Anti-inflammatory effects of oridonin on an in vitro model using LPS-treated human intestinal Caco-2 cells.

Oridonin (Ori) attenuates dextran sulfate sodium-induced ulcerative colitis (UC) in mice, and its underlying mechanism involves the sirtuin 1 (SIRT1)/NF-κB/p53 pathway. In the present study, lipopolysaccharide (LPS)-stimulated Caco-2 cells were used as an in vitro model to mimic human intestinal epithelial inflammation, to ascertain the anti-inflammatory effects of Ori on a cell model of UC. The concentrations of TNF-α and IL-1β were quantified using ELISA, the expression levels of SIRT1, NF-κB and p53 were assessed through western blot analysis, and cell viability was determined using the Cell Counting Kit-8. The results showed that cell viability was affected by treatment with Ori at different doses. Ori significantly inhibited the optical density values in a dose-dependent manner at the doses of 5.0-80.0 µM whereas it did not affect viability at the doses of 0.625-2.50 µM, compared with in the control group. These findings suggested that the inhibitory effect of Ori on intestinal epithelial cells did not result from cytotoxic action at the doses of 0.625-2.50 µM. Furthermore, Ori suppressed the inflammatory response in intestinal epithelial cells by significantly reducing LPS-induced secretion of the pro-inflammatory cytokines TNF-α and IL-1β with a ~2-fold reduction. Additionally, Ori significantly increased the protein expression levels of SIRT1, and decreased the protein expression levels of NF-κB and p53. In conclusion, the present results indicated that the inhibition of NF-κB-mediated inflammation may be a key mechanism by which Ori exerts its therapeutic effects on UC.