number of podocytes labeled with WT1 (14.88% ± 1.73% vs. 9.63% ± 1.69%) significantly increased (P<0.05). Correlation analysis showed that 24 h urine protein quantitation and expression of nephrin protein (r=-0.908), podocin protein (r=-0.916), nephrin mRNA (r=-0.930), podocin mRNA (r=-0.923). There was a negative correlation between serum albumin (r=-0.934) and podocyte count (r=-0.778) (P<0.01), and positive correlation with TC (r=0.814) and TG (r=0.870) (P<0.01). Conclusions The Danhong injection may reduce the urine protein of membranous nephropathy rats by up-regulating the expression of nephrin, podocin mRNA and protein in renal cells of membranous nephropathy. Key words: Glomerulonephritis, membranous; Podocytes; Proteinuria; Dan Hong Zhu She Ye; Rats

Pharmacodynamic effects of Dan-hong injection in rats with blood stasis syndrome

Dan-hong injection (DHI) is extracted from Salvia miltiorrhiza (SM) and Carthamus tinctorius (CT) and is widely used for the treatment of cardiovascular diseases. Our previous results showed DHI could improve hemorheology in rats. Since complex cellular interactions such as inflammation and oxidative stress are believed to be implicated in the pathogenesis of cardiovascular events, investigation of such pathological factors will contribute substantially to the understanding of the features and mechanisms of DHI. Therefore, in this study we used a rat model of blood stasis to explore the overall effects of DHI by detecting twenty three indexes, which were related to inflammation, immune response, vascular endothelial function, myocardial energy metabolism, oxidative stress, platelet aggregation, liver and renal function. Meanwhile, the interaction between SM and CT was discussed by comparing the effects of each single herb. DHI could significantly decrease the serum contents of IL-1β, TNF-α, IL-6, IL-8, IgM, IgG, IgA, MPO, hs-CRP, MDA, LDH, CK-MB, PAF, ALP and Cr, while elevate NO, SOD, TP and UA levels, indicating that DHI could inhibit inflammation and platelet aggregation, thereby relieving immune response and peroxidation, protecting vascular endothelial and organ function, and then prevent and treat cardiovascular diseases. In terms of compatibility, SM and CT showed complementary effects on markers of inflammatory and oxidative status, vascular endothelial damage and myocardial energy metabolism. On the other hand, they counteracted each other and SM reduced the side effects of creatinine caused by CT. This study contributes to comprehensively understand the pharmacodynamics effects and mechanism of DHI.

Danhong injection mobilizes endothelial progenitor cells to repair vascular endothelium injury via upregulating the expression of Akt, eNOS and MMP-9

BackgroudEndothelial progenitor cells (EPCs) have been characterized as one of the key effectors of endothelial healing. The effect of Danhong injection (DHI), the most widely prescribed Chinese medicine for coronary heart disease (CHD), on EPCs mobilization remains unclear. PurposeWe aimed to assess the effect of DHI on EPCs mobilization to repair percutaneous coronary intervention (PCI) induced vascular injury, and to investigate the characteristics and potential mechanism of DHI on EPCs mobilization. MethodForty-two patients with CHD underwent PCI and received stent implantation were enrolled in a Phase II clinical trials. All patients received routine western medical treatment after PCI, patients of DHI group received DHI in addition. The levels of CECs, cytokines (vWF, IL-6, CRP) and EPCs were analyzed at baseline, post-PCI and after treatment. To investigate the characteristics of DHI on EPCs mobilization, 12 healthy volunteers received intravenous infusion of DHI once and the other 12 received for 7 days. EPCs enumeration were done at a series of time points. At last we tested the effect of DHI and three chemical constituents of DHI (danshensu; lithospermic acid, LA; salvianolic acid D, SaD) on EPCs level and expression of Akt, eNOS and MMP-9 in bone marrow cells of myocardial infarction (MI) mice. ResultsIn the DHI group the angina symptoms were improved, the levels of cytokines and CECs were reduced; while EPCs population was increased after treatment. In the phase I clinical trials, EPCs counts reached a plateau phase in 9 h and maintained for more than 10 h after a single dose. After continuous administration, EPCs levels plateaued on the 3rd or 4th day, and maintain till 1 day after the withdrawal, then its levels gradually declined. DHI treatment induced a timely dependent mobilization of EPCs. DHI promoted EPCs mobilization via upregulating the expression of Akt, eNOS and MMP-9 in BM. LA and SaD have played a valuable role in EPCs mobilization. ConclusionThese initial results demonstrated that DHI is effective in alleviating endothelial injury and promoting endothelial repair through enhancing EPCs mobilization and revealed the effect feature and possible mechanisms of DHI in mobilizing EPCs.

