Danshen Decoction Research Articles

DanShen Decoction targets miR-93-5p to provide protection against MI/RI by regulating the TXNIP/NLRP3/Caspase-1 signaling pathway

BackgroundBone marrow mesenchymal stem cells (BMSCs) derived exosomes have demonstrated potential therapeutic efficacy on myocardial ischemia/reperfusion injury (MI/RI). This study has explored the underlying mechanisms of Danshen decoction (DSD) pretreated BMSCs-exosomes to treat MI/RI in vivo and in vitro. MethodsExtracellular vesicles extracted from BMSCs were identified, miRNA sequencing was performed to screen the effects of DSD, and verified to target TXNIP in vivo. After MI/RI modeling, rats were treated with BMSCs-exosomes pretreated with DSD or miRNA inhibitor. BMSCs-exosomes, DSD-pretreated BMSCs-exosomes, and miRNA inhibitor/anti-miRNA-pretreated BMSCs-exosomes were used to treat H9c2 cells or MI/RI rats. CCK-8, Tunnel staining, and flow cytometry were performed to measure cell viability. LDH, CK, CK-MB were detected to evaluate cell injury. MDA, SOD, and ROS were used to confirm oxidative stress. Furthermore, IL-1β, IL-18, cleaved-caspase-1, pro-caspase-1, NLRP3, TXNIP, and GSDMD were quantified for the TXNIP/NLRP3/Caspase-1 signaling activation. In addition, echocardiography was used to observe the heart function, and H&E stain was performed to detect pathological injury. ResultsFollowing DSD pretreatment, there was a marked elevation in the expression levels of miR-93-5p, miR-16-5p, and miR-15b-5p, with miR-93-5p exhibiting the highest baseMean value. The administration of a miR-93-5p inhibitor yielded effects counteractive to those observed with DSD treatment, leading to reduced cell proliferation, heightened oxidative stress (as indicated by increased levels of SOD and ROS, alongside a decrease in MDA), and enhanced cell apoptosis. Furthermore, DSD effectively mitigated the miR-93-5p-induced upregulation of key inflammatory and apoptotic markers, including IL-1β, IL-18, caspase-1, NLRP3, TXNIP, and GSDMD. Notably, exosomes derived from DSD-pretreated BMSCs demonstrated a capacity to alleviate cardiac damage. ConclusionDSD may target miR-93-5p within BMSC-derived exosomes to confer protection against cardiac damage by inhibiting the activation of the TXNIP/NLRP3/Caspase-1 signaling pathway, thereby mitigating cardiomyocyte pyroptosis. This study provides a theoretical foundation for the application of DSD in the treatment of MI/RI.

The Molecular Mechanism of Danshen Decoction and Buxinqi Oral Liquid in Treating Coronary Heart Disease Based on Network Pharmacology

The Molecular Mechanism of Danshen Decoction and Buxinqi Oral Liquid in Treating Coronary Heart Disease Based on Network Pharmacology

Clinical effect of Danshen decoction in patients with heart failure: A systematic review and meta-analysis of randomized controlled trials.

The incidence of heart failure (HF) is increasing year by year, posing a great threat to human health. Although pharmacotherapy has been able to significantly prolong patient survival, pharmacotherapy for HF still has limitations due to its complex pathogenesis and considerable individual variability, there is a great need to explore complementary and alternative therapies to slow down the progression of HF. Danshen decoction is used to treat several cardiovascular diseases including HF, but the efficacy of stabilization is uncertain. This meta-analysis evaluated the clinical efficacy of Danshen Decoction for the treatment of HF. The registration number assigned to this meta-analysis on the PROSPERO platform is CRD42022351918. Four databases were searched, and randomized controlled trials (RCTs) of Danshen decoction combined with conventional treatment (CT) of HF were screened, CT included medical treatments other than Danshen Decoction to which the patient was treated (including but not limited to angiotensin converting enzyme inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitors, β-blockers, diuretics, mineralcorticoid recept antagonist etc.). The clinical efficacy rate (CER), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), brain natriuretic peptide (BNP), N-terminal pro-B type natriuretic peptide (NT-proBNP) and hypersensitive C-reactive protein (hs-CRP) were included as outcome indicators. The GRADE grading scale was used to grade the above indicators. The Cochrane risk-of-bias tool and the Jadad quality scale were used to assess the methodological quality of RCTs. Finally, RevMan V.4.5 software was used for data synthesis, 95% confidence intervals (CI) for dichotomous data, risk ratios (RR), and mean differences (MD) for continuous variables were calculated, Chi-square and I2 were used for heterogeneity assessment. Nine RCTs with a total of 855 patients were included in this study, and all included RCTs had a low overall quality risk of bias and high quality of reported information. The results of the meta-analysis showed that compared with the use of CT, CER (%) was significantly improved due to Danshen decoction combined with CT (MD = 3.95, 95% CI [2.58, 6.04], P < 0.00001), LVEF (%) was significantly improved (MD = 5.46, 95% CI [5.32, 5.60], P < 0.00001), LVEDD (mm) was significantly reduced (MD = -5.27, 95% CI [-6.21, -4.32], P < 0.00001), LVESD (mm) was significantly reduced (MD = -4.60, 95% CI [-5.87, -3.32], P < 0.00001), BNP (pg/mL) was significantly reduced (MD = -88.61, 95% CI [-121.98, -55.24], P < 0.00001), NT-proBNP (pg/mL) was significantly decreased (SMD = -3.33, 95% CI [-5.92, -0.73], P = 0.01), hs-CRP (mg/L) was significantly decreased (MD = -2.73, 95% CI [-4.11, -1.34], P = 0.0001). The quality of the GRADE evidence for all outcomes was moderate to low and no RCTs reported adverse events. Our research demonstrates that Danshen decoction is an effective and safe treatment option for HF. Nevertheless, considering the limitations of methodological and the quality of RCTs, more rigorous, large-scale, multicenter randomized clinical trials are needed to further evaluate the efficacy and safety of Danshen decoction in the treatment of HF patients.

