Sample records for aconitine

  1. A case of fatal aconitine poisoning by Monkshood ingestion.

    Pullela, Ravi; Young, Lorraine; Gallagher, Barry; Avis, Simon P; Randell, Edward W


    Accidental aconitine poisoning is extremely rare in North America. This report describes the confirmation of a case of accidental aconitine poisoning using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The case involved a 25-year-old man who died suddenly following a recreational outing with friends where he consumed a number of wild berries and plants including one that was later identified as Monkshood (Aconitum napellus). Postmortem blood and urine samples were available for analysis. All routine urine and blood toxicology screens were negative. The LC-MS/MS method allowed sensitive quantification of aconitine, the main toxin in A. napellus, and showed 3.6 and 149 microg/L in blood and urine, respectively. These concentrations were similar to that reported in other aconitine-related deaths. This case illustrates the dangers of consuming unidentified plants, and documents concentrations of aconitine in blood and urine in a fatal case of A. napallus-related poisoning.

  2. Een experimenteel onderzoek over de werking van de aconitine op het hart

    Boomsma, Jan Pieter


    Een literatuuroverzicht werd gegeven betreffende de geschiedenis, botanie, toxicologie, chemie en pharmacologie van aconitine. Vervolgens werden de verschijnselen, die gedurende de vergiftiging met aconitine aan het hart optraden, bestudeerd. Hiervoor werden de volgende experimenten verricht: 1. Mec


    ZENG Qing; OUYANG Xing-biao; LI Man; LIU Xiao-chun; GUAN Xin-min


    Objective:To investigate the effect of electroacupuncture (EA) on aconitine-induced ventricular tachyarrhythmia. Methods: Twenty SD rats ate (300 mg/kg, I.p.) were evenly and anesthetized with chloral hydrrandomly divided into control and EA groups. Ventricular arrhythmia was induced by intravenous infusion of 0.001% aconitine (I.v., 3.5 mg/kg, 0.4 mL/min). EA (4~16 Hz, 1~3 V) was applied to "Neiguan"(内关 PC 6) and "Jianshi"(间使 PC 5) for 30 min. ECG was recorded andanalyzed to determine ventricular premature beat (VPB), ventricular tachycardia (VT) and ventricular fibrillation (VF). Results: EA elevated the dose threshold of aconitine-induced VF (P<0.05), delayed the occurrence of VT and VF (P<0.01), prolonged the survival time and reduced the mortality of rats treated with aconitine (P<0.01). Conclusion: EA can suppress aconitine-induced ventricular tachyarrhythmia.

  4. Cladosporium cladosporioides XJ-AC03, an aconitine-producing endophytic fungus isolated from Aconitum leucostomum.

    Yang, Kai; Liang, Jie; Li, Qinfan; Kong, Xiangya; Chen, Rui; Jin, Yimin


    The endophytic fungus XJ-AC03, which was isolated from the healthy roots of Aconitum leucostomum, produced aconitine when grown in potato dextrose agar (PDA) medium. The presence of aconitine was confirmed by the chromatographic and spectroscopic analyses. The yield of aconitine was recorded as 236.4 μg/g by high performance liquid chromatography (HPLC). The mass spectrometry was shown to be identical to authentic aconitine. Further analysis with nuclear magnetic resonance (NMR) spectroscopy to show the chemical structure of the fungal aconitine indicated that the fungal aconitine produced an NMR spectrum identical to that of authentic aconitine. Strain XJ-AC03 was identified as Cladosporium cladosporioides by its characteristic culture morphology and ITS rDNA sequence analysis.

  5. Fatal aconitine intoxication or thyroid storm? A case report.

    Arlt, E M; Keller, T; Wittmann, H; Monticelli, F


    The case of a female in the latter half of her teens found dead in her father's apartment is reported. A glass containing liquid and plant remnants was found at the death scene. There were no indications of any intervention or the application of force by a third party. Autopsy showed unremarkable findings. Toxicological investigations revealed lethal doses of aconitine, a highly poisonous alkaloid and the major active compound of Aconitum napellus, in all specimens. Plant remnants were identified as A. napellus leaves by a botanist and toxicological examination of the liquid in the glass on site showed extremely high concentrations of aconitine. Additionally, laboratory results revealed that the young female was suffering from thyrotoxicosis factitia, an uncommon form of hyperthyroidism caused by misuse or overdosing of thyroid hormones in order to loose weight. A rare but serious and often fatal complication of hyperthyroidism is thyroid storm. Eventually the condition of thyroid storm due to thyrotoxicosis factitia could have contributed to the woman's death from aconitine poisoning.

  6. Analysis of the Aconitine Alkaloids in Chuanwu by Electrospray Ionization/Tandem Mass Spectrometry

    Ai Min SUN; Hui LI; Zhi Ming HUANG; P.P.H.BUT; Xue Qin DING


    An electrospray ionization / tandem mass spectrometric (ESI/MS/MS) method was developed for the simultaneous identification and analysis of three aconitine alkaloids [ mesacontine (MA), hypaconitine (HA), and aconitine (A)] as intact molecules at low nanogram level in Chinese traditional medicine Chuanwu decoction as well as in human whole blood extract without chromatographic separation.

  7. Interaction of aconitine with bovine serum albumin and effect of atropine sulphate and glycyrrhizic acid on the binding

    Huang Yun, E-mail: [Pharmaceutical College, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang City, Hebei Province 050017 (China); Cui Lijian [Traditional Chinese Medical College, Hebei Medical University, Shijiazhuang 050091 (China); Wang Jianming; Huo Kun; Chen Chen; Zhan Wenhong; Wang Yongli [Pharmaceutical College, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang City, Hebei Province 050017 (China)


    The interaction of aconitine with bovine serum albumin (BSA) and effect of atropine sulphate and glycyrrhizic acid on binding constant, binding sites, and conformation were studied in an aqueous buffer solution (pH 7.40) by ultraviolet absorption and fluorescence spectroscopy. The study results show that aconitine quenched the endogenous fluorescence of BSA via a dynamic quenching procedure. Predominant intermolecular forces between aconitine and BSA were hydrophobic interactions, which stabilized the complex of aconitine-BSA. The distance between the donor and acceptor was 2.62 nm. The conformation of BSA was investigated by synchronous fluorescence techniques, indicating that the microenvironment around tryptophan (Trp) residues was changed. Furthermore, with the addition of atropine sulphate or glycyrrhizic acid, binding constant and the number of binding sites of aconitine to BSA were decreased, and the conformation had no change, which provide an important theoretical support for aconitine detoxification by atropine sulphate and glycyrrhizic acid. - Highlights: Black-Right-Pointing-Pointer Effect of atropine or glycyrrhizic acid on aconitine-BSA binding. Black-Right-Pointing-Pointer UV-vis absorption and fluorescence spectroscopic techniques used. Black-Right-Pointing-Pointer Aconitine quenched BSA fluorescence via dynamic quenching with r=2.62 nm. Black-Right-Pointing-Pointer Atropine sulphate and glycyrrhizic acid decreased K{sub A} and n of aconitine-BSA. Black-Right-Pointing-Pointer Support for aconitine detoxification by atropine and glycyrrhizic acid.

  8. Determination of Aconitine and its Metabolites in Animal Experiment by LC/ESI - MSn

    Duan Ming-Yu; ZHANG Hong-gui; ZHONG Da-fang; ZHANG Han-qi


    @@ Aconitum species (Ranunculaceae), which distribute widely in middle and lower reaches of the Yangzi River, northand southwest of China, contain highly toxic diesterditerpene Aconitum alkaloids, especially high content of aconitine.

  9. The susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats

    Min LI; Jin WANG; He-hui XIE; Fu-ming SHEN; Ding-feng SU


    Aim: The present work was designed to investigate the relationship between hemodynamic parameters and the susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats (LH). Methods: Male LH and Lyon low blood pressure rats (LL) were used. After the determination of baroreflex sensitivity (BRS), ventricular arrhythmia was induced by aconitine infusion inconscious rats. Blood pressure (BP) was recorded during the period of infusion. Results: Compared with the LL rats, the LH rats possessed significantly higher BP, blood pressure variability and lower BRS. The threshold of aconitine required for ventricular fibrillation and cardiac arrest in the LH rats were significantly lower than those in the LL rats. It was found that all the hemodynamic parameters studied were not correlated with the tl~eshold of aconitine required for arrhythmia, with the exception of BRS, which was positively related to the threshold of aconitine required for ventricular premature beat. Conclusion: The LH rats possessed greater susceptibility to aconitine-induced ventricular arrhythmias when compared to the LL rats. This greater susceptibility could not be attributed to anyone of the hemodynamic parameters alone studied in the LH rats. It is proposed that various hypertension-associated abnormalities, including the abnormal hemodynamics, may co-contribute to this vulnerability to ventricular arrhythmias.

