【作者】 乌力吉特古斯；

【导师】 白学良；

【作者基本信息】 内蒙古大学 ， 植物学， 2008， 博士

【摘要】 乌头属植物为有毒植物,全世界乌头属植物约有300种,分布于北半球温带,主要分布于亚洲,其次在欧洲和北美洲。我国约有200种,除海南岛外在我国台湾和大陆各省区都有分布。草乌在中国主要分布于内蒙古、北京、山西、吉林、黑龙江、辽宁等地。在我国可供药用的乌头属植物约有76种,其中附子（乌头的子根的加工品）、川乌（乌头的干燥母根）、草乌（蒙医药和中医药用草乌为北乌头的干燥块根,藏医药用的草乌为伏毛铁棒锤的干燥块根）为常用药材品种。乌头属植物多具有祛风除湿、温经止痛之功效,可用于治疗跌打损伤、关节炎、神经性疼痛、中风瘫痪、胃肠炎、月经不调、痈疽疮毒等症。蒙医药学是祖国医学的重要组成部分,随着科学技术的快速发展和各兄弟民族医学的学术交流,蒙医药越来越受到世人的关注。由于蒙医药形成的历史背景、文化交融和分布的地域等诸多因素,使广大蒙医药工作者在同一种组方药材使用上,特别是植物药材的使用上存在着同物异名或同名异物的现象,并且与兄弟民族医药学存在着交叉使用的情况,因此造成名称和原药材使用上的混乱。在草乌使用上,中医药主要是用附子、川乌、北乌头,蒙医药则用主要有北乌头,藏医药所用的乌头属原植物主要有:伏毛铁棒锤、铁棒锤、伏毛直序乌头、工布乌头等。对于草乌的叶子,三种医药学在原植物的认识、药材品种选择及临床应用上各不相同。蒙医药应用草乌叶的历史悠久,临床有效验方较为丰富,对其有效成分的提取和化学结构鉴定方面取得了一定成果。鉴于以上的研究认知和研究背景,我们对三种传统医学常用的植物药材草乌和草乌叶进行了系统深入的研究,并取得了以下研究成果:（1）对草乌和草乌叶的民族医药学认知进行了全面综述,包括中、蒙、藏医对草乌原植物的应用现状研究概况,历史渊源和现代研究进展。中医药使用主要是附子、川乌、草乌（北乌头干燥块根）,同时因产地及习惯上的不同也将黄草乌、多裂乌头、瓜叶乌头、圆锥序乌头、松潘乌头及太白乌头的干燥块根当草乌用。蒙医药所用的乌头,除北乌头为主外,认为乌头属开紫蓝色花、具块根者均可作为草乌入药。故至今蒙医药用乌头属植物约有13种、4个变种,并把它们的干燥块根统称为泵阿（草乌）。分别为草乌头（北乌头）、阴山乌头、兴安乌头、薄叶乌头、紫花高乌头、乌头、白狼乌头、圆叶乌头、细叶黄花乌头、伏毛铁棒锤、黄花乌头、褐紫乌头、美丽乌头、雾灵乌头（变种）、华北乌头（变种）、西伯利亚乌头（变种）和牛扁（变种）。藏医药所用的乌头属原植物主要有:伏毛铁棒锤、铁棒锤、伏毛直序乌头、工布乌头等。因产地及习惯上的不同也将新都桥乌头、多果工布乌头（变种）、格咱乌头、显苞乌头、展毛尖萼乌头（变种）、草黄乌头、长柱乌头、丽江乌头、工布乌头、展毛工布乌头（变种）、本子栏乌头、直序乌头、竟生乌头、显柱乌头当作草乌用。由于蒙药文献对蒙医用乌头属植物学研究还未达成意见一致,存在着乌头属药用植物蒙、藏名称的混淆。对于草乌叶,中药学在临床上不用草乌叶,藏药学主要用伏毛铁棒锤和铁棒锤的干燥叶,蒙药学主要用北乌头的干燥叶。（2）对草乌的蒙医药、藏医药和中医药临床应用现状、炮制学研究、毒理毒性的研究等方面做了较为系统全面的阶段性总结。（3）对近十年来从乌头属植物中获得的生物碱类（包括二萜生物碱和非二萜生物碱）和非生物碱类（主要为黄酮）化合物进行了综述,为乌头属植物化学成分的研究提供了较为全面的参考资料。经研究1998到2007年从乌头属植物中共分离鉴定了的400多种新的生物碱,根据其结构特点,可以分为C₁₉(C₁₈)二萜生物碱、C₂₀二萜生物碱以及非二萜生物碱和黄酮类化合物等。（4）对草乌叶的药理活性与临床应用研究进展进行了综述性的总结,为草乌叶的进一步研究开发提供了较为全面的参考资料。（5）对以草乌叶为君药的不同浓度蒙药巴特日-7味丸药剂对癌细胞抑制作用进行了实验性的初步研究,结果表明不同浓度蒙药巴特日-7味丸作用于体外培养的胃癌MGC803和结肠癌LOVO细胞,两种细胞的生长均受到明显抑制,并且浓度越高,抑制率越高,为众多蒙药成方的抗癌作用实验研究填补了空白,也为今后研究草乌叶在癌症治疗中的新途径、新方法提供基础理论依据。（6）对草乌叶氯仿萃取物的免疫、抗炎、镇痛作用进行了初步研究,结果表明:草乌叶氯仿萃取物具有提高小鼠血清IgG含量,促进体液免疫功能的作用;草乌叶氯仿萃取物能明显抑制二甲苯所致小鼠耳廓肿胀作用、能明显抑制棉球所致小鼠肉芽肿的形成,有抗炎作用;草乌叶氯仿萃取物能明显抑制由热板引起的小鼠致痛作用,有镇痛作用。（7）对草乌叶正丁醇萃取物的免疫、抗炎、镇痛作用进行了初步研究,结果表明:正丁醇萃取物具有提高小鼠血清IgG含量,促进体液免疫功能的作用;正丁醇萃取物能明显抑制棉球所致小鼠肉芽肿的形成,有抗炎作用;草乌叶正丁醇萃取物能明显抑制由热板引起的小鼠致痛作用,有镇痛作用。（8）运用溶剂萃取、酸碱处理、硅胶层析、聚酰胺层析、大孔吸附树脂柱层析、Sephadex LH-20柱层析、重结晶等方法,从草乌叶的乙醇提取物中分离得到了11个化合物,并运用核磁共振波谱、质谱等现代多种波谱技术,鉴定了这些化合物的结构分别为:谷甾醇（AKP-1a）、豆甾醇（AKP-1b）、正三十二烷醇（AKP-2）、苯甲酸（AKC-2）、钝叶素（AKC-4）、胡萝卜苷（AKE-2）、对羟基苯甲酸（AKE-3）、山柰酚-3-（6″-乙酰基）-O-β-D-半乳糖苷（AKE-4）、山奈酚-3-O-β-D-木糖苷（AKE-5）、（10bS）8,9-dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo-[2,1-a]isoquinoline-3-one（AKB-1）、（3S,5R,6R,7E,9S）-megastigman-7-ene-3,5,6,9-tetrol（AKB-3）。以上化合物除甾醇类化合物（AKP-1a、AKP-1b、AKE-2）和长链脂肪醇（AKP-2）外,其它化合物均为首次从乌头属植物中分离得到。其中（10bS）8,9-dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo-[2,1-a]isoquinoline-3-one（AKB-1）为本次实验萃取出的十一种化合物中唯一的非二萜类生物碱,由RuFeng Wang等人在2004年首次从毛茛科植物金莲花中分离得到的一种新的非二萜类生物碱,它的分离成功不仅丰富了草乌叶的生物碱种类,而且为草乌叶的科学研究奠定了新的基础。更多还原

【Abstract】 Poisonous Aconitum L.plants,about 300 species in the Northern Hemisphere temperate zone,are distributed mainly in Asia,and then in the Europe and North America.In China,largely in Inner Mongolia,Beijing,Shanxi,Jilin,Heilongjiang, Liaoning,and etc.,there are 200 kinds of Aconitum L.plants,76 of which as medicines have functions of dispelling wind abd dehumidification,warming meridian and relieving pains in treating such illnesses as traumatic injury,arthiris,neurogenic pain,gestroentenritis,menoxenia,carbuncle abscess and sore toxicity.Of the whole national medicine,one important component is the traditional Mongolian medicine and pharmacy,to which more and more people in the world start to attach great