手参的化学成分研究
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摘要
本博士学位论文对手掌参的基源植物之一手参Gymnadenia conopsea块茎的化学成分及其药理活性进行了较细致的研究。利用现代色谱方法和先进的波谱学技术从手参乙醇提取物的活性部位中分离并鉴定了50个化合物，化合物的名称和结构分别如表1和结构图1。其中，1~*～14~*、15～19、25～40、45、47、48和50为首次从手参属植物中分离得到；14个为新化合物(1~*～14~*)，其中包括4个对羟基苄醇衍生物的双糖酚苷(1~*～4~*)、5个对糖氧基苄醇2-异丁基丁二酸衍单酯或双酯(5~*～9~*)、1个对糖氧基苄醇苹果酸单酯(10~*)、2个环二肽(11~*和12~*)、1个苄基取代的环戊烯-4-烯-1，3-二酮衍生物(13~*)和1个苯基取代的环戊-2-烯-1-酮衍生物(14~*)；经多种药理模型筛选，发现在10~(-6)M浓度时37、39和40对脂质过氧化产物MDA的生成抑制率达到50％以上，24对去血清致SH-SY5Y凋亡细胞有保护活性；在浓度为10~(-5)mol／L时，所有送筛化合物对BGC-823(人胃癌细胞)、A2780(人卵巢癌细胞)、A549(人肺腺癌细胞)、HCT-8(人结肠癌细胞)、Bel7402(人肝癌细胞)5种细胞株均未表现出细胞毒作用，对单胺氧化酶和乙酰胆碱酯酶无抑制率活性。另外，在以上研究基础上，对具有良好镇静和催眠活性的31以及具有对实验动物(小鼠)记忆损伤显著保护作用的17和20的水解产物2-异丁基酒石酸进行了合成，同时得到10个衍生物(S1～S10)。
This PhD dissertation investigated chemical constituents of an ethanolic extract of a plant source of an ethnic medicine "Shou-zhang-shen", the dried tuber of Gymnadenia conopsea R. Br.. By using a variety of chromatographic techniques 50 compounds were isolated, and their structures were characterized by spectroscopic analyses and chemical methods. The names and structures of the purified constituents are listed in Table 1 and Figure 1. Among them, 1~*-14~*、15-19、25-40、45、47、48 and 50 were obtained from the genus Gymnadenia for the first time, and 1~*-14~* possessed new structures consisting of four phenolic diglucosides of 4-hydroxybenzyl alcohol (1~*-4~*), five mono- or bis(4-glycosyloxybenzyl) 2-isobutyltartrates (5~*-4~*), one 4-glycosyloxybenzyl 2-isobutylmalate (10~*), two cyclodipeptide (11~* and 12~*), one 3-benzylcyclopent-4-en-1,3-dione derivative (13~*), and a 3-phynylcyclopent-4-en-2-en-1-one derivative (14~*). These compounds were screened on several pharmacological models. At a concentration of 10~(-6) mol/L, 37,39 and 40 showed antioxidative activity inhibiting Fe~(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rates of 53%, 59% and 52%. At a concentration of 10~(-6) M, 24 was active against serum deprivation-induced SH-SY5Y apoptosis. At a concentration of 10~(-5) M, the tested compounds were inactive against several human cancer cell lines including human colon cancer (HCT-8), hepatoma (Bel7402), stomach cancer (BGC-823), lung adenocarcinoma (A549), and human ovarian cancer (A2780), as well as against acetylcholine esterase (AChE) and monoamine oxidase (MAO). In addition, 31 that showed in vivo sedative-hypnotic actitvity, and 10 derivatives (S1-S10), together with 2-isobutylmaleic acid that showed neuroprotective effects on memory deficits and pathological changes in senescent mice, were synthesized.
