青皮化学成分及其体外抗三阴性乳腺癌活性研究  

Chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro

作　　者：邓徐丽 陈艺燕 张洪川 王一谋 尹蕊 董维茂 陈章贤 朱奎霖 何红平 董发武 DENG Xu-li;CHEN Yi-yan;ZHANG Hong-chuan;WANG Yi-mou;YIN Rui;DONG Wei-mao;CHEN Zhang-xian;ZHU Kui-lin;HE Hong-ping;DONG Fa-wu(Yunnan Provincial Key Laboratory for Southem Medicinal Sustainable Utilization and Research,College of Tradtional Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]云南中医药大学中药学院,云南省南药可持续利用研究重点实验室,云南昆明650500

出　　处：《中成药》2025年第1期118-125,共8页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(31860092,82260758);云南省高层次人才培养支持计划“青年拔尖人才”专项项目(YNWR-QNBJ-2020-255);云南省基础研究计划面上项目(202101AT070254)。

摘　　要：目的研究青皮Citri reticulatae Pericarpium Viride化学成分及其体外抗三阴性乳腺癌活性。方法青皮85%乙醇提取物采用硅胶、聚酰胺、MCI、Sephadex LH-20及半制备HPLC进行分离纯化,根据理化性质及波谱数据鉴定所得化合物的结构。采用SRB法进行抗三阴性乳腺癌活性筛选,评价其对三阴性乳腺癌HCC1806、HCC1937、MDA-MB-231细胞株体外增殖的影响。结果从中分离得到20个化合物,分别鉴定为川陈皮素(1)、桔皮素(2)、5,4′-二羟基-7,8-二甲氧基黄酮(3)、柚皮素(4)、艾黄素(5)、5-去甲基川陈皮素(6)、3,5,6,7,8,3′,4′-七甲氧基黄酮(7)、5,4′-羟基-3,6,7,8,3′-五甲氧基黄酮(8)、5,4′-二羟基-6,7,8-三甲氧基黄酮(9)、对香豆酸(10)、5,4′-二羟基-6,7,8,3′-四甲氧基黄酮(11)、柳穿鱼黄素(12)、4′-羟基-5,6,7-三甲氧基黄酮(13)、粗毛豚草素(14)、4′,5,6,7-四氧基黄酮(15)、柠檬烯-1,2-二醇(16)、7-羟基香豆素(17)、5-羟甲基糠醛(18)、对苯二酚(19)、吲哚-3-甲醛(20)。化合物8显示出显著的抑制作用,其对HCC1806细胞的IC 50值为(5.36±0.24)μmol/L。结论化合物20为首次从柑橘属中分离得到,8、12~13、16~17为首次从该植物中分离得到。化合物8对HCC1806、HCC1937、MDA-MB-231细胞体外增殖均表现出抑制作用,且活性最强;化合物3~4、11~12、15、17、19对HCC1806细胞表现出较强的抑制作用;化合物15、19对HCC1937细胞体外增殖也有抑制作用。AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4′-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3′,4′-pentamethoxy flavonoid(7),5,4′-dihydroxy-3,6,7,8,3′-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4′-dihydroxy-6,7,8,3′-tetramethoxyflavone(11),pectolinarigenin(12),4′-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4′,5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1 H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC 50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

关 键 词：青皮 化学成分 分离鉴定 抗三阴性乳腺癌活性 SRB法 

分 类 号：R284.1[医药卫生—中药学]