Compound Danshen Research Articles

Integration of network pharmacology, UHPLC-Q exactive orbitrap HRMS technique and metabolomics to elucidate the active ingredients and mechanisms of compound danshen pills in treating hypercholesterolemic rats

Ethnopharmacological relevanceHypercholesterolemia (HLC) was a key risk factor for cardiovascular disease (CVD) characterized by elevated cholesterol levels, particularly LDL. While traditional Chinese medicine preparations Compound Danshen Pills(CDP) has been clinically used for hypercholesterolemia and coronary heart disease, its specific therapeutic effect on HLC remains understudied, necessitating further investigation into its mechanisms. Aim of the studyThe aim of this study was to explore the potential of CDP in treating HLC and elucidate its underlying mechanisms and active components. Materials and methodsA hypercholesterolemic lipemia rat model induced by a high-fat diet was employed. Network pharmacology combined with UHPLC-Q exactive orbitrap HRMS technique was used to predict the active components, targets and mechanisms of CDP for HLC. Histological analysis and serum biochemical assays were used to assess the therapeutic effect of CDP and its main active ingredient Sa B on hypercholesterolemic lipemia rat model. Immunofluorescence assays and western blotting were used to verify the mechanism of CDP and Sa B in the treatment of HLC. Metabolomics approach was used to demonstrate that CDP and Sa B affected the metabolic profile of HLC. ResultsOur findings demonstrated that both CDP and its main active ingredient Sa B significantly ameliorated hypercholesterolemic lipemic lesions, reducing levels of TC, LDL, AST, ALT, and ALP. Histological analysis revealed a decrease in lipid droplet accumulation and collagen fiber deposition in the liver, as well as reduced collagen fiber deposition in the aorta. Network pharmacology predicted potential targets such as PPARα and CYP27A1. Immunofluorescence assays and western blotting confirmed that CDP and Sa B upregulated the expression of Adipor1, PPARα and CYP27A1. Metabolomics analyses further indicated improvements in ABC transporters metabolic pathways, with differential metabolites such as riboflavin, taurine, and choline showed regression in levels after CDP treatment and riboflavin, L-Threonine, Thiamine, L-Leucine, and Adenosine showed improved expression after Sa B treatment. ConclusionCDP and Sa B have been shown to alleviate high-fat diet-induced hypercholesterolemia by activating the PPAR pathway and improving hepatic lipid metabolism. Our study demonstrated, for the first time, the complex mechanism of CDP, Sa B in the treatment of hypercholesterolemia at the protein and metabolic levels and provided a new reference that could elucidate the pharmacological effects of traditional Chinese medicine on hypercholesterolemia from multiple perspectives.

Efficacy of Compound Danshen Dripping Pills in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a meta-analysis

Efficacy of Compound Danshen Dripping Pills in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a meta-analysis

Network Meta-analysis of Chinese patent medicines in treatment of chronic pulmonary heart disease

Network Meta-analysis was performed to compare the efficacy and safety of Chinese patent medicines in treating chronic pulmonary heart disease. CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of treating chronic pulmonary heart disease with Chinese patent medicines with the time interval from inception to December 2023. The Cochrane risk-of-bias tool was used for quality assessment of the included articles. RevMan 5.4 and Stata 17.0 were employed to establish the risk of bias map and perform the network Meta-analysis, respectively. Ultimately, a total of 95 RCTs involving 8 787 cases and 11 different Chinese patent medicines were included. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of cardiac function improves clinical total effective rate, SUCRA the top three were Wenxin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(2)For improving forced expiratory volume in the first se-cond(FEV1), SUCRA the top three were Danting Feixin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3)Regarding increasing the FEV1/forced vital capacity(FVC%) value, SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(4)In terms of increasing the partial pressure of oxygen(PaO_2), SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(5)In terms of reducing the partial pressure of carbon dioxide(PaCO_2), SUCRA the top three were Tongxinluo Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(6)In terms of increasing left ventricular ejection fraction(LVEF), SUCRA the top three were Bufei Huoxue Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(7)In terms of decreasing brain natriu-retic peptide(BNP), SUCRA the top three were Compound Danshen Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(8)In terms of improving the hematocrit level, SUCRA the top three were Qishen Yiqi Dropping Pills + conventional western medicine, Compound Danshen Dropping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine. In terms of safety, 26 RCTs reported adverse reactions, which primarily involved the circulatory and digestive systems. The combination of Chinese patent medicines with conventional western medicine has demonstrated enhanced therapeutic effects on chronic pulmonary heart disease. However, due to the varying quality and sample sizes of included studies and the absence of direct comparisons between Chinese patent medicines, the conclusions should be further validated by multicenter studies with larger sample sizes and higher methodological rigor.

