乌头属植物二萜生物碱研究进展

乌头属植物中含有的特征成份二萜生物碱具有较强的毒性和广泛生物活性,多年以来一直是药物学家寻找新药和先导化合物的一个重要来源．也是植物化学分类学家研究的热点。本文从乌头属植物中二萜生物碱的来源,结构及其特点等方面,综述了1998-2008年从乌头属植物中分得的新的二萜生物碱的研究情况。     

Two new diterpenoid alkaloids, beiwusines A and B, from Aconitum kusnezoffii

Two new atisine-type diterpenoid alkaloids, beiwusine A (1) and B (2), have been isolated from the roots of Aconitum kusnezoffii Reichb. Their structures were established on the basis of spectroscopic data. Beiwusines A and B are the first examples of atisine-type diterpenoid alkaloids having a hydroxyl group at C-1. In addition, one known diterpenoid alkaloid spiramine H (3) has been isolated.     

宣威乌头中生物碱成分的研究

目的 研究宣威乌头Aconitum nagarumvar lasiandrum中的生物碱成分.方法 采用酸提碱沉法提取总碱、硅胶层析法分离,用波谱法鉴定结构.结果和结论 从宣威乌头中分得10个单体化合物,应用光谱法鉴定了其结构为:光翠雀碱(denudatine)、宋果灵(songorine)、delnuttaline等3个C20-二萜生物碱和尼奥灵(neoline)、3-去氧乌头碱(3-deoxyaconitine)、8-methoxy-14-benzoylaconine、伏乌碱(flavaconitine)、异塔拉萨敏(isotalatizidine)、乌头碱(aconitine)和nevadensine等7个C19-二萜生物碱.     

Three new diterpenoid alkaloids from the roots of Aconitum duclouxii

Three new C₁₉-diterpenoid alkaloids, ducloudines C (1), D (2), and E (3), were isolated from the roots of Aconitum duclouxii. Their structures were established on the basis of extensive spectroscopic analyses. Ducloudine C (1) is the first aconitine-type C₁₉-diterpenoid alkaloid with a C = O group at C-3 and a C = C bond between C-1 and C-2. All compounds were tested for their biological activities against one pathogenic fungi and two pathogenic bacteria.     

毛苞瓜叶乌头生物碱成分的研究

目的 研究毛苞瓜叶乌头根中的生物碱化学成分.方法 酸提碱沉提取总碱,硅胶层析法分离,波谱法鉴定结构.结果 分离到6个已知的去用二萜生物碱,分别为滇乌碱(yunaconitine)、塔拉萨敏(talasamine)、瓜乌定(hemsleyadine)、拳乌宁乙(circinanine B)、黄草乌碱丁(schaconitine)和senbusine A.结论 应用光谱法和与已知物TLC对照的方法鉴定了所有化合物的结构.     

乌头属药材特征成份二萜生物碱的电喷雾质谱研究进展

本文从乌头属药材中二萜生物碱类成分的鉴定、炮制过程对二萜生物碱类成分种类及其含量的影响、复方制剂中二萜生物碱的鉴定、二萜生物碱类成份的体外生物转化以及二萜生物碱的生物体内代谢过程研究等方面综述了近年来电喷雾质谱在以上研究中的应用。     

Structure,property, biogenesis,and activity of diterpenoid alkaloids containing a sulfonic acid group from Aconitum carmichaelii

Three new C₂₀-diterpenoid alkaloids with a sulfonic acid unit, named aconicarmisulfonines B and C (1 and 2) and chuanfusulfonine A (3), respectively, were isolated from the Aconitum carmichaelii lateral roots (“fu zi” in Chinese). Structures of 1–3 were determined by spectroscopic data analysis. Intriguing chemical properties and reactions were observed for the C₂₀-diterpenoid alkaloids: (a) specific selective nucleophilic addition of the carbonyl (C-12) in 1 with CD₃OD; (b) interconversion between 1 and 2 in D₂O; (c) stereo- and/or regioselective deuterations of H-11α in 1–3 and both H-11α and H-11β in aconicarmisulfonine A (4); (d) TMSP-2,2,3,3-d₄ promoted cleavage of the C-12−C-13 bond of 4 in D₂O; (e) dehydrogenation of 4 in pyridine-d₅, and (f) Na₂SO₃-assisted dehydrogenation and N-deethylation of songorine (5, a putative precursor of 1–4). Biogenetically, 1 and 2 are correlated with 4, for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements via migrations of C-13−C-16 and C-15−C-16 bonds of the napelline-type skeleton, respectively. Meanwhile, 3 is a highly possible precursor or a concurrent product in the biosynthetic pathways of 1, 2, and 4. In the acetic acid-induced mice writhing assay, at 1.0 mg/kg (i.p.), compounds 1, 2, 5, 5a, and 5b exhibited analgesic effects against mice writhing.     

