朗德鹅胆汁化学成分及其生物活性的研究
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摘要
朗德鹅(Anser anser)为鸭科动物(Anser domestica Geese),鸟纲雁形目(Anseriformes)雁属(Anser)大型水禽,又名灰天鹅、灰雁等。朗德鹅是从法国引进的世界优质肉鹅品种,该品种体型中等,羽毛灰褐色,食性广,适应性强,是生产鹅肥肝的优良品种。
国内外关于动物胆汁的化学成分和生物活性等方面的研究非常活跃,迄今为止,各国研究人员已经相继从动物胆汁中获得了十几类化学物质,其中包括胆汁酸、胆色素、胆固醇、脂肪酸、卵磷脂、常量和微量元素以及氨基酸等主要物质。现代药理研究表明,胆汁具有抗菌、抗炎、治疗胆囊结石、解热镇痛、抗氧化、抗癌等药理活性。本文对朗德鹅胆汁做了以下几个方面的研究:
1.综述了国内外动物胆汁的化学成分、生物活性研究的概况。
2.化学成分研究:利用柱层析、萃取、重结晶等化学和物理方法,从朗德鹅胆汁中分离得到10个单体化合物,依据理化性质、光谱学分析和化学方法,确定了其中7个单体化合物的结构,分别为:苯乙酸(Ⅰ);3α, 7α-二羟基-5β-胆甾酸(Ⅱ); 3α, 7α-二羟基-5β-胆甾酸乙酯(Ⅲ);3α-乙酰氧基-7α-羟基-5β-胆甾酸(Ⅳ);顺-6-十八碳烯酸(Ⅴ) ;棕榈酸-α-单甘油酯(Ⅵ) ; (4E)-2-[2′-hydroxyhexadecanoylamino]-4-Octadecane-1,3-diol (Ⅶ)。其中化合物Ⅳ为新化合物,化合物Ⅰ、Ⅲ、Ⅳ、Ⅵ、Ⅶ均为首次从该动物中获得,
3.首次发现从朗德鹅胆汁中分离得到的化合物Ⅱ具有抗金属蛋白酶的活性。
In this paper, the chemical compositions and pharmacological activities of the bile of Anser anser were studied.
According to the references, many kinds of compounds were isolated and identified as so far from animal's bile, such as bile acid,bile pigment,cholesterol,fatty acid,minor element,amino acids and so on. The modern pharmacological studies showed that bile had the effects of antibiosis ,antiinflammatory,antioxygen, anticancer etc.. In order to find out more chemical constituents which have bioactivities in the bile of Anser anser and develop more new healthy maintenances and drug products, our group gave a comprehensive researches. The research methods and results are as follow:
Firstly, pulverized and dried bile of Anser anser (500g) were extensively extracted with 85% alcohol and the combined extract were concentrated in vacuo until
`no-alcohol, then got the total extracts (45g), Which were extracted further by petroleum ether, chloroform, acetic ether, and n-butyl alcohol respectively at room temperature. By using silica gel column chromatography、TLC and recrystallizing methods 10 compounds were obtained from extracts. Among of them, seven compounds′structures were established and identified on the basis of chemical and spectroscopic evidence (1HNMR,13CNMR,2DNMR, MS).They are phenylacetic acid (Ⅰ),Chenodeoxycholic acid (Ⅱ) , 3α,7α-dihydroxy- 5β-cholan-24- carboxylic ethyl ester (Ⅲ), 3α-acetoxy-7α-hydroxy-5β-cholan-24-oic acid(Ⅳ), (Z)-6-Octadecenoic acid (Ⅴ), hexadecanoicacid , 2,3-dihydroxypropyl ester(Ⅵ), (4E)-2-[2′-hydroxyhexadecanoylamino]-4-Octadecane-1,3-diol (Ⅶ).
The inhibiting Matrix Metalloproteinase biological activities of the compoundⅡhave been study firstly. The result showed that it had a clear effect of inhibiting Matrix Metalloproteinase.
