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巴兰斯刺头三萜皂苷的免疫调节、溶血特性及细胞毒性活性

Immunomodulatory, hemolytic properties and cytotoxic activity potent of triterpenoid saponins from Cephalaria balansae.

作者信息

Top Hilal, Sarikahya Nazli Boke, Nalbantsoy Ayse, Kirmizigul Suheyla

机构信息

Department of Chemistry, Faculty of Science, Ege University, 35100, Bornova, Izmir, Turkey.

Department of Bioengineering, Faculty of Engineering, Ege University, 35100, Bornova, Izmir, Turkey.

出版信息

Phytochemistry. 2017 May;137:139-147. doi: 10.1016/j.phytochem.2017.02.015. Epub 2017 Feb 16.

Abstract

Phytochemical investigations on n-butanol extract of Cephalaria balansae Raus. (Caprifoliaceae) led to the isolation of four previously undescribed triterpenoid saponins based on hederagenin type aglycone, namely, balansoides A-D, along with ten known compounds. Their structures were proposed based on 1D and 2D NMR spectroscopic data, HRESIMS analysis and chemical evidence as 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin, 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl ester, 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-galactopyranosyl-(1 → 6)-β-D-glucopyranosyl ester and 3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester. The four saponins were evaluated for their potential cytotoxic activity against HEK-293, A-549, HeLa cells and for hemolytic properties on human blood cells. Balansoide A displayed significant inhibitory effects on cancerous A-549 and HeLa cells, and non-cancerous HEK-293 cells with IC values of 12, 15 and 8 μM, respectively. Balansoides A-D together with n-butanol extract exhibited considerable hemolysis in human erythrocyte cells. Immunomodulatory properties of balansoides A-D were also evaluated in activated whole blood cells by PMA plus ionomycin. While balansoides A-C increased IL-1β concentration with values of 1004.47, 991.57 and 966.50 pg/ml, only balansoide B augmented a slight IFN-γ secretion with value of 5219.14 pg/ml. None of the compounds changed IL-2 levels significantly.

摘要

对巴兰氏刺头菊(Cephalaria balansae Raus.)(忍冬科)正丁醇提取物进行的植物化学研究,分离出了四种基于常春藤皂苷元型苷元的此前未描述的三萜皂苷,即巴兰氏皂苷A - D,以及十种已知化合物。根据一维和二维核磁共振光谱数据、高分辨电喷雾电离质谱分析和化学证据,确定它们的结构分别为3 - O-α-L-鼠李吡喃糖基-(1→3)-β-D-木吡喃糖基-(1→3)-α-L-鼠李吡喃糖基-(1→2)-α-L-阿拉伯吡喃糖基常春藤皂苷元、3 - O-α-L-鼠李吡喃糖基-(1→3)-β-D-木吡喃糖基-(1→3)-α-L-鼠李吡喃糖基-(1→2)-α-L-阿拉伯吡喃糖基常春藤皂苷元28 - O-β-D-葡萄糖吡喃糖基酯、3 - O-α-L-鼠李吡喃糖基-(1→3)-β-D-木吡喃糖基-(1→3)-α-L-鼠李吡喃糖基-(1→2)-α-L-阿拉伯吡喃糖基常春藤皂苷元28 - O-β-D-半乳糖吡喃糖基-(1→6)-β-D-葡萄糖吡喃糖基酯和3 - O-α-L-鼠李吡喃糖基-(1→3)-β-D-木吡喃糖基-(1→3)-α-L-鼠李吡喃糖基-(1→2)-α-L-阿拉伯吡喃糖基常春藤皂苷元28 - O-β-D-葡萄糖吡喃糖基-(1→6)-β-D-葡萄糖吡喃糖基酯。评估了这四种皂苷对人胚肾293细胞(HEK - 293)、人肺癌细胞(A - 549)、人宫颈癌细胞(HeLa)的潜在细胞毒性活性以及对人血细胞的溶血特性。巴兰氏皂苷A对癌性A - 549细胞和HeLa细胞以及非癌性HEK - 293细胞均显示出显著的抑制作用),其半数抑制浓度(IC)值分别为12、15和8 μM。巴兰氏皂苷A - D与正丁醇提取物在人红细胞中均表现出相当程度的溶血作用。还通过佛波酯(PMA)加离子霉素在活化全血细胞中评估了巴兰氏皂苷A - D的免疫调节特性。虽然巴兰氏皂苷A - C使白细胞介素-1β(IL - 1β)浓度升高,值分别为1004.47、991.57和966.50 pg/ml,但只有巴兰氏皂苷B使干扰素-γ(IFN - γ)分泌略有增加,值为5219.14 pg/ml。这些化合物均未显著改变白细胞介素-2(IL - 2)水平。

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