草乌花及其煎煮液中二萜生物碱的电喷雾串联质谱研究草乌花及其煎煮液中二萜生物碱的电喷雾串联质谱研究

目的 对草乌花及其煎煮液中的二萜生物碱进行定性分析,说明煎煮前后化学成分发生的变化。 方法用注射泵自动进样,电喷雾离子阱串联质谱直接分析草乌花及其煎煮液中生物碱混合物。结果 在生草乌花中发现3个新生物碱,草乌花煎煮后其中的双酯型生物碱和三酯型生物碱都发生水解,前者水解为苯甲酰乌头原碱和乌头原碱类生物碱,后者水解为3-乙酰-乌头原碱类生物碱。结论 该法简便、快速、灵敏、特异性强,为乌头属植物煎煮液中的生物碱分析提供了新途径。     

Diterpenoid alkaloids from the roots of Aconitum brachypodum Diels

A new diterpenoid alkaloid, named bullatine H (1), along with 10 known diterpenoid alkaloids were isolated from the roots of Aconitum brachypodum Diels (Ranunculaceae). The structure of 1 was elucidated by analysis of its spectroscopic data. It should be noted that compound 1 is the first example with 11, 13-dioxygenated denudatine-type diterpenoid alkaloid isolated from Aconitum brachypodum.     

Separation and identification of Aconitum alkaloids and their metabolites in human urine.

To study the safety of Aconitum medicinal herbs in clinic and identify Aconitum alkaloids poisoning in forensic medicine, Aconitum alkaloids and their metabolites were separated and identified in human urine by liquid chromatography-electrospray ionization-multi-stage mass spectrometry (LC-ESI-MS(n)) and chemical pathway of metabolism was investigated. The alkaloids and their metabolites in the urine sample were extracted with solid-phase cartridges and separated by HPLC with acetonitrile-water-formic acid (40:60:0.5) mobile phase. Structures of five metabolites and three parent Aconitum alkaloids were identified with multi-stage mass spectrometry data through comparison with authentic substances as aconitine (M(1)), mesaconitine (M(2)), hypaconitine (M(3)), benzoylaconine (M(4)), benzoylmesaconine (M(5)), benzoylhypaconine (M(6)), 16-O-demethylaconitine (M(7)) and 16-O-demethylhypaconitine (M(8)), respectively. Among them, M(8) was identified and reported for the first time. Metabolic pathways of Aconitum alkaloids in human body were proposed.     

Structure-dependent inhibitory action of the Aconitum alkaloids 14-benzoyltalitasamine and talitasamine in rat hippocampal slices

In the present study the effects of the two Aconitum alkaloids 14-benzoyltalitasamine and talitasamine on neuronal activity were investigated in order to obtain further insight into structure-dependent effects of this group of alkaloids on central nervous activity. Both alkaloids are closely related to aconitine, the main alkaloid of plants of Aconitum species. However, they have shortened side chains at position C3 and C8 of the molecule. The experiments were performed as extracellular recordings of orthodromically and antidromically evoked population spikes as well as of field excitatory potentials (EPSPs) from the CA1 region of rat hippocampal slices. 14-Benzoyltalitasamine exerted a reversible inhibition of the field potentials in a concentration-dependent manner. The orthodromic population spike was attenuated at concentrations higher than 1 μM, while the field EPSP was already affected at a concentration of at least 0.3 μM. Both responses were completely blocked at a concentration of 30 μM. The alkaloid failed to affect the presynaptic fiber spike at concentrations less than 10 μM. There was only a up to 30% decrease in the antidromic population spike (10–100 μM). The inhibition of the antidromic spike was increased by using a higher stimulus frequency. In contrast to 14-benzoyltalitasamine, the alkaloid talitasamine which is lacking the benzoylester side chain was a less effective inhibitor of the orthodromic population spike and even failed to affect the antidromic spike. Furthermore, the effects of the alkaloids on experimentally induced epileptiform activity was examined. While talitasamine was lacking any significant effect at concentrations less than 100 μM, 14-benzoyltalitasamine reversibly reduced both stimulus-triggered epileptiform activity in area CA1 elicited by omission of Mg²⁺ from the bathing medium as well as spontaneously occurring epileptiform activity in CA3 elicited by omission of Mg²⁺ and elevation of K⁺ to 5 or 8 mM. The antiepileptiform efficacy of this compound was concentration-dependent (0.3–10 μM) and manifested itself as a decrease in burst frequency as well as in burst amplitude and was significantly increased by the higher K⁺ concentration. Received: 25 August 1997 / Accepted: 15 February 1998     