国内外关于动物胆汁的化学成分和生物活性等方面的研究非常活跃,迄今为止,各国研究人员已经相继从动物胆汁中获得了十几类化学物质,其中包括胆汁酸、胆色素、胆固醇、脂肪酸、卵磷脂、常量和微量元素以及氨基酸等主要物质。现代药理研究表明,胆汁具有抗菌、抗炎、治疗胆囊结石、解热镇痛、抗氧化、抗癌等药理活性。本文对朗德鹅胆汁做了以下几个方面的研究:
1.综述了国内外动物胆汁的化学成分、生物活性研究的概况。
2.化学成分研究:利用柱层析、萃取、重结晶等化学和物理方法,从朗德鹅胆汁中分离得到10个单体化合物,依据理化性质、光谱学分析和化学方法,确定了其中7个单体化合物的结构,分别为:苯乙酸(Ⅰ);3α, 7α-二羟基-5β-胆甾酸(Ⅱ); 3α, 7α-二羟基-5β-胆甾酸乙酯(Ⅲ);3α-乙酰氧基-7α-羟基-5β-胆甾酸(Ⅳ);顺-6-十八碳烯酸(Ⅴ) ;棕榈酸-α-单甘油酯(Ⅵ) ; (4E)-2-[2′-hydroxyhexadecanoylamino]-4-Octadecane-1,3-diol (Ⅶ)。其中化合物Ⅳ为新化合物,化合物Ⅰ、Ⅲ、Ⅳ、Ⅵ、Ⅶ均为首次从该动物中获得,
3.首次发现从朗德鹅胆汁中分离得到的化合物Ⅱ具有抗金属蛋白酶的活性。
In this paper, the chemical compositions and pharmacological activities of the bile of Anser anser were studied.
According to the references, many kinds of compounds were isolated and identified as so far from animal's bile, such as bile acid,bile pigment,cholesterol,fatty acid,minor element,amino acids and so on. The modern pharmacological studies showed that bile had the effects of antibiosis ,antiinflammatory,antioxygen, anticancer etc.. In order to find out more chemical constituents which have bioactivities in the bile of Anser anser and develop more new healthy maintenances and drug products, our group gave a comprehensive researches. The research methods and results are as follow:
Firstly, pulverized and dried bile of Anser anser (500g) were extensively extracted with 85% alcohol and the combined extract were concentrated in vacuo until
`no-alcohol, then got the total extracts (45g), Which were extracted further by petroleum ether, chloroform, acetic ether, and n-butyl alcohol respectively at room temperature. By using silica gel column chromatography、TLC and recrystallizing methods 10 compounds were obtained from extracts. Among of them, seven compounds′structures were established and identified on the basis of chemical and spectroscopic evidence (1HNMR,13CNMR,2DNMR, MS).They are phenylacetic acid (Ⅰ),Chenodeoxycholic acid (Ⅱ) , 3α,7α-dihydroxy- 5β-cholan-24- carboxylic ethyl ester (Ⅲ), 3α-acetoxy-7α-hydroxy-5β-cholan-24-oic acid(Ⅳ), (Z)-6-Octadecenoic acid (Ⅴ), hexadecanoicacid , 2,3-dihydroxypropyl ester(Ⅵ), (4E)-2-[2′-hydroxyhexadecanoylamino]-4-Octadecane-1,3-diol (Ⅶ).
The inhibiting Matrix Metalloproteinase biological activities of the compoundⅡhave been study firstly. The result showed that it had a clear effect of inhibiting Matrix Metalloproteinase.
