目的 以活性追踪为导向对藏木香Inula racemosa根部活性倍半萜成分进行靶向分离，并考察其对尼日利亚菌素（nigericin）诱导人单核细胞白血病THP-1细胞中释放白细胞介素-1β（interleukin-1β，IL-1β）的抑制活性。方法 借助各种色谱手段对其活性成分进行分离纯化，采用现代波谱技术（包括高分辨质谱、核磁共振、旋光等），并结合化学方法对其结构进行鉴定，采用ELISA法初步评价化合物1对nigericin诱导的THP-1细胞中IL-1β释放的抑制作用，并利用LDH法检测其对THP-1细胞的体外毒性。结果 从藏木香石油醚萃取部位分离得到1个桉烷型倍半萜内酯，鉴定为藏木香素I（1），其2个水解产物分别为isotelekin（1a）和3-苯甲酰基丙烯酸（1b）。结论 此桉烷型倍半萜内酯化合物1确定为新化合物，命名为藏木香素I，它对nigericin诱导THP-1细胞释放IL-1β具有显著的抑制活性，半数抑制浓度（IC₅₀）为2.1 μmol/L，而且其对nigericin诱导的THP-1细胞没有细胞毒性，并且表现出一定的保护作用。

Objective To study the active sesquiterpenes and their inhibitory activities on nigericin-induced IL-1β release in THP-1 cells from the roots of Inula racemosa. Methods Based on the bioassay-guided fractionation, the active sesquiterpenes were isolated via various chromatography, and their structures were determined by extensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS, and optical rotation values, as well as chemical method. The inhibitory effect of compound 1 on nigericin-induced IL-1β production in THP-1 cells was evaluated by ELISA assay. The LDH assay was used to detect the release of LDH in THP-1 cells to investigate the cytotoxicity of compound 1. Results One new eudesmane sesquiterpene lactone was isolated from the petroleum ether fraction of I. racemosa, and its structure was identified as racemosin I (1). Two alkaline hydrolysis products of compound 1 were identified as isotelekin (1a) and 3-benzoyl acrylic acid (1b). Conclusion Compound 1 is a new eudesmane sesquiterpene lactone, namely racemosin Ⅰ, which showed significant inhibitory effect on nigericin-induced IL-1β production in THP-1 cells with the IC₅₀ value of 2.1 μmol/L. In addition, compound 1 did not show toxicity to THP-1 cells, but alleviated nigericin-induced cell death.

R284.1

国家自然科学基金资助项目（81973542）；国家自然科学基金资助项目（81903500）