  10. Effects of Matrine on Aconitine-Induced Electrophysiological Changes in Rat Ventricular Myocytes

    SHANHong-li; YANGBao-feng; ZHOUYu-hong; WANGHe; LIBao-xin


    Aim To explore the reason that the antiarrhythmic effect of the extract of traditional Chinese medicinal herb, matrine, is weaker than quinidine and verapamil by comparision of the effect and efficacy of matrine on various kinds of transmembrane ionic currents with those of quinidine and verapamil; and to demonstrate the best targets for antiarrhythinic drugs. Methods Whole-cell patch-clamp techniques were used to record the action potential and ionic currents in single cells of rat ventrictdar myocytes. Aconitine was used to induce the changes of ionic currents, then study the effects of matrine and quinidine, verapamil on aconitine-induced imbalanced channel currents and action potential. Results Aconitine 1μmol·L-1 induced significant changes in transmembrane currents and action potential in single cells of rat ventricular myocytes. APD was significantly prolonged by aconitine. Simtdtaneously, aconitine increased sodium, L-type calcium and in-ward rectifier potassium currents. Matrine 100μmol·L-1 reversed the aconitine-induced changes of sodium current (INa)from (-70.2±10.5) pA/pF to (-39.6±4.0) pA/pF (n=5, P<0.05 vs aconitine) ; L-type calcium current (ICa-L)from (20.4±3.8) pA/pF to (-12.9±2.9) pA/pF (n=6, P<0.01); the inward rectifier potassium current (IK1) from (-32.2±1.08) pA/pF to (-24.0±3.4) pA/pF (n=6, P<0.01 ), and action potential duration. The reversal effectsof quinidine and verapamil on aconitine-induced changes of APD and ionic currents were more marked than matrine. Conclusion Aco-nitine significantly disturbs the normal equilibrium of ion channels in ventricular myecytes. It induces changes of INa, ICa-L, IK1 and prolongation of action potential duration. Matrine at concentration 50 or 100μmol·L-1 statistically significantly suppresses aconitine-induced changes of APD and ionic currents. The potency and efficacy of inhibitory effect of matrine are markedly weaker than those of commonly used verapamil and quinidine.

  11. Reaction product analysis of aconitine in dilute ethanol using ESI-Q-ToF-MS.

    Tan, Peng; Liu, Yong-Gang; Li, Fei; Qiao, Yan-Jiang


    The study was done to identify the reaction products of aconitine in dilute ethanol using electrospray ionization-triple quad time-of-flight mass spectrometry (ESI-Q-TOF-MS). Five hydrolysates were detected, their pseudo-molecules are 632, 604, 586, 570, 500, they are 8-ethyoxyl-14-benzoylaconitine, benzoylaconine, pyraconitine, 8-acetyl-14-ethyoxylaconitine, aconine, respectively. Among them, 8-ethyoxyl-14-benzoylaconitine and 8-acetyl-14-ethyoxylaconitine were identified firstly as reaction products of aconitine in dilute ethanol, and can thus be used as indicators in quality control of medicinal Aconitum preparations used in Traditional Chinese Medicine.

  12. Solid Lipid Nanoparticles Formulated for Transdermal Aconitine Administration and Evaluated In Vitro and In Vivo.

    Zhang, Yong-Tai; Han, Meng-Qing; Shen, Li-Na; Zhao, Ji-Hui; Feng, Nian-Ping


    In this study, solid lipid nanoparticles were formulated for transdermal delivery of aconitine to improve its safety and permeability. Aconitine-loaded solid lipid nanoparticles were formulated as an oil-in-water microemulsion. Drug encapsulation efficiencies for these formulations were higher than 85%, and correlated positively with levels of surfactant and oil matrix. The size of the solid lipid nanoparticles was increased with an increase of the oil matrix, and reduction of the surfactant levels. Compared with an ethanol tincture, all the tested solid lipid nanoparticle formulations achieved improved transdermal fluxes and drug deposition in skin in vitro. Real-time monitoring of drug distribution in rat dermis using in vivo microdialysis showed that aconitine concentration was markedly higher following application of solid lipid nanoparticles, compared to tincture, throughout the experimental period. A regional comparison of rat skin found that application of solid lipid nanoparticles to the scapular region resulted in higher AUC(0-t) and C(max), compared to those achieved with application to the abdomen or chest (p nanoparticles contributed to stronger anti-inflammatory and analgesic effects on mouse in vivo models of pain than the tincture (p in vivo studies indicated that smaller particle sizes of solid lipid nanoparticles enhanced the transdermal permeability of aconitine, which can promote drug efficacy, reduce administration time, and improve medication safety.

  13. Aconitine Challenge Test Reveals a Single Exposure to Air Pollution Causes Increased Cardiac Arrhythmia Risk in Hypertensive Rats - Abstract

    Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

  14. Arctigenin, a Potential Anti-Arrhythmic Agent, Inhibits Aconitine-Induced Arrhythmia by Regulating Multi-Ion Channels

    Zhenying Zhao


    Full Text Available Background/Aims: Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. Methods: A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD, sodium current (INa, L-type calcium current (ICa, L and transient outward potassium current (Ito were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Results: Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90 were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited INa and ICa,L and attenuated the aconitine-increased INa and ICa,L by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Conclusions: Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, INa, ICa, L, and Ito may be multiple targets of arctigenin, leading to its antiarrhythmic effect.

  15. Aconitine-induced Ca{sup 2+} overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Hu, Jin; Zhang, Qiang; Liu, Bo [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Xu, Hui-bo, E-mail: [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Sun, Xiao-bo, E-mail: [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China)


    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na{sup +} channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca{sup 2+} in aconitine poisoning. In this study, we explored the importance of pathological Ca{sup 2+} signaling in aconitine poisoning in vitro and in vivo. We found that Ca{sup 2+} overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca{sup 2+} handling proteins demonstrated that aconitine promoted Ca{sup 2+} overload through the expression regulation of Ca{sup 2+} handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca{sup 2+} overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca

  16. Toxicology in the Old Testament. Did the High Priest Alcimus die of acute aconitine poisoning?

    Moog, Ferdinand P; Karenberg, Axel


    The Bible contains several interesting contributions to the history of neurology, as is the case of the High Priest Alkimos, who died suddenly in 159 BC. He was regarded as a stereotypical stroke victim for a long time. The reports on his death in the Septauginta and the later 'Jewish Antiquities' of Flavius Josephus present some typical symptoms of stroke (collapse, loss of speech and death within a short time), but they also describe severe pains, which are very unusual among patients with stroke. Similar symptoms can be found in the case of the Roman emperor Claudius, who was poisoned by his spouse Agrippina. It was thought that she used aconitine, an ingredient of the monkshood plant (Aconitum napellus L.), which imitates an apoplectic insult, but also causes vehement pains. It was therefore possible that something similar had happened to Alkimos, as aconitine was a common poison in ancient times and the surroundings of his death may confirm the suspicion. Reigning during a time of great upheaval, Alkimos was able to maintain his high office chiefly because of the help of the Seleucides. He has just begun construction work on the temple of Jerusalem, an order, which was regarded as a sacrilege by his foes. This impression was enhanced by his subsequent illness which could be considered as a divine punishment.

  17. Investigation of Aconitine-type Alkaloids from Processed Tuber of Aconitum carmiechaeli by HPLC-ESI-MS/MSn

    YUE Hao; PI Zi-feng; ZHAO Yu-feng; SONG Feng-rui; LIU Zhi-qiang; LIU Shu-ying


    @@ Introduction Aconitine-type alkaloids isolated from the roots of Aconitum carmiechaeli show a potential toxicity and a broad spectrum of bioactivity[1-4]. On the basis of the C8-substituent of C19-diterpenoid skeleton, aconitinetype alkaloids can be divided into diester-diterpenoid alkaloids( DDAs), monoester-diterpenoid alkaloids(MDAs), and lipo-alkaloids( Fig. 1 ).

  18. One versus five-days of exposure to varying concentrations of B100 soya biodiesel exhaust reveals a threshold concentration for increased sensitivity to aconitine-induced arrhythmia

    Although biodiesel (BD) is rapidly being considered as an alternative to diesel fuel, its health effects have not been thoroughly characterized. We previously used the aconitine challenge test to demonstrate that a single exposure to petroleum diesel exhaust (DE) increases the ri...

