诺丽果中化学成分及其抑制滑膜成纤维细胞增殖活性研究

Chemical constituents from fruits of Morinda citrifolia and their inhibitory effects on proliferation of synoviocytes in vitro

综合运用硅胶柱色谱、ODS柱色谱、Sephadex LH-20凝胶柱色谱以及制备型HPLC等色谱分离技术对茜草科巴戟天属植物海滨木巴戟Morinda citrifolia果实(诺丽果)中的化学成分进行系统研究。根据分离得到化合物的理化性质和波谱数据,并通过与文献中已经报道的相应化合物的数据进行对比,鉴定了从诺丽果的90%乙醇提取物中分离得到的22个化合物,分别鉴定为moricitritone(1)、2′-deoxythymidine(2)、cyclo-(L-Pro-L-Tyr)(3)、methyl-5-hydroxy-2-pyridinecarb-oxylate(4)、methyl pyroglutamate(5)、bisbenzopyran(6)、epipinoresinol(7)、3,3′-bisdemethylpinoresinol(8)、3,3′-bisdemethyltanegool(9)、均苯三甲酸(10)、crypticin B(11)、曲酸(12)、香草酸(13)、原儿茶酸(14)、5-羟甲基糠醛(15)、blumenol A(16)、1-O-(9Z,12Z-octadeca-dienoyl) glycerol(17)、mucic acid dimethylester(18)、methyl 2-O-β-D-glucopyranosylbenzoate(19)、2-phenylethyl-O-β-D-glucoside(20)、东莨菪内酯(21)和槲皮素(22)。其中化合物1为1个新的吡喃酮衍生物,化合物2、4~7、10~12和17为首次从巴戟天属植物中分离得到,化合物18为首次从海滨木巴戟中分离得到。此外,采用MTS法对分离得到的所有化合物1~22在体外抑制滑膜细胞增殖的活性进行了测定,基于此初步评价了化合物1~22的抗类风湿性关节炎活性。抗类风湿性关节炎活性评价结果表明新吡喃酮衍生物(1)、生物碱(2~5)、木脂素(6、9)以及糖苷(19~20)均表现出了较为显著的抗类风湿性关节炎活性,它们对MH7A滑膜成纤维细胞增殖抑制活性的IC_(50)为(3.69±0.08)~(168.96±0.98)μmol·L^(-1)。

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2′-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3′-bisdemethyl pinoresinol(8), 3, 3′-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-β-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-β-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) μmol·L^(-1).