Three new hetisine-type diterpenoid alkaloids from Aconitum coreanum

Three new hetisine-type diterpenoid alkaloids, Guan-fu base V (GFV, 1), Guan-fu base W (GFW, 2) and Guan-fu base X (GFX, 3) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics. Their structures were established by direct interpretation of their spectral data, mainly high resolution electrospray ionization mass spectrometry (HR-ESI-MS), ¹D and ²D NMR (¹H–¹H COSY, ROESY, HSQC and HMBC). GFX is the third N-oxygenated hetisine-type diterpenoid alkaloid isolated from A. coreanum.     

Phytochemical Evidence Related to the Phylogeny of Aconitum gymnandrum Maxim.

From the whole plant of Aconitum gymnandrum Maxim., four diterpene alkaloids have been isolated and identified: talatizamine, 14-acetyltalatizamine, condelphine and isotalatizidine. Thus the species nvestigated, belonging to the monotypic subgenus Gymnaconitum (Stapf) Rapaics, secms to be phytochemically closely related to A. nemorum M. Pop. and A. talassicum M. Pop. From the phytochemical point of view however, A. gymnandrum does not seem to be the most advanced species within the genus Aconitum.     

The Chemotaxonomy of Chinese Species of the Genus Aconitum L. (Ranunculaceae)

On the basis of biosynthsis, distribution of diterpenoid alkaloids as well as morphological evolution of Chinese species L. (Ranunculaceae), chemotaxonomy of the genus Aconitum is discussed: 1, Subgen. Lycoctonum, containing lycoctonine-type alkaloids and Subgen. Aconitum containing aconitine-type alkaloids, were probably differetiated at the early stage of evolution of the genus Aconitum and evolved respectively in their own ways. 2, In Subgen. Aconitum: (1) Ser. Bullatifolia, containing mainly atisine-, veatchine-type alkaloids, and amino, alcohol and ester base of aconitine-type, and distributed in Hengduan Mountain and Jingsha River valley, where is the centre of modern differentiation of species of Aconitum, is probably a series from which Chinese species of the genus Aconitum were derived; (2) Ser. Inflata, containing mainly aconitine, mesaconitine and bypaconitine, is an advanced group; (3) Ser. Grsndituberosa, containing mainly aconitine and songorine, is related to Ser. Bulatifolia; (4) Ser. stylosa and Ser. volubilia, containing mainly yunaconitine and other anisyl ester alkaloids form another advanced branch. 3, Ser. Tangutica and A. naviculare of Ser. Rotaundifolia, containing atisine and lactone-type alkaloids may be a specialized group in high mountains and have occurred at early stage of evolution of the genus Aconitum. 4, Subgen. Gymnaconitum, containing atisine-type alkaloids and amino alcohol of aconitine type, may als be a specialized group in high mountains. 5, A. franchetii Finet. et Gagnep. mainly containing ester bases of aconitine-typeand closed to A. chasmanthum Stapf, is best placed into Ser. Ambigua.     

Preparative isolation and purification of two new isomeric diterpenoid alkaloids from Aconitum coreanum by high-speed counter-current chromatography

Preparative high-speed counter-current chromatography (HSCCC) coupled with evaporative light scattering detection (ELSD) was used to isolate and separate bioactive constituents from the roots of Aconitum coreanum. Two new diterpenoid alkaloid isomers were successfully separated for the first time by HSCCC with an optimized two-phase solvent system composed of ethyl acetate-n-butanol-methanol-2% acetic acid (3.5:1.5:2:4.5, v/v/v/v), 25.4mg of GFT (1) and 18.3mg of GFU (2) were isolated form 1g crude extract in one step HSCCC experiment. The purities of the two new compounds were all over 95% as analyzed by HPLC and their structures were identified by ESI-MS, (1)H NMR, (13)C NMR, and 2D NMR analysis.     

The Diterpenoid Alkaloids of Aconitum nagarurn var. lasiandrurn W. T. Wang and Its Chemotaxonomic Significance

From the roots of Aconitum nagarum var. lasiandrum W. T. Wang, seven diterpe- noid alkaloids were isolated and determined as follows: denudatine of atisine-type (7), songorine and songoramine of veatchine-type (1 and 12), virescenine of lycoctonine-type (13), neoline, 14-acetylneoline and fiavaconitine of aconitine-type (2, 3 and 8). A. nagarum var. lasiandrum W. T. Wang is a typical species of Ser. Bullatifolia which contained four types diterpenoid alkaloids. On the basis of distribution of diterpenoid alkaloids, phytogenesis add morphological evolution of Chinese species of genus Aconitum, probably Chinese species of genus Aconitum modernly advanced and divided from this serics.     