  19. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    Yang, Cuiping, E-mail:; Zhang, Tianhong, E-mail:; Li, Zheng, E-mail:; Xu, Liang, E-mail:; Liu, Fei, E-mail:; Ruan, Jinxiu, E-mail:; Liu, Keliang, E-mail:; Zhang, Zhenqing, E-mail:


    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max

  20. Preparation of Aconitine Ethosome and Study on Its Anti-inflammatory and Analgesic Activity%乌头碱醇质体的制备及抗炎镇痛作用研究

    朱凡; 刘小平


    对乌头碱醇质体的制备工艺和抗炎镇痛作用进行研究,以包封率为评价指标,采用乙醇注入法制备乌头碱醇质体,通过正交设计优化制备工艺,用HPLC测定其包封率,并采取二甲苯致炎法和扭体法研究其抗炎镇痛作用.结果表明,乌头碱醇质体最佳制备工艺为:乌头碱与卵磷脂质量比1∶15,磷酸盐缓冲溶液pH为7.6,乙醇浓度10%.以优化工艺制得的乌头碱醇质体包封率较高、稳定性好,且具有良好的抗炎镇痛作用.%To optimize the preparation technology of aconitine ethosome and confirm its anti-inflammatory and analgesic activity,aconitine ethosome was prepared by ethanol injection method. The encapsulation efficiency was taken as inspection target and the preparation was optimized by orthogonal design. HPLC was used to measure the encapsulation efficiency. P-xylene-induced inflammation and writhing were taken to confirm the anti-inflammatory and analgesic activity. It shows that the best prescription was aconitine/lecithin(1:15) with phosphate buffer solution (pH 7. 6) ,the concentration of ethanol was 10%. The optimized formulation of aconitine ethosome is high in encapsulation efficiency and good in stability,and the anti-inflammatory and analgesic activity of aconitine ethosome was significant.

  1. Quantification of aconitine in post-mortem specimens by validated liquid chromatography-tandem mass spectrometry method: three case reports on fatal 'monkshood' poisoning.

    Bicker, Wolfgang; Monticelli, Fabio; Bauer, Andreas; Roider, Gabriele; Keller, Thomas


    The diester-diterpene alkaloid aconitine was quantified by liquid chromatography-tandem mass spectrometry in post-mortem specimens of three cases where suicidal ingestion of Aconitum napellus L. ('monkshood') was supposed. In an attempt at rationalization, sample preparation and chromatographic conditions of plasma/serum drug analysis routine were utilized. Linearity was established from 0.5 to 20 µg L⁻¹ using newborn calf serum (NCS) as a surrogate calibration matrix for all sample types and mesaconitine as an internal standard. Validation (selectivity, sensitivity, precision, accuracy, recovery of the extraction procedure, matrix effect, processed sample stability) confirmed the applicability of the analytical method to various post-mortem matrices. Internal standard selection was based on multi-matrix process efficiency data. In human post-mortem peripheral blood a lower limit of quantification of 0.51 µg L⁻¹ and a limit of detection of 0.13 µg L⁻¹ were accomplished (0.1 ml sample aliquots). Aconitine was degraded to a large extent in different sample types when being stored at +20 °C for 30 days, while at -20 °C and for some matrices also at +4 °C no appreciable degradation occurred. Aconitine concentrations in real samples were 10.3-17.9 µg L⁻¹ (peripheral blood, n = 3), 14.9-87.9 µg L⁻¹ (heart blood, n = 3), 317-481 µg L⁻¹ (urine, n = 2), 609-4040 µg L⁻¹ (stomach content, n = 3), 139-240 µg L⁻¹ (bile, n = 2), 8.4 µg L⁻¹ (vitreous humor, n = 1), 54.7 µg L⁻¹ (pericardial fluid, n = 1), 492 µg kg⁻¹ (liver, n = 1), 15.2-19.7 mg L⁻¹ (unknown liquids secured onsite, n = 3). Together with concomitant circumstances the analytical data provided compelling evidence for acute Aconitum poisoning as being the cause of death.

  2. Quantification of three aconitine- type diester alkaloids in Xiaozhong tablets by UPLC- MS%UPLC-MS法测定消肿片中3个乌头碱类双酯型生物碱的含量

    崔萍; 杨莉; 熊爱珍; 王峥涛; 胡春湘; 詹常森


    Objective:To establish an UPLC -MS method for simultaneous quantification of mesaconitine,aconitine and hypaconitine in Xiaozhong tablets.Methods:The separation was performed on an Agilent ZORBAX SB- C18 (100 mm×2.1mm,l.8 μm)column with acetonitrile -0.1% formic acid(35:65)as the mobile phase.The column temperature was set at 35℃ with flow rate of 0.3 mL o min-1.AP- ESI at positive ion mode and the selected ion monitoring were used.Ions at m/z 632,646 and 616 were selected to quantify mesaconitine,aconitine and hyp aconitine.Results:The linear ranges were 0.2250 -510.0 ng o mL-1(r=0.9996) for mesaconitine, 0.2500 -500.0 ng o mL-1(r = 0.9996 ) for aconitine and 0.2540 -508.0 ng o mL-1 ( r = 0.9996 ) for hypaconitine.The average recoveries( n =9) were 95.1% for mesaconitine,93.6% for aconitine and 93.0% for hypaconitine.Conclusion:The established method is convenient,rapid and accurate,which can be used to determine three poisonous al kaloids in Xiaozhong tablets.The study may provide a scientific basis for the quality control of this preparation.%目的:建立同时测定消肿片中新乌头碱、乌头碱和次乌头碱3个双酯型生物碱含量的超高效液相色谱-质谱分析方法.方法:采用Agilent ZORBAX SB-C18(100 mm ×2.1 mm,1.8μm)色谱柱,以乙腈-0.1%甲酸水溶液(35:65)为流动相,流速0.3mL·min -1,柱温35℃;ESI+模式下选择离子监测(SIM)质荷比(m/z)为632,646,616的离子.结果:新乌头碱、乌头碱、次乌头碱浓度分别在0.2250~510.0 ng·mL-1(r=0.9996)、0.2500~500.O ng·mL-1(r =0.9996)和0.2540~508.0 ng·mL-1(r =0.9996)范围内有良好的线性关系,平均回收率(n=9)分别为95.1%,93.6%,93.O%.结论:该方法简便、快捷、准确,同时检测3个有毒生物碱,可用于消肿片的质量控制.

  3. 乌头碱对大鼠粪样代谢谱影响的代谢组学研究%Metabonomics study of feces from rats treated with aconitine

    王旭彬; 曹瑞丽; 刘巧; 张琪; 许美凤; 孙博; 颜贤忠


    Objective To investigate the metabolic profiles of feces from rats treated with aconitine using NMR-based metabolomics approach.Methods After a 7-day acclimatization period, 15 male Wistar rats were randomly assigned to two treatment groups (control and aconitine), each group were administrated with aconitine at a dose of 2.54 mg/kg or the equal volume of drinking water, respectively.Feces samples were collected at 6 h after the administration, then acquired the main organs (heart, liver, kidney) after anesthesia and calculated their organic indexes.'H-NMR spectra were performed on Varian INOVA 600 NMR spectrometer.OPLS-DA and Pearson's correlation analysis were applied to the aligned integral data.The plots of correlation coefficient were carried out in MATLAB.Additionally, a two-tailed Student's t-test was performed for metabolites by using SPSS 17.0.Results Compared to the control group, organic indexes were reduced in aconitine-induced group, in which heart and liver were caused significant differences (P < 0.05).These metabolites had been confirmed including the short-chain fatty acid (SFCAs), monosaccharides, amino acids, tricarboxylic acid (TCA) cycle intermediates, pyrimidine and purine metabolites in fecal water extracts.Mullivariate statistical analysis showed that when compared to control group, the levels of α-ketoisovalerate, glutamate, phenylalanine in aconitine-induced group decreased significantly (P < 0.05).Therefore, intestinal flora of rats produced significantly toxic effects with aconitine, and reduced gut flora metabolism and ability to decompose the gastrointestinal food, resulting in changes in the fecal metabolite content.These results combined with pathway analysis indicated the disorder of amino acid metabolism and energy metabolism in dosed group.Conclusion This work objectively reflects the relationship of metabolite profiling in rats feces and aconitine toxicity and points out the important role played of the intestinal flora balance

  4. ω-3鱼油脂肪乳对乌头碱诱发大鼠心律失常的影响%Effect of omega-3 fatty acid on the experimental arrhythmic rats induced by aconitine

    郝蓬; 李果; 何东方; 卢春山; 郭成军; 刘兴鹏; 柳景华; 张英川; 方东平; 赵东辉; 刘冰; 汪国忠


    Objective To explore the effect and correlated mechanism of omega-3(co-3) fatty acid on the experimental arrhythmic rats induced by aconitine. Methods Fifty male rats were randomly divided into 0.05), while 3,5,7 minutes after intravenous injection of aconitine, the scores of arrhythmia in o>-3 fatty acids group were lower than these in control group (P 0.05). Conclusion to-3 fatty acids may improve aconitine-induced arrhythmia in rats by promoting the phosphorylation of CX43.%目的 探讨ω-3鱼油脂肪乳对乌头碱诱发大鼠心律失常的影响及相关机制.方法 50只雄性大鼠随机分为ω-3鱼油脂肪乳组和对照组,每组25只.实验前15 d,ω-3鱼油脂肪乳组大鼠隔日经尾静脉注射ω-3鱼油脂肪乳2 mL·kg-1;对照组注射等量的生理盐水.应用乌头碱诱发心律失常大鼠模型,观察记录2组大鼠室性期前收缩、室性心动过速出现的时间及心律失常评分,Western blot检测大鼠心肌组织缝隙连接蛋白43( CX43)的表达.结果 ω-3鱼油脂肪乳组大鼠室性期前收缩和室性心动过速出现时间均显著长于对照组(P<0.05).静脉注射乌头碱后1 min,2组大鼠心律失常评分比较差异无统计学意义(P>0.05);静脉注射乌头碱后3、5、7 min,ω-3鱼油脂肪乳组大鼠心律失常评分均低于对照组(P<0.05).ω-3鱼油脂肪乳组大鼠心肌组织中CX43蛋白的表达高于对照组(P<0.05),但2组大鼠心肌组织中去磷酸化CX43蛋白表达比较差异无统计学意义(P>0.05).结论 ω-3鱼油脂肪乳可能通过促进CX43的磷酸化改善乌头碱诱导的大鼠心律失常.

