Cinnamic Acid Reduces Inflammation and Apoptosis in Necrotizing Enterocolitis

Necrotizing enterocolitis is characterized by an inflammatory condition in the intestine that could result in intestinal necrosis and cell death. Cinnamic acid, an unsaturated carboxylic acid, possesses anti-inflammatory capacity. However, the regulatory role of cinnamic acid on necrotizing enterocolitis has not been investigated yet. To this end, human fetal colon cells were incubated with increasing concentrations of lipopolysaccharides to establish a necrotizing enterocolitis cell model. Data from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis showed that lipopolysaccharides, in a dosage-dependent manner, reduced cell viability of fetal human colon cells. Also, cinnamic acid prevented the cytotoxic effect of lipopolysaccharides on fetal human colon cells and increased the cell viability. Furthermore, cinnamic acid attenuated lipopolysaccharides-induced decrease in interleukin-10 and increase in interleukin-6 and tumor necrosis factor-a caused by lipopolysaccharides. The lipopolysaccharides-induced increase in cell apoptosis in fetal human colon cells was accompanied with upregulated B-cell lymphoma 2 protein-associated X protein and downregulated B-cell lymphoma 2 protein. These changes were reversed by cinnamic acid treatment. Lastly, expression of protein for suppressor of cytokine signaling 3 was reduced, while phosphorylation of Janus kinase 2 and signal transducers and activators of transcription 3 were enhanced in lipopolysaccharides-induced fetal human colon cells. Once again, cinnamic acid reversed the expression of suppressor of cytokine signaling 3, phospho- Janus kinase 2, and phospho-signal transducers and activators of transcription 3 in lipopolysaccharides-induced fetal human colon cells. In conclusion, cinnamic acid exerted antiapoptotic and anti-inflammatory effects and protected enterocytes against necrotizing enterocolitis through regulation of signal transducers and activators of transcription-mediated Janus kinase 2/signal transducers and activators of transcription 3 pathway. Keywords: Apoptosis, Cinnamic acid, Inflammation, JAK2/STAT3, Necrotizing enterocolitis, SOCS3 Abbreviations Used: Bcl-2-associated X protein, Bax; B-cell lymphoma 2 protein, Bcl-2; Dulbecco's modified eagle medium, DMEM; Enhanced chemiluminescence, ECL; Enzyme-linked immunosorbent assay, ELISA; Fetal human colon cells, FHC; Horse radish peroxidase, HRP; Interleukin-10, IL-10; lnterleukin-6, IL-6; Janus kinase 2, JAK2; 3-(4,5-dimethylthia