Danshen injection prevents heart failure by attenuating post-infarct remodeling.

ETHNOPHARMACOLOGICAL RELEVANCE: Danshen 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 STUDY: The present study aimed to examine the effect and mechanism of DSI in LAD induced heart injury. MATERIALS AND METHODS: One 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. RESULTS: DSI 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. CONCLUSION: Myocardial 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.

MicroRNA-155: a Novel Armamentarium Against Inflammatory Diseases.

An increasing number of diseases are being newly closely associated with inflammation, where microRNAs seem to play a critical role in the whole disease process from initiation to development. MicroRNAs are small non-coding RNAs that govern gene expression and modulation by means of mRNA degradation or translational repression. After several profound research studies, new correlations between microRNA-155 and inflammation-related diseases are strongly emerging. Hence, we review in this paper the possible molecular mechanisms of microRNA-155 in inflammatory disorders. Furthermore, we also consider the feasibility of targeting it as a bright alternative to improve the early diagnose statistics and treatments in those diseases. MicroRNA-155 features a novel breakthrough in fine-tuning inflammatory responses and, thereby, in treating a wide spectrum of diseases with inflammation as a common denominator.

Danshensu Promotes Cholesterol Efflux in RAW264.7 Macrophages.

Contemporary research suggests that macrophage foam cell and cholesterol efflux defect play pivotal role in atherogenesis. We reported on the heretofore unknown therapeutic effect of Danshensu (DSS) in reducing intracellular cholesterol level and unraveled the mechanism of DSS promotes cholesterol efflux. Oxidized low-density lipoprotein stimulation of Raw264.7 cells into foam cells, which were treated with DSS and co-treated with Simvastatin and Rosiglitazone. PPARγ, ABCA1, ABCG1, SR-BI, CD36, and LXR-α mRNA were quantified by Real-Time PCR. Western blotting was used to determine protein expression of PPARγ, ABCA1 and CD36. Cellular cholesterol handling was studied by measurement of intracellular lipid droplets concentration and cholesterol efflux. DSS significantly reduced scavenger receptor CD36 and its orthologue SR-BI. In addition, DSS stimulated the upregulation of cellular cholesterol exporters ABCA1 and ABCG1 to reduce intracellular lipid accumulation. DSS can reduce lipid deposition in Raw264.7 foam cells by balancing CD36 and ABCA1 protein expression.

Targeting BNIP3 in inflammation-mediated heart failure: a novel concept in heart failure therapy.

Myocardial injury activates inflammatory mediators and provokes the integration of BCL-2/adenovirus E1B 19KD interacting protein 3 (BNIP3) into mitochondrial membranes. Translocation of BNIP3 to mitochondria inexorably causes mitochondrial fragmentation. Heart failure (HF) epitomizes the life-threatening phase of BNIP3-induced mitochondrial dysfunction and cardiomyocyte death. Available data suggest that inflammatory mediators play a key role in cardiac cell demise and have been implicated in the pathogenesis of HF syndrome. In the present study, we reviewed the changes in BNIP3 protein expression levels during inflammatory response and postulated its role in inflammation-mediated HF. We also identified inflammatory mediators' response such as stimulation of TNF-α and NO as potent inducer of BNIP3. Previous studies suggest that the pro-apoptotic protein has a common regulator with IL-1ß and induces IL-6-stimulated cardiac hypertrophy. These findings corroborate our contention that interventions designed to functionally modulate BNIP3 activity during inflammatory-mediated HF may prove beneficial in preventing HF. Such a revelation will open new avenue for further research to unravel a novel therapeutic strategy in HF diseases. Moreover, understanding of the relationship between BNIP3 and inflammatory mediators in HF pathologies will not only contribute to the discovery of drugs that can inhibit inflammation-mediated heart diseases, but also enhance the current knowledge on the key role BNIP3 plays during inflammation.

Anti-Inflammatory Activity of Tanshinone IIA in LPS-Stimulated RAW264.7 Macrophages via miRNAs and TLR4-NF-κB Pathway.

Inflammation is a physiological response to infection or injury and involves the innate and adaptive immune system. Tanshinone IIA (Tan IIA) is a well-known flavonoid that elicits an important therapeutic effect by inhibiting inflammatory response. In this study, we examined whether Tan IIA exerts anti-inflammatory activity and investigated the possible mechanisms, including Toll-like receptor 4 (TLR4)-MyD88-nuclear factor kappa B (NF-κB) signaling pathway and microRNA expression in lipopolysaccharide (LPS)-induced RAW264.7 cells. Tan IIA could attenuate the inflammatory reaction via decreasing cytokine, chemokine, and acute-phase protein production, including GM-CSF, sICAM-1, cxcl-1, MIP-1α, and tumor necrosis factor alpha (TNF-α), analyzed by Proteome profile array in LPS-induced RAW264.7 cells. Concurrently, the messenger RNA (mRNA) expressions of IL-1ß, TNF-α, and COX-2 were also significantly reduced by Tan IIA. Additionally, Tan IIA decreased LPS-induced NF-κB activation and downregulated TLR4 and MyD88 protein expression levels. We also observed reduced microRNA-155, miR-147, miR-184, miR-29b, and miR-34c expression levels, while LPS-induced microRNA-105, miR-145a, miR-194, miR-383, miR-132, and miR-451a expression levels were upregulated using microRNA (miRNA) qPCR array. Our results indicate that Tan IIA could exert an anti-inflammatory effect on LPS-induced RAW264.7 cells by decreasing TLR4-MyD88-NF-κB signaling pathway and regulating a series of cytokine production and miRNA expression.

Possible mechanisms of C-reactive protein mediated acute myocardial infarction.

Myocardial infarction is a relevant cardiovascular event worldwide for morbidity and mortality. It has been theorized that acute myocardial infarctions (AMIs) and other acute coronary events that are precipitated by atherosclerosis are due to arterial blockage from fat deposits. It is now known, however, that atherosclerosis involves more than just lipids. Inflammation has also been studied extensively to play a substantial role in myocardial infarction. There have been debates and conflicting reports over the past few years about the value of assessing levels of C-reactive protein and other biomarkers of inflammation for the prediction of cardiovascular events. Several studies have shown that CRP is not only an inflammatory marker, but also involved in the pathogenesis of myocardial infarction. Studies have linked atherogenesis and rupture of atherosclerotic lesion to endothelial dysfunction. CRP directly inhibits endothelial cell nitric oxide (NO) production via destabilizing endothelial NO synthase (eNOS). Decreased NO release causes CRP mediated inhibition of angiogenesis, stimulating endothelial cell apoptosis. CRP can also activate the complement system through the classical pathway. Complement activation plays an important role in mediating monocyte and neutrophil recruitment in an injured myocardium and may therefore lead to increase in infarct size. This article discusses the possible roles of CRP in complement activation, endothelial dysfunction and its impact on the development of myocardial infarction. We also reviewed the possible therapeutic approaches to myocardial infarction.