Exploring the Mechanism of Si-miao-yong-an Decoction in the Treatment of Coronary Heart Disease based on Network Pharmacology and Experimental Verification.

BACKGROUND: To investigate the active ingredients and the mechanisms of Si-miaoyong- an Decoction (SMYA) in the treatment of coronary heart disease (CHD) by using network pharmacology, molecular docking technology, and in vitro validation. METHODS: Through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Uniprot database, GeneCards database, and DAVID database, we explored the core compounds, core targets and signal pathways of the effective compounds of SMYA in the treatment of CHD. Molecular docking technology was applied to evaluate the interactions between active compounds and key targets. The hypoxia-reoxygenation H9C2 cell model was applied to carry out in vitro verification experiments. A total of 109 active ingredients and 242 potential targets were screened from SMYA. A total of 1491 CHD-related targets were retrieved through the Gene- Cards database and 155 overlapping CHD-related SMYA targets were obtained. PPI network topology analysis indicated that the core targets of SMYA in the treatment of CHD include interleukin- 6 (IL-6), tumor suppressor gene (TP53), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), phosphorylated protein kinase (AKT1) and mitogen-activated protein kinase (MAPK). KEGG enrichment analysis demonstrated that SMYA could regulate Pathways in cancer, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxiainducible factor-1(HIF-1) signaling pathway, VEGF signaling pathway, etc. Results: Molecular docking showed that quercetin had a significant binding activity with VEGFA and AKT1. In vitro studies verified that quercetin, the major effective component of SMYA, has a protective effect on the cell injury model of cardiomyocytes, partially by up-regulating expressions of phosphorylated AKT1 and VEGFA. CONCLUSION: SMYA has multiple components and treats CHD by acting on multiple targets. Quercetin is one of its key ingredients and may protect against CHD by regulating AKT/VEGFA pathway.

Qishen granules regulate intestinal microecology to improve cardiac function in rats with heart failure.

Introduction: Qishen Granule (QSG), a clinically approved traditional Chinese medicine, has been researched for treating heart failure (HF) for many years. However, the effect of QSG on intestinal microecology remains unconfirmed. Therefore, this study aimed to elucidate the possible mechanism of QSG regulating HF in rats based on intestinal microecological changes. Methods: A rat model with HF induced by myocardial infarction was prepared by left coronary artery ligation. Cardiac functions were assessed by echocardiography, pathological changes in the heart and ileum by hematoxylin-eosin (HE) and Masson staining, mitochondrial ultrastructure by transmission electron microscope, and gut microbiota by 16S rRNA sequencing. Results: QSG administration improved cardiac function, tightened cardiomyocytes alignment, decreased fibrous tissue and collagen deposition, and reduced inflammatory cell infiltration. Electron microscopic observation of mitochondria revealed that QSG could arrange mitochondria neatly, reduce swelling, and improve the structural integrity of the crest. Firmicutes were the dominant component in the model group, and QSG could significantly increase the abundance of Bacteroidetes and Prevotellaceae_NK3B31_group. Furthermore, QSG significantly reduced plasma lipopolysaccharide (LPS), improved intestinal structure, and recovered barrier protection function in rats with HF. Conclusion: These results demonstrated that QSG was able to improve cardiac function by regulating intestinal microecology in rats with HF, suggesting promising therapeutic targets for HF.

The roles of the mitophagy inducer Danqi pill in heart failure: A new therapeutic target to preserve energy metabolism.

