Journal Article

Danshen (Salvia miltiorrhiza) restricts MD2/TLR4‐MyD88 complex formation and signalling in acute myocardial infarction‐induced heart failure

Li, Chun, Qiu, Qi, Li, Weili, Wang, Qiyan, Zhang, Qian, Guo, Dongqing, Wang, Yong, Wang, Xiaoping, Jiang, Yanyan

2020

Overview

Heart failure (HF) represents a major public health burden. Inflammation has been shown to be a critical factor in the progression of HF, regardless of the aetiology. Disappointingly, the majority of clinical trials targeting aspects of inflammation in patients with HF have been largely negative. Many clinical researches demonstrate that danshen has a good efficacy on HF, and however, whether danshen exerts anti‐inflammatory effects against HF remains unclear. In our study, the employment of a water extracted and alcohol precipitated of danshen extract attenuated cardiac dysfunction and inflammation response in acute myocardial infarction‐induced HF rats. Transcriptome technique and validation results revealed that TLR4 signalling pathway was involved in the anti‐inflammation effects of danshen. In vitro, danshen reduced the release of inflammatory mediators in LPS‐stimulated RAW264.7 macrophage cells. Besides, the LPS‐stimulated macrophage conditioned media was applied to induce cardiac H9C2 cells injury, which could be attenuated by danshen. Furtherly, knock‐down and overexpression of TLR4 were utilized to confirm that danshen ameliorated inflammatory injury via MyD88‐dependent TLR4‐TRAF6‐NF‐κB signalling pathway in cardiomyocytes. Furthermore, by utilizing co‐immunoprecipitation, danshen was proved to suppress MD2/TLR4 complex formation and MyD88 recruitment. In conclusion, our results demonstrated that danshen ameliorates inflammatory injury by controlling MD2/TLR4‐MyD88 complex formation and TLR4‐TRAF6‐NF‐κB signalling pathway in acute myocardial infarction‐induced HF.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: acute myocardial infarction / Animals / Biomarkers / Cardiomyocytes / Clinical trials / Congestive heart failure / Culture Media, Conditioned - pharmacology / Danshen / Drug dosages / Drug Evaluation, Preclinical / Gene expression / Heart attacks / Heart failure / Heart Failure - drug therapy / Heart Failure - genetics / Heart Failure - prevention & control / Immunoprecipitation / Inflammation / Kinases / Lipopolysaccharides / Lymphocyte Antigen 96 - antagonists & inhibitors / Lymphocyte Antigen 96 - physiology / Macrophages / Macrophages - metabolism / Mice / Multiprotein Complexes - drug effects / MyD88 protein / Myeloid Differentiation Factor 88 - antagonists & inhibitors / Myeloid Differentiation Factor 88 - physiology / Myocardial infarction / Myocardial Infarction - complications / Myocarditis - prevention & control / Myocytes, Cardiac - drug effects / Myocytes, Cardiac - metabolism / NF-κB protein / Original / Phytotherapy / Plant Extracts - isolation & purification / Plant Extracts - therapeutic use / Public health / Quality control / Rats / Rats, Sprague-Dawley / RAW 264.7 Cells / Recombinant Proteins - metabolism / RNA, Small Interfering - genetics / RNA, Small Interfering - pharmacology / Salvia miltiorrhiza - chemistry / Signal transduction / Signal Transduction - drug effects / Signal Transduction - genetics / Specific Pathogen-Free Organisms / TLR4 / TLR4 protein / Toll-Like Receptor 4 - antagonists & inhibitors / Toll-Like Receptor 4 - physiology / Toll-like receptors / Traditional Chinese medicine / TRAF6 protein / Transcriptome - drug effects / Transcriptomes / Tumor necrosis factor-TNF / Ventricular Dysfunction, Left - etiology / Ventricular Dysfunction, Left - prevention & control