引文
[1] 王凯平, 石朝周. 动物胆汁药用研究的概况与展望[J].中国中医药技, 2000, 7(5):350～352
[2] Kaoru Ishizaki, Teruaki Imada, Makoto Tsurufuji. Hepatoprotective bile acid ‘ursodeoxycholic acid (UDCA)’: Property and difference as bile acids [J]. Hepatology Research , 2005, 33 (2): 174～177
[3] M.P.Guarino, S. Carotti, and M.Sarzano, et al. Short-term ursodeoxycholic acid treatment improves gall bladder bile turnover in gallstone patients: a randomized trial [J]. Neurogastroenterology & Motility, 2005, 17 (5): 680～686
[4] G. Toda, N. Tanaka and Y. Ikeda, et al. The long-term trial of ursodeoxycholic acid treatment in patients with primary biliary cirrhosis [J]. Igaku to yakugaku,1999, 41: 609～633
[5] 李培锋, 关红. 鸡胆汁的有效成分分析及其药理学研究[A].科研鉴定材料, 2001:12
[6] 彭新磊. 胆汁、胆酸和胆汁酸[J]. 生物学通报, 1998,33(3): 23～24
[7] Russell, D.W. The enzymes, regulation, and genetics of bile acid biosynthesis[J]. Ann Rev Biochem, 2003, 72: 137～174
[8] Hofmann, A.F., C.D. Schteingart, and L.R. Hagey. Species differences in bile acid metabolism [M]. Boston : Kluwer Academic Publishers, 1995: 3～30
[9] Moschetta, A. F. Xu, and A.F. Hofmann, et al. A phylogenetic survey of biliary lipids in vertebrates [J]. J Lipid Res ,2005, 46:2221～2232
[10] 王少圣, 徐宜萍. 胆红素提取方法的探讨[J]. 基层中药杂志, 1999, (1): 35～36
[11] 闫兆威, 杨丽, 李平亚. 朗德鹅胆中有机酸酯类成分的 GC-MS 分析[J].特产研究, 2007, 29(3): 48～49
[12] 国家医药管理局中草药情报中心站. 植物药有效成分手册[M]. 北京: 人民卫生出版社, 1986: 1004
[13] 孙文基, 绳金房. 天然活性成分简明手册[M]. 北京:中国医药科技出版社, 1998: 350～422
[14] 张德桐. 鸡胆汁与蛇胆汁组分的对比研究[J]. 中国生化药物杂志, 1994, 15(1): 4～7
[15] 张晓薇, 刘养清, 赵慧辉. 常见动物胆汁宏量和微量元素的原子吸收分析及研究[J]. 山西医药杂志, 2003, 32 (2):110～112
[16] 张中泉, 陈百泉, 杜钢军,等. 猪胆汁乙醇提取物对消化系统的影响[J]. 山西中药, 2002, (4): 49～50
[17] 张新兵. 明矾加鲜猪胆汁根治滴虫性阴道炎 70 例[J]. 中医外治杂志, 2002, (2): 49～50
[18] 李培峰, 关红, 哈斯苏荣,等.鸡胆汁有效成分 CDCA 和 TCDCA 的抗炎作用研究[J]. 中兽医医药杂志, 2002, (1): 7～10
[19] 李武军,张秀芹.人工引流熊胆和天然熊胆药理作用的比较[J].中药材,1990,13(2):12～15
[20] 刘思纯. 胆道结石的治疗进展[J]. 新医学,1998,29 (11) 567～568
[21] 张豁中,温玉鳞主编. 动物活性成分化学[M].天津:天津科学技术出版社,1999:1614～1616
[22] 李培锋, 关红. 鸡胆汁有效成分 Tau 和 CA 的解热镇痛作用研究[J].中兽医医药杂志,2003, 2:3～4
[23] 杨钟. 牛磺酸鹅去氧胆酸对小鼠体内氧自由基代谢的影响[J].中国兽药杂志, 2006,40(5): 32～35
[24] 孙铁民, 梁伟, 张启明,等. 熊胆抑瘤作用研究[J].辽宁中医杂志, 2003, 30 (1):661
[25] WALI RK, STOIBER D, NGUYENL, et al. Ursodeoxycholic acid inhibits the initiation and postinitiation phases of azoxymethane-induced colonic tumor development[J] .Cancer Epidemiol Biomarkers Prev,2002 ,11 (11) : 1316～1321
[26] IM EO, CHOI YH, PAIK KJ, et al. Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells[J]. Cancer Lett,2001, 163 (1) 83～93