BACKGROUND: Mitophagy can regulate mitochondrial homeostasis, preserve energy metabolism and cardiomyocytes survival effectively to restrain the development of heart failure (HF). Danqi Pill (DQP), composed of the dry roots of Salvia miltiorrhiza Bunge and Panax notoginseng, is included in the 2015 national pharmacopeia and effective in the clinical treatment of coronary heart diseases. Our previous studies have approved that DQP exerted remarkable cardioprotective effects on HF. However, the effect and mechanism of DQP on mitophagy have not been proved yet. HYPOTHESIS/PURPOSE: We aim to explore whether DQP regulates mitophagy to protect against HF and to elucidate the in-depth mechanism. STUDY DESIGN: The HF rat model for evaluating DQP's efficacy was established with left anterior descending coronary artery ligation. The oxygen-glucose deprivation-reperfusion-induced cardiomyocyte model was conducted to clarify the potential mechanism of DQP. METHODS: The mitochondria-targeted fluorescent protein Keima (mt-Keima) was applied for detecting mitophagy flux. Co-immunofluorescence and co-immunoprecipitation were performed to detect protein co-localization. Flow cytometry for JC-1 and Annexin-FITC/PI staining was utilized for assessing mitochondrial activity and function. RESULTS: In vivo, medium dose of DQP (1.5 g/kg) notably improved cardiac function and inhibited cardiac apoptosis in HF rats. Co-immunofluorescent staining of LC3B and TOM20 showed that DQP restored mitophagy. Further co-immunoprecipitation demonstrated that DQP increased the co-localization of FUNDC1 with either ULK1 or PGAM5. In vitro, DQP markedly protected mitochondrial membrane potential damage, reduced cardiomyocytes apoptosis, decreased the level of mitochondrial ROS, and increased the ATP level. Parallel with the in vitro results, DQP increased the interaction of FUNDC1 and LC3B, while knockdown of FUNDC1 diminished the interaction. Besides, Mt-Keima signaling detection further confirmed that DQP significantly promoted mitophagy. Intriguingly, knockdown of ULK1 or PGAM5 separately weakened rather than eliminated these effects of DQP on FUNDC1-mediated mitophagy, mitochondrial homeostasis and energy metabolism. CONCLUSION: Our results demonstrated that DQP protected against HF by improving FUNDC1-mediated mitophagy to perverse energy metabolism through the coordinated regulation of ULK1 and PGAM5.

Mechanistic Insights of Qingre Jiedu Recipe Based on Network Pharmacology Approach against Heart Failure.

Qingre Jiedu (QJ) recipe exerted significant cardioprotective efficacy against heart failure (HF), which is a growing health concern that continues to endanger patients' lives. To investigate the protective properties and mechanism of the QJ recipe, we established hydrogen peroxide (H2O2)-induced H9C2 cells and HF rats. The predicted targets and significant pathways of QJ against HF were collected and screened based on network pharmacology from key ingredients and validated by in vivo and in vitro experiments. The decoction of QJ (0.823 g/kg/day) was intragastrically administered for four weeks. QJ (400 µg/mL) was cultured with H2O2 stimulated in the H9C2 cells. A total of 31 effective active compounds were screened in QJ and covered 277 targets, of which 85 were shared with HF-related targets. In vivo, the QJ recipe remarkably protected heart function and reduced serum IL-1, IL-6, PIIINP, and CIV levels. Furthermore, QJ downregulated the key proteins mediating inflammatory responses (p-IKKα/ß, p-NFκB, and IL-6) and cardiac fibrosis (STAT3 and MMP-9). In vitro, QJ protected the cardiomyocytes against H2O2-stimulated reactive oxygen species (ROS) production and upregulated PI3K and AKT expressions. Further experiments demonstrate that PI3K inhibitor LY294002 remarkably compromised the effects of QJ. In conclusion, our findings indicate that QJ could exert a cardioprotective effect and inhibit fibrosis and inflammation in HF rats via the PI3K-AKT signaling pathway.

Identification of Potential Bioactive Ingredients and Mechanisms of the Guanxin Suhe Pill on Angina Pectoris by Integrating Network Pharmacology and Molecular Docking.

The Guanxin Suhe pill (GSP), a traditional Chinese medicine, has been widely used to treat angina pectoris (AP) in Chinese clinical practice. However, research on the bioactive ingredients and underlying mechanisms of GSP in AP remains scarce. In this study, a system pharmacology approach integrating gastrointestinal absorption (GA) evaluation, drug-likeness (DL) evaluation, target exploration, protein-protein-interaction analysis, Gene Ontology (GO) enrichment analysis, network construction, and molecular docking was adopted to explore its potential mechanisms. A total of 481 ingredients from five herbs were collected, and 242 were qualified based on GA and DL evaluation. Target exploration identified 107 shared targets between GSP and AP. Protein-protein interaction identified VEGFA (vascular endothelial growth factor A), TNF (tumor necrosis factor), CCL2 (C-C motif chemokine ligand 2), FN1 (fibronectin 1), MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), IL10 (interleukin 10), CXCL8 (C-X-C motif chemokine ligand 8), IL6 (interleukin 6), and INS (insulin) as hub targets for GSP, which were involved in the inflammatory process, ECM proteolysis, glucose metabolism, and lipid metabolism. GO enrichment identified top pathways in the biological processes, molecular functions, and cell components, explaining GSP's potential AP treatment mechanism. Positive regulation of the nitric oxide biosynthetic process and the response to hypoxia ranked highest of the biological processes; core targets that GSP can regulate in these two pathways were PTGS2 and NOS2, respectively. Molecular docking verified the interactions between the core genes in the pathway and the active ingredients. The study lays a foundation for further experimental research and clinical application.

