Investigating the molecular mechanism of Compound Danshen Dropping Pills for the treatment of epilepsy by utilizing network pharmacology and molecular docking technology.

Background: Compound Danshen Dropping Pills (CDDP) is widely used in clinical treatment of epilepsy. But the underlying active ingredients and molecular mechanisms are unclear. Our study aims to investigate the active components and functional mechanisms of CDDP in treating epilepsy using a network pharmacology approach. Methods: Candidate constituents and targets of CDDP were searched on the Traditional Chinese Medicine Systems Pharmacology database. NCBI and Genecards were used to establish a database of epilepsy targets. Next, used Cytoscape software, the interactive network diagram of "drug-active component-target" was drawn. Based on the STRING database we constructed protein-protein interaction network and analyzed protein-protein interaction relationships. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for the common targets. Molecular docking provided an evaluation tool for verifying the combination of components and targets, which was performed using Auto-dock. Results: Sixty bioactive components, corresponding to 79 therapeutic targets for epilepsy, were successfully identified. Functional enrichment analysis showed that CDDP plays a pharmacological role in the treatment of epilepsy by regulating serotonergic synapses, morphine addiction, nicotine addiction and other pathways, as well as the NF-κB signaling pathway. Molecular docking analysis showed that representative components may be closely bound to key targets. Conclusions: This network pharmacology study revealed the synergistic effects of multiple components, targets, and pathways of CDDP in the treatment of epilepsy, which will deepen our understanding of the underlying molecular mechanisms of CDDP in the treatment of epilepsy and lay the foundation for further experimental studies.

The Effects of Aspirin With Combined Compound Danshen Dropping Pills on Hemorheology and Blood Lipids in Middle-Aged and Elderly Patients With CHD: A Systematic Review and Meta-Analysis.

Background: Coronary heart disease (CHD) is one of the most common diseases in clinical cardiovascular practice, mainly afflicting the middle-aged and elderly. It will greatly affect elderly quality of life, and even affect their psychological and physical health. At present, CHD is treated with western drugs alone, but this can produce drug dependency. In recent years, Traditional Chinese Medicine (TCM) combine western drugs has been used as a complementary and alternative therapy, and its effectiveness and safety have been proven, attracting the attention of numerous researchers. Objective: Our study aimed to compare the efficacy of Aspirin with Combined Compound Danshen Dropping Pills had a superior effect on the treatment of Hemorheology and Blood Lipids in Middle-aged and Elderly Patients with CHD. Determine the effectiveness and safety of Aspirin with Combined Compound Danshen Dropping Pills in the treatment of CHD, and obtain high quality clinical evidence. Methods: Based on the PRISMA Statement, inclusion and exclusion criteria were formulated. Randomized controlled trials (RCTs) on the Effects of Aspirin with Combined Compound Danshen Dropping Pills on Hemorheology and Blood Lipids in Middle-aged and Elderly Patients with CHD were found following a search of 4 mainstream medical databases. RCTs found to meet the study's requirement were included; data information was then extracted, and the quality assessed using the Cochrane bias risk assessment tool. Through RevMan software, Meta analysis was carried out for overall TC, TG, HDL-C, LDL-C hematocrit, high shear viscosity, low shear viscosity, plasma viscosity, PAGM, and TXB2 effective rate. The relative risk (RR) and 95% confidence interval (95% CI) were calculated; heterogeneity was tested and its source found; publication bias was assessed through the Egger and Begg tests, and by means of funnel plots. Result: 22 RCTs were found, involving 1,987 cases. The results of the Meta analysis showed that, compared to drug therapy alone, Aspirin with Combined Compound Danshen Dropping Pills had a superior effect on the treatment of Hemorheology and Blood Lipids in Middle-aged and Elderly Patients with CHD. The meta analysis results show the effects on TC [MD = -0.91, 95% CI (-1.09, -0.73)], on TG [MD = -0.94, 95% CI (-1.22, -0.66)], on HDL-C [MD = 0.40, 95% CI (0.27, 0.53)], on LDL-C [MD = -0.99, 95% CI (-1.24, -0.74)], on hematocrit [MD = -2.69, 95% CI (-3.73, -1.65)], on high shear blood viscosity [MD = -1.11, 95% CI (-2.18, -0.05)], on low shear viscosity [MD = -0.79, 95% CI (-0.89, -0.68)], on plasma viscosity [MD = -0.26, 95% CI (-0.52, 0.01)], on PAMG [MD = -10.75, 95% CI (-16.84, -4.67)], and on TXB2 [MD = -11.84, 95% CI (-14.75, -8.92)]. The source of heterogeneity might be related to the state of patient, efficacy of drugs in the control group and difference in judgment criteria for efficacy. The Egger test and Begg test showed that publication bias did not occur in our study. Conclusions: The combination of compound dropping pill DSP with aspirin has some therapeutic effect on blood lipids and hemorheology in patients with CHD, ince some of the RCTs featured a very small sample size, the reliability and validity of our study's conclusion may have been affected as well; therefore, the explanation should be treated with some caution. In the future, a large number of higher-quality RCTs are still needed to confirm the results of our study.

