Ginsenoside Rg3 alleviates inflammation in a rat model of myocardial infarction via the SIRT1/NF-κB pathway

Abstract

Inflammation serves an important role in myocardial infarction (MI). Ginsenoside Rg3 (Rg3), an activator of sirtuin 1 (SIRT1), has been identified to elicit anti-inflammatory effects via the NF-κB pathway. However, the function of Rg3 in MI remains unknown. In the present study, a MI rat model was established by coronary artery ligation and treated with Rg3 to explore whether Rg3 could inhibit inflammation in MI rats by inhibiting the SIRT1/NF-κB pathway. At 28 days post-MI, it was identified that Rg3 not only decreased the ST-segment ECG values in MI rats, but also significantly decreased serum LDH, CK-MB and cTnI levels in MI rats. In addition, Rg3 also significantly decreased serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 levels and increased serum IL-10 levels in MI rats. In the heart tissues of the MI rats, Rg3 attenuated myocardial pathological changes and cell apoptosis caused by MI, decreased the gene expression levels of TNF-α, IL-1β and IL-6, but increased the gene expression level of IL-10. In addition, the expression levels of the SIRT1 and transcription factor RelB proteins were significantly increased following Rg3 treatment, and the expression level of p-p65/p65 protein was significantly decreased in the heart tissues of MI rats with Rg3 treatment compared with that in heart tissues of MI rats without Rg3 treatment. In conclusion, Rg3 alleviates inflammation in a rat model of MI via the SIRT1/NF-κB pathway.

Keywords: ginsenoside Rg3; inflammation; myocardial infarction; sirtuin 1/NF-κB.

Figure 1

Effect of Rg3 on cardiac function in rats following MI. (A) The values of electrocardiograms in ST segment in different groups of rats at different times. (B-D) 28 days after MI, serum (B) CK-MB, (C) LDH and (D) cTnI levels in different groups of rats. There were 7 rats per group and 3 independent repetitions per measurement. ^***P<0.001 vs. sham group. ^#P<0.05, ^##P<0.01 and ^###P<0.001 vs. MI group. Rg3, Ginsenoside Rg3; MI myocardial infarction; CK-MB, creatine kinase myocardial band; LDH, lactate dehydrogenase; cTnI, cardiac troponin-1.

Figure 2

Effect of Rg3 on pathological changes of heart tissues in rats following MI. (A-D) Hematoxylin & eosin staining was used to observe pathological changes in the heart tissues of the (A) sham, (B) Rg3, (C) MI and (D) Rg3 + MI groups of rats in 28 days after MI. (E-H) The cell apoptosis was measured in the heart tissues of the (E) sham, (F) Rg3, (G) MI and (H) Rg3 + MI groups of rats in 28 days after MI. There were 7 rats per group and 3 independent repetitions per measurement. Scale bar =50 µm. Rg3, Ginsenoside Rg3; MI, myocardial infarction.

Figure 3

Effect of Rg3 on inflammatory factors in heart tissues in rats following MI. (A and B) At 28 days post-MI, the expression levels of TNF-α, IL-1β, IL-6 and IL-10 mRNA in the heart tissues of rats were measured by RT-qPCR, and proteins were measured by western blot. There were 7 rats per group and 3 independent repetitions per measurement. ^*P<0.05, ^**P<0.01 and ^***P<0.001 vs. sham group. ^#P<0.05, ^##P<0.01 and ^###P<0.001 vs. MI group. Rg3, Ginsenoside Rg3; MI, myocardial infarction; TNF-α, tumor necrosis factor α; IL, interleukin.

Figure 4

Effect of Rg3 on serum inflammatory factors in rats following MI. (A-D) At 28 days post-MI, serum (A) TNF-α, (B) IL-1β, (C) IL-6 and (D) IL-10 levels in different groups. There were 7 rats per group and 3 independent repetitions per measurement. ^***P<0.001 vs. sham group. ^###P<0.001 vs. MI group. Rg3, Ginsenoside Rg3; MI, myocardial infarction; TNF-α, tumor necrosis factor α; IL, interleukin.

Figure 5

Effect of Rg3 on the SIRT1/NF-κB pathway of heart tissue in rats following MI. At 28 days post-MI, the expression levels of SIRT1, RelB and p-p65/p65 protein in heart tissues of rats were measured by western blot analysis. There were 7 rats per group and 3 independent repetitions per measurement. ^**P<0.01 and ^***P<0.001 vs. sham group. ^###P<0.001 vs. MI group. Rg3, Ginsenoside Rg3; MI, myocardial infarction; SIRT1, sirtuin 1; RelB, transcription factor RelB; p65, transcription factor p65; p-, phosphorylated.