  5. Quantification of three aconitine-type diester alkaloidsin Fengshigutong pills by HPLC%高效液相色谱法测定风湿骨痛丸中双酯型生物碱的限度

    刘军玲; 班永生; 蒲婧哲; 张亚中


    Objective To establish an HPLC method for determing three alkaloids ( aconitine,hypaconitine and mesaconitine ) in Fengshigutong pills. Methods The separation was performed on a Phenomenex C18 column(5 μm,4.6 mm×250 mm) with column temperature of 30℃. The mobile phase consisted of acetonitrile-trahydrofuran-0. 1 mol· L-1 ammonium acetate (per 1 000 mL contains 0. 5 mL) (12. 5=7. 5:80)at the flow rate of 1.0 mL·min-1 and detection wavelength at 230 nm. Results The separation showed a good result. Conclusion The method is accurate and reproducible . It can be used for the quality control of Fengshigutong pills .%目的 建立高效液相色谱法测定风湿骨痛丸中双酯型生物碱的限度.方法 供试品采用超声处理法,双酯型生物碱中三种成分通过菲罗门C18被检测,柱温30℃,以乙腈-四氢呋喃-0.1 mol·L-1的乙酸铵溶液(每1 000 mL中加冰醋酸0.5 mL)(12.5:7.5:80)为流动相,检测波长230 nm.结果 乌头碱、次乌头碱、新乌头碱峰分离度均良好,且无干扰.结论 此法准确,重复性好,可用于控制该处方中制川乌、制草乌中双酯型生物碱的限度.

  6. Effect of sophocarpine on aconitine induced rat arrhythmic model and its mechanism%槐果碱抗乌头碱诱发大鼠心律失常及其作用机制

    陈雯雯; 罗章源; 陈颖敏; 徐瑾; 陈曙霞; 何奔


    AIM To study the antiarrhythmic effect of sophocarpine and its mechanism. METHODS A rapid cardiac arrhythmic SD rat model induced by aconitune was used, dividing into 3 groups such as model group, sophocarpine group (5 mg·kg-1, iv) and amiodarone group (2.5μg·kg-1, iv). Continuous EKG monitoring and printing were applied to keep track of the appearing time of ventricular premature beat, ventricular tachycardia, ventricular flutter, ventricular fibrillation and cardiac arrest, which could be changed into total consumption dose of aconitine so as to be compared among groups, then the antiarrhythmia effect of sophocarpine could be evaluated. Capillary grass microelectrode was used to record action potential of guinea pig papillary muscles in vitro. Sophocarpine of different concentrations (1、5、10 μmol·L-1) were added to the perfusion sulotion separately in order to investigate how they would affect action potential duration (APD) , effective refractory period (ERP), maximal depolarization velocity (Vmax), action potential amplitude (APA) and resting potential (RP). RESULTS The appearance of ventricular premature beat, ventricular tachycardia, ventricular flutter, ventricular fibrillation and cardiac arrest were all delayed in the sophocarpine group and the amiodarone group in comparison with the model group (P 0.05). Sophocarpine (1、5、10 μmol·L-1) prolonged APD50, APD90, APD100 and ERP while Vmax declined (P 0.05). CONCLUSION Sophocarpine has significant antiarrhythmic effect on the aconitine induced , arrhythmia rat mode, which is possibly due to prolongation of APD and ERP.%目的 研究槐果碱的抗心律失常作用及其机制.方法采用乌头碱诱发的快速型心律失常的SD大鼠,分为模型组、槐果碱组(5 mg· kg-1,iv)与胺碘酮组(2.5 μg· kg-1,iv)3组.心电图连续示波观察,电脑实时显示并存储,记录室性早搏、室性心动过速、心室扑动-心室颤动、心脏停搏出现时间,换算成乌

  7. 基于偏最小二乘法的乌头碱类化合物毒性的定量构效关系研究%Study on the quantitative structure-toxicity relationships of aconitine compounds basing on partial least squares method

    李佐静; 王琳; 闫心丽; 高志祥; 孟繁浩


    乌头碱类化合物属于二萜类生物碱,存在于乌头属欧乌头、川乌、北草乌和华乌头等多种毛茛科植物中,该类化合物既是其活性成分,也是其毒性成分。利用化合物定量结构-毒性效应关系(QSTR)方法研究了14个乌头碱类化合物的各种量化参数对其毒性的影响,并建立了毒性预测模型。由于该类化合物是从中药中提取分离的生物碱,样本数量相对较少,本文采用了偏最小二乘回归方法(PLS)进行降维,进行4个成分的提取及建模。毒性预测模型为:Log(toxi)=0.1593*Mass+0.2908*LogP+1.5475*SAA-0.5222*SAG-0.6104*Volume+0.3112*Ref+0.1784*Polar+0.1785*BE+0.1634*HF-0.1387*Dipole+0.1412,结果表明该模型具有较好的毒性预测能力。%Aconitine compounds are found in Aconitum Ouwu head, Chuan Wu, Aconitum, and the North China and other Ranunculaceae Aconitum plants, which are not only the active ingredient but also the toxic component. The quantum chemistry parameters of 14 kinds of aconitine compounds were studied using the quantitative structure toxicity relationships (QSTR) method to affect its toxicity and to build the forecast model. In this paper, Partial least squares method was taken into account to reduce the dimension and build the model using 4 principle components because of the limitation of sample space. It is tested that the model has a good forecasting ability. The model is: Log(toxi)=0.1593*Mass+0.2908*LogPf 1.5475*SAA-0.5222*SAG-0.6104*Volume+0.3112*Ref+0.1784*Polar+0.1785*BE+0.1634*HF-0.1387*Dipole+0.1412.

  8. Effects of BmKIM on sodium current of isolated cardiomyocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits%东亚钳蝎毒素多肽对家兔心室肌细胞钠电流和在体动作电位的影响以及抗心律失常作用研究

    王腾; 黄从新; 江洪; 唐其柱; 杨波; 李庚山


    目的 探讨基因表达得到重组的东亚钳蝎毒素多肽(BmKXM)对家兔单个心室肌细胞钠电流(INa)和在体动作电位的影响,以及对抗乌头碱诱发的心律失常电活动的作用.方法 用酶解法分离家兔心室肌细胞,全细胞膜片钳技术记录所需INa.采用浮置式玻璃微电极记录在体心肌细胞跨膜动作电位,并监测体表心电图.结果 (1)BmKIM 能明显抑制心肌细胞INa,使INa的电流-电压(I-V)曲线显著上移,但I-V曲线的形态没有发生改变.BmKIM使失活曲线显著左移,50%的INa失活电压分别由用药前的(-70.8±2.6)mV变为(-84.84±3.5)mV(P<0.05).在BmKIM作用下,心肌细胞INa失活后恢复时间明显延长,用药前快、慢恢复时间常数(Tf和Ts)分别是(28.9±6.1)ms和(107±21.6)me,给予BmKIM后,τf和τs分别是(54.2±7.9)ms(P<0.05)和(211.1±34.6)ms(P<0.01).(2)BmKIM 能明显改变记录在体心肌细胞跨膜动作电位时程(APD)和幅度(APA)以及最大上升速率(Vmax),使APD50和APD90都明显缩短,APA和Vmax显著减小.心电图上表现为QT间期缩短,心率明显加快.(3)乌头碱能明显触发后除极,诱发室件心动过速(室速),动作电位上表现为早期后除极和(或)延迟后除极.相对心电图上表现为插入性室性早搏或尖端扭转型室速(发生率为77.8%).BmKIM能明显降低乌头碱诱发的心律失常发生率(22.2%,P<0.01),更不能触发室速.结论 BmKIM对兔的心室肌细胞,INa有明显的抑制作用,这种抑制作用是通过与失活态的钠通道结合而发挥生理学效应,BmKIM 可抑制形成动作电位的钠离子内流,对抗乌头碱所致的心律失常发生,为开发具有选择性直接针对钠通道的阻滞剂BmKIM的应用前景打下基础.%Objective To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (INa) of isolated ventricular myocytes,transmembrane action potential and aconitine induced

  9. 乌头碱和甘草酸作用的研究%Study of Interaction of Aconitine and Glycyrrhizic Acid by HPLC

    马鸿雁; 刘小彬; 李楠; 杨明


    目的从化学角度揭示附子甘草配伍的机理.方法应用高效液相分析方法,比较了乌头碱单煎、乌头碱甘草酸合煎物质变化的规律.结果乌头碱单煎、乌头碱甘草酸合煎,乌头碱都发生水解;比较单煎、合煎高效液相色谱(HPLC) 结果,甘草酸加速了乌头碱的水解.结论甘草酸加速乌头碱水解是附子甘草配伍减毒机理之一.

