Abstract
The present study aimed to investigate the cardioprotective role of berberine in sepsis-induced cardiac dysfunction and consider the underlying mechanisms. C57BL/6J mice were randomized into four groups, namely, Control, lipopolysaccharide (LPS), LPS + berberine and LPS + Nω-nitro-L-arginine methyl ester (L-NAME) + berberine. A single dose (10 mg/kg body weight) of LPS was intraperitoneally administered to mice to induce cardiac dysfunction, whereas the Control group was administered with an equivalent volume of saline. In the LPS + berberine and LPS + L-NAME + berberine group, berberine (10 mg/kg body weight) dissolved in hot water was intraperitoneally administered 30 min after the LPS treatment. In the LPS + L-NAME + berberine group, L-NAME (100 mg/kg body weight) dissolved in saline was intraperitoneally administered 30 min before the LPS treatment. Then, ~6 h after the LPS treatment, a significant decrease was observed in the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Meanwhile, the plasma myocardial injury markers, inflammatory factors and oxidative stress levels were significantly increased in the LPS group compared with the Control group. The administration of berberine improved the ventricular function and decreased the plasma myocardial injury markers, inflammatory factors and oxidative stress levels. In addition, it increased the heart total nitric oxide synthase (NOS) activity and upregulated the protein expressions of p-Akt and phosphorylated endothelial (e)NOS, which indicated that the Akt/eNOS pathway was activated by berberine. However, the cardioprotective effects of berberine were counteracted by L-NAME, an NOS inhibitor, which inhibited the eNOS activity. In conclusion, berberine attenuated sepsis-induced cardiac dysfunction by upregulating the Akt/eNOS pathway in mice.