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

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.