Protective Effect of Huoxue Dingtong Prescription on Myocardial Ischemia Reperfusion Injury in Animal Model Based on NF-κB Signal Pathway / 中国实验方剂学杂志

Objective::To explore the protective effect of Huoxue Dingtong prescription on myocardial ischemia reperfusion injury in animal model based on nuclear transcription factor-κB(NF-κB) signal pathway. Method::In compound Danshen dropping pill group, SD rats were randomly divided into sham group, model group, compound salvia miltiorrhiza dropping pill group, high-dose Huoxue Dingtong group low-dose Huoxue Dingtong group, high-dose Huoxue Dingtong+ NF-κB inhibitor group. The rats in each group were administered continuously for 2 weeks. The rats in high-dose Huoxue Dingtong group+ pyrrolidine dithiocarbamate(PDTC) group were intraperitoneally administered the next day after modeling. Injection with PDTC and ligation of anterior descending branch of left coronary artery were performed to detect left ventricular function and Na+ -K+ -ATPase activity. Blood was collected from each animal abdominal aorta, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum creatine kinase isoenzyme (CK-MB), troponin T (cTnT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), superoxide gasification enzyme (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px). Western blot was used to detect the expressions of NF-κB, NF-κB inhibitor α (IκBα) and IκB kinase(IκκB) in myocardium. Result::Compared with model group, compound Danshen dropping pill group, high-dose Huoxue Dingtong group and low-dose Huoxue Dingtong group could reduce serum CK-MB, cTnT, TNF-α, IL-6, IL-1β, MDA, increase SOD and GSH-Px contents, increase the protein expressions of IκBα and IκB in myocardial tissue, and increase the activity of Na+ -K+ -ATPase in myocardial energy metabolism in myocardial ischemia-reperfusion model rats (P<0.05). However, high-dose Huoxue Dingtong group+ PDTC did not decrease serum CK-MB, cTnT, TNF-α, IL-6, IL-1β and MDA, increase SOD, GSH-Px, and increase the protein expression levels of IκBα and IκκB in myocardial tissue. There was no significant difference between high-dose Huoxue Dingtong group+ PDTC and model group. Conclusion::Huoxue Dingtang prescription can inhibit the activation of NF-κB signaling pathway, reduce the expression of inflammatory mediators and the production of free radicals, and increase the activity of Na+ -K+ -ATPase in the process of myocardial energy metabolism by up-regulating the expressions of IκBα and IκκB proteins in myocardial tissue of myocardial ischemia-reperfusion model.

Meta analysis on efficacy of Compound Danshen Dropping Pills in treating angina based on syndrome differentiation / 中草药