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.

Clinical effect of Danhong injection combined with acupuncture in the treatment of vascular parkinson

Objective To study the clinical effect of Danhong injection combined with acupuncture in the treatment of vascular Parkinson syndrome (VP). Methods A total of 98 patients with VP who were treated in the hospital from January 2015 to January 2017 were enrolled in this study. According to the digital random table method, the patients were divided into two groups, the observation group and the control group with each 49 cases. Both groups were given basic treatment, and based on that, the observation group was treated with Danhong injection and acupuncture treatment. Both groups were compared before and after 8 weeks of treatment with the outcome indices of exercise and motor function score, blood rheology index and cerebral hemodynamic indexes, as well as adverse reactions. Results The total effective rate of the observation group was 87.76% (43/49), while the control group was 71.43% (35/49), and the difference was statistically significant (χ2=4.021, P 0.05). Conclusions The Danhong injection combined with acupuncture showed better effect on VP patients, and it could improve the clinical symptoms and blood circulation. Key words: Parkinson disease,secondary; Danhong injection; Acupuncture therapy; Integrated Chinese traditional and western medicine therapy

Effects of Danhong Injection on platelet aggregation in hyperlipidemia rats

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 reported to have effects on inflammatory, anti-fibrinolytic properties, antithrombotic and decrease blood-lipid. It is extensively used for the clinical treatment of cardiovascular disease. This study aimed to investigate the effects of DHI on blood-lipid levels and platelet aggregation rate in hyperlipidemia rats. Materials and methodsRats were randomly divided into 6 groups: normal control (NC), model control (MC), DHI-treated control at doses of 1.0mL/kg, 2.0mL/kg, 4.0mL/kg, respectively, and Simvastatin positive control at dose of 2.0mg/kg. All DHI treated groups were intraperitoneally injected for 7 days. The effects of DHI on serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were evaluated. And platelet activating factor (PAF), platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa) and 6-keto-prostaglandin F1а (6-K-PGF1а) were determined by enzyme-linked immunosorbent assay (ELISA). Moreover, the expression of prostaglandin I-2 (PGI2), prostaglandin E-2 (PGE2) and thromboxane A2 (TXA2) in liver was determined by real-time PCR. ResultsCompared with the MC group, the rats treated with DHI had significantly reduced TC, TG, LDL-C, FIB, GP IIb/IIIa and platelet aggregation. Meanwhile, the thrombin time (TT), activated partial thrombin time (APTT), prothrombin time (PT), 6-K-PGF1а was significantly increased. Expression of PGI2 and PGE2 mRNA was significantly increased, whereas the TXA2 was significantly reduced. ConclusionsThis study demonstrated that the blood lipid and platelet aggregation has a regulatory effect after DHI treatment. The insights gained from this study will improve understanding of the mechanisms involved in the effect of DHI on hyperlipidemia and the pharmacological rationale for the use of DHI in diseases caused by formation of thrombosis and lipid metabolic disorders.

Effect of danhong injection on the mobilisation of endothelial progenitor cells to vascular repair after percutaneous coronary intervention: a randomised controlled trial