  10. The effects of B0, B20 and B100 soy biodiesel exhaust on aconitine-induced cardiac arrhythmia in spontaneously hypertensive rats

    CONTEXT: Diesel exhaust (DE) has been shown to increase the risk of cardiac arrhythmias. Although biodiesel has been proposed as a "safer" alternative to diesel, it is still uncertain whether it actually poses less threat.OBJECTIVE: We hypothesized that exposure to pure or 20% so...

  11. A New Method for Preparation and Characterization of Lipo-alkaloid

    WANG Yong; XU Qing-xuan; SONG Feng-rui; LIU Zhi-qiang; LIU Shu-ying


    A simple route for the preparation of lipo-alkaloid is presented. When aconitine or one of its analogues is heated with a fatty acid for 20 min at 100 ℃ in water, the C8 acetyl group of aconitine is displaced by a long chain fatty acyl group. The structures of the products were characterized by electrospray ionization tandem mass spectrometry.

  12. Study on Metabolites of Aconitum Alkaloids in Human Urine

    SUN Ying; ZHANG Hong-gui; ZHONG Da-fang; ZHANG Han-qi


    @@ The aconite belongs to plants of genus Aconitum in family of Ranunculacea and have notable clinical functions intreating rheumatic arthritis, heart failure, etc. However, accidents of aconitine(from aconite) poisoning frequently occurto many people taking these herbs.

  13. 氧化苦参碱对正常及乌头碱诱发心律失常大鼠动作电位的影响%Effects of oxymatrine on action potential in normal rats and arrhythmic rats induced by aconitine

    陈霞; 李英骥; 葛静岩; 张文杰; 钟国赣


    目的:观察氧化苦参碱(OMT)对正常及乌头碱诱发大鼠心律失常模型动作电位(AP)的影响.方法:采用悬浮微电极技术记录大鼠在体心室肌细胞的动作电位.结果:给予 3、15和30 mg·kg-1的OMT能剂量依赖性地延缓乌头碱所致大鼠心律失常的发生,静脉给予30 mg·kg-1的OMT能减小AP的幅值,缩短APD50和APD90,降低Vmax.结论:OMT对心肌细胞AP的影响可能为其抗心律失常作用机制之一.

  14. Synthesis and Insecticidal Activity of Derivants of 3,13-Ester Mesaconitine%3,13-酯基中乌头碱衍生物的合成及其杀虫活性的研究

    王晓东; 袁小红; 杨海君; 侯大斌; 王惠; 许源


    [Objective] The experiment aimed to explore the relations between structure of aconitine, aconitine derivatives and insecticide. [Method] The aconitine derivatives such as 3-acetyl mesaconitine, 3-propionyl mesaconitine, 3-acetyl-13-Benzoyl-mesaconitine and 3-propionyl-13-Benzoyl-mesaconitine were synthesized by mesaconitine with acetic anhydride or propionic anhydride and their insecticidal activities were also determined. [Result] When the concentration was 500 mg/L, the insecticidal activities of mesaconitine against Nilaparvata legen and Aphis were 50% and 30% respectively while the insecticidal activities of 3-acetyl mesaconitine, 3-propionyl mesaconitine, 3-acetyl-13-Benzoyl-mesaconitine and 3-propionyl-13-Benzoyl-mesaconitine against Aphis medicagini were 40%, 30%, 30% and 20% respectively at 500 mg/L. [Conclusion] After hydroxyl esterification, the insecticidal activity of mesaconitine was declined and the existence of hydroxyl at 3rd position in mesaconitine played very important influences on insecticidal activity.

  15. Severe acute poisoning with homemade Aconitum napellus capsules: toxicokinetic and clinical data.

    Moritz, Fabienne; Compagnon, Patricia; Kaliszczak, Isabelle Guery; Kaliszczak, Yann; Caliskan, Valérie; Girault, Christophe


    Aconitum napellus is an extremely dangerous plant that contains various toxic diterpenoid alkaloids, mainly aconitine primarily concentrated in the roots. We report a case of acute intoxication of a 21-year-old man admitted to our Emergency Department after the ingestion, in order to sleep, of three homemade Aconitum napellus capsules. Capsules were measured to contain 237 mg of root and 19 microg of aconitine. The patient experienced the first symptoms on wakening 5 hours later with generalized paresthesia, nausea, diarrhea, vertigo, thoracic pain dyspnea, and dyschromatopsia. At admission, 7 hours after intake electrocardiographic analysis showed a sinusal bradycardia with polymorphic and bigeminal ventricular extrasystolia. Cardiovascular and neurological symptoms disappeared, respectively within 11 and 13 hours of ingestion. The patient was discharged from the ICU on day 2. Plasmatic concentrations at H7, H9, H14 H19, and after ingestion were, respectively, of 1.75, 0.75, 0.35, and 0.02 ng/mL. The calculated half-life of aconitine was 3 hours. To our knowledge, this is the first reported case with an aconitine toxicokinetic-effect relationship. The authors stress that clinicians must be aware of possible occurrence of acute poisoning with Aconitum napellus in European countries and in the United States as herbal medicine is becoming increasingly popular.

  16. A study of the diterpene alkaloids of Aconitum napellus ssp. neomontanum during its onthogenetic cycle.

    Colombo, M L; Bravin, M; Tome, F


    Qualitative and quantitative variations in the diterpene alkaloids content in the neomontanum subspecies of Aconitum napellus, growing near lake of Como, were studied throughout its complete onthogenetic cycle. Aconitine, N-deethylaconitine and two compounds with m.w. = 688 and m.w. = 629 have been detected in the various organs of plant almost at any time during the vegetative cycle.

  17. Environ: E00359 [KEGG MEDICUS

    Full Text Available E00359 Aconitum japonicum tuberous root Crude drug Aconitine [CPD:C06091], Mesaconi...amine [CPD:C06346], Coryneine chloride Aconitum japonicum, Aconitum [TAX:49188] Ranunculaceae (buttercup family) Aconitum... japonicum tuberous root Crude drugs [BR:br08305] Dicot plants: others Ranunculaceae (buttercup family) E00359 Aconitum tuberous root ...

  18. Two new C19-diterpenoid alkaloids from roots Aconitum hemsleyanium var. atropurpureum

    Pei Tang; Dong Lin Chen; Xi Xian Jian; Feng Peng Wang


    A new franchetine-type C19-diterpenoid alkaloid 3-hydroxyfranchetine 1 and a new aconitine-type C19-diterpenoid alkaloid atropurpursine 2 have been isolated from the roots of Aconitum hemsleyanium var.atropurpureum.The structures of these new alkaloids were established on the basis of spectral data.

  19. Drug: D07152 [KEGG MEDICUS

    Full Text Available D07152 Crude, Drug Processed aconite root Aconitine [CPD:C06091], Jesaconitine [CPD...Same as: E00256 Therapeutic category: 5100 Ranunculaceae (buttercup family) Processed... drugs and Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs D07152 Processed aconite root PubChem: 51091491 ...

  20. Environ: E00256 [KEGG MEDICUS

    Full Text Available E00256 Aconitum carmichaeli mother root Crude drug Aconitine [CPD:C06091], Jesaconi...onitine [CPD:C08704]), Coryneine chloride Aconitum carmichaeli [TAX:85363] Same as: D07152 Ranunculaceae (bu...ttercup family) Aconitum carmichael mother root Crude drugs [BR:br08305] Dicot pl...ants: others Ranunculaceae (buttercup family) E00256 Aconitum carmichaeli mother root ...