Calycosin attenuates doxorubicin-induced cardiotoxicity via autophagy regulation in zebrafish models.

Anthracyclines are highly effective chemotherapeutics for antineoplastic treatment. However, cumulative cardiotoxicity is the main side effect with poor prognosis. No mechanism-based therapy is currently available to reverse chronic anthracycline-induced cardiotoxicity (AIC) after the deterioration of cardiac function. Calycosin (CA) is the main compound extracted from the traditional Chinese medicine Astragalus, and it has diverse beneficial effects, including autophagy modulation, anti-inflammatory and anti-tumor effects. Autophagy dysregulation is an important pathological event in AIC. Our study demonstrated a cardioprotective effect of CA in a zebrafish embryonic AIC model. To assess the effect of CA on late-onset chronic AIC, adult zebrafish were treated with CA 28 days after doxorubicin (DOX) injection, at which point heart function was obviously impaired. The results demonstrated that DOX blocked autophagic activity in adult zebrafish 8 weeks post-injection, and CA treatment improved heart function and restored autophagy. Further in vitro experiments demonstrated that atg7, which encodes an E1-like activating enzyme, may play an essential role in the CA regulation of autophagy. In conclusion, we used a rapid pharmacological screening system in embryo-adult zebrafish in vivo and elucidated the mechanism of gene targeting in vitro.

Multitarget Effects of Danqi Pill on Global Gene Expression Changes in Myocardial Ischemia.

Danqi pill (DQP) is a widely prescribed traditional Chinese medicine (TCM) in the treatment of cardiovascular diseases. The objective of this study is to systematically characterize altered gene expression pattern induced by myocardial ischemia (MI) in a rat model and to investigate the effects of DQP on global gene expression. Global mRNA expression was measured. Differentially expressed genes among the sham group, model group, and DQP group were analyzed. The gene ontology enrichment analysis and pathway analysis of differentially expressed genes were carried out. We quantified 10,813 genes. Compared with the sham group, expressions of 339 genes were upregulated and 177 genes were downregulated in the model group. The upregulated genes were enriched in extracellular matrix organization, response to wounding, and defense response pathways. Downregulated genes were enriched in fatty acid metabolism, pyruvate metabolism, PPAR signaling pathways, and so forth. This indicated that energy metabolic disorders occurred in rats with MI. In the DQP group, expressions of genes in the altered pathways were regulated back towards normal levels. DQP reversed expression of 313 of the 516 differentially expressed genes in the model group. This study provides insight into the multitarget mechanism of TCM in the treatment of complex diseases.

QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p53 signaling pathway.

The ancient traditional Chinese medicine Qishenkeli (QSKL) is widely used in the treatment of heart failure (HF) in China. Previous studies have shown that QSKL has definite effects on HF. The purpose of this study is to identify the regulation of QSKL on apoptosis and clarify the underlying mechanism. An apoptosis model of H9C2 cells was induced by oxygen-glucose deprivation/recovery (OGD/R). An animal model of HF was induced by ligation of left anterior descending (LAD) coronary artery in rat. We found that QSKL reduced intracellular ROS generation, increased mitochondrial membrane potential and protected H9C2 cells against OGD/R-induced apoptosis. In vivo results showed that QSKL administration could improve cardiac functions, decrease fibrotic area, infarct size and apoptotic rate in HF model. QSKL regulated the expressions of key apoptotic molecules, including increasing Bcl-2/Bax ratio, reducing the expressions of P53, Bax and Cleaved-caspase-3. Interestingly, QSKL also regulated the phosphorylated expressions of PI3K and Akt without significantly affecting PTEN. Taken together, the protective and anti-apoptotic effects of QSKL could be mediated partly through modulating the PI3K/Akt-P53 apoptotic pathway.