This PhD dissertation investigated chemical constituents of an ethanolic extract of a plant source of an ethnic medicine "Shou-zhang-shen", the dried tuber of Gymnadenia conopsea R. Br.. By using a variety of chromatographic techniques 50 compounds were isolated, and their structures were characterized by spectroscopic analyses and chemical methods. The names and structures of the purified constituents are listed in Table 1 and Figure 1. Among them, 1~*-14~*、15-19、25-40、45、47、48 and 50 were obtained from the genus Gymnadenia for the first time, and 1~*-14~* possessed new structures consisting of four phenolic diglucosides of 4-hydroxybenzyl alcohol (1~*-4~*), five mono- or bis(4-glycosyloxybenzyl) 2-isobutyltartrates (5~*-4~*), one 4-glycosyloxybenzyl 2-isobutylmalate (10~*), two cyclodipeptide (11~* and 12~*), one 3-benzylcyclopent-4-en-1,3-dione derivative (13~*), and a 3-phynylcyclopent-4-en-2-en-1-one derivative (14~*). These compounds were screened on several pharmacological models. At a concentration of 10~(-6) mol/L, 37,39 and 40 showed antioxidative activity inhibiting Fe~(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rates of 53%, 59% and 52%. At a concentration of 10~(-6) M, 24 was active against serum deprivation-induced SH-SY5Y apoptosis. At a concentration of 10~(-5) M, the tested compounds were inactive against several human cancer cell lines including human colon cancer (HCT-8), hepatoma (Bel7402), stomach cancer (BGC-823), lung adenocarcinoma (A549), and human ovarian cancer (A2780), as well as against acetylcholine esterase (AChE) and monoamine oxidase (MAO). In addition, 31 that showed in vivo sedative-hypnotic actitvity, and 10 derivatives (S1-S10), together with 2-isobutylmaleic acid that showed neuroprotective effects on memory deficits and pathological changes in senescent mice, were synthesized.
引文
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[4]李敏，郭顺星，王春兰，肖培根．手参块茎化学成分研究[J]．中国药学杂志，2007，42：1696-1698．
[5] Morikawa T., Xie H., Matsuda H., Yoshikawa M. Glucosyloxybenzyl 2-Isobutylmalates from the Tubers of Gymnadenia conopsea [J]. Journal of Natural Products, 2006,69: 881-886.
[6] Yoshikawa M., Morikawa T., Xie H., Yoshikawa M. Antiallergic Phenanthrenes and Stilbenes from the Tubers of Gymnadenia conopsea [J]. Planta Medica, 2004, 70: 847-855.
[7]李敏，王春兰，郭顺星，杨峻山，肖培根．手参属植物化学成分及药理活性研究进展[J]．中草药，2006，37：1264-1268．
[8] Yoshikawa W., Matsuda H., Morikawa T. Active oxygen scavenging or antiallergic compositions containing Orchidaceae plants, their alcohol extracts, or their components, and drugs or foods containing the compositions for human or animals [P]. JP: 2005/02/20:
[9]卢卫红，张洪娟，王文芝．手参的药效学研究[J]．中医药研究，2002，18：43-44．
[10] Huang S. Y, Shi J. G, Yang Y. C, Hu S. L. Two New Isobutyltartrate Monoesters fromCoeloglossum viride (L.) Hartm. var. bracteatum (Willd.) Richter [J]. Chinese Chemical Letters, 2002,13:551-554.
[11] Huang S. Y, Shi J. G, Yang Y C, Tu P. F. Two New Tartrate Derivative Glucosides fromCoeloglossum viride ( L.) Hartm. var. bracteatum ( Willd.) Richter [J]. Chinese Chemical Letters, 2003,14:814-817.
[12] Huang S.-Y, LI G-Q., Shi J.-G, Mo S.-Y, Wang S.-J., Yang Y.-C. Chemical Constituents of therhizomes of Coeloglossum Viride VAR. Bracteatum [J]. Journal of Asian Natural Products Research,2004,6:49-61.
[13]黄胜阳，石建功，杨永春，胡世林．藏药旺拉的氨基酸成分分析[J]．中国民族民间医药杂志，2002：229-231．
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