Rapid separation and binding configuration prediction of the components in Danshen decoction to endothelin A receptor using affinity chromatography and molecular dynamics simulation.

As a famous traditional Chinese formula, Danshen Decoction has the potential to relieve the pain of pulmonary arterial hypertension patients, however, the functional components remain unknown. Herein, we reported a method to screen the functional components in Danshen Decoction targeting endothelin receptor A, an accepted target for the treatment of the disease. The receptor was functionalized on the macroporous silica gel through an epidermal growth factor receptor fusion tag and its covalent inhibitor. Using the affinity gel as the stationary phase, the bioactive compound was identified as salvianolic acid B by mass spectrometry. The binding kinetic parameter (dissociation rate constants kd ) of salvianolic acid B with the receptor was determined via peak profiling. Using the specific ligands of the receptor as probes, the binding configuration prediction of salvianolic acid B with the receptor was performed by molecular dynamics simulation. Our results indicated that salvianolic acid B is a potential bioactive compound in Danshen Decoction targeting the receptor. This work showed that receptor chromatography in combination with molecular dynamics simulation is applicable to predicting the binding kinetics and configuration of a ligand to a receptor, providing crucial insight for the rational design of drugs that recognize functional proteins.

Network pharmacology approach and experimental verification of Dan-Shen Decoction in the treatment of ischemic heart disease

Context Dan-Shen Decoction, which is composed of Danshen, Tanxiang and Sharen, has a good therapeutic effect on ischemic heart disease (IHD). However, systematic research on the exact mechanism of action of Dan-Shen Decoction is still lacking. The anti-IHD effect of Dan-Shen Decoction was examined in this study using a systematic pharmacological method. Objective This study validates the efficacy and explores the potential mechanisms of Dan-Shen Decoction in treating IHD by integrating network pharmacology analyses and experimental verification. Materials and methods The active components, critical targets and potential mechanisms of Dan-Shen Decoction against IHD were predicted by network pharmacology and molecule docking. H9c2 cells were pretreated with various 1 µg/mL Dan-Shen Decoction for 2 h before induction with 1000 µmol/L CoCl2 for 24 h. The cell viability was detected by CCK8, and protein expression was detected by western blots. Results The network pharmacology approach successfully identified 69 active components in Dan-Shen Decoction, and 122 potential targets involved in the treatment of IHD. The in vitro experiments indicate that the anti-IHD effect of Dan-Shen Decoction may be closely associated with targets such as AKT1 and MAPK1, as well as biological processes such as cell proliferation, inflammatory response, and metabolism. Conclusions This study not only provides new insights into the mechanism of Dan-Shen Decoction against IHD, but also provides important information and new research ideas for the discovery of anti-IHD compounds from traditional Chinese medicine.

TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury

BackgroundEvery year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influences cardiac function and prognosis in cardiac surgery patients. Jiawei Danshen Decoction (JWDSD) is a traditional Chinese herbal prescription that has been used clinically for many years in China to treat MIRI. The underlying molecular mechanisms, however, remain unknown. To investigate the proteomic changes in myocardial tissue of rats given JWDSD for MIRI therapy-based proteomics.MethodsMIRI rat model was created by ligating/releasing the left anterior descending coronary artery. For seven days, the drugs were administered twice daily. The model was created following the last drug administration. JWDSD's efficacy in improving MIRI was evaluated using biochemical markers and cardiac histology. Tandem mass tag-based quantitative proteomics (TMT) technology was also used to detect proteins in the extracted heart tissue. To analyze differentially expressed proteins (DEPs), bioinformatics analysis, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways, were employed. Furthermore, western blotting confirmed the potential targets regulated by JWDSD.ResultsThe histopathologic characteristics and biochemical data showed JWDSD's protective effects on MIRI rats. A total of 4549 proteins were identified with FDR (false discovery rate) ≤1%. Twenty overlapping were identified (162 DEPs and 45 DEPs in Model/Control or JWDSD/Model group, respectively). Of these DEPs, 16 were regulated by JWDSD. GO analysis provided a summary of the deregulated protein expression in the categories of biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment analysis revealed that the signaling pathways of neutrophil extracellular trap formation, RNA polymerase, serotonergic synapse, and linoleic acid metabolism are all closely related to JWDSD effects in MIRI rats. Furthermore, T-cell lymphoma invasion and metastasis 1 (TIAM1) was validated using western blotting, and the results were consistent with proteomics data.ConclusionsOur study suggests that JWDSD may exert therapeutic effects through multi-pathways regulation in MIRI treatment. This work may provide proteomics clues for continuing research on JWDSD in treating MIRI.

Danshen Decoction in the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis Protocol of Randomized Controlled Trials.

Background. Hyperlipidemia is a common clinical chronic disease that increases the incidence of cardiovascular disease. However, although oral drug therapy can reduce blood lipids, long-term drug treatment may cause various side effects. Therefore, it is important to find suitable alternatives for the treatment of hyperlipidemia. The classic traditional Chinese medicine (TCM) prescription Danshen decoction (DSD) has been found effective for the treatment of hyperlipidemia. This protocol aims to evaluate the efficacy and safety of DSD in the treatment of hyperlipidemia. Methods and Analysis. We will screen all the randomized controlled trials (RCTs) which research DSD in the treatment of hyperlipidemia from 7 databases from their inception to July 2022; three investigators will independently screen and select RCTs and extract data and assess the risk of bias. The Cochrane scale, Jadad scale, and GRADE scale will be used to assess the risk of bias, literature quality, and outcome quality, respectively. Review Manager V.5.4 will be used for the meta-analysis, and the results will be presented as the risk ratio (RR) for the binary data and the mean difference (MD) or standardized mean difference (SMD) for the continuous data. Ethical approval and Dissemination. This protocol for a systematic review will be submitted to a peer-reviewed journal for publication and ethical approval is not applicable. PROSPERO registration number.CRD42022352467.

Material basis and integrative pharmacology of danshen decoction in the treatment of cardiovascular diseases

BackgroundCardiovascular diseases (CVDs) are among the primary and predominant threats to human health with increasing incidence. Danshen Decoction (DSD) as an adjuvant therapy can benefit CVDs patients by improving clinical efficacy. PurposeThe purpose of this study was to identify the active components and potential pharmacological mechanisms of DSD by combining mass spectrometry with a network pharmacology strategy and to review the use of DSD in the treatment of CVDs. MethodFirst, the composition of DSD was analyzed by ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC–MS/MS). Second, the network pharmacology method was used to elucidate the underlying material basis and possible pharmacological mechanism of DSD for the treatment of CVDs. Finally, clinical and experimental studies on DSD in the past ten years were retrieved from the PubMed and CNKI database, and the content of these studies was used to summarize the latest progress in DSD treatment of CVDs. OutcomeA total of 35 compounds were found in DSD by manual identification from the analysis of MS, which may be the material basis for the therapeutic effect of DSD. After taking the intersection of 2086 targets related to CVDs, these 35 compounds are considered to play a role in the treatment of CVDs through 210 targets including signal transducer and activator of transcription 3 (STAT3), sarcoma (SRC) and phosphoinositide-3-kinase regulatory subunit (PIK3R), and a total of 168 signaling pathways were involved in the regulation of CVDs by DSD, including PI3K-AKT signaling pathway, Alzheimer disease, and Rap1 signaling pathway. A total of 29 clinical studies using DSD in the treatment of CVDs were included in the literature review, and these studies showed the positive significance of DSD as adjuvant therapy, while 14 experimental studies included in the literature review also demonstrated the effectiveness of DSD in the treatment of CVDs. ConclusionDSD plays a role in the treatment of CVDs through a variety of active ingredients. Large-scale clinical research and more in-depth experimental research will help to further reveal the mechanism of DSD in the treatment of CVDs.

Danshen decoction in the treatment of heart failure: A systematic review and meta-analysis protocol of randomized controlled trials.