A Review of Chinese Herbal Medicine for the Treatment of Chronic Heart Failure.

Heart failure is one of the major causes of mortality worldwide and it is the end stage of several cardiovascular diseases. Traditional Chinese medicine has been used in the management of heart failure for a long time. Only until recently, well-designed clinical trials have been put into practice to study the efficacies of Chinese herbs. Extensive studies have also been carried out to explore the underlying mechanisms of pharmaceutical actions of Chinese herbs. In this study, we will summarize the frequently used Chinese herbs, formulae and patent Chinese drugs in treating patients with heart failure and review published clinical evaluations of Chinese herbs in treating cardiovascular diseases. The mechanisms by which Chinese herbs exert cardio-protective effects will also be reviewed. In the end, we will point out the limitations of current studies and challenges facing modernization of traditional Chinese medicine.

Cardioprotective effects of Qishen Granule () on sarcoplasmic reticulum Ca2+ handling in heart failure rats.

OBJECTIVE: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Ca2+ handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms. METHODS: HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca2+ concentration and sarco-endoplasmic reticulum ATPase 2a (SERCA2a) activity were detected by specifific assay kits. Expressions of the critical regulators in SR Ca2+ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. RESULTS: HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca2+ release-uptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca2+ level. QSG prevented defective Ca2+ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca2+ uptake by up-regulating expression and activity of SERCA2a and promoting phosphorylation of phospholamban. CONCLUSION: QSG restored SR Ca2+ cycling in HF rats and served as an ideal alternative drug for treating HF.

Multipronged Therapeutic Effects of Chinese Herbal Medicine Qishenyiqi in the Treatment of Acute Myocardial Infarction.

Background: Based on global gene expression profile, therapeutic effects of Qishenyiqi (QSYQ) on acute myocardial infarction (AMI) were investigated by integrated analysis at multiple levels including gene expression, pathways involved and functional group. Methods: Sprague-Dawley (SD) rats were randomly divided into 3 groups: Sham-operated, AMI model (left anterior descending coronary artery ligation) and QSYQ-treated group. Cardiac tissues were obtained for analysing digital gene expression. Sequencing and transcriptome analyses were performed collaboratively, including analyses of differential gene expression, gene co-expression network, targeted attack on network and functional grouping. In this study, a new strategy known as keystone gene-based group significance analysis was also developed. Results: Analysis of top keystone QSYQ-regulated genes indicated that QSYQ ameliorated ventricular remodeling (VR), which is an irreversible process in the pathophysiology of AMI. At pathway level, both well-known cardiovascular diseases and cardiac signaling pathways were enriched. The most remarkable finding was the novel therapeutic effects identified from functional group analysis. This included anti-inflammatory effects mediated via suppression of arachidonic acid lipoxygenase (LOX) pathway and elevation of nitric oxide (NO); and amelioration of dyslipidaemia mediated via fatty acid oxidation. The regulatory patterns of QSYQ on key genes were confirmed by western blot, immunohistochemistry analysis and measurement of plasma lipids, which further validated the therapeutic effects of QSYQ proposed in this study. Conclusions: QSYQ exerts multipronged therapeutic effects on AMI, by concurrently alleviating VR progression, attenuating inflammation induced by arachidonic acid LOX pathway and NO production; and ameliorating dyslipidaemia.

The effect of Chinese herbs and its effective components on coronary heart disease through PPARs-PGC1α pathway.

