摘要
洋金花为茄科植物白曼陀罗Datura metel L.的干燥花,又名曼陀罗花、风茄花、山茄子、大颠茄和白花曼陀罗等。洋金花生理活性较强,药用历史悠久,应用十分广泛。《中国药典》2005版记载其性味辛、温,有小毒;具平喘止咳、镇痛解痉、麻醉之功效。近年来临床应用洋金花制剂治疗银屑病取得了显著的治疗效果,但对洋金花中治疗银屑病活性成分及其药理作用的研究鲜有报道。为了确定洋金花中治疗银屑病的有效部位,并深入阐明有效部位中的活性成分,对洋金花50%EtOH提取组分进行了药理学实验和化学成分研究。
本文首次从病理环节入手,进行了抗炎、抗瘙痒、抗增殖及对免疫功能的影响等方面的药理学研究,结果表明洋金花50%EtOH提取组分制成的洋金花胶囊具有抗炎、抗皮肤瘙痒、促进皮肤鳞片角化、抗过敏、对抗有丝分裂数等药理作用,其对体液免疫有一定的抑制作用,但对细胞免疫无明显影响。首次确定了洋金花50%EtOH提取组分是治疗银屑病的有效部位。
本文对洋金花治疗银屑病的有效部位进行了系统的提取分离和结构鉴定研究。通过硅胶、ODS、Sephadex LH-20等柱色谱和HPLC等手段,分离出58个化合物,采用~1H-NMR、~(13)C-NMR、~1H-~1HCOSY、~1H-~(13)CCOSY、HMBC和NOESY等1D及2D-NMR波谱学测试技术,并结合ESI-MS、FAB-MS等质谱,鉴定了40个化合物的结构,其中有25个醉茄内酯类化合物、2个酰胺类化合物、3个木脂素类化合物、3个倍半萜类化合物,7个芳香族类化合物。在这40个化合物中,确定有17个醉茄内酯类化合物和2个酰胺类化合物为新化合物,另有15个化合物在该植物中首次发现。19个新化合物分别被命名为洋金花素A(5α,12β,15β-trihydroxy-6α,7α-epoxy-(20R,22R)-1-oxo-witha-2,24-dienolide)、洋金花素B(5α,6β,15β,21-tetrahydroxy-(20R,22R)-1-oxo-witha-24-enolide)、洋金花素C(5α,6β,12β,21-tetrahydroxy-27-O-methyl-(20R,22R)-1-oxo-witha-2,24-dienolide)、洋金花素D(5α,6β,12β,21-tetrahydroxy-(20R,22R)-1-oxo-witha-24-enolide)、洋金花素E(5α,6β,12β,21-tetrahydroxy-(20R,22R)-1-oxo-witha-2,24-dienolide)、洋金花素F(5α,6β,12β-trihydroxy-27-methoxy-21,24-epoxy-(20S,22R,25S)-1-oxo-witha-2-enolide)、洋金花素G(5α,6β,12β,27-tetrahydroxy-21,24-epoxy-(20S,22R,25S)-1-oxo-witha-2-enolide)、洋金花素H[E-1,10-seco-6β,12β,27-trihydroxy-(20R,22R)-witha-3,5,24-trieno-lide-1-acid]。洋金花苷B(5α,27-dihydroxy-6α,7α-epoxy-(20R,22R)-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside)、洋金花苷C(5α,12β,27-trihydroxy-6α,7α-epoxy-(20R,22R)-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside)、洋金花苷D(5α,6α,7β,27-tetrahydroxy-(20R,22R)-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside)、洋金花苷E(5α,6β,7α,27-tetrahydroxy-(20R,22R)-1-oxo-witha-2,24-dienolide-27-O-β-D-glucopyranoside)、洋金花苷F(5α,6β,7α,12β,27-pentahydroxy-(20R,22R)-1-oxowitha-2,24-dienolide-27-O-β—glucopyranoside)、
Flos Datura is the dry flower of Datura metel L which belongs to the family of Solananeae. It was recorded originally in 《Compendium of Materia Medica 》 and has been recorded in every edition of 《Chinese Pharmacopoeia》 including the newest edition in 2005. It has the long history to be used as traditional Chinese medicine and utilized widely to cure many diseases such as cough, asthma, convulsion, etc. due to its strong and wide biological activities. It has been reported that clinical use of Flos Datura showed significant effect on the treatment of psoriasis .However.few of works on its active constituents and pharmacological effects related to the treatment of psoriasis are reported .Chemical and pharmaceutical research have been conducted on the part extracted with 50% ethanol from Flos Datura for the aims of searching the effective section and further determining the active compounds for psoriasis. The experiment results confirmed that the capsules made from the extracted with 50% ethanol from Flos Datura had the effects of antiinflammation, inhibiting skin itch, improving the cutinization of skin scales , antiallergic and inhibiting mitosis. This suggested that the capsules of Flos Datura could inhibit the immunity of body