蟾酥和蟾皮活性成分研究

【作者】 张英；

【导师】 裴月湖； 邱鹰昆； 窦德强；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2007， 硕士

【摘要】 中华大蟾蜍(Bufo bufo gargarizans Cantor)是我国分布较广的蟾蜍科(Bufondae)蟾蜍属动物，其药用部位为：皮、蟾酥、干燥全体。蟾蜍是中医临床应用较早的药物，在我国已有上千年的临床应用历史。现代药理学研究表明蟾酥及蟾皮具有强心、抗肿瘤、局麻、镇痛、抗炎等作用，临床用于治疗肿瘤、痈疽疔疮、呼吸循环衰竭等病症。本文对蟾酥和蟾皮乙醇提取物进行了系统研究，经大孔吸附树脂、反复硅胶柱、ODS反相柱、制备液相、制备薄层和重结晶等手段分离，从蟾酥中分离得到14个化合物以及从蟾皮中分离得到6个化合物，并根据化合物的理化性质、波谱解析、对照品比较以及与文献报道对比鉴定了其化合物结构，蟾酥中14个化合物分别为：华蟾毒精(1)、蟾毒灵(2)、华蟾毒它灵(3)、日蟾毒它灵(4)、脂蟾毒配基(5)、沙蟾毒精(6)、蟾毒它灵(7)、远华蟾毒精(8)、去乙酰蟾毒它灵(9)、南美蟾毒精(10)、16—去乙酰—19氧代华蟾毒它灵(11)、去乙酰华蟾毒精(12)、去乙酰华蟾毒它灵(13)、蟾毒它里灵(14)；蟾皮中6个化合物分别为：胆固醇(Ⅰ)、棕榈酸胆甾烯酯(Ⅱ)、沙蟾毒精(Ⅲ)、蟾毒它灵(Ⅳ)、嚏根草配基(Ⅴ)、嚏根草配基-3-辛二酸半酯(Ⅵ)。其中蟾皮中化合物Ⅵ(嚏根草配基-3-辛二酸半酯)为新化合物，沙蟾毒精和蟾毒它灵为蟾酥及蟾皮中共同得到的化合物。利用文献资料并结合本论文工作系统地归纳了蟾毒配基类化合物的波谱学规律。本文通过蟾酥和蟾皮醇提取物小鼠体内抑瘤实验和所分离得到的蟾毒配基类化合物体外细胞毒实验对其进行了抗肿瘤活性评价，结果表明蟾酥和蟾皮醇提取物有抑制小鼠U14宫颈癌细胞生长作用以及这些单体化合物在体外对不同肿瘤细胞株有抑制增殖作用。更多还原

【Abstract】 Bufo bufo gargarizans Cantor, the species of Bufondae, was widely distributed in China, its dried skin, Venenum Bufonis, dried body were used as a traditional Chinese medicine for thousand years. Modern pharmacology research indicated that Venenum Bufonis and the toad skin possessed cardiotonic, anti-tumor, local anesthesia, balmy, anti-inflammatory effect and has been used as a medicine to treat tumor, superficial infection and furunculosis, breathing circulatory collapse.Fourteen compounds were separated from Venenum Bufonis and six compounds were isolated from toad skin by various chromatographic methods, such as macroporous resin, silica gel, ODS reversed-phase column, HPLC , PTLC, recrystallisation and so on.On the basis of physico-chemical properties and spectroscopic analysis, fourteen compounds separated from Venenum Bufonis were identified as: cinobufagin(1), bufalin(2), cinobufotalin(3),gamabufotalin(4),resibufagin(5),arenobufagin(6),bufotalin(7),telocinobufagi n(8),desacetybufotalin(9),marinobufagin(10), 16-desacetyl-19-Oxocinobufotalin(11),desacetyl cinobufagin(12),desacetylcinobufotalin(13),bufotalinin(14). Six compounds separated from toad skin were identified as: cholesterol( I ),cholesteryl palmitate(II), arenobufagin(III),bufotalin(IV),hellebrigenin( V ),hellebrigenin-3-hemisuberate(VI). Among them, compound VI separated from toad skin was a new compound, arenobufagin and bufotalin were the common compounds separated from Venenum Bufonis and toad skin.A review on the spectroscopic character of bufogenins was summarized based on the spectral data of the related references.Anti-tumor experiment of Venenum Bufonis and toad skin ethanol extracts in vivo and the cytotoxicity experiment of these obtained bufogenins in vitro indicated that Venenum Bufonis and toad skin ethanol extracts can inhibit the growth of mouse U14 cervical cancer cells in vivo, and these bufogenins can inhibited the proliferation of different tumor cells in vitro.更多还原