绿升麻生物活性成分的研究
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摘要
绿升麻为土家族传统医药,应用历史悠久,为毛茛科植物类叶升麻(Actaea asiatica Hara)的根茎。绿升麻味辛、微苦、性平,具有散风热、袪风湿,透疹,解毒的功效。为了深入系统地研究绿升麻植物中所含有的活性成分,我们采用萃取、常压柱层析、中压柱层析、凝胶柱层析以及制备高效液相色谱等分离手段,从绿升麻的乙醇提取物中共分得46个化合物。并综合利用IR、MS、HNMR、CNMR、H-HCOSY、HMBC、HSQC、NOESY和旋光等现代波谱技术和化学方法,从中鉴定了38个结构。鉴定的结构中10个为文献未见报道新化合物,2'-O-acetyl-25-anhydrocimigenol-3-O-β-D-xylopyranoside (1),25-O-ethyl-cimigenol -3-O-β-D-xylopyranoside (2),2'-O-acetyl-25-O-ethyl-cimigenol-3-O-β-D-xylopyrano side (3), 2'-O-acetyl-25-O-methyl-cimigenol-3-O-β-D-xylopyranoside (4) , 25 ,4′-O-diacetyl-cimigenol-3-O-β-D-xylopyranoside (5),12,3′-O-diacetyl- cimigenol- 3-O-β-D-xylopyranoside (6),23(R), 24(S)-24:25-epoxy-3β,15-dihydroxy-23-O- acetyl-9,19-cyclolanostan-16-one-3-O-β-D-(2′-O-acetyl)xylopyranoside (7), 20(S), 22(R),23(S), 24(R)-16β:23;22:25-diepoxy-3β,23,24-trihydroxy-9,19-cyclolanostane -3-O-β-D-(2′-O-acetyl)xylopyranoside (8) , 3′-O-acetylcimicifugoside (9) ,4′-O-acetyl-23-epi-26-deoxycimifugoside (10)。化合物11 (23R, 24S)- 16:23;16:24-diepoxy-15α,25-dihydroxy-9,19-cyclolanost-1-en-3-one为新的天然产物。分离到的已知化合物中,化合物28,29,30是首次从类叶升麻属中得到的降4碳环阿屯烷型三萜类化合物。阿魏酰胺类化合物35是从类叶升麻属中首次发现的结构类型。化合物10-38均为首次从该植物中得到。
我们以L929、Hela细胞系作为药理活性研究对象,考察了绿升麻的乙醇提取物中不同极性的萃取物和分离到的单体化合物的抗肿瘤作用。试验结果表明乙酸已酯萃取物是绿升麻抗肿瘤的活性部位。分离得到的单体化合物12和15对Hela细胞的生长具有较强的抑制作用, 12,20, 26对L929细胞生长具有较强的抑制作用。另外,分离到的其它化合物的药理活性试验还在进行中。
Actaea asiatica Hara (Ranunculaceae) is widely distributed in the southwest and northwest of the People’s Republic of China. As a Chinese folk medicine, its rhizomes is used to treat headache, sore throat, measles, pertussis, prolapse of uterus. In order to search the bioactive constituents from natural source , we began to study the chemical consitituents from A. asiatica. By column chromatography, including Silica gel, Toyopearl HW-40 and preparative HPLC, ten new cycloartane triterpene glycosides along with 28 known compounds were isolated from the EtOH extract of A. asiatica. The new compounds structure were determined by 1H NMR, 13C NMR, 2D-NMR spectra and chemical methods as follow: 2'-O-acetyl-25-anhydrocimigenol- 3-O-β-D-xylopyranoside (1),25-O-ethyl-cimigenol-3-O-β-D-xylopyranoside (2),2'-O-acetyl-25-O-ethyl-cimigenol-3-O-β-D-xylopyran-oside (3), 2'-O-acetyl-25-O- methyl-cimigenol-3-O-β-D-xylopyranoside (4),25,4′-O-diacetyl- cimigenol-3-O-β-D-xylopyranoside (5),12,3′-O-diacetyl- cimigenol-3-O-β-D-xylopyranoside (6),23(R), 24(S)-24:25-epoxy-3β,15-dihydroxy-23-O-acetyl-9,19-cyclolanostan-16-one -3-O-β-D-(2′-O-acetyl)xylopyranoside (7), 20(S),22(R),23(S), 24(R)-16β:23;22:25- diepoxy-3β,23,24-trihydroxy-9,19-cyclolanostane-3-O-β-D-(2′-O-acetyl)xylopyranoside (8),3′-O-acetylcimicifugoside(9),4′-O-acetyl-23-epi-26-deoxycimifugoside (10)。(23R, 24S)-16:23;16:24-diepoxy-15α,25-dihydroxy-9,19-cyclolanost-1-en-3-one (11) is a new natural compound. Compound 28,29 and 30 are Tetranor-cycloartane glycosides from Actaea specie for the first time, and ferulamide 35 is also a new structure type from the specie for the first time. Compound 10-38 were isolated from this plant for the first time.
Our previous study showed that the EtOAc extracts revealed significant antitumor actitities, and the further research for isolated compounds were screened by cytotoxity effect with Hela and L929 cells. Compounds 12 and 15 revealed significant inhibitory effects on Hela and 12, 20, 26 revealed significant inhibitory effects on L929 cell line.