fluid, but not the cell immunity. It is the first time that the chemical constituents extracted with 50% ethanol from Flos Datura was confirmed to be the effective part for the treatment of psoriasis .In the course of our studies on chemical constituents in effective parts of treating psoriasis, 58 compounds were isolated with silica, gel, reversed-phase (ODS) , Sephadex LH-20 column chromatography and HPLC, of which the structures of 40 compounds were fully determined according to the chemical and physicochemical evidence (1D and 2D-NMR). 19 novel compounds were firstly reported and 15 compounds were firstly found in Datara metel L .Among them there are 25 withanolide compounds, 3 lignans compounds, 3 sesquiterpenoids compounds, 2 amide compounds and 7 others.The withanolides comprise a group of complex sterodial lactones which occur in the Solanaceae family. They are of considerable phytochemical, chemotaxonomic and biological interest.The structures of the nine hovel withanolide glycosides were identified as Daturameteloside B (5α, 27-dihydroxy-6α, 7α- epoxy-(20R, 22R)-1-oxo-witha-2, 24-dienolide -27-O-β-D-glucopyranoside), Daturameteloside C (5α, 12β, 27-trihydro-xy-6α, 7α-epoxy- (20R, 22R) -1- oxo-witha-2,24-dienolide- 27-O-β-D-glucopyranosi-de), Daturameteloside D (5α,6α,7β,27-tetrahydroxy - (20R, 22R) -1-oxo-witha-2, 24-dienolide -27-O-β-D-Glucopyranoside), DaturametelosideE (5α, 6β, 7a, 27-tetrahydroxy - (20R, 22R) -1-oxo-witha-2, 24-dienolide -27-O-β-D-glucopyranoside),
引文
[1] 江苏新医学院编,中药大辞典。上海人民出版社,上册:
[2] 国家药典委员会编,中国药典2005年版。北京:化学工业出版社,2005:219-220。
[3] 匡可伍 路安民 主编,中国植物志,第67卷第一分册。科学出版社,1978。
[4] 黄泰康 丁志遵 赵守训 主编,现代本草纲目。中国医药科技出版社,2000:2049～2052。
[5] 肖培根 刘昌孝,国外药用植物的研究、生产和需求概况[J]。中草药,1983,14(6):40～44。
[6] 李英霞 彭广芳 张素芹,洋金花概况[J]。山东医药工业,1989,8 (1):40～43。
[7] DAVID W.PATE and JOHN E.AVERETT Flavonoids of Datura Biochemical Syst ematics and Ecology. 1986;14(6):647-649
[8] 杨炳友 硕士论文《洋金花中治疗银屑病有效部位的化学成分研究》黑龙江中医药大学 2002年
[9] 唐玲 硕士论文《洋金花中治疗银屑病有效部位的化学成分研究》 黑龙江中医药大学 2003年
[10] Kazushi S. Tetsuya K. Furusawa T. et al. The Structures of Daturametelin A and B. Chem.Phann.Bull. 1987, 35(10): 4359～4361.
[11] Kazushi S. Yoriko F. Toshihiro N. et al. New Withanolides, Daturametelins C, D,E,F and G-Ac from Datura metel.L. Chem.Pharm. Bull. 1989,37(8):2132～2135.
[12] Yoshiteru O. Anjana B. Hiroshi H. et al. Withametelin, A Nexacyclic Withanolide of Datura metel. Tetrahedrom Letters, 1987, 28(18): 2025～2028.
[13] Mohini G. Manickam M. Subhash C. et al. Withanolides of Datura metel. Phytochemistry 1992, 31 (7): 2423～2425.
[14] Mahmood T. et al. Daturametelins, Withanolides of Datura metel. Planta Medical, 1988, 54(5): 468～470.
[15] Hugo E.Gottlieb I Kirson et al.~(13)C-NMR Spectroscopy of the Withanolides and Other Highly oxygenated C_(28) Steroids Organic Magnetic Resonance. 1981, 16(1): 20～25.
[16] E. Glotter et al. Withanolides and Related Ergostane-type Steroids. Natural Product Reports, 1991, 415～440.
[17] Manfred Lischewski. Nguyen Thibich H. Andrea Porael. et al. Withanolide Glycosides from Danalia Australis. Phytochemistry, 1992, 31 (3): 939～942.