BackgroundEndothelial progenitor cells (EPCs) derived from bone marrow are associated with the repair of vascular injury by accelerating re-endothelisation, and represent a potential therapeutic target for ischaemic disease. Danhong injection (DHI), a Chinese Materia Medica standardised product extracted from Radix Salvia miltiorrhiza and Flos Carthamus tinctorius L, is effective in the treatment of ischaemic heart disease. We assessed the effect of DHI on the mobilisation of EPCs and vascular repair mediated by EPCs after percutaneous coronary intervention (PCI). MethodsIn a prospective, randomised clinical trial (ChiCTR-ONRC-14004100), patients with coronary heart disease and chest pain (n=54) who were referred to coronary angiography and underwent PCI were enrolled; 12 dropped out because of incomplete blood sample collection. The remaining 42 patients (age 35–75 years) were randomly assigned by random number table method to either a control group (14 men, seven women) that received standard medical treatment or a DHI group (14 men, seven women) that received standard medical treatment combined with DHI (40 mL per day) for 7 days at the affiliated cardiovascular hospital of Qingdao University. The primary outcomes were endothelial lesion and endothelial regeneration. Endothelial lesion was assessed by enumeration of CD45– CD146+ KDR+ circulating endothelial cells (CECs) and inflammatory factors (interleukin 6, C-reactive protein [CRP], tumour necrosis factor α [TNFα]). Endothelial regeneration was evaluated by measurement of CD45dim CD34+ KDR+ EPCs, as determined by flow cytometry. Measurements were taken before PCI, 1 day after PCI, and 7 days after treatment by two investigators masked to treatment assignment. All healthy participants and those with coronary heart disease gave informed consent to participate in the study. All protocols were approved by each of the local ethics committees. FindingsBaseline cytokines, CECs, and EPCs did not differ between DHI and control groups. PCI increased interleukin 6 (p=0·004 in control group; p=0·045 in DHI group), TNF α (p=0·001 in control group; p=0·16 in DHI group), and CECs concentrations (p=0·008 in control group; p=0·005 in DHI group), whereas EPCs decreased (p=0·002 in control group; p=0·001 in DHI group). Compared with the control group, the mean expression levels of cytokines were significantly reduced (interleukin 6 14·98 pg/mL [SD 13·51] vs 7·25 pg/mL [8·03], p=0·001; TNFα 594·17 pg/mL [368·34] vs 388·48 pg/mL [210·24], p<0·0001; CRP 38·07 ng/mL [18·93] vs 22·42 ng/mL [5·94], p=0·04), and CECs were significantly reduced (0·1228% of PBMC [0·0669] vs 0·0564% of PBMC [0·0445], p<0·0001). EPC population significantly increased (0·0962% of PBMC [0·044] vs 0·2569 of PBMC [0·1215], p<0·0001) in DHI group after treatment. InterpretationThese initial results suggest that DHI is effective in improving endothelial repair and protecting the endothelial lesion by mobilising EPCs, by inhibiting the inflammatory response, and by inhibiting of shedding of endothelial cells after PCI in patients with coronary heart disease. FundingChina National Basic Research Program (973 programme, number 2012CB518404).

Effects of Danhong Injection (丹红注射液) and its main components on anticoagulation and fibrinolysis in cultured vein endothelial cells

To observe the effects of Danhong Injection (丹红注射液) and its main components, including daiclzein and hydroxysafflor yellow A (HSYA), on the anticoagulation, fibrinolysis, anti-apoptosis in hypoxia model of vein endothelial cells (VECs). VECs were prepared and were put in a hypoxia environment, which consisted of mixed gas of 95% N and 5% CO mixed gas, when reached confluent culture. Five groups used different treatments, including normal control group, hypoxia group, daiclzein group, HSYA group and Danhong Injection group. The VECs were identified by fluorescence double labeling methods. The morphology was observed by a phase contrast microscopy. The effects of Danhong Injection, daiclzein and HSYA on 6 keto prostaglandin F1α (6-keto-PGF1α) level was measured by the method of radioimmunoassay (RIA). Superoxide dismutase (SOD) activity was tested by water soluble tetrazolium salt. The content of malondialdehyde (MDA) was measured by thiobarbituric acid. The activities of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were measured by the method of chromogenic substrate. The contents of endothelin (ET) and nitric oxide (NO) were detected by non-equilibrium RIA and enzymelinked immunosorbent assay. Cells apoptosis rate was determined by flow cytometry. Compared with the normal control group, the floating cells number, PAI activity, ET and MDA contents, and cells apoptosis rate in the culture solution of hypoxia group were all significantly increased, whereas the 6-keto-PGF1α and NO contents, and t-PA and SOD activities were decreased significantly (P<0.01). Compared with the hypoxia group, Danhong Injection markedly increased the 6-keto-PGF1α content and SOD activity, regulated PAI and t-PA activities, ET and NO contents, and decreased MDA content and cells apoptosis rate (P<0.05 or P<0.01). Danhong Injection and its main components played an important role in protecting primary VECs from hypoxic damage by regulating the secretion and vasomotor function of VECs. The function of Danhong Injection was most remarkable.