[27] OYAMA K, SHIOTA G, ITOH, et al. Reduction of hepatocarcinogenesis by ursodeoxycholic acid in rats[J]. Carcinogenesis, 2002, 23 (5) : 885～892
[28] Jiang W, Bond J S. Famillies of metalloendopeptidases and their relationships[J].FEBS Lett ,1992,312:110～114
[29] Schartz, G K. Defining the Invasine Phenotype of Proximal Gastric Cancer Cells[J].Cancer, 1994,73: 22
[30] 庄黎译. Bayer 公司及 A gouron 公司在 MMP 抑制剂领域的竞争[J].中国医药工业信息,1995,(5):6
[31] 张海龙. 海洋细菌 Bacillus sp.发酵液中的化学成分[J].中国药物化学杂志,2003,5(13):294～296
[32] Lee, S.P., R. Lester, and J.S. Pyrek. Vulpecholic acid (1α,3α,7α- trihydroxy-5β-cholan-24-oic acid): a novel bile acid from a marsupial, Triosurus vulpecula[J]. Lipid Res,1987, 28:19～31
[33] 冷蕾. 林下参种子化学成分及其生物活性的研究:[学位论文][D].长春:吉林大学, 2007
[34] 巢志茂, 刘静明. 双边栝楼化学成分研究[J].中国中药杂志,1991,16 (2):97
[35] 秦文杰,王钢力,林瑞超. 短柱肖菝葜化学成分的研究[J].中药材, 2007,8(30):959～961
[36] Jiyoung R. ,Ju S.K., Sam S.K. Cerebrosides from Longan Arillus[J]. Arch . Pharm. Res., 2003,26(2): 138～142
[37] 华会明, 裴月湖. 神经鞘苷的研究概况[J]. 沈阳药科大学学报, 2001, 18(4):299～306
[38] 赵春超. 凤眼草和蓬子菜化学成分及生物活性研究:[学位论文][D].沈阳:沈阳药科大学, 2007
[39] 周光雄, 黄美燕, 石建功. 一种草苔虫中的神经酰胺类化合物[J] .中国海洋药物杂志, 2005, 24(6): 37～40
[40] JIN Feng-Hai, WANG Hui-ling,ZHAO Shu-hua, et al. Inhibition of Metallo proteinase Activity by Chinese Formulations Used to Treat Inflammatory Disease[J]. Chem. Res. Chinese U, 2006, 22(2) : 21～23
[2] Kaoru Ishizaki, Teruaki Imada, Makoto Tsurufuji. Hepatoprotective bile acid ‘ursodeoxycholic acid (UDCA)’: Property and difference as bile acids [J]. Hepatology Research , 2005, 33 (2): 174～177
[3] M.P.Guarino, S. Carotti, and M.Sarzano, et al. Short-term ursodeoxycholic acid treatment improves gall bladder bile turnover in gallstone patients: a randomized trial [J]. Neurogastroenterology & Motility, 2005, 17 (5): 680～686
[4] G. Toda, N. Tanaka and Y. Ikeda, et al. The long-term trial of ursodeoxycholic acid treatment in patients with primary biliary cirrhosis [J]. Igaku to yakugaku,1999, 41: 609～633
[5] 李培锋, 关红. 鸡胆汁的有效成分分析及其药理学研究[A].科研鉴定材料, 2001:12
[6] 彭新磊. 胆汁、胆酸和胆汁酸[J]. 生物学通报, 1998,33(3): 23～24
[7] Russell, D.W. The enzymes, regulation, and genetics of bile acid biosynthesis[J]. Ann Rev Biochem, 2003, 72: 137～174
[8] Hofmann, A.F., C.D. Schteingart, and L.R. Hagey. Species differences in bile acid metabolism [M]. Boston : Kluwer Academic Publishers, 1995: 3～30
[9] Moschetta, A. F. Xu, and A.F. Hofmann, et al. A phylogenetic survey of biliary lipids in vertebrates [J]. J Lipid Res ,2005, 46:2221～2232
[10] 王少圣, 徐宜萍. 胆红素提取方法的探讨[J]. 基层中药杂志, 1999, (1): 35～36
[11] 闫兆威, 杨丽, 李平亚. 朗德鹅胆中有机酸酯类成分的 GC-MS 分析[J].特产研究, 2007, 29(3): 48～49
