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.

Fermentation products of Danshen relieved dextran sulfate sodium-induced experimental ulcerative colitis in mice

“…Danshen (Salvia Miltiorrhiza) is a very valuable herb in Chinese traditional medicine. It has been reported that Danshen has the antioxidant, antiin ammatory and antibacterial activities 33 . The anti-in ammation e cacy of Danshen is generally played by the main biological activities in it, such as cryptotanshinone, tanshinone IIA and dihydrotanshinone I 34 .…”

Calycosin as a Novel PI3K Activator Reduces Inflammation and Fibrosis in Heart Failure Through AKT–IKK/STAT3 Axis

“…Rats in the sham group underwent sham surgery, while HF was induced in other rats by direct left anterior descending (LAD) artery ligation as described in our previous study ( Zhang et al, 2018 ). Based on our previous literature ( Zhang et al, 2019 ; Wang et al, 2020a ), 24 h after surgery, the acute myocardial infarction model was established, and the drug treatment was started. Rats in the Cal group were treated with Cal at a dosage of 80 mg/kg per day ( Li et al, 2020 ).…”

“…Nuclear factor kappa-B (NFκB) is a crucial heterodimeric transcription factor in inflammatory responses, which is regulated by the IκB kinase (IKK) complex ( Israël, 2010 ). Studies have shown that the persistently activated NFκB pathway in HF progression mediated the excessive release of various inflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-1 (IL-1) ( Wang et al, 2020a ). Herein, the IKK-NF-κB pathway is believed to be one of the most attractive targets for HF.…”

Modulations of Cardiac Functions and Pathogenesis by Reactive Oxygen Species and Natural Antioxidants

“…This compound has significantly attenuated cardiac dysfunction and injury induced by isoproterenol and enhanced mitochondrial respiratory function [ 220 ]. In addition, it has shown protective effects against inflammatory injury by modulating forming MD2-TLR4-MyD88 complex and TLR4-TRAF6-NF-κB signaling pathway in acute MI rats [ 221 ]. This compound also suppressed L-type Ca 2+ channels, contraction, and Ca 2+ transients in adult rat cardiac myocytes [ 222 ].…”