Background:Heart failure (HF) is considered the clinical endpoint of all cardiovascular diseases (CVDs). Although a large number of HF drugs and therapies have been developed, it is still need to find therapies with better clinical efficacy and fewer side effects. The purpose of this systematic evaluation is to assess the efficacy and safety of Danshen decoction on HF and the improvement of cardiac function (CF).Methods:Four databases will be searched to identify any eligible studies, and this protocol does not require ethics committee review as the research is based on published articles. There are no restrictions set for the language, publication date, or status of the study. The clinical effective rate (CER) of HF treatment is considered to be the main result. CF, various serum inflammatory factors, and adverse events were defined as secondary outcomes. When more than 1 article is used to study the changes and results of the same index, we will conduct a meta-analysis. If the heterogeneity is not statistically significant (P > .10 or I2 < 50%), a fixed-effect model will be established to estimate the overall intervention effect. Otherwise, random effect models will be used to provide more conservative results.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This study will provide reliable evidence-based basis for the clinical application of Danshen decoction in the treatment of HF.

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy.

Background Danshen Decoction comprises Salvia miltiorrhiza, Santalum album, and Amomum villosum. It can promote blood circulation and remove blood stasis, and is commonly used in the treatment of gastric and duodenal ulcers, coronary heart disease, angina pectoris, etc. This research is based on network pharmacology and is experimentally verified to explore the potential mechanism of Danshen Decoction in the treatment of ischemic cardiomyopathy (ICM). Methods The effective components and targets of Danshen Decoction were firstly extracted from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, the drug-component-target-disease network was then constructed, the protein-protein interaction (PPI) network was constructed, the Gene Ontology (GO) enrichment analysis was carried out, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed in order to find the potential active components and therapeutic mechanisms. Finally, the in vitro hypoxia/reoxygenation model in H9c2 cells was established to verify the predicted active components and therapeutic mechanisms. Results The results showed that Danshen Decoction has 67 potential active components and 109 therapeutic targets in treating ICM. These targets were rich in a variety of gene functions and different signaling pathways; the main gene targets include TP53, c-Jun, and Akt1. Go enrichment analysis showed that response to drug, membrane raft, and G protein-coupled amine receiver activity rank first in each process, and the main signaling pathways include PI3K-Akt signaling pathway. Through molecular docking and experimental verification of the major active components and core therapeutic targets, the active components of Danshen Decoction demonstrated an ability to reduce the cell damage caused by hypoxia/reoxygenation in H9c2 cells by regulating the core therapeutic target including Akt1, c-Jun, and TP53. Conclusion Danshen Decoction has the effect of treating ICM in multiple ways, which is consistent with the results of network pharmacology. This laid a foundation for further study in exploring the active principles and pharmacological mechanism of Danshen Decoction.

The therapeutic effect of Jiawei Danshen Decoction on myocardial ischemia-reperfusion injury by inhibiting H2S-mediated autophagy signaling pathway

ObjectiveTo investigate the protective effects of Jiawei Danshen Decoction (加味丹参饮, JWDSD) on myocardial ischemia-reperfusion injury (MIRI) via the regulation of serum Hydrogen sulfide (H2S) and cardiac Beclin1, light Chain 3A/B (LC3A/B), p62, and autophagy protein5 (ATG5). MethodsSeventy specific pathogen free (SPF) Sprague-Dawley (SD) rats were randomly assigned to seven groups (n = 10 in each group), including normal control, sham operation, MIRI model (model), ischemic preconditioning, NaHS, JWDSD, and JWDSD +CSE inhibitor (JWDSD + PPG) groups, and orally administered the indicated drugs for 14 d. Two hours after the last administration, the left anterior decreased branch of the coronary artery of each rat in model, NaHS, JWDSD, and JWDSD + PPG groups was ligated for 30 min and subsequently reperfused for 90 min to establish the MIRI model, and the rats in the sham operation group were only exposed to the thorax after surgery without coronary ligation. Blood samples were collected to detect H2S levels using an enzyme-linked immunosorbent assay (ELISA). Heart tissues were harvested for histopathological and immunohistochemical examination and quantitative reverse transcription polymerase chain reaction analysis of Beclin1 and ATG5 mRNA expression and Western blot analysis of Beclin1, LC3A/B, and p62 protein expression. Results(1) The serum H2S content in model group rats was significantly reduced (P < 0.01), JWDSD significantly increased the serum H2S content of model group rats (P < 0.01), and the CSE inhibitor (PPG) significantly reduced H2S levels in the JWDSD group rats (P < 0.01). (2) Compared with the normal control group, the myocardial tissue necrosis and cell destruction occurred in the MIRI model group, and JWDSD could alleviate the myocardial tissue necrosis of model rats, but the ameliorative effect of JWDSD could be reversed by PPG. (3) Beclin1, LC3A/B, and p62 expression levels in the heart tissues of the model group were significantly increased (P < 0.001), whereas decreased by JWDSD (P < 0.05, P < 0.01, and P < 0.001, respectively), and the inhibitory effects of JWDSD on Beclin1, LC3A/B, and p62 expression were partially reversed by PPG (P < 0.01, P < 0.05, and P < 0.01, respectively). (4) The expression levels of autophagy-related genes Beclin1 and ATG5 were significantly increased in the model group (P < 0.001). JWDSD clearly downregulated the expression levels of Beclin1 and ATG5 (P < 0.05 and P < 0.001, respectively), which were reversed by PPG (P < 0.001). ConclusionOur experimental data show that JWDSD can exhibit an anti-MIRI role by increasing endogenous H2S generation, and downregulating the expression of Beclin1, LC3A/B, p62 and ATG5, which are related to inhibiting autophagy signaling.