[18] 徐州医学院药理教研组,关于莨菪碱的中枢作用原理的初步探讨[J]。新医药学杂志,1976,(1):27～31。
[19] 阴健.中药现代研究与临床应用Ⅰ.学院出版社.509～517.
[20] 徐州医学院药理组.中华医学杂志,1976,56(11):697
[21] 河南医学院药理教研组气管炎小组.第一届全国药理学会学术会议论文摘要汇编,1979,7
[22] 上海大屯矿工医院.中麻通讯,1977,(4):38.
[23] 周金黄.中药药理学.上海:科学技术出版社.1990.231
[24] 张向清,孙琦.莨菪类药物对烧伤休克临床过程的影响.山东医药,1981,5:22
[25] 张向清,金淑静,张继芬.中麻通讯.1979,13(6):215.
[26] 周建华 贺永香 张建国 等,洋金花总碱注射液治疗银屑病100例临床观察[J]。吉林中医药,1986,(6) 14。
[27] 黑龙江中医学院银屑病科研组,中药洋金花为主治疗银屑病242例报告[J]。中医杂志,1985,26 (2):32。
[28] 卢锦 欧阳宪,洋金花治疗精神分裂症85例临床观察[J]。广西中医药,1985,8 (2):9～10。
[29] 刘康平,洋金花酊剂治疗慢性支气管炎118例临床观察[J]。黑龙江中医药,1992,(1):18～19。
[30] 李英霞,彭广芳,张素芹.洋金花概况.山东医药工业,1989,8(1):40～43.
[31] Witte Ludger W. et al. Plant Med, 1987, 53(2): 192～197.
[32] 卞春甫,刑淑华,金淑静,等.东莨菪碱对痛和镇痛的影响.中麻通讯,1977,(4):58
[33] I.Kirson I. Zaretskii E. Glotter et al J.Chem. Soc. Perkin Trans/,1976,1244.
[34] David Lavie, Erwin, Youval shvo,Constituents of Withania ,J.of organic chemistry 1965,30,1774～1778.
[35] Issac Kirson ,Ariela Cohem ,Arieh Abraham,Withanolides Q and R ,Two new 23-Hydroxy-steroidal Lactones ,J.chem..soc.1975(21),2136～2138.
[36] Frank W.Eastwood, Isaac Kirson, David Lavie et al.New withanolides from a cross of a south African chemotype by chemotype Ⅱ (Israel) in withania somnifera, Phytochemistry 1980,(19), 1503～1507.
[37] S.Chatterjee,S.K.Chakraborti,Antimicrobial activities and other withanolides ,Antonie van Leeuwehoek 46(1980)59～63.
[38] Vincent vande velde and David Lavie ,New withanolides of biogenetic interest from, Phytochemistry 1981,(20),6,1359～1364.
[39] E. glotter , I.Kirson , A.Abraham and D.Lavie, Constituents of Withania somnifera Dun, Tetrahedron 1987,vol 29,1353～1364.
[40] Mohammed All, Mohammed Shuaib and Shahid Husain Ansari ,Withanolides from the stem bark of withania somnifera
[41] Atta-ur-Rabrnan,M.Iqal Chouhary ,Samina Qureshi, et al.Two new ergostane-Type Steroidal Lactones from withania coagulans ,J.Nat. Prod. 1998,61,812～814.
[42] B.singh ,A.K.Saxena ,ca tl,Adaptogenic Activity of a novel ,Withanolide-free Aqueous Fraction from the Roots of, Phytochemistry 2001 ,(15),311～318.
[43] Hisashi Matsuda ,Toshiyuki Murakami ,Akinobu kishi and Masayuki yoshikawa ,Structure of Withanolides Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,Ⅵ,and Ⅶ,New Withanolide Glycosides ,from the Roots of Indian DUNAI.and Inhibitory Activity for Tachyphylaxis to Ctonidine in Isolated Guinea-Pig Ileum , Bioorganic medicinal chemistry 9(2001)1499～1507.
[44] Swagata Ray ,Sumita Jha ,Production of Withferin A in Shoot Cultures of Withania Somnifera, Planta Med 67,(2001),432～436.
[45] E.Glotter,R.Waitman ,and D.Lavie ,Constituents of Withaniasomnifera Dun. ,part Ⅷ.A NewSteroidal Lactone ,27-Deoxy- 14-hydroxy-with aferin A.,J.chem. soc. 1966 (19) 1765～1767.
[46] Ahmad M.Abou-Douh New Withanolides and Other Constiuents from the Fruit of Withania Somnifera, Arch.pharm.Med.Chem.2002,6,267～276.
