Elucidating direct kinase targets of compound Danshen dropping pills employing archived data and prediction models.
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ABSTRACT:
SUBMITTER: Wang T
PROVIDER: S-EPMC8100098 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCompound 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.MethodsCandidate 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.ResultsSixty 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.ConclusionsThis 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.
| S-EPMC8908140 | biostudies-literature
Project description:Objective. This paper systematically evaluated the efficacy and safety of compound Danshen dropping pill (CDDP) in patients with acute myocardial infarction (AMI). Methods. Randomized controlled trials (RCTs), comparing CDDP with no intervention, placebo, or conventional western medicine, were retrieved. Data extraction and analyses were conducted in accordance with the Cochrane standards. We assessed risk of bias for each included study and evaluated the strength of evidence on prespecified outcomes. Results. Seven RCTs enrolling 1215 patients were included. CDDP was associated with statistically significant reductions in the risk of cardiac death and heart failure compared with no intervention based on conventional therapy for AMI. In addition, CDDP was associated with improvement of quality of life and impaired left ventricular ejection fraction. Nevertheless, the safety of CDDP was unproven for the limited data. The quality of evidence for each outcome in the main comparison (CDDP versus no intervention) was "low" or "moderate." Conclusion. CDDP showed some potential benefits for AMI patients, such as the reductions of cardiac death and heart failure. However, the overall quality of evidence was poor, and the safety of CDDP for AMI patients was not confirmed. More evidence from high quality RCTs is warranted to support the use of CDDP for AMI patients.
| S-EPMC3703382 | biostudies-literature
Project description:Introduction: Diabetic retinopathy (DR) represents a major cause of adult blindness, and early discovery has led to significant increase in the number of patients with DR. The drugs currently used for treatment, such as ranibizumab, mainly focus on the middle and late periods of DR, and thus do not meet the clinical need. Here, the potential mechanisms by which compound Danshen Dripping Pills (CDDP) might protect against early DR were investigated. Methods: Db/db mice were used to establish a DR model. The initial weights and HbA1c levels of the mice were monitored, and retinal pathology was assessed by hematoxylin-eosin (HE) staining. The vascular permeability of the retina and thickness of each retinal layer were measured, and electroretinogram were performed together with fundus fluorescein angiography and optical coherence tomography. The levels of inflammatory factors were examined in retinal tissue, as well as those of intercellular adhesion molecule 1 (ICAM-1), IL-6, and monocyte chemoattractant protein 1 (MCP-1) in the serum using ELISA. Immunohistochemistry was used to evaluate levels of vascular endothelial growth factor (VEGF), B-cell lymphoma 2 (Bcl-2), and Bclassociated X protein (Bax). Retinal cell injury and apoptosis were examined by TdT-mediated dUTP Nick End Labeling (TUNEL) assays. Results: The data showed that CDDP significantly improved cellular disarrangement. Imaging data indicated that CDDP could reduce vascular permeability and the amplitude of oscillatory potentials (OPs), and restore the thickness of the ganglion cell layer. Moreover, CDDP reduced the expression levels of inflammatory factors in both the retina and serum. Conclusion: These findings strongly suggest that CDDP prevents early DR through vascular and neuroprotection.
| S-EPMC10839082 | biostudies-literature
Project description: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.
| S-EPMC8249928 | biostudies-literature
Project description:Diabetic retinopathy (DR) is increasingly becoming a main complication of diabetes, and is difficult to cure. In our research, network pharmacology analysis suggested that both compound Danshen dripping pills (CDDP) and bezafibrate (BZF) have potential protective effects against DR and the two drugs may act synergistically. The pharmacological effects of the coadministration of CDDP and BZF were elucidated in db/db mice, which simulate DR. Fluorescein fundus angiography showed that coadministration attenuated vascular leakage. Optical coherence tomography and hematoxylin and eosin staining showed that coadministration improved retinal thickness better than CDDP monotherapy. In addition, cell fluorescence images of reactive oxygen species revealed that coadministration of CDDP and BZF had more potent effects against oxidative stress than CDDP monotherapy. Metabolomics analysis showed that coadministration reduced the ratio of oxidized glutathione to reduced glutathione further than CDDP monotherapy. Coadministration of CDDP and BZF may provide additional protective effects by resisting vascular leakage, increasing retinal thickness, and inhibiting inflammation and oxidative stress in DR.
| S-EPMC9579276 | biostudies-literature
Project description:The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic.