Herbal Medicine after Interventional Therapy in Cardiovascular Diseases: Efficacy, Mechanisms, and Safety

Despite recent medical advances, cardiovascular diseases (CVDs) remain the predominant cause of morbidity and mortality all over the world. Interventional therapy (IT) is the milestone of therapy of CVDs and has developed rapidly in recent years. Despite its proven benefit, recurrent cardiovascular events are still a big challenge in cardiology field. Plants have been used for medicinal purposes for as long as history has been recorded. Great varieties of plants are used for medicinal treatments and many new drugs have been discovered from herbal sources. Herbal medicine (HM) means use of natural plant substances (botanicals) to treat and prevent illness. Based on the integrative medicine of eastern and western, the application of HM has valuable significance in reducing the risk of cardiovascular event. During the past decades, some HM products went into Europe and United States for prevention and treatment of CVDs or prevention of in-stent restenosis after IT, however, as the complementary and alternative remedies. Widespread use has increased much demands that HM be regulated as drugs to insure the efficacy, mechanisms, and safety. This special issue is a collection of seven articles describing the use of herbal medicines after interventional therapy in cardiovascular diseases. There are two clinical research articles describing the efficacy and mechanisms of HM. An article by S.-L. Wang et al. evaluated the 10-year effectiveness of HM plus conventional treatment versus conventional treatment alone with decision-analytic model for ACS after PCI. The authors found that treatment with HM, as an adjunctive therapy, in combination with conventional treatment for 6 months might improve the long-term clinical outcome in ACS patients after PCI. M. Xue et al.' study showed that Xuefuzhuyu oral liquid could effectively improve blood stasis syndrome and aspirin resistance by inhibiting ADP-induced platelet aggregation and patients with the rs5911 genetic variant exhibited better drug response. There are three experimental articles that make in-depth exploration about mechanisms of HM for cardiovascular diseases. Study by J. Su et al. showed luteolin could ameliorate hypertensive vascular remodeling mediated by the regulation of MAPK signaling pathway and the production of ROS. A study by W. Liu et al. demonstrated antihypertensive mechanism of gastrodin involved in regulation of the renin-angiotensin-aldosterone system (RAAS) and PPARγ. F. Wu et al. found that activation of local CSE-H2S-VEGF axis might participate in proangiogenesis effects of Danhong injection, suggesting a potential therapy for diabetic patients with critical limb ischemia. An interesting article by H. Berrougui et al. gives evidence from the beneficial role of extra virgin olive oil (EVOO) consumption towards oxidative stress and cardiovascular diseases. The only meta-analysis as a part of this special issue by A. Liu et al. demonstrated possible efficacy of active compounds of rhubarb root and rhizome that have potential neuroprotective effect for experimental ischemic stroke but should be interpreted with caution because of shortage of the methodology. From the above-mentioned articles, this special issue provides recent evidence about efficacy, mechanisms, and safety of herbal medicine after interventional therapy in CVDs. We hope this special issue will offer a new scientific understanding of the effect of herbal medicine for CVDs. Dazhuo Shi Michael Y. H. Shen Honglin Luo Yan Ma

Protective Effects of Danhong Injection against Cerebral Damage during On-Pump Coronary Artery Bypass Graft Surgery.

To explore the protective effects of Danhong injection against cerebral damage during on-pump coronary artery bypass graft surgery and its mechanism. Methods. Fifty patients scheduled for on-pump CABG surgery were randomly divided into Danhong injection group (group D) and control group (group C). Group D was given Danhong injection while group C was given the same volume of normal saline when the artery was cut open. Jugular bulb blood right before the operation began (T1), when body temperature rewarming to 36°C (T2), 30 min after the termination of cardiopulmonary bypass (T3), and 6 hrs after the termination of CPB (T4) was collected. The superoxide dismutase activity by using xanthine oxidase method and concentration determination of malondialdehyde were examined. Results. In group C, SOD activity was less at T2–T4 than at T1. It was also less active comparatively in group D at T2–T4. The MDA concentration increased in both groups but was more obvious in group C. Levels of TNF-α, IL-6, IL-8, and IL-10 increased in both groups C and D at T3 and T4, compared to T1. Conclusions. Danhong injection shows significant protective effects against cerebral damage during on-pump coronary artery bypass graft surgery.