Potential therapeutic effects of traditional Chinese medicine in acute mountain sickness: pathogenesis, mechanisms and future directions.

Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS. Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed. We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism. The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.

Elucidation of the Molecular Mechanism of Compound Danshen Dripping Pills against Angina Pectoris based on Network Pharmacology and Molecular Docking.

Compound Danshen dripping pills (CDDP), a traditional Chinese medicine, has had an extensive application in the treatment of angina pectoris (AP) in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to angina pectoris (AP) were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein- protein interaction networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through the above process were investigated through molecular docking. Seventy-six active ingredients were selected with the following criteria: OB ≥ 30%, DL ≥ 0.18. 383 targets of CDDP and 1488 targets on AP were gathered, respectively. Afterwards, 194 common targets of CDDP and anti-AP targets were defined, of which 12 were core targets. GO enrichment analysis indicated that CDDP acted on AP by response to lipopolysaccharide, regulating the reactive oxygen species and metal ion metabolism, and epithelial cell proliferation. In addition, KEGG enrichment analysis indicated that the signaling pathways were notably enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, and TNF signaling pathway. Moreover, the molecular docking manifested excellent binding capacity between the active ingredients and targets on AP. This study comprehensively illustrated the bioactive, potential targets, and molecular mechanisms of CDDP against AP, offering fresh perspectives into the molecular mechanisms of CDDP in preventing and treating AP.

Inhibition of vascular calcification by Compound Danshen Dripping Pill through multiple mechanisms

BackgroundVascular calcification refers to the abnormal accumulation of calcium in the walls of blood vessels and is a risk factor often overlooked in cardiovascular disease. However, there is currently no specific drug for treating vascular calcification. Compound Danshen Dripping Pill (CDDP) is widely used to treat cardiovascular diseases, but its effect on vascular calcification has not been reported. PurposeWe investigated the effects of CDDP on vascular calcification in ApoE−/− mice and in vitro and elucidated its mechanism of action. Study designFirstly, we found that CDDP has the potential to improve calcification based on network pharmacology analysis. Then, we performed the following experiments: in vivo, ApoE−/− mice were fed a high-fat diet randomly supplemented with CDDP for 16 weeks. Atherosclerosis and vascular calcification were determined. In vitro, human aortic smooth muscle cells (HASMCs), human umbilical vein endothelial cells (HUVECs), and human aortic endothelial cells (HAECs) were used to determine the mechanisms for CDDP-inhibited vascular calcification. ResultsIn this study, we observed that CDDP reduced intimal calcification in atherosclerotic lesions of ApoE-deficient mice fed a high-fat diet, as well as the calcification in cultured SMCs and ECs. Mechanistically, CDDP inhibited the Wnt/β-catenin pathway by up-regulating the expression of DKK1 and LRP6, which are upstream inhibitors of Wnt, leading to a reduction in the expression of osteoblastic transition markers (ALP, OPN, BMP2, and RUNX2). Furthermore, CDDP enhanced the secretion of DKK1, which plays a role in mediating EC-SMC crosstalk in calcification. Additionally, VC contributes to vascular aging by inhibiting Sirt1 and increasing senescence parameters (SA-β-gal, p21, and p16). However, CDDP reversed these changes by activating Sirt1. CDDP also reduced the levels of pro-inflammatory cytokines and the senescence-associated secretory phenotype in vivo and in vitro. ConclusionsOur study suggests that CDDP reduces vascular calcification by regulating the DKK1/LRP6/β-catenin signaling pathway in ECs/SMCs and interactions with the crosstalk of ECs and SMCs. It also reduces the senescence of ECs/SMCs, contributing to the Sirt1 activation, indicating CDDP's novel role in ameliorating vascular calcification.

Research of the dynamic regulatory mechanism of Compound Danshen Dripping Pills on myocardial infarction based on metabolic trajectory analysis

BackgroundMyocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely. PurposeIt is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process. MethodsThe MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology. ResultsCDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1–7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14–21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids. ConclusionThe dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.