importance.Due to the different historical background,culture mix and various locations of the Mongolian medicine,there exists the phenomenon that the Mongolian pharmacists use different names to indicate the same material or address different materials by the same name and that there is an overlap in the terminology between the Mongolian,Tibetan and Chinese medicine,so that there is a confusion about the names and raw materials they represent.As for aconite,in the Chinese medicine there is mainly Fuzi(processed products of daughter roots of A.carmichaeli),Chuanwu(dried mother roots of A.carmichaeli), and Caowu(dried tuber roots of A.kusnezoffii).In the Mongolian medicine,the very materal is dried tuber roots of A.kusnezoffii.And in the Tibetan medicine,there is A. flavum,A.pendulum,A.kongboense,and A.richardsonianum Lauener var. pseudosessiliflorum.Concerning the leaves of aconite,there are also differences in recognition of its original plants,variety of medicine materials and clinical application.This paper carries out a systematic and thorough study on aconite and its leaves, and consequently obtained the following results:(1)This paper summarizes the recognitions of aconite and its leaves comprehensively,including its history and current applications in the Chinese, Mongolian and Tibetan medicine.In the Chinese medicine,A.carmichaeli and A. kusnezoffii are mainly used as Caowu,and owing to different locations and customs, the dried tuber of A.vilmorinianum,A.karakolicum,A.hemsleyanum,A. paniculigerum,A.sungpanense,and A.Taipeicum are used as its substitute.In the Mongolian medicine,it is believed that every Aconitum L.plant with purple-blue flower and tuberous root could be used as Caowu.Consequently,there have been 13 species and 4 varieties of Aconitum L.used as Benga(Caowu),which are A. Kusnezoffii,A.yinshanicum,A.ambiguum,A.fischeri,A.septentrioale,A. carmichaeli,A.bailangense,A.rotundifolium,A.barbatum,A.flavum,A.coreanum, A.beunneum,A.pulchellum,A.paniculigerum var.wulingense,A.jeholense var. anguius,A.barbatum var.hispidum and A.barbatum var.puberulum respectively.In the Tibetan medicine,A.flavum,A.pendulum,A.richardsonianum and A. kongboense are mainly used as Benga.Due to different original places and customs, as Caowu’s substitute there is the dried tuber of A.tongolense,A.kongboense var. villosum,A.gezaense,A.bracteolosum,A.acutiusculum var.aureopilisum,A. stramineiflorum,A.dolichorhynchum,A.forrestii,A.kongboense,A.kongboense var. polycarpu,A.benzilanense,A.richardsonianum,A.yangii and A.styloseum.Because there has been no agreement achieved in the Mongolian medicine on the study in Aconitum L.plants,there is still confusion between the Mongolian names and the Tibetan names of Aconitum L.plants.In the Chinese medicine,aconite’s leaves are not used in clinic practice,but in the Tibetan medicine,the dried leaves of A.pendulum and A.pendulum are used,and in the Mongolian medicine the dried leaves of A.Kusnezoffii are mainly used.(2) This paper concludes a relatively systematic and comprehensive summary about the pharmacology,drug-processing,toxicology research and present clinical practice of Caowu which is used in the traditional Mongolian Medicine,Tibetan Medicine and Chinese Medicine.