A series of β-ionone-curcumin hybrid derivatives were designed and chosen to merge the biological characteristics 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-1β and tumor necrosis factor-α, and the translocation of nuclear factor (NF)-κB 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-κB 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.
Keywords: Anti-inflammation; Curcumin; Hybrid derivatives; Raw264.7 macrophage cells; Ulcerative colitis; β-Ionone.
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