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Experimental and therapeutic medicine

Berberine ameliorates neonatal necrotizing enterocolitis by activating the phosphoinositide 3-kinase/protein kinase B signaling pathway.


PMID 29545879

Abstract

Neonatal necrotizing enterocolitis (NEC) is a severe acquired disease that predominantly affects the small intestine of neonates. NEC is caused by a combination of metabolic products, dysfunctions of the blood vessels, mucus and other unknown factors. Berberine may induce beneficial effects on necrotic and cardiovascular diseases due to its anti-inflammatory and anti-apoptotic effects on epithelial cells. In the present study, the therapeutic effects of berberine were investigated and the potential mechanisms by which it functions within a neonatal NEC mouse model were analyzed. Inflammation and levels of associated factors were measured in the serum of mice with NEC prior to and following treatment with berberine. Apoptotic rates in epithelial cells were analyzed following treatment with berberine. The expression of genes associated with apoptosis and apoptosis signaling were determined in epithelial cells in the small intestines of mice with NEC following treatment with berberine. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was investigated in epithelial cells isolated from mice following treatment with either berberine or PBS. Histology and immunohistochemistry were used to determine the area of infarction and apoptosis. Body weight and food intake were measured to evaluate the physical effects of berberine on mice with NEC. The results indicated that berberine attenuated the inflammation caused by NEC in mice after 10 days of treatment. The apoptosis rate of epithelial cells isolated from experimental mice was decreased following berberine treatment. Western blot analysis indicated that the expression of the anti-apoptotic genes c-Myc and p53 were upregulated by berberine, whereas caspase-3 and -9 levels were downregulated in epithelial cells following treatment with berberine. In addition, the expression and phosphorylation levels of PI3K and AKT were downregulated in epithelial cells following treatment with berberine. An in vitro assay indicated that treatment with PI3K alone increased the expression of AKT and promoted the apoptosis of epithelial cells. Treatment with berberine markedly increased epidermal growth factor (EGF) and Bcl-2 expression levels, the activity of epithelial cells and decreased the infarction area of the small intestine. Accordingly, the body weight and food intake of mice with NEC were increased following berberine treatment. Therefore, the results of the present study demonstrate that berberine inhibits inflammation and apoptosis via the PI3K/AKT signaling pathway and may therefore attenuate the progression of NEC. These results suggest that berberine may be a potential therapeutic agent for the treatment of patients with NEC.