(3) This paper summarizes the alkaloids(including diterpene alkaloid and non-diterpene alkaloid) and non-alkaloids(mainly flavonoids) obtained from aconite in last ten years.It provides a relatively comprehensive reference to the research on the chemical components of aconite.From 1998 to 2007,more than 400 species of new alkaloids have been isolated and identified from aconite.According to the structure characteristics,the alkaloids can be classified as C19(C18) diterpene alkaloid,C20 diterpene alkaloid,non-diterpene alkaloid,compounds of flavonoids, etc.(4) This paper summarizes the pharmacological activity and clinical application of the leaves of A.kusnezoffii,providing a relatively comprehensive reference to the further study.(5) An initial experiment of different concentrations of Bateri-7 pills,whose main component is the leaves of A.kusnezoffii,has been done in order to know the the inhibition effect on cancer cell growth.It is found that different concentrations of Bateri-7 pills can inhibit external cultivate MGC803 of cancer in stomach and LOVO cell of cancer of colon,and the effect is proportional to the concentration.The findings not only fill in the blank of Mongolian set prescriptions in preventing cancer, but also provide a new way and basic theory of the leaves of A.kusnezoffii in curing the cancer.(6) An initial study has been carried on immunity,anti-inflammation,pain-ease of extraction of chloroform from the leaves of A.kusnezoffii.It is indicated that the extraction could increase the content of IgG in serum,and promote the immune function of body fluid,that the extraction could inhibit the rat’s auricle swelling causted by xylene and the rat’s granuloma causted by cotton ball,and have anti-inflammation function,and that the extraction could inhibit rat’s pain causted by heat board and have the function of pain-ease. (7) A primary study has been carried on immunity,anti-inflammation,pain-ease of extraction of butana from the leaves of A.kusnezoffii.It is indicated that the extraction could increase the content of IgG in serum,and promote the immune function of body fluid,that the extraction could inhibit the rat’s granuloma causted by cotton ball,and have anti-inflammation function,and that the extraction could inhibit rat’s pain causted by heat board and have the function of pain-ease.(8) From alcohol extracts of the leaves of A.kusnezoffii,11 compounds have been separated by using the methods of Solvent Extraction,Acid-base Treatment, Silica Gel Chromatography,Polyamide Chromatography,Macroporous Adsorption Resin Chromatography,Sephadex LH-20 Column Chromatography,Recrystallization etc.By employing nmr spectrum,mass sepectrometry and other spectrum technology, it is identified that these structure of compounds are AKP-1a,AKP-1b,AKC-2,AKC-4, AKC-2,AKE-2,AKE-3,kaempfero1-3-(6"-acetyl)-o-β-D-AKE-4,kaempferol -3-(6"-acetyl)-oβ-D-AKE-5,(10bs)8,9-dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo-[2, 1-a]isoquinoline-3-one(AKB-1),(3S,5R,6R,7E,9S)-tetrol(AKB-3).Besides sterol compounds(AKP-1a,AKP-1b,AKE-2)and long-chain fatty alcohol(AKP-2),the rest compounds are separated from Aconitum L.plants for the first time.Among the 11 kinds of chemical compounds,(10bS)8,9-dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo -[2,1-a]isoquinoline-3-one(AKB-1) from the extracting experiment is the only non-diterpene alkaloid,which is a new non-diterpene alkaloid extracted from Trollius chinensis for the first time by Ru Feng Wang and his colleagues in 2004.This findings not only enrich the alkaloid varieties of the leaves of A.kusnezoffii,but also lay the scientific foundation for the research.on the leaves of A.kusnezoffii.更多还原