  1. 苦参碱影响豚鼠乳头肌细胞动作电位的实验研究%Influence of Matrine on Cell Action Potential in Guinea Pig Papillary Muscle

    唐汉庆; 李妙玲; 王勇; 郭健; 李国彰; 宋宁; 庞宇舟


    Objective; To observe influence of matrine on cell action potential in guinea pig papillary muscles thus to clarify its antiarrhythmic mechanism. Method; Guinea pigs were divided into control group, matrine group (10, 50, 100 μmol -L ) , aconitine group 1 μmol - L , aconitine 1 μmol- L + matrine 50 μmol- L group, aconitine 1 u.mol- L + matrine 100 u.mol - L group. Conventional microelectrode technique was used to record action potential duration ( APD) , action potential amplitude ( APA) , 50 % and 90 % of APD repolarization (APD50 and APD90 ). Result; Matrine could prolong moderately APD50 and APD90 in a dose-dependent manner (10, 50, 100 p,mol -L-1 ) and reduce APA. Aconitine could excessively prolong APD ( vs control group, P <0. 05) , APD50 and APD90. Matrine (100 (μmol -L-1 ) could remedy for excessive elonggation of aconitine on APD , APD50 and APD90 ( vs aconitine group , P < 0. 05 or P < 0. 01) . Matrine ( 100 (μmol -L -1 ) also could reduce APA ( vs aconitine group, P < 0. 05 ). Conclusion; Matrine could remedy for excessive elonggation of aconitine on APD, APD50 and APD;,,, and reduce APA of aconitine-induced arrhythmia, which could maitain action potential in a normal range, and was probably one of matrine antiarrhythmic mechanisms.%目的:观察苦参碱对豚鼠心室肌动作电位的影响,探讨其抗心律失常的作用机制.方法:豚鼠分为对照组、苦参碱组(10,50,100 μmol·L-1)、乌头碱组(1 μmol·L-1)、乌头碱(1 μmol·L-1)+苦参碱(50 μmol· L-1)组,乌头碱(1μmol·L-1)+苦参碱(100 μmol·L-1)组;采用标准微电极记录技术记录动作电位时程(APD)、动作电位0相幅值(APA)、动作电位50%复极化时程(APD50)和90%复极化时程(APD90).结果:苦参碱浓度依赖性(10,50,100 μmol·L-1)适度延长APD50和APD90,降低APA;乌头碱明显延长APD(和对照组比较P<0.05),APD50,APD90;苦参碱(100 μmol·L-1)能纠正乌头碱对APD,APD50,APD90的过度延长

  2. Acute toxic herbal intake in a suicide attempt and fatal refractory ventricular arrhythmia.

    Strzelecki, Antoine; Pichon, Nicolas; Gaulier, Jean M; Amiel, Jean B; Champy, Pauline; Clavel, Marc


    This report involves a 54-year-old man who died following refractory ventricular fibrillation after ingestion of a plant in a suicide attempt. Repeated direct-current cardioversions were unsuccessful and no single anti-arrhythmic agent was effective for arrhythmia control. The routine blood toxicological screening was negative. Aconitine, the main toxin of Aconitum napellus was identified using a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The whole blood concentration (24 microg/l) was higher than those reported in other aconitine-related deaths. The patient had found information about the life-threatening nature of such a toxic herb intake on a free medical encyclopedia online.

  3. 3-Deoxyaconitine from the root of Aconitum Carmichaeli Debx.

    Feng Gao


    Full Text Available The title compound (systematic name: 8β-acetoxy-14α-benzoyloxy-N-ethyl-13β,15α-dihydroxy-1α,6α,16β-trimethoxy-4β-methoxymethyleneaconitane, C34H47NO10, is a typical aconitine-type C19-diterpenoid alkaloid, and was isolated from the roots of the Aconitum carmichaeli Debx. The molecule has an aconitine carbon skeleton with four six-membered rings and two five-membered rings, whose geometry is similar to these observed in other C19-diterpenoid alkaloids; both of five-membered rings have the envelope configurations and the six-membered N-containing heterocyclic ring displays a chair conformation. Intramolecular O—H...O hydrogen bonding occurs. Weak intermolecular C—H...O hydrogen bonding is observed in the crystal structure.

  4. Rapid quality assessment of Radix Aconiti Preparata using direct analysis in real time mass spectrometry

    Zhu Hongbin; Wang Chunyan; Qi Yao [Changchun Center of Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); University of Chinese Academy of Sciences, Beijing 100039 (China); Song Fengrui, E-mail: [Changchun Center of Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Liu Zhiqiang; Liu Shuying [Changchun Center of Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)


    Highlights: Black-Right-Pointing-Pointer DART MS combined with PCA and HCA was used to rapidly identify markers of Radix Aconiti. Black-Right-Pointing-Pointer The DART MS behavior of six aconitine-type alkaloids was investigated. Black-Right-Pointing-Pointer Chemical markers were recognized between the qualified and unqualified samples. Black-Right-Pointing-Pointer DART MS was shown to be an effective tool for quality control of Radix Aconiti Preparata. - Abstract: This study presents a novel and rapid method to identify chemical markers for the quality control of Radix Aconiti Preparata, a world widely used traditional herbal medicine. In the method, the samples with a fast extraction procedure were analyzed using direct analysis in real time mass spectrometry (DART MS) combined with multivariate data analysis. At present, the quality assessment approach of Radix Aconiti Preparata was based on the two processing methods recorded in Chinese Pharmacopoeia for the purpose of reducing the toxicity of Radix Aconiti and ensuring its clinical therapeutic efficacy. In order to ensure the safety and effectivity in clinical use, the processing degree of Radix Aconiti should be well controlled and assessed. In the paper, hierarchical cluster analysis and principal component analysis were performed to evaluate the DART MS data of Radix Aconiti Preparata samples in different processing times. The results showed that the well processed Radix Aconiti Preparata, unqualified processed and the raw Radix Aconiti could be clustered reasonably corresponding to their constituents. The loading plot shows that the main chemical markers having the most influence on the discrimination amongst the qualified and unqualified samples were mainly some monoester diterpenoid aconitines and diester diterpenoid aconitines, i.e. benzoylmesaconine, hypaconitine, mesaconitine, neoline, benzoylhypaconine, benzoylaconine, fuziline, aconitine and 10-OH-mesaconitine. The established DART MS approach in

  5. 乌头类生物碱对心肌的毒性作用及分子毒理学研究进展%The toxicity of aconitum alkaloids on cardiocytes and the progress of its research using the methods of molecular toxicology

    刘艳; 章诗伟; 周兰; 刘良


    乌头属植物是被子植物亚门毛茛科中一类重要的有毒植物,也是我国最早有记载的药用有毒植物之一;其块根中多含有剧毒的二萜类双酯型生物碱-乌头碱,因个体差异、用法不当以及误服或投毒等原因而发生乌头中毒、甚至死亡的报道屡见不鲜.目前,对乌头碱的研究多局限在临床救治方面,缺乏对乌头碱毒性作用机制研究.本文参考国内外相关文献资料,对乌头碱的心肌细胞毒性作用机制进行了综述.%Aconltium plants are a group of important poisonous plants in the Ranunculaeeae family of Angiosperm subphylum.and one of the earliest recorded poisonous plants in China as well.In their tubers(root)have hypertoxic Aconitium alkaloids,which belong to the group of diesterditerpene alkaloids.It is repeatedly reported in China that aconitine poisoning,and even death from aconitine poisoning,caused by the individual differences in pharmaceutical tolerance of aconitine,taking the wrong medicine or inadequate dosage,or put in the poison by homicide.At present,the research on aconitine is mainly limited to clinical treatment,but lack of research on toxicity mechanism of aeonitine.This paper reviews some progress relating to the toxicological mechanisms of this kind of alkaloid.

  6. A case of fatal poisoning with the aconite plant: quantitative analysis in biological fluid.

    Elliott, S P


    In recent years recorded cases of plant poisoning have become rare, this may in part be due to the possibility of plant ingestion not being indicated at the beginning of an investigation. Aconitum napellus (aconite, Wolfsbane, Monkshood) is one of the most poisonous plants in the UK. It contains various potent alkaloids such as aconitine, isoaconitine, lycaconitine and napelline. Ingestion of Aconitum plant extracts can result in severe, potentially fatal toxic effects. This paper describes the analytical findings in a recent death in the UK. resulting from deliberate ingestion of Aconitum napellus extract. The concentrations of aconitine measured by HPLC-DAD in the post mortem femoral blood and urine were 10.8 micrograms/L and 264 micrograms/L, respectively. The aconitine concentration in the ante mortem urine was 334 micrograms/L and was estimated to be 6 micrograms/L in the ante mortem serum. Hence, accidental, suicidal or homicidal poisoning due to the ingestion of plant material remains a possibility and should be borne in mind when investigating sudden or unexplained death.

  7. [Toxicity of monkshood. Review.].