Compound Danshen Tablets ameliorate myocardial ischemia/reperfusion injury-induced ventricular remodeling by regulating autophagy via AMPK/mTOR signaling pathway

ObjectiveLeft ventricular remodeling induced by myocardial ischemia/reperfusion injury (MI/RI) is a common cardiac dysfunction. Accumulating evidence has demonstrated that autophagy plays a vital role in protecting against ventricular remodeling. This study aims to investigate the performance of compound Danshen Tablets (CDT) in rescuing ventricular remodeling and whether autophagy as the potential mechanism. MethodsThe left anterior descending arteries of rats were temporarily ligated for 30 min to construct the MI/RI model. Ventricular remodeling was induced by reperfusion for 28 d, during which the MI/RI rats were administered CDT (300 mg/kg and 600 mg/kg), atorvastatin (2 mg/kg), and diltiazem (16 mg/kg). Cardiac function and structure were examined by echocardiography. Immunohistochemistry, Masson's trichrome staining, and hematoxylin-eosin (H & E) staining were utilized to assess the fibrosis and histological alterations in the heart tissue. The expression of autophagy-related proteins was detected using Western blotting. ResultsCDT attenuated the cardiac dysfunction, structural changes, histopathological changes and fibrosis induced by MI/RI. CDT significantly enhanced the level of Beclin1 and microtubule-associated protein 1 light chain 3 beta (LC3β), and reduced p62 levels in MI/RI rats. Moreover, CDT significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) phosphorylation. ConclusionCDT ameliorated MI/RI-induced ventricular remodeling by activating autophagy and improving autophagic flux via the AMPK/mTOR signaling pathway.

Effectiveness and safety of Danshen injections in treatment of cardiac failure: a network meta-analysis.

Objective: The purpose of this network meta-analysis (NMA) was to compare the therapeutic effects of various Danshen (Salvia miltiorrhiza Bunge [Lamiaceae; Salviae miltiorrhizae radix et rhizoma]) injections on heart failure to determine the optimal Danshen injection combined with conventional treatment. Methods: 8 databases were searched from the inception of these databases to May 2023 to collect randomized controlled trials (RCTs) on the effectiveness and safety of Danshen injections in the treatment of heart failure. This NMA was performed using Stata 16.0 software and R 4.1.3 software. Results: A total of 24 RCTs involving 2,186 subjects were included. The intervention group received Danshen injections plus conventional treatment, involving the following 7 Danshen injections. The results of the NMA showed that Compound Danshen injection + Common (SUCRA: 79.6%) and Sodium tanshinone ⅡA sulfonate injection + Common (SUCRA: 78.0%) exhibited higher total effective rates. Sodium tanshinone ⅡA sulfonate injection + Common (SUCRA: 94.3%) and Danshen injection + Common (SUCRA: 68.2%) were superior to other traditional Chinese medicines in improving left ventricular ejection fraction (LVEF). Danshen injection + Common (SUCRA: 99.9%) and Shenxiong glucose injection + Common (SUCRA: 77.2%) were the most effective in reducing brain natriuretic peptide (BNP). In addition, compared with conventional treatment, all Danshen injections did not increase the risk of adverse reactions. Conclusion: Current evidence shows that all seven Danshen injections are effective for heart failure. Due to the limited quantity and quality of the included studies, our findings need to be verified by more high-quality studies.

Compound Danshen Dripping Pill effectively alleviates cGAS-STING-triggered diseases by disrupting STING-TBK1 interaction