Objective: To evaluate the efficacy and safety of the combination therapy of Compound Danshen Dropping Pills and conventional chemical drugs in the treatment of the angina by Meta-analysis. Methods: Databases including CNKI, WanFang, CBM, VIP, PubMed, and Cochrane Library were searched to collect qualified researches, and the quality of articles was evaluated according to Cochrane Handbook. Meta-analysis including subgroup analysis was performed by using Stata 13.1 and RevMan 5.3 software. All these methods were used to systematically evaluate the safety and clinical efficacy of Compound Danshen Dropping Pills in the treatment of angina pectoris under two circumstances (with or without syndrome differentiation). Results: A total of 39 studies involving 3 941 patients were studied, including 1 991 patients in the experimental group and 1 950 in the control group. The results of Meta analysis showed that: the clinical efficacy [RR = 1.24, 95%CI (1.20, 1.28), P < 0.000 01], ECG efficacy [RR = 1.29, 95%CI (1.21, 1.37), P < 0.000 01], angina attack frequency [WMD = -1.82, 95%CI (-3.28, -0.36), P = 0.01], duration of angina attack [WMD = -2.09, 95%CI (-2.67, -1.50), P < 0.000 01], hs-CRP [WMD = -2.63, 95%CI (-4.39, -0.86), P = 0.003], ET [WMD = -16.22, 95%CI (-19.37, -13.06), P < 0.000 01], platelet aggregation [WMD=-7.46, 95%CI (-11.15, -3.78), P < 0.000 1], GMP-140 [WMD=-5.64, 95%CI (-6.88, -4.39), P < 0.000 01] and fibrinogen [WMD = -0.73, 95%CI (-1.00, -0.46), P < 0.000 01] of routine western medicine treatment combine with Compound Danshen Dripping Pills group had significant difference compared with the control group; In terms of clinical efficacy, the combination effect of dialectical medication group and non dialectical medication group had no significant difference (P = 0.55, I2 = 0). A total of 15 studies described adverse reactions, with 43 cases in the experimental group and 65 cases in the control group. There was no significant publication bias on funnel plot and Egger's test. Conclusion: It is safe and effective to use Compound Danshen Dropping Pills in patients with coronary heart disease and angina, which can further improve the clinical effect compared with the simple routine treatment. There is no significant difference between the therapeutic effect of Compound Danshen Dropping Pills and that of non-syndrome differentiation. However, these conclusions still need to be verified with more high-quality and large-sample literature.

Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β1 by miRNA-200b / 中国实验方剂学杂志

Objective: To study the protective effect and mechanism of compound Danshen dropping pills on the heart of rats with type 2 diabetic cardiomyopathy. Method: Seventy-five male SD rats were randomly divided into blank group (15 rats) and model group (60 rats). The model group was fed with high-sugar and high-fat diet, high-sugar and high-fat milk and sucrose water. Six weeks later, rats with foodborne obesity (body mass ≥ the mean body mass of blank control group + 2 times standard deviation) were selected and intraperitoneally injected with 1% streptozotocin (STZ)28 mg·kg-1. After 12 weeks, rats with fasting blood glucose ≥ 11.1 mmol·L-1 and polydipsia, diuresis, polyphagia and weight loss were randomly divided into model group, compound Danshen dropping pills group (0.5 g·kg-1) and metformin group (0.5 g·kg-1) and intervened for 12 weeks. At the end of the experiment, echocardiography was used to evaluate cardiac function. Blood samples were taken to determine the corresponding biochemical indicators of rats. Histopathological changes of myocardium were observed by hematoxylin-eosin (HE) and Masson staining. The ultrastructure of myocardium was observed under electron microscope. Western blot was used to detect the expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGF-β1) and type Ⅰ collagen (Collagen Ⅰ). Real-time fluorescence quantitative analysis (Real-time PCR) was used to detect the expression of miRNA-200b. Result: Compared with the blank group, the heart weight index (HMI), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterin(LDL-C) levels in the model group were significantly increased (PPPPPβ1 and Collagen I increased (PPPPPPβ1 and Collagen I was decreased (PPConclusion: Compound Danshen dropping pills may play a protective role in the heart of type 2 diabetic cardiomyopathy rats by lowering lipid, up-regulating the expression of miR-200b and inhibiting the expression levels of VEGF, TGF-β1 and Collagen I.

Effect of Compound Danshen Dropping Pills combined with simvastatin treatment on level of regulatory T cells in patients with carotid atherosclerotic cerebral infarction / 中草药

Objective: To study the correlation of regulatory T cells (Tregs) and carotid atherosclerosis (CAS) in patients with acute cerebral infarction, and the effects of Compound Danshen Dropping Pills and simvastatin on Tregs level in CAS patients. Methods: Flow cytometry (FCM) was used to detect the percentage of Tregs in the peripheral blood of treatment group and control group before and after treatment. Plasma levels of interleukin 10 (IL-10), and transforming growth factor β1 (TGF-β1) were measured by enzyme linked immunosorbent assay (ELISA) method to detect IL-10 and TGF-β1 of peripheral blood plasma. Results: With CAS aggravation, percentage of Tregs, IL-10, and TGF-β1 levels reduced. After two weeks of treatment, the levels of Tregs, IL-10, and TGF-β1 were higher than those before treatment. In severe CAS patients, Tregs and IL-10 increased significantly in treatment group than those in control group. Conclusion: The proportion of Tregs in peripheral blood CD4+T cells can indirectly reflect the degree of CAS lesions. The combination of simvastatin and Compound Danshen Dropping Pills has lipid-regulation, anti-inflammatory, and anti-oxidant effect, and also up-regulates the levels of Tregs and IL-10, which can achieve the role of anti-atherosclerosis.

