Berberine attenuates myocardial ischemia reperfusion injury by suppressing the activation of PI3K/AKT signaling - PubMed (original) (raw)

Berberine attenuates myocardial ischemia reperfusion injury by suppressing the activation of PI3K/AKT signaling

Zhu Qin-Wei et al. Exp Ther Med. 2016 Mar.

Abstract

Berberine (BBR), an isoquinoline alkaloid originally isolated from the Chinese herb Coptis chinensis (Huanglian), exhibits anti-inflammatory and immunosuppressive properties. Since myocardial ischemia/reperfusion (I/R) injury is associated with an excessive immune response, the current study was conducted to investigate the impact of BBR on myocardial I/R injury, a common disorder in clinical settings. Preconditioning of Sprague-Dawley rats with BBR (100 mg/kg/day, by gavage) for 14 days prior to the induction of I/R significantly attenuated myocardial I/R injury as manifested by a reduction in the incidence of ventricular arrhythmia and the amelioration of myocardial histological changes. These effects were found to be associated with the suppression of the phosphoinositide 3-kinase/AKT signaling pathway and the subsequent reduction of the expression of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in the serum and myocardial tissue. These results indicate that BBR has the potential be an effective alternative therapy for the prevention and treatment of myocardial I/R injury in clinical practice.

Keywords: berberine; inflammation; myocardial ischemia reperfusion injury; phosphoinositide 3-kinase; protein kinase B.

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Figures

Figure 1.

Figure 1.

Histological analysis of myocardial tissues. Representative hematoxylin and eosin (H&E) staining results for myocardial sections in rats of the (A) sham (B) ischemia-reperfusion injury (IRI) and (C) berberine (BBR) groups (magnification, ×200). (D) Semi-quantitative analysis of H&E staining in the rats (n=3 per group). ***P<0.001, ##P<0.01.

Figure 2.

Figure 2.

Administration of BBR inhibited the activation of PI3K/AKT signaling. The phosphorylated proteins were measured by western blotting to assess the activity of p85 and AKT. Representative western blots for (A) p85 and p-p85 and (B) AKT and p-AKT. Quantitative analysis of (C) p-p85 and (D) AKT activities. The relative activity for p85 and AKT was assessed as a ratio between the phosphorylated form and all forms of the protein (n=10 rats/group). ***P<0.001, ##P<0.01; ###P<0.001. BBR, berberine; IRI, ischemia/reperfusion injury; PI3K, phosphoinositide 3-kinase; p, phospho.

Figure 3.

Figure 3.

BBR treatment suppresses I/R-induced cytokine expression in the myocardium. Reverse transcription-quantitative polymerase chain reaction was employed to evaluate the expression of inflammatory cytokines in the myocardial tissue. The expression levels of (A) TNF-α, (B) IL-1β and (C) IL-6 were examined after 4 h of myocardial I/R insult. ***P<0.001, ##P<0.01, #P<0.05. Ten rats were included in each study group. BBR, berberine; I/R, ischemia/reperfusion; IRI, I/R injury; TNF, tumor necrosis factor; IL, interleukin.

Figure 4.

Figure 4.

BBR treatment suppresses IR-induced cytokine expression in the serum. ELISA was employed to assess the expression of inflammatory cytokines in the serum. The expression levels of (A) TNF-α, (B) IL-1β and (C) IL-6 were determined after 4 h myocardial I/R insult. ***P<0.001, ##P<0.01, ###P<0.001. Ten rats were included in each study group. BBR, berberine; I/R, ischemia/reperfusion; IRI, I/R injury; TNF, tumor necrosis factor; Il, interleukin; ELISA, enzyme-linked immunosorbent assay.

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