BackgroundThe cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) genes (STING) pathway is critical in the innate immune system and can be mobilized by cytosolic DNA. The various inflammatory and autoimmune diseases progression is highly correlated with aberrant cGAS-STING pathway activation. While some cGAS-STING pathway inhibitor were identified, there are no drugs that can be applied to the clinic. Compound Danshen Dripping Pill (CDDP) has been successfully used in clinic around the world, but the most common application is limited to cardiovascular disease. Therefore, the purpose of the present investigation was to examine whether CDDP inhibits the cGAS-STING pathway and could be used as a therapeutic agent for multiple cGAS-STING-triggered diseases. MethodsBMDMs, THP1 cells or Trex1−/− BMDMs were stimulated with various cGAS-STING-agonists after pretreatment with CDDP to detect the function of CDDP on IFN-β and ISGs productionn. Next, we detect the influence on IRF3 and P65 nuclear translocation, STING oligomerization and STING-TBK1-IRF3 complex formation of CDDP. Additionally, the DMXAA-mediated activation mice model of cGAS-STING pathway was used to study the effects of CDDP. Trex1−/− mice model and HFD-mediated obesity model were established to clarify the efficacy of CDDP on inflammatory and autoimmune diseases. ResultsCDDP efficacy suppressed the IRF3 phosphorylation or the generation of IFN-β, ISGs, IL-6 and TNF-α. Mechanistically, CDDP did not influence the STING oligomerization and IRF3-TBK1 and STING-IRF3 interaction, but remarkably eliminated the STING-TBK1 interaction, ultimately blocking the downstream responses. In addition, we also clarified that CDDP could suppress cGAS-STING pathway activation triggered by DMXAA, in vivo. Consistently, CDDP could alleviate multi-organ inflammatory responses in Trex1−/− mice model and attenuate the inflammatory disorders, incleding obesity-induced insulin resistance. ConclusionCDDP is a specifically cGAS-STING pathway inhibitor. Furthermore, we provide novel mechanism for CDDP and discovered a clinical agent for the therapy of cGAS-STING-triggered inflammatory and autoimmune diseases.

Compound Danshen Dripping Pills combined with isosorbide mononitrate for angina pectoris: A systematic review and a Meta-analysis

ObjectiveTo evaluate the efficacy of Compound Danshen Dripping Pills (CDDP) combined with isosorbide mononitrate (ISMN) versus ISMN alone for treating angina pectoris in patients. MethodsThe PubMed, Web of Science, Cochrane Library, Embase China National Knowledge Infrastructure, China Biomedical Literature Service System, Chinese Medical Journal Database, and Wan Fang MED databases were searched from inception to November 2022. Randomized controlled trials (RCTs) and cohort studies were included. The primary outcomes were angina symptom and electrocardiography (ECG) efficacy, angina symptom efficacy, and ECG efficacy. The protocol was registered with PROSPERO No. CRD42022314774. ResultsOur study included 7 245 patients with angina (59 RCTs, 11 cohort studies). When ISMN was combined with CDDP, the efficacy of angina symptom and ECG [odds ratio (OR) = 4.824, 95% confidence interval (CI) = 3.636–6.401, P = 0.000], the efficacy of angina symptom (OR = 4.347, 95% CI = 3.635–5.198, P = 0.000), the efficacy of ECG (OR = 3.364, 95% CI = 2.767–4.089, P = 0.000) was better than that of patients treated with ISMN alone. CDDP combined with ISMN was superior to ISMN alone in reducing triglyceride (TG) [mean difference (MD) = −35.176, 95% CI = −37.439 to −32.912, P = 0.000], total cholesterol (TC) (MD = −24.296, 95% CI = −26.429 to −22.163, P = 0.000), the duration of angina attack (MD = −1.991, 95% CI = −2.349 to −1.633, P = 0.000), and the frequency of angina attack [standardized MD (SMD) = −2.840, 95% CI = −3.416 to −2.265, P = 0.000]. There was no increase in adverse events between CDDP combined with ISMN and ISMN alone (OR = 0.513, 95% CI = 0.421–0.626, P = 0.000). ConclusionsCDDP combined with ISMN improved treatment efficacy and was well tolerated. Therefore, this combination could be used as an alternative treatment. However, clinical and patient conditions should be considered.

The efficacy of Chinese herbal drugs for adults with angina pectoris: Bayesian network meta-analysis of 331 RCTs involving 36,467 individuals

