目的 研究单羰基姜黄素类似物22的抗炎活性及机制。方法 利用MTT实验评价化合物22的细胞毒性，采用脂多糖（LPS）刺激原代腹膜巨噬细胞为模型，ELISA和qRT-PCR实验检测化合物22对炎症因子蛋白和基因表达的影响，UV吸收实验检测化合物的稳定性，并且用Western blotting实验探讨化合物22的抗炎机制。结果 化合物22作用原代巨噬细胞24 h后，没有产生明显的细胞毒性；与姜黄素相比，化合物22能剂量依赖性地抑制炎症因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的释放，并且体外稳定性优于姜黄素；化合物22能够显著地抑制LPS诱导的炎症基因IL-1β、IL-12、IL-6和TNF-α的表达，且抗炎机制与抑制ERK和JNK的磷酸化以及IκB的降解有关。结论 姜黄素类似物22能够通过抑制ERK和JNK信号通路以及核因子-κB（NF-κB）通路的激活发挥抗炎活性。

Objective To study the anti-inflammatory activity and mechanism of mono-carbonyl curcumin analog 22. Methods The cell cytotoxicity of compound 22 was detected by MTT assay. LPS activated peritoneal macrophages was used as cell model. The effect of compound 22 on inflammatory cytokines protein and gene expression was detected by ELISA and RT-qPCR, respectively. UV-absorbing assay was used to determine the stability of compound 22. The anti-inflammatory mechanism of compound 22 was detected by Western blotting assay. Results Compound 22 showed no cytotoxicity after incubated cells 24 h. Compared with curcumin, compound 22 dose-dependently inhibited LPS-induced production of inflammatory cytokines TNF-α and IL-6. Compound 22 showed more stability than curcumin in vitro. Meanwhile, compound 22 inhibited LPS-induced inflammatory gene IL-1β, IL-12, IL-6, and TNF-α expression through qRT-PCR assay. Compound 22 inhibited the phosphorylation of ERK/JNK, also reversed the LPS-induced degradation of IκB. Conclusion Compound 22 exhibits its anti-inflammatory activity through inhibiting ERK/JNK signaling pathway, as well as NF-κB activation.

“十二五”国家科技支撑计划（2011BAI04B04）；浙江省自然科学基金资助项目（LY15H280014）；云南大理药业股份有限公司横向课题（KJHX1603）