土耳其海绵Ircinia variabilis中溴代生物碱的分离与鉴定

目的研究土耳其海绵Ircinia variabilis的化学成分。方法采用多种色谱方法分离纯化,依据理化性质、波谱数据和文献对照的方法鉴定结构。结果从土耳其海绵Ircinia Variabilis提取物中分离鉴定了5个溴代生物碱类化合物：fistularin-3（1）,2-oxazolidinone（2）,（E）-1-acetamide-3,5-dibromo-4-ethoxy-4-methoxy-1-hydroxy-2,5-cyclohexaddienone（3）,（Z）-1-acetamide-3,5-dibromo-4-ethoxy-4-methoxy-1-hydroxy-2,5-cyclohexaddienone（4）,3,5-dibromotyrosine（5）。结论化合物1从该种内首次分离得到,化合物2～4从该种属中首次分离得到。     

不同品种附子生物碱和多糖含量的比较

目的:比较不同品种附子生物碱和多糖的含量。方法:采用酸性染料比色法测定附子总生物碱含量,反相高效液相色谱法测定双酯型生物碱含量,蒽酮-硫酸法测定多糖含量。结果:不同品种附子总生物碱和双酯型生物碱含量差异较大,附子多糖含量差异不显著。附子炮制后,黑附片中总生物碱、双酯型生物碱含量显著下降,附子多糖含量稍有增加。结论:本试验结果可为附子品种选育提供一定的科学依据。     

HPLC-ELSD法测定贝母中异甾类生物碱及糖苷类成分的含量

目的建立同时测定贝母中5种异甾类生物碱——peimissine, imperialine, sinpeinine A, imperialine-3β-glucoside和yibeinoside A含量的HPLC分析方法。方法C₁₈柱;流动相:乙腈-水(含0.1%二乙胺);梯度洗脱,流速1.0 mL·min^-1;检测器:Alltech 500蒸发光散射检测器(ELSD)。结果线性范围为peimissine 13.1～288.2 mg·L^-1(r²=0.997 5), imperialine-3β-glucoside 7.7～169.4 mg·L^-1 (r²=0.999 3), yibeinoside A 7.3～160.6 mg·L^-1 (r²=0.999 7), imperialine 16.5～363.0 mg·L^-1 (r²=0.999 2), sinpeinine A 8.7～191.4 mg·L^-1 (r²=0.994 2)。 5个化合物的精密度和重现性RSD均<5%。结论本方法简便、有效、可行,可用于贝母中5种异甾类生物碱的含量测定。     

RP-HPLC法测定蒙药那如-3丸中乌头类生物碱含量

目的建立测定蒙药那如 3丸中乌头类生物碱含量的RP HPLC法。方法采用C18色谱柱,以甲醇 水 氯仿 三乙胺(体积比6 0∶4 0∶2∶0 1)为流动相,流速0 8mL·min-1,柱温为室温,检测波长2 5 4nm ,进样体积10 μL,外标法计算含量。结果乌头碱、中乌头碱和次乌头碱在0 3～1 5g·L-1内峰面积与质量浓度呈良好线性关系,相关系数r分别为0 9996、0 9998、0 9998,平均回收率分别为10 1 0 %、10 0 9%、10 0 3% ,RSD分别为1 9%、1 2 %、1 4 % (n =9) ;测得那如 3丸中乌头碱、中乌头碱和次乌头碱的质量分数分别为0 0 0 12 6 %、0 0 0 2 78%、0 0 0 335 %。结论RP HPLC法可用于那如 3丸中乌头类生物碱的质量控制。     

胆木总生物碱的含量测定方法研究

目的建立胆木总生物碱含量测定方法。方法采用紫外分光光度法测定胆木中总生物碱的含量。结果建立了胆木总生物碱的含量测定方法,测定波长为222nm,标准曲线为Y=62．841X＋0．0363,R=0．9997（n=9）,线性范围0．00096-0．0192mg／mL,平均回收率为100．45％,RSD为0．62％（n=9）。结论该方法稳定、可靠、专属性强,可用于胆木总生物碱的含量测定,为胆木的质量控制提供了新方法。     