    Ingolfsdottir, K; Olafsson, K


    Monkshood, Aconitum napellus L. (Ranunculaceae), is considered one of the most poisonous plants growing in Europe. Monkshood and other Aconitum species are still used in Oriental and homeopathic medicine as analgesics, febrifuges and hypotensives. The neurotoxin aconitine is the principal alkaloid in most subspecies of monkshood. A review is presented, which includes historical aspects of monkshood as a poisonous and medicinal plant, the mode of action of aconitine, symptoms of toxicity, treatment and reports of recent poisoning incidents. In addition, results of quantitative HPLC examination of hypogeous and epigeous organs from a population of A. napellus ssp. vulgare cultivated in Iceland are discussed. The fact that children in Iceland have commonly been known to eat the sweet tasting nectaries in monkshood prompted an investigation of the alkaloidal content of these organs specifically. The low aconitine content found in the nectaries as well as in whole flowers accords with the absence of reported toxicity arising from the handling of flowers and consumption of nectaries from A. napellus in this country.

  8. Changes underlying arrhythmia in the transgenic heart overexpressing Refsum disease gene-associated protein.

    Koh, Jeong Tae; Jeong, Byung Chul; Kim, Jae Ha; Ahn, Young Keun; Lee, Hyang Sim; Baik, Yung Hong; Kim, Kyung Keun


    Previously, we identified a novel neuron-specific protein (PAHX-AP1) that binds to Refsum disease gene product (PAHX), and we developed transgenic (TG) mice that overexpress heart-targeted PAHX-AP1. These mice have atrial tachycardia and increased susceptibility to aconitine-induced arrhythmia. This study was undertaken to elucidate the possible changes in ion channels underlying the susceptibility to arrhythmia in these mice. RT-PCR analyses revealed that the cardiac expression of adrenergic beta(1)-receptor (ADRB1) was markedly lower, whereas voltage-gated potassium channel expression (Kv2.1) was higher in PAHX-AP1 TG mice compared with non-TG mice. However, the expression of voltage-sensitive sodium and calcium channels, and muscarinic receptor was not significantly different. Propranolol pretreatment, a non-specific beta-adrenoceptor antagonist, blocked aconitine-induced arrhythmia in non-TG mice, but not in PAHX-AP1 TG mice. Our results indicate that, in the PAHX-AP1 TG heart, the modulation of voltage-gated potassium channel and ADRB1 expression seem to be important in the electrophysiological changes associated with altered ion channel functions, but ADRB1 is not involved in the greater susceptibility to aconitine-induced arrhythmia.

  9. [Fatal exposure to Aconitum napellus].

    German Jørgensen, Jørgen Rahr; Andersen, Anne Elsborg


    Fatal exposure to poisonous plants in northern Europe is a rare condition. In this case report we describe an intended poisoning with Aconitum napellus (monkshood), which contains the toxin aconitine. The lethal dose in adults is 3-6 mg. The toxin affects excitable cells such as neurons and myocytes causing degrees of unconsciousness, hypotension and cardiac arrhythmias. There is no antidote and treatment is symptomatic. We describe a patient who had eaten monkshood. She was treated with infusion of lidocaine and survived. After 24 hours of treatment and monitoring she was discharged from the intensive care unit.

  10. Alkaloids with antioxidant activities from Aconitum handelianum.

    Yin, Tian-Peng; Cai, Le; Xing, Yun; Yu, Jing; Li, Xue-Jiao; Mei, Rui-Feng; Ding, Zhong-Tao


    A new C20-diterpenoid alkaloid handelidine (1) and twenty-seven known alkaloids (2-28) were isolated from the roots of Aconitum handelianum. Their structures were established on the basis of extensive spectroscopic analyses. The study indicated that denudatine-type C20-diterpenoid alkaloids with vicinal-triol system and benzyltetrahydroisoquinoline alkaloids exhibited significant antioxidant activities measured by three antioxidant test systems. The aconitine-type C19-diterpenoid alkaloids could serve as potential secondary antioxidants for their strong binding effects to metal ions.

  11. [Studies on the antiarrhythmic effects of leaves of Dendropanax chevalieri (Vig.) Merr. et Chun].

    Huang, J Y; Liu, C M; Qi, P L; Liu, K M


    Aqueous extract of the leaves of Dendropanax chevalieri (DC), administrated orally, showed prominent protective effect against arrhythmias induced by iv aconitine CaCl2 (120mg/kg) in mice and BaCl2 (4mg/kg) in rats. In anesthetized rabbits, the duration of arrhythmia elicited by ivAdr 75 micrograms/kg was markedly shortened by iv DC 0.4g/kg. It might also obviously delay the onset of arrhythmias and cardiac electricity disappearance evoked by ouabain perfusing consistently into isolated guinea-pig hearts.

  12. Important Poisonous Plants in Tibetan Ethnomedicine

    Lijuan Ma


    Full Text Available Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and unique cultural background. Many poisonous plants have been widely used to treat disorders in the Tibetan medicinal system. In the present review article, some representative poisonous plant species are introduced in terms of their significance in traditional Tibetan medicinal practices. They are Aconitum pendulum, Strychnos nux-vomica, Datura stramonium and Anisodus tanguticus, for which the toxic chemical constituents, bioactivities and pharmacological functions are reviewed herein. The most important toxins include aconitine, strychnine, scopolamine, and anisodamine. These toxic plants are still currently in use for pain-reduction and other purposes by Tibetan healers after processing.

  13. [Case of fatal aconite poisoning, and its background].

    Kazuma, Kohei; Satake, Motoyoshi; Konno, Katsuhiro


    Two people out of three who accidentally ate boiled aconite leaves died in 2012. This was a typical case of aconite poisoning in Japan: Aconite (Aconitum spp.) was mistakenly collected instead of Anemone flaccida, an edible wild plant. The leaves of these plants are quite similar to each other. Chemical analyses of the aconite plant left at the scene suggested intake of a fatal amount of aconitine alkaloids by each person. The collector, who died, had missed the botanical differences between the two plants, even though he owned a wild plant guidebook. A. flaccida should be collected with its flowers in order to aid positive indentification and avoid aconite poisoning.

  14. Identification of diterpene alkaloids from Aconitum napellus subsp. firmum and GIRK channel activities of some Aconitum alkaloids.

    Kiss, Tivadar; Orvos, Péter; Bánsághi, Száva; Forgo, Peter; Jedlinszki, Nikoletta; Tálosi, László; Hohmann, Judit; Csupor, Dezső


    Diterpene alkaloids neoline (1), napelline (2), isotalatizidine (3), karakoline (4), senbusine A (5), senbusine C (6), aconitine (7) and taurenine (8) were identified from Aconitum napellus L. subsp. firmum, four (2-4, 6) of which are reported for the first time from this plant. The structures were determined by means of LC-MS, 1D and 2D NMR spectroscopy, including (1)H-(1)H COSY, NOESY, HSQC and HMBC experiments. Electrophysiological effects of the isolated compounds, together with nine diterpene alkaloids previously obtained from Aconitum toxicum and Consolida orientalis were investigated on stable transfected HEK-hERG (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cell lines using automated patch clamp equipment. Significant blocking activity on GIRK channel was exerted by aconitine (7) (45% at 10 μM), but no blocking activities of the other investigated compounds were detected. The tested compounds were inactive on hERG channel in the tested concentration. The comparison of the previously reported metabolites of A. napellus subsp. firmum and compounds identified in our experiment reveals substantial variability of the alkaloid profile of this taxon.

  15. Diterpenoid alkaloid toxicosis in cattle in the Swiss Alps.

    Puschner, Birgit; Booth, Marcia C; Tor, Elizabeth R; Odermatt, Arnold


    Between 1995 and 1999, several cattle of a group of 80 heifers died acutely on a pasture in the Swiss Alps. The animals were Found dead between July 9th and 15th eachyear. Only 1 animal was examined on post-mortem, and no significant lesions were found. Aconitum vulpera, A napellus, and Delphinium elatum were identified in the pasture. The presence of diterpenoid alkaloid-containing plants in the pasture, the rapid death of the animals, and the lack of pathologic lesions suggested diterpenoid alkaloid toxicosis as a cause of death. A multiresidue alkaloid screen using gas chromatography with a mass spectrometric detector was employed on rumen, abomasal, small intestine, and cecal contents from the I heifer. Deltaline, deltamine, and lycoctonine were identified. Aconitine was found in all gastrointestinal samples using a sensitive and highly specific liquid chromatography/mass spectrometry methodology for aconitine analysis. The findings ofditerpenoid alkaloids in the gastrointestinal contents confirmed exposure to Delphinium and Aconitum spp, possibly resulting in sudden death.

  16. Ultra-fast LC-ESI-MS/MS method for the simultaneous determination of six highly toxic Aconitum alkaloids from Aconiti kusnezoffii radix in rat plasma and its application to a pharmacokinetic study.