Dahuang Danshen Decoction Inhibits Pancreatic Fibrosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.

Background In Traditional Chinese Medicine (TCM), Dahuang Danshen decoction (DD) is used to treat pancreatic fibrosis. Pancreatic fibrosis is a typical manifestation of chronic pancreatitis (CP), which affects the digestive system. The therapeutic mechanisms of DD in pancreatic fibrosis are unclear. Aim This study aimed to investigate the regulatory mechanisms of DD on oxidative stress and endoplasmic reticulum stress in CP. Materials and Methods Experimental rats were intraperitoneally injected with 500 mg/kg BW of diethyldithiocarbamate (DDC) twice a week for six weeks to induce CP. At the same time, DD was administered orally at daily doses of 1.37 g/kg BW, 2.74 g/kg BW, and 5.48 g/kg BW to evaluate its treatment effects on CP. After all treatments, pancreatic tissues were harvested and subjected to H&E staining. Transmission electron microscopy (TEM) was also performed to show the endoplasmic reticulum structure in the pancreatic tissues. Immunohistochemistry was used to detect the α-SMA expression level in the pancreatic tissues. Metabolomics analysis of the serum and proteomics analysis of the pancreatic tissues were performed to reveal the changes of endogenous metabolites and proteins, respectively. Concentrations of GSH, MDA, SOD, ROS, col-1, and col-3 were determined using corresponding kits. The western blotting method was used to determine the protein levels of Keap-1, HO-1, NQO1, Nrf2, GRP, JNK, and caspase 12. The pancreatic mRNA levels of NQO1, GPX1, HO-1, GST-π, GRP, JNK, and caspase 12 were also determined by quantitative PCR. The interactions between TCM components and Keap-1 were investigated by molecular docking modeling. Results The pathohistological results demonstrated that DD could ameliorate DDC-induced CP in vivo, indicated by reduction of α-SMA, col-1, col-3, TNF-α, and IL-6. DD increased serum levels of GSH and SOD but reduced pancreatic ROS. DD decreased cytoplasmic Keap-1 and increased Nrf2 nuclear localization. Correspondingly, DD increased the expression levels of Nrf2 downstream antioxidant genes NQO1, GPX1, HO-1, and GST-π. DD also decreased ERS hallmarks caspase 12 cleavage and GRP expression. Eventually, DD inhibited PSC activation by reducing JNK phosphorylation and MMK-3/p38 expression. Molecular docking analysis showed that salvianolic acid B and emodin had a good binding affinity toward Keap-1. Conclusions These results demonstrated that DD could ameliorate the oxidative and endoplasmic reticulum stress through releasing Nrf2 from Keap-1 binding and inducing the downstream antioxidant enzymes. As a result, DD could thwart pancreatic fibrosis by inhibiting PSCs activation, which was induced by OS and ERS through JNK and MMK3/p38 pathways.

Comparative study of Danshen and Siwu decoction based on the molecular structures of the components and predicted targets

