金佛山雪胆化学成分及其生物活性研究

发布时间：2018-03-20 23:05

  本文选题：雪胆属　切入点：金佛山雪胆　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：金佛山雪胆(Hemsleya pengxianensis var.jinfushanensi)为葫芦科雪胆属植物,主要分布于云南、贵州、四川、重庆等地。主要用于治疗肠炎、上呼吸道感染、支气管炎、细菌性痢疾、尿路感染等病。现代研究表明,金佛山雪胆主要含有葫芦烷三萜类、木脂素类、有机酸类等成分,具有抗肿瘤、抗HIV、抗菌消炎、治疗胃溃疡等生理活性。为了全面研究金佛山雪胆的化学成分,揭示金佛山雪胆的生物活性,阐明其药效物质基础,本课题组对金佛山雪胆块根的化学成分进行了系统研究;对分离得到的单体化合物进行了体外抗肿瘤活性筛选;建立了金佛山雪胆中9个葫芦烷型三萜及其苷类的UPLC MS/MS检测法,为更好的利用雪胆属资源奠定基础。主要研究结果如下:1.采用现代分离技术及分析方法对金佛山雪胆块根的乙酸乙酯和正丁醇萃取部位分别进行了的化学成分研究,共分离得到单体化合物82个单体化合物,鉴定了其中72个化合物。包括三萜类成分70个,木脂素类成分1个,脂肪酸1个。其中30个为新化合物,1个化合物首次从雪胆属植物中分离得到。30个新化合物分别命名为:hemsleyaoside A(A1)、hemsleyaoside A1(A2)、hemsleyaoside B(A3)、hemsleyaoside C(A4)、hemsleyaoside D(A5)、hemsleyaoside E(A6)、hemsleyaoside E1(A7)、hemsleyaoside E2(A8)、hemsleyaoside E3(A9)、hemsleyaoside F(A10)、hemsleyaoside F1(A11)、hemsleyaoside F2(A12)、hemsleyacin A(A13)、hemsleyaoside G(A14)、hemsleyaoside H(A15)、hemsleyacin B(A16)、hemsleyacin C(A17)、hemsleyacin D(A18)、hemsleyaoside I(A19)、hemsleyaoside J(A20)、hemsleyacin E(A21)、hemsleyacin E1(A22)、hemsleyacin F(A23)、hemsleyacin G(A24)、hemsleyacin I(A25)、hemsleyacin J(A26)、hemsleyacin K(A27)、hemsleyacin L(A28)、hemsleyacin M(A29)、hemsleyacin N(A30),以上新化合物均为葫芦烷型三萜及其苷类成分,包含一系列16,23-吡喃环葫芦烷三萜与7-羰基葫芦烷型三萜及其苷类。其中,本文首次从雪胆属植物中分离得到侧链含有α,β不饱和酮(27-去甲基)葫芦烷型三萜皂苷。2.在以上工作的基础上,本文依据分离得到的化合物的波谱数据,结合已报道的化学成分,对雪胆属葫芦烷型三萜及其苷类的波谱规律进行了归纳总结,为雪胆属植物中葫芦烷类成分的快速识别提供参考。3.在化学研究的基础上,采用MTT法对分离得到的新化合物和部分已知化合物进行了抑制肿瘤细胞增殖试验,结果显示hemsleyaoside F2、hemsleyacin N、雪胆甲素、雪胆乙素、hemslepenside A、hemsleyacin B、巨花雪胆 G、cuburbitacine F,16-O-acetyl-cucurbitacin F具有不同程度的抑制Hela细胞增殖活性,其中化合物hemslepenside A对Hela细胞增殖抑制作用最强,IC50为1.39 μmol/l。并初步探讨了葫芦烷型三萜及其苷类的构效关系。4.利用LC-MS/MS技术,同时测定金佛山雪胆中9个葫芦烷型三萜类成分的含量,该方法高效快速、灵敏度高,适合于金佛山雪胆药材和制剂中的多指标含量测定,为药材及其制剂的质量控制和品质评价奠定基础。结果表明金佛山雪胆中雪胆甲素、雪胆乙素、巨花雪胆G、jinfushanencins F、短柄雪胆D、hemsleyaoside A、hemsleyacin N、cucuibitacin F 和 jinfushanoside C 的含量分别为25.87,3.48,0.34,0.10,0.34,9.09,0.04,0.06,0.55 mg/g,为金佛山雪胆的体内活性研究和药代动力学研究提供前期研究基础。综上所述,本文通过对金佛山雪胆开展化学成分及体外抗肿瘤活性的研究,为金佛山雪胆的药效物质和发现先导化合物的基础研究奠定基础,同时为挖掘先导化合物提供物质基础。成功建立了同时测定金佛山雪胆中葫芦烷类成分含量的UPLC MS/MS方法,为金佛山雪胆药材的质量控制与品质评价提供方法依据。
[Abstract]:Jinfo Mountain (Hemsleya pengxianensis var.jinfushanensi) Xuedan gourd Kexue bile genus, mainly distributed in Yunnan, Guizhou, Sichuan, Chongqing and other places. Mainly used in the treatment of upper respiratory tract infection, bronchitis, enteritis, bacillary dysentery, urinary tract infections and other diseases. Modern research showed that Jinfo Mountain Xuedan mainly contains three cucurbitane triterpene, lignans, organic acids and other ingredients, anti-tumor, anti HIV, anti inflammation, treatment of gastric ulcer and other physical activity. In order to study chemical composition of comprehensive Jinfo Mountain Xuedan, revealing Jinfo Mountain Xuedan biological activity, clarify its efficacy material basis, the research group of chemical components of the root of Jinfo Mountain Xuedan the research on the system; isolated compounds were screened in vitro antitumor activity; establish UPLC MS/MS method for detection of 9 cucurbitane Xuedan in Jinfo Mountain three terpene glycosides, for the better To lay the foundation for Hemsleya resources. The main results are as follows: 1. the study on the chemical constituents of modern separation techniques and analysis methods of Jinfo Mountain Xuedan root of ethyl acetate and n-butanol extract respectively, were isolated from the monomeric compounds, 82 compounds, 72 of them were identified including three terpene compounds. Compounds 70, 1 lignans, fatty acid 1. 30 of them were new compounds, 1 compounds were first isolated from Xuedan plant.30 a new compound named hemsleyaoside A (A1), hemsleyaoside A1 (A2), hemsleyaoside B (A3), hemsleyaoside C (A4), hemsleyaoside D (A5), hemsleyaoside E (A6), hemsleyaoside E1 (A7), hemsleyaoside E2 (A8), hemsleyaoside E3 (A9), hemsleyaoside F (A10), hemsleyaoside F1 (A11), hemsleyaoside F2 (A12), hemsleyacin A (A13), hemsleyaoside G (A14) Hemsl. eyaoside H(A15),hemsleyacin B(A16),hemsleyacin C(A17),hemsleyacin D(A18),hemsleyaoside I(A19),hemsleyaoside J(A20),hemsleyacin E(A21),hemsleyacin E1(A22),hemsleyacin F(A23),hemsleyacin G(A24),hemsleyacin I(A25),hemsleyacin J(A26),hemsleyacin K(A27),hemsleyacin L(A28),hemsleyacin M(A29),hemsleyacin N(A30),浠ヤ笂鏂板寲鍚堢墿鍧囦负钁�鑺︾兎鍨嬩笁钀滃強鍏惰嫹绫绘垚鍒�,鍖呭惈涓，

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