药用狗牙花化学成分及其抑制滑膜成纤维细胞增殖活性研究  

Chemical constituents from Tabernaemontana bovina and their inhibitory activities on proliferation of synovioblasts in vitro

作　　者：王若超 石倪霏 王然 陈子昭 梁财欢 邓猛妮 刘艳萍[1,2] 付艳辉[1,2,3] WANG Ruo-chao;SHI Ni-fei;WANG Ran;CHEN Zi-zhao;LIANG Cai-huan;DENG Meng-ni;LIU Yan-ping;FU Yan-hui(Engineering Research Center for Key Technologies on Industrialization of Southern Medicinal Plants Resources of Hainan Province,Hainan Normal University,Haikou 571126,China;Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education,Hainan Normal University,Haikou 571126,China;Key Laboratory of Key Technologies on Industrialization of Southern Medicinal Plants Resources of Haikou City,Hainan Normal University,Haikou 571126,China)

机构地区：[1]海南师范大学南药资源产业化关键技术研究海南省工程研究中心,海南海口571126 [2]海南师范大学热带药用资源化学教育部重点实验室,海南海口571126 [3]海南师范大学南药资源产业化关键技术研究海口市重点实验室,海南海口571126

出　　处：《中草药》2023年第7期2036-2043,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(32070390);国家自然科学基金项目(22067005);国家自然科学基金项目(21967008);海南省自然科学基金项目(2019RC198,222RC655,220RC596);海南省重点研发专项(ZDYF2022SHFZ028);海口市重点研发计划项目(2017050,2020054);海南省省级大学生创新训练项目(S202211658028和S202211658025);海南师范大学校级大学生创业实践项目(HSRS21-037)。

摘　　要：目的研究夹竹桃科狗牙花属植物药用狗牙花Tabernaemontana bovina枝叶中的化学成分及其抑制滑膜成纤维细胞增殖活性。方法综合运用硅胶柱色谱、ODS柱色谱、SephadexLH-20凝胶柱色谱以及制备型HPLC等色谱方法进行系统分离和纯化,根据分离得到化合物的理化性质及其波谱数据,并通过与文献中报道的相应化合物的波谱数据进行对比,鉴定分离得到化合物的化学结构;通过对分离得到化合物的体外抑制滑膜细胞增殖的活性测试以评价其抗类风湿性关节炎活性。结果从药用狗牙花枝叶的85%乙醇提取物中分离得到了19个化合物,分别鉴定为苏门树脂酸(1)、2α,19α-dihydroxy-3-oxo-12-ursen-28-oic acid(2)、6α-羟基齐墩果酮酸(3)、19α-羟基齐墩果酮酸(4)、garcinielliptone Q(5)、阿里二醇(6)、款冬二醇(7)、taraxast-20-ene-3β,30-diol(8)、马尼拉二醇(9)、16β-羟基羽扇豆烷-20(29)-烯-3-酮(10)、eupha-8,24-diene-3β,11β-diol-7-one(11)、2α,3β-二羟基-12-烯-28-乌苏酸(12)、busaliol(13)、tripterygiol(14)、polystachyol(15)、rosalaevin B(16)、cephafortin B(17)、burselignan(18)和latifoliamide A(19)。对分离得到的化合物的抑制滑膜成纤维细胞增殖活性研究评价结果表明,化合物13~18对MH7A滑膜成纤维细胞增殖抑制活性的IC50值为(6.49±0.08)~(123.58±0.23)μmol/L。结论所有化合物均为首次从药用狗牙花中分离得到,化合物13~18表现出了较为显著的抗类风湿性关节炎活性。Objective To study the chemical constituents from the stems and leaves of Tabernaemontana bovina and their inhibitory activities on the proliferation of synovioblasts.Methods The chemical constituents from the stems and leaves of T.bovinas were isolated and purified by silica gel,ODS,Sephadex LH-20 gel column chromatographies and preparative HPLC.Their structures were identified by physicochemical properties,spectroscopic analysis,as well as the comparisons with the data reported in literatures.Moreover,all isolated compounds were evaluated for their anti-rheumatoid arthritis activities using MTS method on the basis of measuring their anti-proliferative activities on synovioblasts in vitro.Results Nineteen compounds were isolated from the ethanol extract of the stems and leaves of T.bovinas,which were identified as sumaresinolic acid(1),2α,19α-dihydroxy-3-oxo-12-ursen-28-oic acid(2),6α-hydroxy oleanonic acid(3),19α-hydroxy oleanonic acid(4),garcinielliptone Q(5),arnidiol(6),faradiol(7),taraxast-20-ene-3β,30-diol(8),maniladiol(9),16β-hydroxylupane-20(29)-en-3-one(10),eupha-8,24-diene-3β,11β-diol-7-one(11),2α,3β-dihydroxy-urs-12-en-28-oic acid(12),busaliol(13),tripterygiol(14),polystachyol(15),rosalaevin B(16),cephafortin B(17),burselignan(18)and latifoliamide A(19).Compounds 13-18 exhibited the inhibitory effects on the proliferation of MH7A synovioblasts with the IC50 values ranging from(6.49±0.08)to(123.58±0.23)μmol/L.Conclusion All compounds are isolated from T.bovinas for the first time,compounds 13-18 displayed notable anti-rheumatoid arthritis activities.

关 键 词：狗牙花属 药用狗牙花 三萜 木脂素 生物碱 抗类风湿性关节炎活性 苏门树脂酸 busaliol tripterygiol 

分 类 号：R284.1[医药卫生—中药学]