BackgroundThe sentence of “Danshen (Salvia Miltiorrhizae Radix et Rhizoma) and Siwu decoction are similar in function” was first recorded in an ancient Chinese medical book “Fu Ren Ming Li Lun”. This theory has far-reaching influence on the clinical practice of Chinese medicine and is highly respected by Chinese medical doctors. However, the theory has limitations and controversial part for there is no in-depth and system comparative study.MethodsWe collected the molecular structures of 129 compounds of Danshen and 81 compounds of Siwu decoction from the literatures. MACCS fingerprints and Tanimoto similarity were calculated based on the molecular structures for comparing the structural feature. Molecular descriptors which represent physical and chemical properties were calculated by Discovery Studio. Principal component analysis (PCA) of was performed based on the descriptors. The ADMET properties were predicted by FAF-Drugs4. The effect targets for the compounds with good ADMET properties were confirmed from experimental data and predicted using the algorithm comprising Bernoulli Naive Bayes profiling.ResultsBased on the molecular structures, the presented study compared the structural feature, physical and chemical properties, ADMET properties, and effect targets of compounds of Danshen and Siwu decoction. It is found that Danshen and Siwu decoction do not have the same main active components. Moreover, the 2D structure of compounds from Danshen and Siwu decoction is not similar. Some of the compounds of Danshen and Siwu decoction are similar in 3D structure. The compounds with good ADMET properties of Danshen and Siwu decoction have same predicted targets, but some have different targets.ConclusionsIt can be inferred from the result that Danshen and Siwu decoction have some similarities, but also present differences from each other in the structure of the compounds and predicted targets. This may be the material basis of the similar and different traditional efficacy of Danshen and Siwu decoction. The setence of “ Danshen and Siwu decoction are similar in function. “ which is used in clinical has its material basis and target connotation to some extent. However, the traditional effects of Danshen and Siwu decoction are not exactly the same.

Study on drug properties and syndrome-symptom-formula-herb network of traditional Chinese medicine in treatment of effort angina pectoris based on data visualization

This article aims to explore drug properties and syndrome-symptom-formula-herb network of traditional Chinese medicine(TCM) in the treatment of effort angina pectoris based on data visualization, and provide useful references for clinical diagnosis and treatment. Literatures about TCM formula for effort angina pectoris from databases of CNKI, WanFang, VIP, and CBM were retrieved from the database-building to August 31, 2019. The name of syndromes, symptoms, formulas, and herbs were standardized, and the corresponding databases were established. Frequency, four properties, five flavors, and meridian were analyzed. Visualized syndrome-symptom-formula-herb network relationships were constructed by bioinformatic analysis. A total of 202 formulas were included, and 218 kinds of TCM were involved. There were 56 herbs with the use frequency of more than 10, involving 78 syndromes and 162 symptoms. TCM formulas in the treatment of effort angina pectoris mainly included herbs with effects in invigorating blood circulation and eliminating stasis, tonifying deficiency, Qi-regulating, resolving phlegm and relieving cough and asthma, relieving exterior disorder, and heat-clearing. The main properties were warm, cold and mild(accounting for 95%); the main flavors were sweet, bitter and pungent(accounting for 89%); and meridians were mainly spleen, heart, liver, lung, stomach, and kidney(accounting for 89%). Syndrome-symptom-formula-herb network of TCM in the treatment of effort angina pectoris were successfully constructed. The high-frequency syndromes of this disease were Qi deficiency and blood stasis, Qi stagnation and blood stasis, heart blood stasis, and turbid phlegm and blood stasis, and its high-frequency symptoms were chest tightness, chest pain, palpitation, shortness of breath, fatigue, dark purple tongue, spontaneous sweating, and abundant phlegm. High-frequency core formulas of this disease included Xuefu Zhuyu Decoction, Gualou Xiebai Banxia Decoction, Danshen Decoction, Taohong Siwu Decoction, Shengmai Powder, Buyang Huanwu Decoction and Zhigancao Decoction, and their core herbs included Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Chuanxiong Rhizoma, Ginseng Radix et Rhizoma, Trichosanthis Fructus, Allium Macrostemonis Bulbus, Notoginseng Radix et Rhizoma, Persicae Semen, Carthami Flos, Atractylodis Macrocephalae Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Poria, Pinelliae Rhizoma Praeparatum. Drug properties and syndrome-symptom-formula-herb networks of TCM in the treatment of effort angina pectoris can realize data visualization, objectively reflect the clinical syndrome differentiation and rule of medication, and provide reference for clinical diagnosis and treatment.

Distribution Analysis of Salvianolic Acids in Myocardial Ischemic Pig Tissues by Automated Liquid Extraction Surface Analysis Coupled with Tandem Mass Spectrometry.