多根乌头中二萜生物碱成分

为研究多根乌头(AconitumkarakolicumRapaics)中二萜生物碱成分,本研究采用正反相硅胶柱和高效液相等色谱分离方法,从中分离得到15个二萜生物碱;通过多种波谱手段以及文献对比的方法鉴定其结构分别为aconitine(1),3-deoxyaconitine(2),16-epipyroaconine(3),neoline(4),indaconitine(5),14-benzoyl-8-O-methylaconitine(6),spicatineA(7),15-α-hydroxyneoline(8),taurenine(9),14-benzoylaconine(10),14-benzoylaconine-8-oleate(11),lappaconitine(12),beiwudine(13),13-hydroxyfranchetine(14)和8-O-linoleoyl-14-benzoylaconine(15),化合物3~15为首次从该植物中分离得到。采用MTT法和叶碟法分别考察了部分化合物的抗肿瘤和拒食活性,化合物14-benzoylaconine-8-oleate(11)对人乳腺癌MCF-7细胞、人肺癌H460细胞、肝癌HepG2细胞的IC50值分别为11.9、27.6和31.8μM。乌头碱型的二萜生物碱aconitine(1)、3-deoxyaconitine(2)、indaconitine(5)和beiwudine(13)表现出一定的拒食活性的活性(EC50<2mg/cm^2)。     

Norditerpenoid Alkaloids from Aconitum spicatum Stapf

To search for pharmacologically and structurally interesting substances from traditional Chinese medicines, we Investigated the chemical compounds of Aconitum spicatum Stapf. Two new nordlterpenold alkaloids, namely spicatlne A （compound 1） and splcatine B （compound 2）, as well as 11 known norditerpenoid alkaloids were Isolated from the CHCIs portion of the 90% ethanol extract of the roots of A. spicatum. The structures of the alkaloids were characterized on the basis of their spectral data. One of the Isolated compounds showed significant cytotoxic activities （IC50 values 〈 200μmol/l.） against the HL-60 cell line.     

Quantification of Aconitum alkaloids in aconite roots by a modified RP-HPLC method

The three Aconitum alkaloids, aconitine (1), mesaconitine (2) and hypaconitine (3), are pharmacologically active but also highly toxic. A standardised method is needed for assessing the levels of these alkaloids in aconite roots in order to ensure the safe use of these plant materials as medicinal herbs. By optimising extraction, separation and measurement conditions, a reliable, reproducible and accurate method for the quantitative determination of all three Aconitum alkaloids in unprocessed and processed aconite roots has been developed. This method should be appropriate for use in the quality control of Aconitum products. The three Aconitum alkaloids were separated by a modified HPLC method employing a C18 column gradient eluted with acetonitrile and ammonium bicarbonate buffer. Quantification of Aconitum alkaloids, detected at 240 nm, in different batches of samples showed that the content of 1, 2 and 3 varied significantly. In general, the alkaloid content of unprocessed roots was higher than that of processed roots. These variations were considered to be the result of differences in species, processing methods and places of origin of the samples.     

乌头须根总生物碱提取工艺的考察

目的:考察乌头须根中总生物碱的最佳提取工艺条件。方法:酸碱滴定法测定乌头须根中总生物碱含量,以总生物碱提取率为指标,采用L9(3)~4正交实验法筛选乌头须根总生物碱的最佳提取工艺。结果:乌头须根总生物碱含量为1.094%,影响提取的主次因素为:乙醇浓度>提取次数>提取时间>乙醇用量;优选得到的最佳提取工艺为A_3B_1C_3D_3,即以8倍量80%的乙醇提取3次,每次1.5小时。结论:乌头须根总生物碱含量较高,提取工艺条件稳定、经济、可行。     

栾川乌头,河南毛茛科一新种

描述了自河南省发现的毛茛科乌头属一新种——栾川乌头,并给出了此种与近缘种黄花乌头的区别特征。     

Simultaneous quantitation of aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetics evaluation of "SHEN-FU" injectable powder

