本文選題：雪膽屬　切入點(diǎn)：金佛山雪膽　出處：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文　論文類型：學(xué)位論文

【摘要】：金佛山雪膽(Hemsleya pengxianensis var.jinfushanensi)為葫蘆科雪膽屬植物,主要分布于云南、貴州、四川、重慶等地。主要用于治療腸炎、上呼吸道感染、支氣管炎、細(xì)菌性痢疾、尿路感染等病。現(xiàn)代研究表明,金佛山雪膽主要含有葫蘆烷三萜類、木脂素類、有機(jī)酸類等成分,具有抗腫瘤、抗HIV、抗菌消炎、治療胃潰瘍等生理活性。為了全面研究金佛山雪膽的化學(xué)成分,揭示金佛山雪膽的生物活性,闡明其藥效物質(zhì)基礎(chǔ),本課題組對(duì)金佛山雪膽塊根的化學(xué)成分進(jìn)行了系統(tǒng)研究;對(duì)分離得到的單體化合物進(jìn)行了體外抗腫瘤活性篩選;建立了金佛山雪膽中9個(gè)葫蘆烷型三萜及其苷類的UPLC MS/MS檢測(cè)法,為更好的利用雪膽屬資源奠定基礎(chǔ)。主要研究結(jié)果如下:1.采用現(xiàn)代分離技術(shù)及分析方法對(duì)金佛山雪膽塊根的乙酸乙酯和正丁醇萃取部位分別進(jìn)行了的化學(xué)成分研究,共分離得到單體化合物82個(gè)單體化合物,鑒定了其中72個(gè)化合物。包括三萜類成分70個(gè),木脂素類成分1個(gè),脂肪酸1個(gè)。其中30個(gè)為新化合物,1個(gè)化合物首次從雪膽屬植物中分離得到。30個(gè)新化合物分別命名為: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),以上新化合物均為葫蘆烷型三萜及其苷類成分,包含一系列16,23-吡喃環(huán)葫蘆烷三萜與7-羰基葫蘆烷型三萜及其苷類。其中,本文首次從雪膽屬植物中分離得到側(cè)鏈含有α,β不飽和酮(27-去甲基)葫蘆烷型三萜皂苷。2.在以上工作的基礎(chǔ)上,本文依據(jù)分離得到的化合物的波譜數(shù)據(jù),結(jié)合已報(bào)道的化學(xué)成分,對(duì)雪膽屬葫蘆烷型三萜及其苷類的波譜規(guī)律進(jìn)行了歸納總結(jié),為雪膽屬植物中葫蘆烷類成分的快速識(shí)別提供參考。3.在化學(xué)研究的基礎(chǔ)上,采用MTT法對(duì)分離得到的新化合物和部分已知化合物進(jìn)行了抑制腫瘤細(xì)胞增殖試驗(yàn),結(jié)果顯示hemsleyaoside F2、hemsleyacin N、雪膽甲素、雪膽乙素、hemslepenside A、hemsleyacin B、巨花雪膽 G、cuburbitacine F,16-O-acetyl-cucurbitacin F具有不同程度的抑制Hela細(xì)胞增殖活性,其中化合物hemslepenside A對(duì)Hela細(xì)胞增殖抑制作用最強(qiáng),IC50為1.39 μmol/l。并初步探討了葫蘆烷型三萜及其苷類的構(gòu)效關(guān)系。4.利用LC-MS/MS技術(shù),同時(shí)測(cè)定金佛山雪膽中9個(gè)葫蘆烷型三萜類成分的含量,該方法高效快速、靈敏度高,適合于金佛山雪膽藥材和制劑中的多指標(biāo)含量測(cè)定,為藥材及其制劑的質(zhì)量控制和品質(zhì)評(píng)價(jià)奠定基礎(chǔ)。結(jié)果表明金佛山雪膽中雪膽甲素、雪膽乙素、巨花雪膽G、jinfushanencins F、短柄雪膽D、hemsleyaoside A、hemsleyacin N、cucuibitacin F 和 jinfushanoside C 的含量分別為25.87,3.48,0.34,0.10,0.34,9.09,0.04,0.06,0.55 mg/g,為金佛山雪膽的體內(nèi)活性研究和藥代動(dòng)力學(xué)研究提供前期研究基礎(chǔ)。綜上所述,本文通過(guò)對(duì)金佛山雪膽開展化學(xué)成分及體外抗腫瘤活性的研究,為金佛山雪膽的藥效物質(zhì)和發(fā)現(xiàn)先導(dǎo)化合物的基礎(chǔ)研究奠定基礎(chǔ),同時(shí)為挖掘先導(dǎo)化合物提供物質(zhì)基礎(chǔ)。成功建立了同時(shí)測(cè)定金佛山雪膽中葫蘆烷類成分含量的UPLC MS/MS方法,為金佛山雪膽藥材的質(zhì)量控制與品質(zhì)評(píng)價(jià)提供方法依據(jù)。
[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負(fù)钁姦鐑峰瀷涓夎悳鍙?qiáng)鍏惰嬶L(fēng)被鎴愬垎,鍖呭惈涓，

本文編號(hào)：1641189