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

Abstract

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.

• Authors: Xiaoping Wang, Dongqing Guo, Weili Li, Qian Zhang, Yanyan Jiang, Qiyan Wang, Chun Li, Qi Qiu, Yong Wang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 18 Pg. 10677-10692 (09 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32757377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Culture Media, Conditioned
• Lymphocyte Antigen 96
• Multiprotein Complexes
• Myd88 protein, rat
• Myeloid Differentiation Factor 88
• Plant Extracts
• RNA, Small Interfering
• Recombinant Proteins
• Tlr4 protein, rat
• Toll-Like Receptor 4

Topics

• Animals
• Biomarkers
• Culture Media, Conditioned (pharmacology)
• Drug Evaluation, Preclinical
• Heart Failure (drug therapy, genetics, prevention & control)
• Lymphocyte Antigen 96 (antagonists & inhibitors, physiology)
• Macrophages (metabolism)
• Mice
• Multiprotein Complexes (drug effects)
• Myeloid Differentiation Factor 88 (antagonists & inhibitors, physiology)
• Myocardial Infarction (complications)
• Myocarditis (prevention & control)
• Myocytes, Cardiac (drug effects, metabolism)
• Phytotherapy
• Plant Extracts (isolation & purification, therapeutic use)
• RAW 264.7 Cells
• RNA, Small Interfering (genetics, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (metabolism)
• Salvia miltiorrhiza (chemistry)
• Signal Transduction (drug effects, genetics)
• Specific Pathogen-Free Organisms
• Toll-Like Receptor 4 (antagonists & inhibitors, physiology)
• Transcriptome (drug effects)
• Ventricular Dysfunction, Left (etiology, prevention & control)