[47] Atta-ur-Rahman, Dur-e-Shawar, Aniqa Naz, Iqbal Choudhary ,Withanolides from Withania coagulans, Phytochemistry 2003,(63),387～390.
[48] Subhash C.Sinha, Abid Ali ,Anjana Bagchi et al,Physalidicanols,New Biogenetic Precursors of C_(28)-Steroidal Lactones from Physalis minima var.indica ,Planta Meal 1987,55～57.
[49] E.GIotter ,Miriam Cojocaru,Subhash C.sinha,et al .Withanolide from Physalis minima,
[50] O.E.Vasina ,V.A.Maslennikova ,N.D.Abdullaev,Withasteroids of Phsalis.Ⅶ.14a-Hydroxyixocarpano- lideand 24,25-Epoxywithanolide D,Chem.Nat.Comp. 1987,22(5,)560-565.
[51] KAZUSHI Shingu ,Shoji Yahara,Toshiro Nohara ,and Hikaru Okabe,Three New Withanolides Physagulins A,B and D from angulata L.,Chem.Pharm.Bull. 1992,40(8) ,2088-2091.
[52] GL.Silva , A.Pacciaroni, J.C.Obertl ,A.S.Veleiro and GBurton,Apregnane structurally Related to Withanolides from Physalis Viscosa, Phytochemistry 1993,(34),871~873
[53] Shinya Nagafuji ,Hikaru Okabe,Hiroshige Akahane ,and Fumiko Abe,Trypanocidal Constituents in Plants 4.Withanolides from the Aerial Parts of Physalis angulata.
[54] Tariq Mahmood ,S.Salman Ahmad ,and Salimuzzaman Siddiqui,Daturilinol-A New Withanolide from the leaves of Datural Metel ,Heterocycies 1988,(27),l,101 -103.
[55] Subhash C.Sinha ,Sujata Kundu ,Rakesh Maurya and Anil B.Ray, Structure of withametelin and Isowithametelin, Withanolides of Datura Metel Leaves ,Tetrahetron ,1989,(45),7,2165~2176.
[56] Mohini Gupta ,Anjana Bagchi ,and Anil B.Ray, Additional Withanolides of Datura Metel,J.Nat.Prod. 1991 ,(54),2,599~602.
[57] M.A.Farboodniay Jahromi ,M.Manickam,Mohini Gupta ,Yoshiteru Oshima ,Withametelins F and G ,Two New Withanolides of Datura metel ,J.Chem.
[58] M.Manickam ,S.B.Awasthi,Yoshiteru Oshima ,Kanehiko Hisamichi Additional C-21 Oxygenated Withanolides from Datura Fastuosa ,J.Chem Research 1994,306-307.
[59] Kazushi Shingu Shoji Yahara and Toshihiro Nohara , New Withanolides , Daturataturins A and B from Datura tatura L.Chem .Pharm.Bull.l990,38(12)3485-3487.
[60] M.Manickam,S.Kumar,A.Sinha-Bagchi ,S.C.Sinha, and A.B.Ray.Withametelin H and Withafastuosin C,Two New Withanolides from the Leaves of Datura Species .
[61] Adriana S.Veleiro,Adriana M.Cirigliano ,Juan C.Oberti,andGerardo Burton 7-Hydroxywithanolides from Datura ferox ,J.Nat.Prod. 1999,62,1010-1012.
[62] Bina S.Siddiqui Imran Ali Hashmi ,and Sabira Begum,Two New Withanolides from the aerial parts of Datura innoxia ,Heterocycles,2002,(57),4,715~721.
[63] Adriana S.Veleiro, Juan C.Oberti and Gerardo Burton ,A Ring -Daromatic Withanolide from Salpichroa Origanifolia, Phytochemistry 1992,(31),3,935-937.
[64] Adriana S.Veleiro ,Gerardo Burton ,New withanolidesa fromSalpichroa origamifolia,J. Nat.Prod. 1994,(57), 12,1741-1745.
[65] M.Cristina Tetamanzi ,Adriana S.Veleiro,Juan C.Oberti and Gerardo Burton ,Ring D Aromatic Ergostane Derivatives from Salpichroa origanifolia, Phytochemistry 1996,(43),2,461-463.
[66] M.Cristina Tettamanzi, Adriana S.Veleiro Juan C.Oberti ,and Gerardo Burton ,New Hydroxylated Withanolides from Salpichroa origanifolia,J.Nat.Prod.l998,(61),338-342.
[67] GMareggiani ,M.I.Picollo ,E.Zerba,G.Burton ,M.O.V.Benedetti-Doctorovich, and A.S.Veleiro,Anti- feedant Activity of Withanolides from Salpichroa origanifolia on Musca dome4stica,J.Nat .Prod. 2000,(63), 1113-1116.