我们以L929、Hela细胞系作为药理活性研究对象,考察了绿升麻的乙醇提取物中不同极性的萃取物和分离到的单体化合物的抗肿瘤作用。试验结果表明乙酸已酯萃取物是绿升麻抗肿瘤的活性部位。分离得到的单体化合物12和15对Hela细胞的生长具有较强的抑制作用, 12,20, 26对L929细胞生长具有较强的抑制作用。另外,分离到的其它化合物的药理活性试验还在进行中。
Actaea asiatica Hara (Ranunculaceae) is widely distributed in the southwest and northwest of the People’s Republic of China. As a Chinese folk medicine, its rhizomes is used to treat headache, sore throat, measles, pertussis, prolapse of uterus. In order to search the bioactive constituents from natural source , we began to study the chemical consitituents from A. asiatica. By column chromatography, including Silica gel, Toyopearl HW-40 and preparative HPLC, ten new cycloartane triterpene glycosides along with 28 known compounds were isolated from the EtOH extract of A. asiatica. The new compounds structure were determined by 1H NMR, 13C NMR, 2D-NMR spectra and chemical methods as follow: 2'-O-acetyl-25-anhydrocimigenol- 3-O-β-D-xylopyranoside (1),25-O-ethyl-cimigenol-3-O-β-D-xylopyranoside (2),2'-O-acetyl-25-O-ethyl-cimigenol-3-O-β-D-xylopyran-oside (3), 2'-O-acetyl-25-O- methyl-cimigenol-3-O-β-D-xylopyranoside (4),25,4′-O-diacetyl- cimigenol-3-O-β-D-xylopyranoside (5),12,3′-O-diacetyl- cimigenol-3-O-β-D-xylopyranoside (6),23(R), 24(S)-24:25-epoxy-3β,15-dihydroxy-23-O-acetyl-9,19-cyclolanostan-16-one -3-O-β-D-(2′-O-acetyl)xylopyranoside (7), 20(S),22(R),23(S), 24(R)-16β:23;22:25- diepoxy-3β,23,24-trihydroxy-9,19-cyclolanostane-3-O-β-D-(2′-O-acetyl)xylopyranoside (8),3′-O-acetylcimicifugoside(9),4′-O-acetyl-23-epi-26-deoxycimifugoside (10)。(23R, 24S)-16:23;16:24-diepoxy-15α,25-dihydroxy-9,19-cyclolanost-1-en-3-one (11) is a new natural compound. Compound 28,29 and 30 are Tetranor-cycloartane glycosides from Actaea specie for the first time, and ferulamide 35 is also a new structure type from the specie for the first time. Compound 10-38 were isolated from this plant for the first time.
Our previous study showed that the EtOAc extracts revealed significant antitumor actitities, and the further research for isolated compounds were screened by cytotoxity effect with Hela and L929 cells. Compounds 12 and 15 revealed significant inhibitory effects on Hela and 12, 20, 26 revealed significant inhibitory effects on L929 cell line.
引文
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[2] 刘勇,陈迪华,陈雪松。升麻属植物的化学、药理与临床研究。国外医药(植物药分册),2001,16(2):55-58
[3] Yu Shao,Amanda Harris,Mingfu Wang,et al. Triterpene Glycosides from Cimicifuga racemosa, J.Nat. Prod., 2000,63(7):905-910
[4] Kazuki Watanabe, Yoshihiro Mimaki, Hiroshi Sakagami. Cycloartane Glycosides from the Rhizomes of Cimicifuga racemosa and their cytotoxic activities. Chem. Pharm. Bull. 2002,50(1):121-125
[5] Kusano A., Takahira M., Shibano M., Studies on the Consitituents of Cimicifuga species.XXVI. Twelve New Cyclolanostanol Glycosides from the underground Parts of Cimicifuga simplex WORMSK. Chem. Pharm. Bull., 1999,47(4): 511-516
[6] Erdal Bedir, Ikhlas A. Khan. Cimiracemoside A: A new cyclolanostanol xyloside from the Rhizome of Cimicifuga racemosa. Chem. Pharm. Bull., 2000, 48(3): 425-427
[7] Shao-nong Chen, Wenkui Li, Daniel S. Faricant,Isolation, Structure elucidation, and Absolute Configuration of 26-Deoxyactein from Cimicifuga racemosa and Clarification of Nomenclature Associated with 27-Deoxyactein. J. Nat. Prod., 2002, 65(4): 601-605
[8] Kriatian Wende, Clemens Mügge, Kerstin Thurow. Actaeaepoxide 3-O-β-D-xylopyranoside, a new cycloartane Glycoside from the Rhizome of Actaea racemosa(Cimicifuga racemosa) ,J. Nat., Prod., 2001, 64(7):986-989
[9] Hamburger M., Wegner Ch, Benthin B., Cycloartane glycosides from Cimicifuga racemosa, Pharmaceutical and Pharmacological Letters 2001, 11(2):98-100
[10] Matthias Hamburger, Christian Wegner, Bjorn Benthin, Cycloartane glycosides from Cimicifuga racemosa, Pharmaceutical and Pharmacological Letters, 2001, 11(1):15-17.
[11] Chun Dan, Kai-bei Yu, Shu-lin Peng, et al. Cimicidol-3-one: A cycloartenol triterpenoid from the rhizomes of Cimicifuga racemosa. Acta Crystallographica, 2006, Section E62, o1114-o1115
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