Berberine up‐regulates miR‐340‐5p to protect myocardial ischaemia/reperfusion from HMGB1‐mediated inflammatory injury

Abstract

Aims Myocardial ischaemia/reperfusion injury (MIRI) is a major cause of heart failure after myocardial infarction. Berberine (BBR) presents anti‐inflammatory and immunosuppressive properties in many diseases. Our research looked into the therapeutic effects and mechanism of BBR in MIRI. Methods and results MIRI animal and cell models were established. The mRNA and protein expressions were assessed using reverse transcription and quantitative real‐time polymerase chain reaction and western blot. The haemodynamic parameters (left ventricular ejection fraction and left ventricular ejection fraction) were detected by echocardiography. The myocardial infarct size and myocardium lesion were assessed by triphenyltetrazolium chloride and haematoxylin–eosin staining. The levels of injury factors were determined by ELISA. Terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling staining was performed to analyse cell apoptosis. Dual luciferase reporter gene and RNA immunoprecipitation assays were carried out to verify the interaction between miR‐340‐5p and HMGB1. BBR administration could improve the haemodynamic parameters and infarct size in MIRI rats (all P < 0.05). In MIRI rat model, BBR reduced cardiomyocyte apoptosis and inflammation (all P < 0.05). BBR could promote miR‐340‐5p expression (0.64 ± 0.21, P < 0.05), which is lowly expressed in MIRI group (0.24 ± 0.10, P < 0.01) in compare with the sham group (0.99 ± 0.01). MiR‐340‐5p knockdown abolished the protective effects of BBR on H/R‐treated cardiomyocytes (all P < 0.05). BBR suppressed the HMGB1/TLR4/NF‐κB pathway activation in MIRI. HMGB1 functioned as the target of miR‐340‐5p, and its silencing reversed the effect of miR‐340‐5p inhibitor on BBR‐treated MIRI. Conclusions In MIRI, BBR repressed HMGB1‐mediated TLR4/NF‐κB signalling pathway through miR‐340‐5p to suppress cardiomyocyte apoptosis and inflammation.

Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1

“…Specifically, our findings reveal that miR-340-5p and miR-281c-5p effectively suppress HMGB1 expression. These miRNAs have been associated with the suppression of tissue inflammation and the reduction of myocardial and neural damage following ischemia [36,37].…”

“…BBR suppressed HMGB1 expression in RCN9 cells (Figure 5B), resulting in approximately a sixfold reduction in HMGB1 concentration in the culture medium (Figure 5C). Moreover, BBR increased the expression of miR-181c-5p [36] and miR-340-5p [37], which are miRNAs known to suppress HMGB1 expression (Figure 5D). Subsequently, we examined HMGB1 expression using miRNA mimics and inhibitors (Figure 5E).…”

METTL3-dependent N6-methyladenosine modification is involved in berberine-mediated neuroprotection in ischemic stroke by enhancing the stability of NEAT1 in astrocytes

“…For example, berberine inhibited the migration and proliferation of endometrial cancer cells by miR-101 [13]. Berberine upregulates miR-340-5p to protect against HMGB1-mediated myocardial ischemia/ reperfusion injury [14]. Above studies suggest that the natural drug berberine is a promising treatment for acute ischemic stroke.…”

Ginkgolic acid promotes inflammation and macrophage apoptosis via SUMOylation and NF-κB pathways in sepsis

“…Once NF-κB is activated, the secretions of a large number of inflammatory cytokines will aggravate secondary damage and induce cell apoptosis in sepsis (13,14). In many disease models, inhibition of NF-κB activation also has been shown to effectively reduce cell apoptosis (8,13,(15)(16)(17). Therefore, NF-κB is considered as an important therapeutic target for sepsis and inflammatory diseases.…”