BACKGROUND: DanQi pill (DQP) is prescribed widely in China and has definite cardioprotective effect on coronary heart disease. Our previous studies proved that DQP could effectively regulate plasma levels of high density lipoprotein (HDL) and low density lipoprotein (LDL). However, the regulatory mechanisms of DQP and its major components Salvianolic acids and Panax notoginseng saponins (DS) on lipid metabolism disorders haven't been comprehensively studied so far. METHODS: Rat model of coronary heart disease was induced by left anterior descending (LAD) artery ligation operations. Rats were divided into sham, model, DQP treated, DS treated and positive drug (clofibrate) treated groups. At 28 days after surgery, cardiac functions were assessed by echocardiography. Expressions of transcription factors and key molecules in energy metabolism pathway were measured by reverse transcriptase polymerase chain reaction or western blotting. RESULTS: In ischemic heart model, cardiac functions were severely injured but improved by treatments of DQP and DS. Expression of LPL was down-regulated in model group. Both DQP and DS could up-regulate the mRNA expression of LPL. Membrane proteins involved in lipid transport and uptake, such as FABP4 and CPT-1A, were down-regulated in ischemic heart tissues. Treatment with DQP and DS regulated lipid metabolisms by up-regulating expressions of FABP4 and CPT-1A. DQP and DS also suppressed expression of cytochrome P450. Furthermore, transcriptional factors, such as PPARα, PPARγ, RXRA and PGC-1α, were down-regulated in ischemic model group. DQP and DS could up-regulate expressions of these factors. However, DS showed a better efficacy than DQP on PGC-1α, a coactivator of PPARs. Key molecules in signaling pathways such as AKT1/2, ERK and PI3K were also regulated by DQP and DS simultaneously. CONCLUSIONS: Salvianolic acids and Panax notoginseng are the major effective components of DanQi pill in improving lipid metabolism in ischemic heart model. The effects may be mediated by regulating transcriptional factors such as PPARs, RXRA and PGC-1α.

Qishen granules inhibit myocardial inflammation injury through regulating arachidonic acid metabolism.

Qishen granules (QSG), a traditional Chinese medicine, have been prescribed widely in the treatment of coronary heart diseases. Previous studies demonstrated that QSG had anti-inflammatory and cardio-protective effects in mice with acute myocardial infarction (AMI). However, the mechanisms by which QSG attenuate inflammation and prevent post-AMI heart failure (HF) are still unclear. In this study, we explored the anti-inflammatory mechanisms of QSG by in vitro and in vivo experiments. A novel inflammatory injury model of H9C2 cells was induced by lipopolysaccharide (LPS)-stimulated macrophage-conditioned media (CM). An animal model of AMI was conducted by ligation of left anterior descending (LAD) coronary artery in mice. We found that QSG inhibited release of cytokines from LPS-stimulated RAW 264.7 macrophages and protected H9C2 cardiac cells against CM-induced injury. In vivo results showed that QSG administration could improve cardiac functions and alter pathological changes in model of AMI. QSG regulated multiple key molecules, including phospholipases A2 (PLA2), cyclooxygenases (COXs) and lipoxygenases (LOXs), in arachidonic acid metabolism pathway. Interestingly, QSG also targeted TNF-α-NF-κB and IL-6-JAK2-STAT3 signaling pathways. Taken together, QSG achieve synergistic effects in mitigating post-AMI HF by regulating multiple targets in inflammatory pathways. This study provides insights into anti-inflammatory therapeutics in managing HF after AMI.

Metabolomic profiling reveals distinct patterns of tricarboxylic acid disorders in blood stasis syndrome associated with coronary heart disease.

OBJECTIVE: To investigate the underlying metabolomic profifiling of coronary heart disease (CHD) with blood stasis syndrome (BSS). METHODS: CHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group (n=9) and a control group (n=6), respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter (LVED), left ventricular end-diastolic diameter (LVEDd), ejection fraction (EF), fractional shortening (FS) and other indicators. Gas chromatography coupled with mass spectrometry (GC-MS) and bioinformatics were applied to analyze spectra of CHD plasma with BSS. RESULTS: The results of hemorheology analysis showed signifificant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased signifificantly (P <0.05). The echocardiograph results demonstrated that cardiac EF and FS showed signifificant difference (P <0.05), with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters. CONCLUSIONS: Glucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classifification of CHD with BSS.

Qishenyiqi Dropping Pill attenuates myocardial fibrosis in rats by inhibiting RAAS-mediated arachidonic acid inflammation.