[68] M.Cristina Tettamanzi ,Adriana S.Velerio Juana R.de la Fuente ,and Gerardo Burton .Withanolides from Salpichroa origanifolia, J.Nat.Prod.2001,(64),783~786.
[69] Masood Parvez ,Victor Fajardo and Maurice Shamma, Structure and Abosolute Configuration of (23 R)-6α-Chloro-5β,17β-dihydroxy-12β-methoxy-1-oxo-12,22,-epoxyergosta-2,24-dien-23,26-olide, a New Witholide from Jaborosa magellanica,Acta Cryst. 1991,(47),757～759.
[70] Adriana S.Veleiro,Claudia E.Trocca ,et al .A Phenolic withanolide from Jaborosa Leucotricha , Phytochemistry 1992,(31),7,2550～2551.
[71] Rosana I.Misico,Juan C.Oberti, New 19-Hydroxysithanolides from Jaborosa Leucotricha, J.Nat.Prod. 1996,(59),66～68.
[72] Rosana I.Misico ,Adriana S.Veleiro ,Gerardo Burton and Juan C.Oberti,Withanolides from Jaborosa Leucotricha, Phytochemistry 1997,(45),5,1045～1048.
[73] Adriana M.Cirigliano ,Adriana S.Veleiro ,Spiranoid Withanolides from Jaborosa odonelliana, J.Nat. Prod,2002,65,1049～1051.
[74] Viviana E.Nicotra ,Roberto R.Clarisa Vaccarini ,Juan C.Oberti .and -Gerardo Burton, 15,21-Cyclo withanolides from Jaborosa bergii.
[75] Adriana S. Veleiro, Claudia E. Trocca, Gerardo. Burtom and Juan C. Oberti, A phendic withanolide from Jaborosa Leucotricha, Phytochemistry 1992,(31),7,2550～2551.
[76] Rosana I Misico,Rober to R. Gil, Juan C. Oberti, et al. Withanalides from vassobia lorentzil,J. Nat. Prod, 2000,63,1329～1332.
[77] Gloria L. Silua, Gerardo Burton,and Juan C. Oberti, 18,20-Hemiacetal-type, and other withanalides from Dunalia brachyacantha, J. Nat.Prod, 1999,62,949-953.
[78] Sandro Minguzzi, Lauro E. S. Barata, Young Geun Shin, etal.,Cytotoxic withanolides from Aenistus avborescens, Phytochemistvy ,2002,59,635～641.
[79] Roberto R. Gil,Rosana. J Misico, Ignacio R Sotes ,and Juan C oberti, 16-Hydroxylated withanlides from Exodeconus maritimus, J Nat. Prod. 1997,60,568～572.
[80] Pir Muhammad Khan, Abdul Malik ,Saeed Ahmad ,and Hafiz Rub Nawaz.,Withanalides from Ajuga Paruiflora, J. Nat Prod 1999,62,1290～1292.
[81] Akihito Yokosuka ,Yoshihiro mimaki ,and Yutaka sashida, Chantriolides A and B, Two New. Withanolide Glucosides from the Rhizomes of Tacca chantrieri, J Nat. Prod .2003,66,876～878.
[82] Rosana I. Misico,Lynda L.song,Adriana S.Veleiro et al ,Induction of Quinone Reductase by Withanolides, J Nat. Prod. 2002,65,677～680.
[83] 卞春甫 刑淑华 金淑静等,东莨菪碱对痛和镇痛的影响[J]。药学学报,1979,14(7):397～401。
[84] 钮心懿 王维君 金荫昌,东莨菪碱及其与几种中枢药物合并应用对大鼠回避性条件反射的影响[J]。生理学报,1965,28(1):47～48。
[85] 张英鸽 可君,莨菪类药物对大鼠脑、心肌血流量和心指数的影响[J]。中国药理学与毒理学杂 志,1992,6 (2):110～112。
[86] 张忠懋 彭宝良 万清顺 等,东莨菪碱对狗心肌力学的影响[J]。中华麻醉学杂志,1983,3(3):138～140。
[87] 张向清 孙奇,莨菪类药物对烧伤休克临床过程的影响[J]。山东医药,1981,5:229～230。
[88] 高从光 杨玲芬 何昌镯 等,山莨菪碱治疗急性胰腺炎63例疗效观察[J]。中华内科杂志,1982,21(12):755。
[89] 冯卫生,毕跃峰,郑晓珂等.马尾松松针中木脂素类化学成分的研究.药学学报,2003,38(3);