Ethnopharmacological relevanceHundreds of randomized controlled trials (RCT) on Chinese herbal drugs (CHDs) including Shexiang baoxin pill (BXP), compound Danshen dripping pill (DSP), compound Danshen tablet (DST), Suxiao jiuxin pill (JXP), Naoxintong capsule (NXT), Tongxinluo capsule (TXL), and Di'ao xinxuekang capsule (XXK) and conventional chemical drugs, such as isosorbide dinitrate (ISDN), for angina pectoris are available but have not been evaluated by a PRISMA-compliant network meta-analysis (NMA). Aim of the studyThis study aimed to compare the efficacy of nine anti-anginal drugs through NMA on RCTs. MethodsRCTs of drug treatment for adult patients with angina pectoris for improvements in symptoms and electrocardiography were retrieved. Odds ratios and 95% credible intervals were computed to measure effect sizes. RCT quality was evaluated with the Cochrane risk of bias tool. Evidence synthesis was performed with Bayesian NMA. Essential analyses including subgroup analysis, sensitivity analysis, meta-regression analysis, publication bias analysis, and ranking analysis were conducted to assess the robustness of efficacies. Evidence strength was assessed with the GRADE approach. ResultsA total of 331 RCTs with 36,467 participants were eligible. The overall quality of all included RCTs was low. Overall efficacy estimates from different approaches of evidential synthesis found that BXP, TXL, and DSP were more efficacious than DST and ISDN. Essential analyses indicated consistent efficacy estimates, insignificant publication bias, and corroborative ranking results. The overall GRADE evidence strength was low. ConclusionThis comprehensive Bayesian NMA found BXP, TXL, and DSP to be the top three candidates among the seven tested CHDs for treating adults suffering from angina pectoris. However, the quality and the evidence strength of eligible RCTs were low. Further high-quality RCTs with more outcome measures and their NMAs are warranted. RegistrationPROSPERO CRD42014007035.

Compound Danshen dripping pills prevent early diabetic retinopathy: roles of vascular protection and neuroprotection.

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.

Network Meta-analysis of Chinese patent medicines in treatment of coronary heart disease complicated with heart failure

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.

Effects of Compound Danshen Dripping Pills in the Treatment of Angina Pectoris in Coronary Heart Disease: A Meta-Analysis

Effects of Compound Danshen Dripping Pills in the Treatment of Angina Pectoris in Coronary Heart Disease: A Meta-Analysis

Preventive effect and mechanism of compound Danshen dripping pills on contrast-induced nephropathy after percutaneous coronary interventional.

Contrast-induced nephropathy (CIN) is one of the most common complications after coronary stent implantation due to the extensive development of coronary catheterization technology. Compound Danshen dripping pills (CDDP) are clinically used as cardiovascular drugs, relieving systemic inflammatory response. Previous studies have observed that CDDP can decrease CIN incidence after coronary stent implantation with uncertain effectiveness. We conducted a prospective, randomized, single-center, single-blind, controlled trial. We enrolled patients 18 years and older with unstable angina pectoris and NSTEMI who underwent PCI at the Tianjin Chest Hospital between November 1, 2021, and November 31, 2022, and followed for 30 days. Patients were randomized to CDDP and hydration therapy (10 capsules three times/day; N = 411) or hydration only (N = 411). The primary outcome was the contrast nephropathy incidence, defined as an elevation in serum creatinine by more than 25% or 44 μmol/L from baseline within 48-72 h of contrast exposure. Secondary outcomes included major adverse cardiovascular events post-surgery and during follow-up. After 48 h of operation, the two groups had statistical significance in Scr and BUN values (80.0 ± 12.59 vs. 84.43 ± 13.49, P < 0.05; 6.22 ± 1.01 vs. 6.40 ± 0.93, P < 0.05). The difference in Scr in 72 h between the two groups was statistically significant (76.42 ± 10.92 vs. 79.06 ± 11.58, P < 0.05). The CIN incidence was significantly lower in the CDDP group than in the hydration group. The CIN risk was significantly elevated in patients with LVEF <50%, contrast volume ≥160 ml, and hypertension, after 48 and 72 h of operation. The serum inflammation index levels NGAL, TNF-α, oxidative stress indexes SOD, and MDA significantly differed between the two groups. However, there was no significant difference in serum apoptosis indexes Bax, Bcl-2, and Casepase-9. CDDP pre-treatment could prevent contrast-induced nephropathy. Inflammatory response and oxidative stress could be significant in the CDDP mechanism.

Effectiveness and safety of traditional Chinese medicine for diabetic retinopathy: A systematic review and network meta-analysis of randomized clinical trials.