Brain inducible nitric oxide synthase is involved in interleukin-1beta-induced activation of the central sympathetic outflow in rats

Nitric oxide (NO) has been recognized as a neurotransmitter or a neuromodulator in the central nervous system. Brain NO is mainly generated either by neuronal NO synthase (NOS) or by inducible NOS. Previously we reported that central NO is involved in the elevation of plasma noradrenaline levels induced by intracerebroventricularly (i.c.v.) administered interleukin-1beta in rats [Eur. J. Phamacol. 317 (1996) 61]. In the present study, therefore, we tried to characterize which type of NOS isoforms is involved in the cytokine-induced responses using selective inhibitors of each NOS isoform in urethane-anesthetized rats. I.c.v. administered interleukin-1beta (100 ng/animal) elevated plasma levels of noradrenaline but not adrenaline. The cytokine-induced elevation of plasma noradrenaline levels was attenuated by cycloheximide, an inhibitor of protein synthesis, in a dose-dependent manner (10 and 20 microg/animal, i.c.v.). S-ethylisothiourea (0.1 and 0.5 microg/animal, i.c.v.), an inhibitor of inducible NOS, dose-dependently reduced the cytokine-induced elevation of plasma noradrenaline levels, while 7-nitroindazole (5 and 10 microg/animal, i.c.v.), an inhibitor of neuronal NOS, had no effect. These results suggest the involvement of brain inducible NOS in the interleukin-1beta-induced activation of the central sympathetic outflow in rats.     

半夏生物碱含量测定及止呕研究

目的提取并测定半夏生物碱含量,研究其对水貂的止呕作用。方法提取半夏生物碱,采用酸性染料比色法测定含量;观察在顺铂(7.5mg·kg-1,ip)、阿朴吗啡(l.6mg·kg-1,sc)、硫酸铜(40mg·kg-1,ig)水貂呕吐模型的止呕作用;观察半夏生物碱对水貂运动呕吐模型(100r·min-1,1h)的影响。结果半夏生物碱含量为2.83mg·g-1,对顺铂、阿朴吗啡致水貂呕吐均有抑制作用(P<0.05),对硫酸铜及运动致水貂呕吐无效。结论半夏生物碱具止呕作用,其机制与中枢抑制有关。     

Multiple pathways involved in the biosynthesis of anandamide

Endocannabinoids, including anandamide (arachidonoyl ethanolamide) have been implicated in the regulation of a growing number of physiological and pathological processes. Anandamide can be generated from its membrane phospholipid precursor N-arachidonoyl phosphatidylethanolamine (NAPE) through hydrolysis by a phospholipase D (NAPE-PLD). Recent evidence indicates, however, the existence of two additional, parallel pathways. One involves the sequential deacylation of NAPE by alpha,beta-hydrolase 4 (Abhd4) and the subsequent cleavage of glycerophosphate to yield anandamide, and the other one proceeds through phospholipase C-mediated hydrolysis of NAPE to yield phosphoanandamide, which is then dephosphorylated by phosphatases, including the tyrosine phosphatase PTPN22 and the inositol 5' phosphatase SHIP1. Conversion of synthetic NAPE to AEA by brain homogenates from wild-type and NAPE-PLD(-/-) mice can proceed through both the PLC/phosphatase and Abdh4 pathways, with the former being dominant at shorter (<10 min) and the latter at longer (60 min) incubations. In macrophages, the endotoxin-induced synthesis of anandamide proceeds uniquely through the phospholipase C/phosphatase pathway.     

Risk of breast cancer in relation to the use of rauwolfia alkaloids

Summary In a case-control study of 1881 women with breast cancer and 1523 controls with benign conditions, 65 cases (3.5%) and 64 controls (4.2%) reported having used a drug that contained rauwolfia, giving a rate ratio estimate of 0.8 (95% confidence interval, 0.5–1.1). Use that ended more than a year previously was negatively associated with breast cancer (rate ratio, 0.5; 95% confidence interval, 0.2–0.9). The risk of breast cancer did not vary significantly according to duration of use. Nor did it vary within strata of varying base-line risk, such as age at first pregnancy. The data suggest that rauwolfia alkaloids do not increase the risk of breast cancer.