The distribution of active compounds of traditional Chinese medicine Salvia miltiorrhiza Bunge (Chinese name: Danshen) in vivo was determined by establishing a liquid extraction surface analysis coupled with the tandem mass spectrometry (LESA-MS/MS) method. Stability analysis and distribution analysis were designed in the present study using normal animals or a myocardial ischemia model. The model assessment was performed four weeks after surgery, and then three groups were created: a normal-dose group, a model-blank group, and a model-dose group. Meanwhile, Danshen decoction administration began in dose groups and lasted for four weeks. In stability analysis, four salvianolic acids—Danshensu (DSS), caffeic acid (CAA), rosmarinic acid (RA), and salvianolic acid A (SAA)—in kidney tissues from the normal-dose group were detected by LESA-MS/MS under four conditions, and then distribution analysis was conducted in different tissues using the same method. Ejection fraction (EF) and fractional shortening (FS) in animals from two model groups decreased significantly four weeks after surgery (P < 0.01) and were improved after four weeks of Danshen decoction administration (P < 0.01). Results of stability analysis demonstrated that this method was basically stable since there were no significant differences in signal intensities of DSS, CAA, and SAA under four conditions (P > 0.05). Distribution analysis showed the signal intensities of DSS in the liver and kidney and SAA in the heart were higher in the model-dose group than in the normal-dose group (P < 0.05 or P < 0.01). Signal intensities of RA in the liver and kidney, and SAA in the liver were lower in the model-dose group compared with the normal-dose group (P < 0.05 or P < 0.01). In conclusion, Danshen decoction has the effect of improving the ischemic condition in a chronic myocardial ischemia model, and the content of two active compounds increased in the targets. These findings contribute to an understanding of the therapeutic role of Danshen in cardiovascular disease.

Metabolomics Analysis Reveals the Protection Mechanism of Huangqi-Danshen Decoction on Adenine-Induced Chronic Kidney Disease in Rats.

Huangqi–Danshen decoction (HDD) is a commonly used drug pair for clinical treatment of chronic kidney disease (CKD) in traditional Chinese medicine with good efficacy. However, the potential mechanisms of this action have not been well elucidated. The aim of this study was to explore the metabolic profiling variations in response to HDD treatment in a CKD rat model. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. The rats in the treatment group received HDD extract orally at the dose of 4.7 g/kg/day during the experiment. At the end of the experiment, serum and kidney samples were collected for biochemical and pathological examination. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) was used to analyze metabolic profiling variations in the kidney. The results showed that treatment with HDD markedly attenuated kidney injury and improved renal function. A total of 28 metabolites contributing to CKD phenotype were found and identified in the kidney samples. The primary metabolic pathways disordered in the kidney of CKD rats were glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, and citrate cycle. Partial least squares discriminant analysis (PLS-DA) score plot showed that the three groups of renal samples were obviously divided into three categories, and the metabolic trajectory of the HDD treatment group moved to the control group. (E)-Piperolein A, phosphatidylcholines (PC) (18:1/22:6), phosphatidylinositols (PI) (13:0/18:1), PI (15:0/20:3), phosphatidylserines (PS) (O-20:0/12:0), and triglyceride (TG) (22:4/24:0/O-18:0) represented potential biomarkers of the renoprotective effects of HDD against CKD. In conclusion, HDD has renoprotective effect against adenine-induced CKD, which may be mediated via partially restoration of perturbed metabolism in the kidney.

Huangqi Danshen decoction attenuates isoproterenol-induced myocardial remodeling via STIM1, TRPC1, CaN and NFATc3 pathways in rats

To investigate the inhibitory effect of Huangqi Danshen decoction (HDD) on isoproterenol (ISO)-induced myocardial remodeling and explore its effect on STIM1, TRPC1, CaN and NFATc3 expressions. ISO (2.5 mg•kg⁻¹•d⁻¹×14 d) was given by subcutaneous injection to establish myocardial remodeling models in rats, and then were randomly divided into control group, ISO model group, HDD5 group (HDD 5 g•kg⁻¹•d⁻¹+ISO), and HDD10 group (HDD 10 g•kg⁻¹•d⁻¹+ISO). After intervention for 4 weeks, the heart mass index (HW/BW) and the left ventricular mass index (LVW/BW) were calculated; the structure of myocardium was observed by echocardiography; the pathological changes of myocardium were observed by HE staining; levels of BNP, CaN and CaM kinases II in serum were detected by ELISA, and the protein expression levels of STIM1, TRPC1, p-CaN, p-NFATc3, and NFATc3 in left ventricular tissues were detected by Western blot. The results showed that the HW/BW and LVW/BW in ISO group were greater than those in HDD5 group and HDD10 group (P<0.05); Echocardiography showed that HDD inhibited ISO-induced increase in LVEDD and LVESD; ELISA results showed that HDD could significantly inhibit the increase of BNP, CaN and CaM kinases II levels in serum of rats with ISO-induced myocardial remodeling (P<0.01). Western blot results showed that STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression levels were increased in the myocardial tissues of ISO group rats, and after HDD administration, the above expression levels were decreased in group ISO, HDD for myocardial tissue after administration of STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression decreased (P<0.05). Our findings indicated that HDD can attenuate the myocardial remodeling induced by ISO, and its mechanism may be related to down-regulating the expression levels of STIM1, TRPC1, CaM kinases II, p-CaN/CaN and p-NFATc3/NFATc3.

