Anti-inflammatory effects of ?-ionone-curcumin hybrid derivatives against ulcerative colitis

A series of beta-ionone-curcumin hybrid derivatives were designed and chosen to merge the biological character-istics of two parent molecules and to obtain a leading compound with higher biological activity. Through the initial screening, the structure activity relationship of their hybrid derivatives as inhibitors of nitric oxide (NO) production showed that meta-substituted derivatives exhibited the best inhibitory activity, among which 1h was the best one. In lipopolysaccharide-induced Raw264.7 macrophage cells, 1h showed anti-inflammatory activity by inhibiting the productions of NO and reactive oxygen species, the expressions of Interleukin-1 beta and tumor necrosis factor-alpha, and the translocation of nuclear factor (NF)-kappa B from the cytosol to the nucleus. Furthermore, molecular docking simulation displayed that 1h could interact with cluster of differentiation 14 to inhibit the toll-like receptor 4/NF-kappa B signaling. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) of mice, 100 mg/kg of 1h could significantly reduce the colon length shortening and protect against colon injury, liver injury and oxidative stress in DSS-induced UC of mice. Besides, 1h was safety in vivo. In conclusion, 1h was the potential anti-inflammatory agent, and further investigations were underway in our laboratory.

Automated summary

This study designed a series of hybrid derivatives to combine the biological characteristics of two parent molecules and obtained a leading compound with higher biological activity. The compound showed excellent anti-inflammatory activity and protective effects in both in vitro and in vivo experiments.