[关键词]
[摘要]
目的 研究构树Broussonetia papyrifera枝条的化学成分,从中筛选具有原发性渗出性淋巴瘤(primary effusion lymphoma,PEL)细胞毒活性的化合物。方法 采用硅胶、RP-18、Sephadex LH-20凝胶、MCI柱色谱及高效液相色谱等方法进行分离纯化,通过波谱技术进行结构鉴定。运用CCK-8法评估化合物对PEL细胞系(BC-3、BCBL-1)的毒性,利用流式细胞术等技术分析化合物对细胞凋亡及细胞周期的影响。结果 从构树枝提取物中分离鉴定出19个化合物,分别鉴定为楮树黄酮醇B(1)、8-异戊烯基槲皮素-3-甲醚(2)、二氢槲皮素(3)、甘草素(4)、(+)-梣皮树脂醇(5)、(+)-丁香树脂酚(6)、dadahol B(7)、diospyrosin(8)、蛇菰宁(9)、5-甲氧基蛇菰宁(10)、isokhellactone(11)、紫花前胡内酯(12)、芸香霉素(13)、smyrindiol(14)、异紫花前胡内酯(5)、8-甲氧基异紫花前胡内酯(16)、7-去甲基软木花椒素(17)、伞形花内酯(18)、反式对羟基桂皮酸二十六烷酯(19)。化合物1、7和17能显著抑制PEL细胞活性,其中7对BC-3和BCBL-1细胞的半数抑制浓度(half inhibitory concentration,IC50)分别为16.05、16.90μmol/L。进一步检测发现7可显著诱导PEL细胞凋亡并阻滞细胞周期。结论 化合物8、17和19为首次在桑科植物中分离得到,化合物9~11和13为首次从构属植物中分离得到。化合物7通过诱导PEL细胞凋亡并阻滞细胞周期发挥抗PEL细胞活性。
[Key word]
[Abstract]
Objective To investigate the chemical constituents of the branches of Broussonetia papyrifera and screen for compounds with cytotoxic activity against primary effusion lymphoma (PEL) cells. Methods The compounds were isolated and purified by various chromatographic techniques including silica gel, RP-18, Sephadex LH-20, and MCI column chromatographies, as well as high-performance liquid chromatography (HPLC). Their structures were identified by spectroscopic methods. The cytotoxicity of the isolates against PEL cell lines (BC-3 and BCBL-1) was evaluated using the CCK-8 assay. The effects of active compounds on cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Results Nineteen compounds were isolated and identified as broussoflavonol B (1), 8-prenylquercetin-3-methyl ether (2), taxifolin (3), liquiritigenin (4), (+)-medioresinol (5), (+)-syringaresinol (6), dadahol B (7), diospyrosin (8), balanophonin (9), 5-methoxybalanophonin (10), isokhellactone (11), nodakenetin (12), rutamarin (13), smyrindiol (14), marmesin (15), 8-methoxymarmesin (16), 7-demethylsuberosin (17), umbelliferone (18), and n-hexacosyl (E)-p-coumarate (19). Compounds 1,7 and 17 exhibited significant inhibitory activity against PEL cells. Among them, compound 7 showed half-maximal inhibitory concentration (IC50) values of 16.05 and 16.90 μmol/L against BC-3 and BCBL-1 cells, respectively. Further studies indicated that compound 7 could notably induce apoptosis and arrest cell cycle in PEL cells. Conclusion Compounds 8,17 and 19 were isolated from the Moraceae for the first time, while compounds 9—11 and 13 were obtained from the genus Broussonetia for the first time. Compound 7 exerts its anti-PEL activity by inducing cell apoptosis and blocking cell cycle progression.
[中图分类号]
R284.1
[基金项目]
国家自然科学基金资助项目(82060367);云南省中青年学术技术带头人后备人才项目(202205AC160073);陕西省高校优秀青年人才项目(GXYQ004);延安大学研究生教育创新计划项目(YCX2024036)