ETHNOPHARMACOLOGICAL SIGNIFICANCE: In China, Qishenyiqi Dropping Pill (QSDP), a Chinese medicine formula containing Astragalus membranaceus (Fisch.) Bunge, Salvia miltiorrhiza Bunge, Panax notoginseng (Burkill) F.H.Chen and Dalbergia odorifera T.C.Chen, has been used frequently in traditional folk medicine for treatment of coronary heart diseases (CHD) and heart failure (HF). AIM OF STUDY: Previous study has shown that QSDP has definite therapeutic effects on promoting the heart function on CHD patients. The present study was designed to study the anti-fibrosis effects of QSDP on HF rats and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: HF rat model was induced by left anterior descending (LAD) coronary artery ligation. Two-dimensional (2D) echocardiography was adopted to evaluate heart functions. Immunohistochemical (IHC) method and Western-blot were used to detect expression of critical proteins in renin-angiotensin-aldosterone system (RAAS) or arachidonic acid (AA) metabolic pathway. RESULTS: Heart functions were seriously injured in the model group. Expressions of fibrotic markers, such as collagen Ⅰ, collagen Ⅲ, matrix metallopeptidase 2 (MMP2) and MMP9 were elevated in the model group. RAAS pathway was activated. Interestingly, AA pathway was also up-regulated in the model group and it was down-regulated by angiotensin converting enzyme inhibitors (ACEIs) drug Captopril. Expressions of the important signal-transuding proteins, including NF-κB, JAK1/STAT3 and Akt, all increased remarkably in the model group. Treatment with QSDP could attenuate myocardial fibrosis by inhibiting RAAS-activated pathway, as indicated by decreased angiotensin type 1 receptor (AT1) and increased AT2 expression. Expressions of phospholipase A2 (PLA2), cyclooxygenase 1 (COX1) and COX2 were also down-regulated in the QSDP-treated group. In addition, "therapeutic" QSDP administration seemed to down-regulate expressions of NF-κB, JAK1/ STAT3 and Akt which may play important roles in myocardial fibrosis. CONCLUSION: QSDP can exert anti-fibrosis effect by down-regulating RAAS pathway, and subsequently inhibiting expressions of proteins in AA pathway.

Mechanism of QSYQ on anti-apoptosis mediated by different subtypes of cyclooxygenase in AMI induced heart failure rats.

BACKGROUND: Qi-shen-yi-qi (QSYQ), one of the most well-known traditional Chinese medicine (TCM) formulas, has been shown to have cardioprotective effects in rats with heart failure (HF) induced by acute myocardial infarction (AMI). However, the mechanisms of its therapeutic effects remain unclear. In this study, we aim to explore the mechanisms of QSYQ in preventing left ventricular remodelling in rats with HF. The anti-apoptosis an anti-inflammation effects of QSYQ were investigated. METHODS: Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham group, model group, QSYQ treatment group and aspirin group. Heart failure model was induced by ligation of left anterior descending (LAD) coronary artery. 28 days after surgery, hemodynamics were detected. Echocardiography was adopted to evaluate heart function. TUNEL assay was applied to assess myocardial apoptosis rates. Protein expressions of cyclooxygenase1 and 2 (COX1and COX2), Fas ligand (FasL), P53 and MDM2 were measured by western-blot. RT-PCR was applied to detect expressions of our subtype receptors of PGE2 (EP1, 2, 3, and 4). RESULTS: Ultrasonography showed that EF and FS values decreased significantly and abnormal hemodynamic alterations were observed in model group compared to sham group. These indications illustrated that HF models were successfully induced. Levels of inflammatory cytokines (TNF-α and IL-6) in myocardial tissue were up-regulated in the model group as compared to those in sham group. Western-blot analysis showed that cyclooxygenase 2, which is highly inducible by inflammatory cytokines, increased significantly. Moreover, RT-PCR showed that expressions of EP2 and EP4, which are the receptors of PGE2, were also up-regulated. Increased expressions of apoptotic pathway factors, including P53 and FasL, might be induced by the binding of PGE2 with EP2/4. MDM2, the inhibitor of P53, decreased in model group. TUNEL results manifested that apoptosis rates of myocardial cells increased in the model group. After treatment with QSYQ, expressions of inflammatory factors, including TNF-α, IL-6 and COX2, were reduced. Expressions of EP2 and EP4 receptors also decreased, suggesting that PGE2-mediated apoptosis was inhibited by QSYQ. MDM2 was up-regulated and P53 and FasL in the apoptotic pathway were down-regulated. Apoptosis rates in myocardial tissue in the QSYQ group decreased compared with those in the model group. CONCLUSIONS: QSYQ exerts cardiac protective efficacy mainly through inhibiting the inflammatory response and down-regulating apoptosis. The anti-inflammatory and anti-apoptosis efficacies of QSYQ are probably achieved by inhibition of COXs-induced P53/FasL pathway. These findings provide experimental evidence for the beneficial effects of QSYQ in the clinical application for treating patients with HF.