| S-EPMC5131350 | biostudies-literature
Project description:Introduction: In clinical practice, warfarin is often combined with Compound Danshen dripping pill (CDDP) for the treatment of cardiovascular diseases. However, warfarin has a narrow therapeutic index, wide interindividual variability (genetic and non-genetic factors), and is susceptible to drug-drug interactions. Our previous study indicated that CDDP might interact with warfarin in individuals with the epoxide hydrolase gene (EPHX1; single-nucleotide polymorphism: rs2292566) A/A subtype. We sought to clarify the interaction between CDDP and warfarin associated with EPHX1 in a comprehensive and accurate manner. Methods: Here, EPHX1 A and EPHX1 G cell lines were established. Expression of microsomal epoxide hydrolase (mEH), vitamin K epoxide reductase (VKOR), and vitamin K-dependent clotting factors (FII, FVII, FIX, FX) was measured by western blotting upon incubation with CDDP and warfarin. mEH activity was evaluated by measuring the transformation of epoxyeicosatrienoic acids into dihydroxyeicosatrienoic acids. Then, healthy volunteers (HVs) with the EPHX1 A/A genotype were recruited and administered warfarin and CDDP to investigate the pharmacokinetics and pharmacodynamics of warfarin. Results: CDDP combined with warfarin could decrease expression of mEH and VKOR, and increase protein expression of FII, FVII, FIX, and FX, in EPHX1 A cells. CDDP could slightly influence the pharmacokinetics/pharmacodynamics of warfarin in HVs with the EPHX1 A/A genotype. Discussion: Rational combination of CDDP and warfarin was safe with no risk of bleeding, but the therapeutic management is also needed. The clinical study is posted in the China Clinical Trial Registry (ChiCTR190002434).
| S-EPMC10192880 | biostudies-literature
Project description:Suxiao Xintong dropping pills (SXXTDP), a traditional Chinese medicine, is widely applied for treating myocardial infarction (MI). However, its therapy mechanisms are still unclear. Therefore, this research is designed to explore the molecular mechanisms of SXXTDP in treating MI. The active ingredients of SXXTDP and their corresponding genes of the active ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. MI-related genes were identified via analyzing the expression profiling data (accession number: GSE97320). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to study the shared genes of drug and disease. Through protein-protein interaction (PPI) network and the Cytoscape plugin cytoHubba, the hub genes were screened out. The compounds and hub targets binding were simulated through molecular docking method. We obtained 21 active compounds and 253 corresponding target genes from TCMSP database. 1833 MI-related genes were identified according to P<0.05 and |log2FC| ≥ 0.5. 27 overlapping genes between drug and disease were acquired. GO analysis indicated that overlapping genes were mainly enriched in MAP kinase activity and antioxidant activity. KEGG analysis indicated that overlapping genes were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. We obtained 10 hub genes via cytoHubba plugin. Six of the 10 hub genes, including PTGS2, MAPK14, MMP9, MAPK1, NFKBIA, and CASP8, were acted on molecular docking verification with their corresponding compounds of SXXTDP. SXXTDP may exert cardioprotection effect through regulating multiple targets and multiple pathways in MI.
| S-EPMC8350434 | biostudies-literature
Project description:Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.
| S-EPMC7354663 | biostudies-literature
Project description:BACKGROUND:Compound danshen dripping pills (CDDP) and trimetazidine (TMZ) are commonly used in the treatment of unstable angina pectoris (UAP). Currently, the combination of CDDP and TMZ has been widely used for UAP. However, the clinical evidence CDDP combined with TMZ for treating UAP is not sufficient. METHODS:We searched for randomized controlled trials testing CDDP combined with TMZ for the treatment of UAP in Chinese National Knowledge Infrastructure database, VIP database, Chinese Biological and Medicine database, Wangfang database, MEDLINE, EMBASE, Cochrane Library, and Web of Science. Extracted data are analyzed using Review Manager 5.3 software. The quality evaluation, forest plots and funnel plots will be conducted by RevMan5.3 software. Moreover, subgroup analysis and sensitivity analysis will also be completed by RevMan5.3. RESULTS:This systematic review will provide powerful clinical evidence of combination CDDP and TMZ for treating UAP. CONCLUSIONS:This systematic review will be provided up-to-date clinical evidence to evaluate the effectiveness and safety of CDDP combined with TMZ for the treatment of parents with UAP.Registration Number: PROSPERO CRD42019143100.
| S-EPMC6919410 | biostudies-literature