A rapid, specific and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous quantitation of six Aconitum alkaloids, i.e. aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconine (BAC), benzoylmesaconine (BMA) and benzoylhypaconine (BHA) in human plasma collected from 18 healthy volunteers after intravenous drop infusion of "SHEN-FU" injectable powder in three different dosages. Lappaconitine was selected as the internal standard (IS). LC/MS/MS system coupled with an electrospray ionization (ESI) source was performed in multiple-reaction monitoring (MRM) mode. The transitions of the Aconitum alkaloids executed as following: m/z 646.3-->586.0 for AC; m/z 632.4-->573.1 for MA; m/z 616.2-->556.1 for HA; m/z 604.2-->104.8 for BAC; m/z 590.1-->104.8 for BMA; m/z 574.1-->104.8 for BHA; m/z 585.2-->161.8 for IS. Sample preparation was performed with solid-phase extraction (SPE) on a 1 mL HLB cartridge prior to analysis. The separation was applied on a Waters C(18) column (1.7 microm, 2.1 mm x 100 mm) and a gradient elution of methanol and 0.1% formic acid-water was used as mobile phase. The retention time was less than 4.5 min. The concentrations ranged from 0.1 to 1000 ng/mL for all six Aconitum alkaloids and showed a good linearity with the correlation coefficient (r(2)) >0.995. The validated method was employed to simultaneous quantitation and successfully used for the first time for the pharmacokinetic evaluation of the six Aconitum alkaloids after intravenous drop administration of "SHEN-FU" injectable powder in phase I clinical trial.     

青藏高原毛茛科3种特有植物核型和进化研究

对青藏高原高山冰缘地区毛茛科３种特有植物的核型进行了分析。它们的核型公式（Ｋ）、染色体相对长度组成（Ｃ．Ｒ．Ｌ．）和核型不对称系数（Ａｓ．Ｋ％）分别为：青藏金莲花Ｔｒｏｌｉｕｓｐｕｍｉｌｕｓｖａｒ．ｔａｎｇｕｔｉｃｕｓ：Ｋ（２ｎ）＝６ｍ＋８ｓｍ（２ＳＡＴ）＋２ｓｔ,Ｃ．Ｒ．Ｌ．＝４Ｌ＋４Ｍ２＋４Ｍ１＋４Ｓ,Ａｓ．Ｋ％＝６３．５７,核型属２Ｂ型;甘青乌头Ａｃｏｎｉｔｕｍｔａｎｇｕｔｉｃｕｍ为Ｋ（２ｎ）＝６ｍ＋１０ｓｍ,Ｃ．Ｒ．Ｌ．＝４Ｌ＋８Ｍ１＋４Ｓ,Ａｓ．Ｋ％＝６２．５４,２Ｂ型;单花翠雀花Ｄｅｌｐｈｉｎｉｕｍｃａｎｄｅｌａｂｒｕｍｖａｒ．ｍｏｎａｎｔｈｕｍ为Ｋ（２ｎ）＝６ｍ＋８ｓｍ＋２ｓｔ,Ｃ．Ｒ．Ｌ．＝４Ｌ＋４Ｍ２＋４Ｍ１＋６Ｓ,Ａｓ．Ｋ％＝６４．３４,属３Ｂ型。经同相关近缘种核型资料比较,青藏金莲花核型不对称性和进化程度比金莲花Ｔ．ｃｈｉｎｅｎｓｉｓ低;甘青乌头的核型不对称性和进化程度在其近缘类群（乌头组Ｓｅｃｔ．Ａｃｏｎｉｔｕｍ）已报道的种之内最低;单花翠雀花核型不对称性和进化水平比翠雀组（Ｓｅｃｔ．Ｄｅｌｐｈｉｎａｓｔｒｕｍ）已报道的展毛翠雀花Ｄ．ｋａｍａｏｅｎｓｅｖａｒ．ｇｌａｂｒｅｓｃｅｎｓ、     

宽叶蔓乌头中新的二萜生物碱

本文研究一种民间药物宽叶蔓乌头 Aconitum sczukinii Turcz.的基本成分,分离出三种新的 C_(20)-二萜生物碱:宽乌宁(sczukinine),宽乌定(sczu-kidine),宽乌享(sczukititie).经分析各种谱图(IR,MS,~1H和~(13)C-NMR,2D-NMR,CD 或 NOE)实验及化学反应,确定了其结构.     