[12] 国家医药管理局中草药情报中心站. 植物药有效成分手册[M]. 北京: 人民卫生出版社, 1986: 1004
[13] 孙文基, 绳金房. 天然活性成分简明手册[M]. 北京:中国医药科技出版社, 1998: 350～422
[14] 张德桐. 鸡胆汁与蛇胆汁组分的对比研究[J]. 中国生化药物杂志, 1994, 15(1): 4～7
[15] 张晓薇, 刘养清, 赵慧辉. 常见动物胆汁宏量和微量元素的原子吸收分析及研究[J]. 山西医药杂志, 2003, 32 (2):110～112
[16] 张中泉, 陈百泉, 杜钢军,等. 猪胆汁乙醇提取物对消化系统的影响[J]. 山西中药, 2002, (4): 49～50
[17] 张新兵. 明矾加鲜猪胆汁根治滴虫性阴道炎 70 例[J]. 中医外治杂志, 2002, (2): 49～50
[18] 李培峰, 关红, 哈斯苏荣,等.鸡胆汁有效成分 CDCA 和 TCDCA 的抗炎作用研究[J]. 中兽医医药杂志, 2002, (1): 7～10
[19] 李武军,张秀芹.人工引流熊胆和天然熊胆药理作用的比较[J].中药材,1990,13(2):12～15
[20] 刘思纯. 胆道结石的治疗进展[J]. 新医学,1998,29 (11) 567～568
[21] 张豁中,温玉鳞主编. 动物活性成分化学[M].天津:天津科学技术出版社,1999:1614～1616
[22] 李培锋, 关红. 鸡胆汁有效成分 Tau 和 CA 的解热镇痛作用研究[J].中兽医医药杂志,2003, 2:3～4
[23] 杨钟. 牛磺酸鹅去氧胆酸对小鼠体内氧自由基代谢的影响[J].中国兽药杂志, 2006,40(5): 32～35
[24] 孙铁民, 梁伟, 张启明,等. 熊胆抑瘤作用研究[J].辽宁中医杂志, 2003, 30 (1):661
[25] WALI RK, STOIBER D, NGUYENL, et al. Ursodeoxycholic acid inhibits the initiation and postinitiation phases of azoxymethane-induced colonic tumor development[J] .Cancer Epidemiol Biomarkers Prev,2002 ,11 (11) : 1316～1321
[26] IM EO, CHOI YH, PAIK KJ, et al. Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells[J]. Cancer Lett,2001, 163 (1) 83～93
[27] OYAMA K, SHIOTA G, ITOH, et al. Reduction of hepatocarcinogenesis by ursodeoxycholic acid in rats[J]. Carcinogenesis, 2002, 23 (5) : 885～892
[28] Jiang W, Bond J S. Famillies of metalloendopeptidases and their relationships[J].FEBS Lett ,1992,312:110～114
[29] Schartz, G K. Defining the Invasine Phenotype of Proximal Gastric Cancer Cells[J].Cancer, 1994,73: 22
[30] 庄黎译. Bayer 公司及 A gouron 公司在 MMP 抑制剂领域的竞争[J].中国医药工业信息,1995,(5):6
[31] 张海龙. 海洋细菌 Bacillus sp.发酵液中的化学成分[J].中国药物化学杂志,2003,5(13):294～296
[32] Lee, S.P., R. Lester, and J.S. Pyrek. Vulpecholic acid (1α,3α,7α- trihydroxy-5β-cholan-24-oic acid): a novel bile acid from a marsupial, Triosurus vulpecula[J]. Lipid Res,1987, 28:19～31
[33] 冷蕾. 林下参种子化学成分及其生物活性的研究:[学位论文][D].长春:吉林大学, 2007
[34] 巢志茂, 刘静明. 双边栝楼化学成分研究[J].中国中药杂志,1991,16 (2):97
[35] 秦文杰,王钢力,林瑞超. 短柱肖菝葜化学成分的研究[J].中药材, 2007,8(30):959～961
[36] Jiyoung R. ,Ju S.K., Sam S.K. Cerebrosides from Longan Arillus[J]. Arch . Pharm. Res., 2003,26(2): 138～142
[37] 华会明, 裴月湖. 神经鞘苷的研究概况[J]. 沈阳药科大学学报, 2001, 18(4):299～306
[38] 赵春超. 凤眼草和蓬子菜化学成分及生物活性研究:[学位论文][D].沈阳:沈阳药科大学, 2007
[39] 周光雄, 黄美燕, 石建功. 一种草苔虫中的神经酰胺类化合物[J] .中国海洋药物杂志, 2005, 24(6): 37～40
[40] JIN Feng-Hai, WANG Hui-ling,ZHAO Shu-hua, et al. Inhibition of Metallo proteinase Activity by Chinese Formulations Used to Treat Inflammatory Disease[J]. Chem. Res. Chinese U, 2006, 22(2) : 21～23