橘叶化学成分及其抗炎活性研究  

Chemical constituents from the leaves of Citrus reticulata and their anti-inflammatory activities

作　　者：杨发科 杨兴 张志毕[3] 尹蕊 张洪川 邓徐丽 董维茂 王一谋 何红平 董发武 YANG Fa-ke;YANG Xing;ZHANG Zhi-bi;YIN Rui;ZHANG Hong-chuan;DENG Xu-li;DONG Wei-mao;WANG Yi-mou;HE Hong-ping;DONG Fa-wu(School of Chinese Materia Medica,Yunnan University of Chinese Medicine,Yunnan Key Laboratory for Southem Medicinal Resource,Kunming 650500,China;The Third Affiliated Hospital of Kunming Medical University,Kunming 650500,China;Academy of Biomedical Engineering,Kunming Medical University,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重点实验室,云南昆明650500 [2]昆明医科大学第三附属医院,云南昆明650500 [3]昆明医科大学生物医学工程研究院,云南昆明650500

出　　处：《中成药》2024年第9期2972-2979,共8页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金资助项目(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);云南省南药可持续利用研究重点实验室开放课题重点项目(202105AG070012ZD2201)。

摘　　要：目的研究橘Citrus reticulata Blanco叶化学成分及其抗炎活性。方法橘叶85%乙醇提取物采用硅胶、D101大孔树脂、MCI、ODS、Sephadex LH-20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Griess法测定化合物对脂多糖诱导RAW 264.7细胞产生NO的抑制活性。建立角叉菜胶致小鼠足肿胀炎症模型,检测IL-1β、TNF-α水平。结果从中分离得到12个化合物,分别鉴定为川陈皮素(1)、橘红素(2)、5-去甲川陈皮素(3)、5,4′-二羟基-6,7,8,3′-四甲氧基黄酮(4)、5-羟基-7,8,3′,4′-四甲氧基黄酮(5)、3,5,6,7,8,3′,4′-七甲氧基黄酮(6)、橙皮素(7)、5-羟基-6,7,3′,4′-四甲氧基黄酮(8)、β-香树脂醇(9)、豆甾-5-烯-3β-醇(10)、对羟基苯甲醛(11)、香草醛(12)。化合物1~4、6~7、10、12对脂多糖诱导RAW 264.7细胞释放NO有较强抑制活性,IC_(50)值分别为(25.21±2.10)、(37.77±0.50)、(38.19±1.58)、(21.89±1.73)、(43.81±1.18)、(47.98±2.55)、(41.23±1.11)、(43.80±1.43)μmol/mL。化合物2~3可降低IL-1β、TNF-α水平(P<0.05,P<0.01)。结论化合物6~7、9为首次从该植物中分离得到。化合物1~4、8有较强的体外抗炎活性,化合物2~3有明显的体内抗炎活性。AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-αwere detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4′-dihydroxy-6,7,8,3′-tetramethoxy flavone(4),5-hydroxy-7,8,3′,4′-trimethoxyflavanone(5),3,5,6,7,8,3′,4′-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3′,4′-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC_(50)values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1βand TNF-αlevels(P<0.05,P<0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.

关 键 词：橘 叶 化学成分 分离鉴定 抗炎活性 

分 类 号：R284.1[医药卫生—中药学]