Efficacy of Aspirin in Combination with Compound Danshen Dropping Pills for Asymptomatic Coronary Artery Disease / 中国药房

OBJECTIVE:To evaluate the efficacy of aspirin in combination with compound Danshen Dropping pills for asymptomatic coronary artery disease(CAD).METHODS:A total of 108 patients with asymptomatic CAD were randomized to 3 groups:Aspirin(Group A),compound Danshen Dropping Pills(Group B),and Aspirin in combination with compound Danshen Dropping Pills(Group C).After 4-week treatment,the clinical response was compared among the 3 groups.RESULTS:The responsive rate in Group C(89.5%)was significantly higher than in either Group A(69.4%)or Group B(70.6%)(P

Comparative Study of the Pharmacokinetics of Borneolum Syntheticum and Borneol in Herbal Preparations / 中药新药与临床药理

Objective To compare the pharmacokinetics of borneolum syntheticum(BS)and borneol in compound Danshen dropping pills in rats.Method Rats were administrated orally with BS or Danshen dropping pills containing equal amount of borneol in a single dose.The blood contents of borneol at a series of time points were assayed by GC-MS and GC-FID after administration.The drug-time curve was estimated by PK Solution 2.0 pharmacokinetic software(USA).Results The pharmacokinetic parameters are quite different between the single dose of BS and the borneol in the compound Danshen dropping pills:the velocity constants of absorption(2.630h-1),distribution(1.788 h-1)and elimination(0.273 h-1)of BS were much greater than those(1.635h-1,0.784h-1,0.116h-1)of the same quantity of borneol in compound Danshen dropping pills,while the Tmax(0.5 h)of former was shorter than that(0.75 h)in the latter,and the Cmax(16.8 ?g/mL)in the former was about half of the latter(31.02 ?g/mL).And,at the 18h after administration,the former blood concentration(0.043 ?g/mL)was approximately one tenth of the latter.Conclusion It is suggested that we should pay attention to the influence of other ingredients on the main objective component in the study of pharmacokinetics of compound traditional chinese drug.

Synchronously Quantitative Analysis of Protocatechuic Aldehyde and Danshensu in Preparation of Radix Salviae Miltiorrhizae / 中成药

Objective:To determine synchronously protocatechuic aldehyde and danshensu in Compound Danshen Lozenge and Dropping Pills.Methods:HPLC method was used.Results:The average recoveries(n=5) were 100.47% for Danshensu of Compound Danshensu Lozenge(RSD=1.08%) and 99.27% for protocatechuic aldehyde(RSD=1.22%), respectively. And the average recoveries(n=3) were 100.40% for Danshensu of Compound Danshen Dropping Pills(RSD=0.65%) and 98.47% for protocatechuic aldehyde(RSD=1.76%).Conclusion:This method is simple, quick with a good separation.

Digitized HPLC fingerprints of Compound Danshen Dropping Pills / 中成药

AIM:To establish a digitized HPLC fingerprint of Compound Danshen Dropping PilLs (CDDP). METHODS:The RP-HPLC condition was optimized by the chromatographic fingerprint relative index (Fr). The chromatographic fingerprints were characteristically digitized and evaluated by the software of the digitized evaluation system of Traditional Chinese Medicine (TCM) with the super information characteristics. RESULTS:15 co-possessing peaks were selected as the fingerprint peaks of CDDP by taking protocatechualdehyde peak as the referential peak to establish the digitized fingerprint and the important digitized information for its quality control was obtained. The stabilities among different lots of samples were evaluated by the dual qualitative and dual quantitative similarity method. CONCLUSION:The fingerprints can perfectly reflect the authentical quality of CDDP.