Shenlian extract attenuates myocardial ischaemia-reperfusion injury via inhibiting M1 macrophage polarization by silencing miR-155

Abstract

Context Shenlian extract (SL) is a combination of Salvia miltiorrhiza Bge. (Labiatae) and Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts, which promote blood circulation and clear endogenous heat toxins. Myocardial ischaemia-reperfusion injury (MI/RI) is aggravated myocardial tissue damage induced by reperfusion therapy after myocardial infarction. Objectives This study explores the effect of SL on MI/RI and the underlying mechanism. Materials and methods Primary peritoneal macrophages (pMACs) were treated with LPS and SL (5, 10 or 20 μg/mL) for 24 h. The myocardial ischaemia-reperfusion (MI/R) model was established after administration of different doses of SL (90, 180 or 360 mg/kg). Myocardial tissue injury was assessed by methylthiazolyl tetrazolium (TTC) staining and levels of creatine kinase (CK), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in mice. The double immunofluorescence staining of iNOS/F4/80 and CD86/F4/80 was used to detect macrophage M1 polarization. The levels of miR-155 , inflammatory factors and chemokines were detected by qRT-PCR or ELISA. CD86, iNOS, SOCS3, JAK2, p-JAK2, STAT3 and p-STAT3 proteins expressions in macrophages were analyzed by western blotting. Conditioned medium transfer systems were designed to unite M1 macrophages with H/R cardiomyocytes, and cell apoptosis was detected by TUNEL staining, western blotting or immunohistochemistry. Results SL reduced apoptosis, diminished CK and LDH levels, raised SOD concentration and decreased infarct size in the MI/R model. Meanwhile, SL decreased miR-155 level, inhibited M1 macrophage polarization and inflammation. Furthermore, SL promoted SOCS3 expression and blocked JAK2/STAT3 pathway in vitro . Conclusions SL may be a promising TCM candidate for MI/RI. The underlying mechanisms could be associated with inhibition of M1 macrophage polarization via down-regulating miR-155 .

Islet-resident macrophage-derived miR-155 promotes β cell decompensation via targeting PDX1

“…In addition, previous studies have revealed that silencing miR-155 can inhibit M1 macrophage polarization that reduces inflammation. 41 , 42 Our work focused on M1 macrophage-derived exosomal miR-155 entering β cells and contributing to β cell dysfunction, in which we neglected the effect of miR-155 sponge on M1 macrophage polarization that might also delay the progression of T2D.…”

The Role of ncRNAs in Cardiac Infarction and Regeneration

“…MCPIP is not only expressed in CMs but plays an essential role in myocardial cells during inflammation after MI by down-regulating miR-155 and NF-κB signaling ( Figure 1 ) [ 45 ]. miR-155 regulates the differentiation and polarization of macrophages through the JAK2/STAT3 signaling pathway, particularly targeting SOC3 ( Figure 1 ) [ 46 , 47 , 48 , 49 , 50 ].…”

The macrophage polarization by miRNAs and its potential role in the treatment of tumor and inflammation (Review)

“…Among them, the miRNAs in macrophage polarization, have received widespread attention from domestic and foreign scholars, and some important progress has been made. First, as a star miRNA, miRNA-155 has been widely studied for its role in macrophage polarization, and many studies so far revealed that miRNA-155 was involved in promoting M1 polarization ( 60 – 65 ), for example, the expression of miRNA-155 was significantly upregulated when macrophages polarized to the M1 phenotype, however, its expression was obviously downregulated when macrophages polarized to M2 phenotype. In addition, silencing miR-155 significantly promoted the polarization of M2 macrophages, and overexpression of miRNA-155 could induce a switch from M2 to M1 phenotype ( 60 ).…”

“…Besides, miR-155-5p can regulate M1 polarization by other pathways, such as SOCS1/NF-κB pathway ( 63 ), and let-7a-5p can also target suppressor of cytokine signaling 1 (SOCS1) to modulate NF-κB, and activate M1 macrophages ( 64 ). Shenlian extract was demonstrated to inhibit the M1 polarization by inhibiting miR-155, upregulating SOCS3 and blocking the JAK2/STAT3 signaling pathway, thereby reducing tissue damage and cell apoptosis ( 65 ). Another literature study on the role of miRNA-155 in macrophage polarization suggested that miR-155 could induce M1 polarization by way of directly targeting the IL13Rα1 (IL-13 receptor α 1, IL13Rα1), which interferes with the activation of STAT6 and indirectly regulates the expression of other M2 related genes ( 66 ).…”