Four New Diterpenoid Alkaloids from the Roots of Aconitum carmichaelii

Aconitum carmichaelii Debeaux is a widely used traditional Chinese medicine and an important source of clinical drugs, of which the parent and lateral roots are known as ‘Chuanwu’ and ‘Fuzi’, respectively. Four new C₁₉‐diterpenoid alkaloids, carmichasines A – D ( 1 – 4 ), were isolated from the roots of Aconitum carmichaelii, together with twelve known compounds ( 5 – 16 ). Their structures were elucidated via spectroscopic analyses, including HR‐ESI‐MS, IR, and NMR. Carmichasine A ( 1 ) is the first natural C₁₉‐diterpenoid alkaloid possessing a cyano group. Most of the diterpenoid alkaloids isolated were C₁₉‐category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The cytotoxicity of the new compounds was also investigated against several human cancer cell lines, including MCF‐7, HCT116, A549, and 786‐0, and none of them showed considerable cytotoxic activity.     

乌头属植物化学成分、药理作用及其内生菌的研究进展

毛茛科乌头属植物广泛分布于北温带地区,具有重要的药用价值。乌头属植物主要的化学成分是生物碱,其中二萜生物碱是历来的研究热点。现代药理学研究证明,乌头属植物具有镇痛、抗炎、抗肿瘤及杀虫等作用。目前乌头属植物内生菌的研究也逐渐开展。本文对乌头属植物近年来报道的新的化学成分、药理研究和利用植物内生菌产生活性成分等进行了综述,可为乌头属植物的进一步开发利用提供参考。     

Salade malade: malignant ventricular arrhythmias due to an accidental intoxication with Aconitum napellus

Intoxication with Aconitum napellus is rare in our regions. Aconite alkaloids can cause ventricular arrhythmia by a prolonged activation of sodium channels. Because the margin of safety is low between the analgesic and toxic dose, intoxication is not rare when Aconite is used in herbal medicine. We present a case in which a 39-year-old male was accidentally intoxicated with Aconite. Even though no antidote or adequate therapy is available he was successfully resuscitated. (Neth Heart J 2008;16: 96-9.)     

HPLC和TLC法测定准噶尔乌头中的生物碱成分

采用高效液相色谱和薄层色谱对准噶尔乌头中生物碱进行分析,建立了HPLC法测定其中各生物碱含量的方法。结果确定准噶尔乌头中主要含有12-表-欧乌碱、宋果灵、尼奥灵、准噶尔碱和欧乌碱,其中准噶尔碱和欧乌碱为首次在该植物中发现;其疗效与川乌和草乌相近但化学成分差异较大。色谱条件为:Inertsil NH2柱(150 mm×4.6 mm,5μm),流动相正己烷∶乙醇(92∶8),流速1.0 mL/min,检测波长270 nm,进样量10μL。本方法操作简便,结果可靠,重现性好,为准噶尔乌头的质量标准研究提供了实验依据。     

辽宁地区产6种乌头(Aconitum)的细胞分类学研究

对我国辽宁地区毛莨科(Ranunculaceae)乌头属(Aconitum) 6个种的染色体的数目和形态进行了研究,并进行了核型分析。其染色体基数为X=8,核型公式为:两色乌头:2n=2x=2m+10sm+4st;蛇岛乌头为:2n=4x=10m+20sm(SAT)+2st+2B;黄花乌头为:2n=4x=4m+12sm(SAT)+8st+1B;北乌头三倍体为:2n=3x=2M+4m+18sm;北乌头4倍体为2n=4x=4m+28sm。同时,对乌头属下某些种的分类学问题进行了探讨。     

Comparative Anatomical Studies on Chinese Medicinal Plants of the Genus Aconitum

This paper reports the result of comparative anatomical studies on medicinal roots of 53 species and varieties in the genus Aconitum from China. The anatomical structures of the roots can be classified into 6 types and 18 subtypes according to the level of their evolution. The anatomy of Aconitum roots is discussed in relation to phylogeny based on chemotaxonomy, cytology and other related disciplines. It was found that the six types of Aconitum roots are correlated with chemical components, chromosomes, toxicity and the gross morphology. The relatively advanced Types I and II roots always contain highly toxic alkaloids of diterpenoid diester of aconitine type, distributed mainly in Ser. 3, 5-11 of Sect. Aconitum of Subgen. Aconitum, while the relatively primitive Types III, IV and II roots with small diameters contain mainly atisine and aminal alcohol alkaloids, which have lower toxicity, present in Subgen. Gymnaconitum and Ser. 1, 2 of Sect. Aconitum of Subgen. Aconitum. The primitive Types V and VI roots of Subgen. Lycoctonum contain mainly the most low-toxic alkaloids of lycoctonine Type. The result is of significance both in theory or practice for the development of medicinal plant resourcesand the safety of clinical usage of these of plants.