Danshen injection prevents heart failure by attenuating post-infarct remodeling

Ethnopharmacological relevanceDanshen Injection (DSI) is a traditional Chinese medicine extracted from Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge. Danshen is an ancient antipyretic traditional Chinese medicine which is mostly used to improve blood circulation and dispel blood stasis. Danshen decoction or liquor-fried Danshen (with grain-based liquor) which is cool in nature is traditionally used to ‘cool the blood’ and reduce the swelling of sores and abscesses. Aim of studyThe present study aimed to examine the effect and mechanism of DSI in LAD induced heart injury. Materials and methodsOne day after LAD surgery, adult male Sprague-Dawley rats were randomized to 3 groups: MI group; DSI group (1.5ml/kg/d, intramuscular); and Valsartan group (10mg/kg/d, intragastric). Echocardiography and hemodynamic measurements (Pressure-Volume loop) were performed to evaluate cardiac function. Pathological methods (Masson, and Sirus red staining) were used to check myocardial fibrosis. Western blotting assay was used to detect the protein expression of MMP-2. RT-PCR was used to detect the gene expression of MMP-9, MPO, iNOS, Bcl-2 and Bax. ResultsDSI administration to LAD rats resulted in improved cardiac functions, hemodynamic parameters and normalized ventricular mass. Furthermore, DSI-treated group demonstrated potential regulation of myocardial collagen I and III deposition associated with MMP-2 expression. Also, DSI administration decreased gene expression of iNOS, MPO and MMP-9, and increased Bcl-2/Bax ratio. ConclusionMyocardial fibrosis, cardiac hypertrophy, hemodynamic deterioration as well as systolic and diastolic dysfunctions which characterize a failing hearts were significantly prevented by DSI. Our study may provide future directions to focus on the anti-hypertrophic mechanisms of DSI and pathological roles played by MMP-2 in myocardial hypertrophy. Meanwhile, DSI also performed the effect of anti-inflammation by the way of decreasing iNOS and MPO. The way Danshen Injection increasing Bcl-2/Bax presented the possibility that it may has the effect of inhibiting cell death.

Establish quality evaluation method based on standard decoction of Danshen extract

The quality of Danshen extract granules on market is largely different from each other mainly due to the heterogeneous quality of raw materials of Salvia miltiorrhiza, various producing procedures and lack of good quality evaluation method. Formula granule and "standard decoction" have the same quality. In this paper, a systematic evaluation method for the quality of Danshen decoction was established from the perspective of "standard decoction", in order to explore the main factors affecting the quality uniformity of Danshen extract granules. Danshen standard decoction was prepared; then the fingerprint method was developed to determine the content of salvianolic acid B; and the main peaks in the fingerprint were identified with UPLC-QTOF/MS to clarify the chemical compositions of Danshen decoction. Three indexes were calculated to evaluate the stability of whole process, including the extraction ratio; transfer rate of index components and pH value. The results showed that the main components of Danshen decoction were phenolic acids, while the extraction rate, the transfer rate of salvianolic acid B and pH value were in a relatively stable level, and the similarity in the fingerprint of standard decoction was high, indicating that the preparation procedure was stable. The level of salvianolic acid B in the standard decoction was in a large range, which was mainly due to the difference in the quality of Salviae Miltiorrhizae Radix et Rhizoma.

The in vivo absorbed constituents and metabolites of Danshen decoction in rats identified by HPLC with electrospray ionization tandem ion trap and time-of-flight mass spectrometry.

Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge, is widely used for the treatment of cardiovascular and cerebrovascular diseases. This research focuses on the in vivo metabolism of Danshen decoction (DSD) in rats. After oral administration of DSD, the absorptive constituents and their metabolites in urine and plasma were analyzed by HPLC coupled with a photodiode array detector and electrospray ionization hybrid ion trap and time-of-flight mass spectrometry. Samples were separated on a C18 column by gradient elution using 0.1% (v/v) aqueous formic acid and acetonitrile. As a result, 93 compounds from urine and 38 compounds from plasma were identified. Among them, lipo-soluble diterpenoids (24 in urine and 15 in plasma) were reported for the first time as in vivo metabolites of DSD. According to the quantities and contents of the identified compounds, tanshinone IIA, cryptotanshinone and tanshinone I were deduced to be the major absorptive diterpenoids of DSD. Moreover, nine water-soluble phenolics (caffeic acid, ferulic acid, danshensu, etc.) were proved to be the major absorptive constituents as reported. Most of the absorbed constituents underwent sulfation, glucuronidation, hydrogenation and hydroxylation in vivo. This investigation provided scientific evidence to obtain a more comprehensive metabolic profile of DSD.