Diabetic retinopathy (DR) is currently recognized as one of the most serious diabetic microangiopathies and a major cause of adult blindness. Commonly used clinical approaches include etiological control, microvascular improvement, and surgical intervention, but they are ineffective and have many side effects. Oral Chinese medicine (OCM) has been used for thousands of years to treat DR and is still widely used today, but it is unclear which OCM is more effective for DR. To estimate relative effectiveness and safety profiles for different classes of OCMs for DR, and provide rankings of the available OCMs. The search time frame was from the creation of the database to January 2023. RevMan 5.3 and Stata 14.0 software were used to perform the systematic review and Network meta-analyses (NMA). A total of 107 studies and 9710 patients were included, including 4767 cases in the test group and 4973 cases in the control group. Based on previous studies and clinical reports, and combined with the recommendations of Chinese guidelines for the prevention and treatment of DR, 9 OCMs were finally included in this study, namely Compound Xueshuantong Capsules, Qiming Granules, Compound Danshen Dripping Pills, Hexue Mingmu Tablets (HXMM), Qiju Dihuang Pills (QJDH), Shuangdan Mingmu Capsules (SDMM), Danggui Buxue Decoction (DGBX), Xuefu Zhuyu Decoction and Buyang Huanwu Decoction. When these nine OCMs were analyzed in combination with conventional western medicine treatment (CT) compared with CT alone, the NMA results showed that HXMM + CT has better intervention effect on the overall efficacy of DR patients, HXMM + CT has better effect on improving patients' visual acuity, SDMM + CT has better effect on inhibiting vascular endothelial growth factor, DGBX + CT has better effect on reducing fundus hemorrhage area, HXMM + CT has better effect on reducing fasting blood glucose, and QJDH + CT has better effect on reducing glycated hemoglobin. When there are not enough clinical indicators for reference, SDMM + CT or HXMM + CT treatments can be chosen because they are effective for more indicators and demonstrate multidimensional efficacy. This study provides evidence that combining OCMs with CT leads to better outcomes in all aspects of DR compared to using CT alone. Based on the findings, we highly recommend the use of SDMM or HXMM for the treatment of DR. These two OCMs have demonstrated outstanding efficacy across multiple indicators.

Retracted: Exploration on Molecular Mechanism of Reversal Effect of Compound Danshen Tablets on Hepatic Fibrosis Based on Network Pharmacology.

[This retracts the article DOI: 10.1155/2022/7241719.].

Evaluation of herb-drug interactions between compound Danshen dripping pills and clopidogrel based on the pharmacokinetics and pharmacodynamics in rats.

Compound Danshen dripping pills (CDDP), a well-known traditional Chinese medicine, is widely used to prevent and treat cardiovascular diseases. CDDP is usually prescribed in combination with clopidogrel (CLP), but the herb-drug interactions are rarely reported. This study evaluated the effects of CDDP on the pharmacokinetics and pharmacodynamics of coadministered CLP, and ensured the safety and efficacy of their usage. The trial design included a single-dose administration and multidose test for 7 consecutive days. Wistar rats received CLP alone or CLP combined with CDDP. After the final dose, plasma samples were collected at various time points, and the active metabolite H4 of CLP was analyzed by ultrafast liquid chromatography coupled with triple quadrupole tandem mass spectrometry. The main pharmacokinetic parameters of Cmax (maximum [or peak] serum concentration), Tmax (peak plasma time), t1/2 (half-time), AUC0-∞ (area under the concentration-time curve from dosing (time 0) to infinite time), and AUC0-t (area under the concentration-time curve from dosing [time 0] to time t) were calculated using the non-compartment model. In addition, prothrombin time, activated partial thromboplastin time, bleeding time, and adenosine diphosphate-induced platelet aggregation were evaluated for anticoagulation and antiplatelet aggregation activity. In this study, we found that CDDP had no significant effect on the metabolism of CLP in rats. In pharmacodynamic studies, the combination group showed significant synergistic antiplatelet activity compared with the CLP or CDDP groups alone. Based on pharmacokinetic and pharmacodynamic results, CDDP and CLP have synergistic effects on antiplatelet aggregation and anticoagulation.

Quality assessment of traditional Chinese medicine using quality biomarkers: Compound DanShen dripping pills as an example.

The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy. To solve the problem that the association between quality control and efficacy is lacking. The present study was designed to establish a methodology for quality control based on quality biomarkers (Q-biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case. Guided by the basic principles of Q-biomarkers, the compounds in TCM were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q-biomarkers were further screened through proteomics and partial least squares regression analysis. The protein-protein interaction network that combines both predicted targets and potential Q-biomarkers was constructed to screen Q-biomarkers. There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q-biomarkers of CDDP. Our preliminary study suggested the feasibility of the Q-biomarkers theory in the quality of TCM. The concept of Q-biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.