    Liu, Jingjing; Li, Qing; Yin, Yidi; Liu, Ran; Xu, Huarong; Bi, Kaishun


    A fast, sensitive, and efficient ultra-fast LC-ESI-MS/MS method was developed for the simultaneous quantitation of six highly toxic Aconitum alkaloids, that is, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypaconine, in rat plasma after oral administration of crude ethanol extracts from Aconiti kusnezoffii radix by ultrasonic extraction, reflux extraction for 1 h, and reflux extraction for 3 h, respectively. The separation of six Aconitum alkaloids and aminopyrine (internal standard) was performed on an InertSustain® C18 column, and the quantification of the analytes was performed on a 4000Q ultra-fast LC-MS/MS system with turbo ion spray source in the positive ion and multiple-reaction monitoring mode. Absolute recoveries ranged within 65.06-85.1% for plasma samples. The intra- and interday precision and accuracy of analytes were satisfactory. The methods were validated with sensitivity reaching the lower LOQ for aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypaconine, which were 0.025, 0.025, 0.050, 0.025, 0.025, and 0.100 ng/mL, respectively. The method was successfully applied to a pharmacokinetic study of six Aconitum alkaloids in rat plasma after oral administration of crude ethanol extracts from the raw root of Aconitum kusnezoffii Reichb. by three different extraction processes.

  17. The comparative research on constituents of Radix Aconiti and its processing by HPLC quadrupole TOF-MS.

    Wu, Jian; Hong, Bo; Wang, Jia; Wang, Xi; Niu, Sijia; Zhao, Chunjie


    Based upon the regulations stipulated by the State Food and Drug Administration of China, only the processed, detoxified tubers and roots of Aconitum are allowed to be administered orally, used in clinical decoctions and adopted as raw materials for pharmaceutical manufacturing, so the processing principle of preparation of Radix Aconiti is important for ensuring the Radix Aconiti praeparata quality. A simple approach was described for HPLC-Q-TOF-MS screening and identification of many of the aconitine alkaloids present in unprocessed Radix Aconiti and Radix Aconiti praeparata. To compare their fingerprints, the processing principle of preparation of Radix Aconiti was developed. Twenty-nine compounds and 26 compounds were assigned to aconitine alkaloids and tentatively identified by comparing accurate mass and fragments information with that of the authentic standards or by mass spectrometry analysis and retrieving the reference literature. The nonester alkaloids were almost the same. The diester diterpene alkaloids were decreased, the monoester-diterpene alkaloids were increased and lipo-alkaloids decreased obviously in the processing of the preparation. These transformed components could be regarded as potential chemical markers that can be used to distinguish between raw and processed herbs.

  18. The Bibilographic studies on Aconiti Ciliare Tuber and Radix Aconiti

    Chang-Kil Yoo


    Full Text Available Objectives : Through the literature on the effect of Aconiti Cliare Tuber, Radix Aconiti, we are finding out the clinical posibility and revealing the more effective to intractable disease. Methods : We inverstigated the literatures of Oriental Medicine and experimental reports about Aconiti Cliare Tuber, Radix Aconiti. Results : 1. The taste of Aconiti Cliare Tuber, Radix Aconiti is hot, sweet, bitter, warm and hot, and the effect is dehumidification, warm up and relieve the pain, so it can be used for arthritis, hemiplegia, carpopedal spasm, sciatica, cancer, numbness. 2. A toxic constituent of Aconiti Cliare Tuber, Radix Aconitiis is induced by aconitine alkaloid, develope toxic symptoms and result in death. So it needs suitabe treatment for safety. 3. It is known that the toxicopathy due to Radix Aconiti was 3-30g(dosage for adult and Aconiti Ciliare Tuber was 1-9g. But only using aconitine alkaloid to oral feeding, the toxicopathy due to 0.2mg/kg and lethal dose is 3-4mg. So we using this for treating, we must be careful and need more varialble study about toxicopathy, lethal dose. 4. On clinical treatment, we thought Aconiti Cliare Tuber, Radix Aconiti is so effective to intractable disease after control the toxicity, it may be need variable study on toxicity and clinical effects.

  19. Biological Evaluation of Polyherbal Ayurvedic Cardiotonic Preparation “Mahamrutyunjaya rasa”

    Pallavi D. Rai


    Full Text Available Mahamrutyunjaya rasa (MHR, an Ayurvedic formulation, used as cardiotonic, contains potentially toxic compounds like aconitine, which are detoxified during preparation using traditional methods. Comparative toxicological evaluation of laboratory prepared formulation (F1 and two marketed formulations (F2 and F3 were performed based on their effects on viability of H9c2 cells and after single oral dose administration in mice. Cardioprotective effect of formulations at 25 and 50 mg/kg doses were studied in isoproterenol- (ISO- induced myocardial infarcted rats. F1 and F2 did not affect the cell viability, while F3 decreased the cell viability in concentration and time-dependent manner. Rats administered with ISO showed significant increase in the serum levels of glutamate oxaloacetate transaminase, alkaline phosphotase, creatinine kinase isoenzymes, lactate dehydrogenase, and uric acid, while F1 and F2 treatment showed significant reduction in the same. F3 showed further increase in the serum levels of enzymes and uric acid in ISO-challenged rats. High pressure liquid chromatographic analysis of formulations showed higher concentration of aconitine in F3. Study shows that F1 and F2 possess cardioprotective property with higher safety, while formulation F3 cannot be used as cardioprotective due to its cytotoxic effects. Thus, proper quality assessment methods are required during preparation of traditional formulations.

  20. Ammonium Ion Exchanged Zeolite for Laser Desorption/Ionization Mass Spectrometry of Phosphorylated Peptides

    Mengrui Yang


    Full Text Available α-Cyano-4-hydroxycinnamic acid (CHCA, an organic matrix molecule for matrix-assisted laser desorption/ionization mass spectrometry, was adsorbed to NH4+-type zeolite surface, and this new matrix was used for the detection of low-molecular-weight compounds. It was found that this matrix could simplify the mass spectrum in the low-molecular-weight region and prevent interference from fragments and alkali metal ion adducted species. CHCA adsorbed to NH4+-type ZSM5 zeolite (CHCA/NH4ZSM5 was used to measure atropine and aconitine, two toxic alkaloids in plants. In addition, CHCA/NH4ZSM5 enabled us to detect phosphorylated peptides; peaks of the protonated peptides had higher intensities than the peaks observed using CHCA only.

  1. Simultaneous determination of ten Aconitum alkaloids in rat tissues by UHPLC-MS/MS and its application to a tissue distribution study on the compatibility of Heishunpian and Fritillariae thunbergii Bulbus.

    Yang, Bin; Xu, Yanyan; Wu, Yuanyuan; Wu, Huanyu; Wang, Yuan; Yuan, Lei; Xie, Jiabin; Li, Yubo; Zhang, Yanjun


    A rapid, sensitive and selective ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for simultaneous determination of ten Aconitum alkaloids in rat tissues. The tissue samples were prepared by a simple procedure protein precipitation with acetonitrile containing 0.1% acetic acid and separated on an Agilent XDB C18 column (4.6 mm×50mm, 1.8μm) using gradient elution with a mobile phase consisting of water and acetonitrile (both containing 0.1% formic acid) at a flow rate of 0.3mL/min. The quantitive determination was performed on an electrospray ionization (ESI) triple quadrupole tandem mass spectrometer using selective reaction monitoring (SRM) under positive ionization mode. The established method was fully validated according to the USA Food and Drug Administration (FDA) bioanalytical method validation guidance and the results demonstrated that the method was sensitive and selective with the lowest limits of quantification (LLOQ) at 0.025ng/mL in rat tissue homogenates. Meanwhile, the linearity, precision, accuracy, extraction recovery, matrix effect and stability were all within the required limits of biological sample analysis. After method validation, the validated method was successfully applied to the tissue distribution study on the compatibility of Heishunpian (HSP, the processed product of Aconitum carmichaelii Debx) and Fritillariae thunbergii Bulbus (Zhebeimu, ZBM). The results indicated that the distribution feature of monoester diterpenoid aconitines (MDAs), diester diterpenoid aconitines (DDAs) and non-ester alkaloids (NEAs) were inconsistency, and the compatibility of HSP and ZBM resulted in the distribution amount of DDAs increased in tissues. What's more, the results could provide the reliable basis for systematic research on the substance foundation of the compatibility of the herbal pair.

  2. Pyrethroids and Nectar Toxins Have Subtle Effects on the Motor Function, Grooming and Wing Fanning Behaviour of Honeybees (Apis mellifera.

    Caitlin J Oliver

    Full Text Available Sodium channels, found ubiquitously in animal muscle cells and neurons, are one of the main target sites of many naturally-occurring, insecticidal plant compounds and agricultural pesticides. Pyrethroids, derived from compounds found only in the Asteraceae, are particularly toxic to insects and have been successfully used as pesticides including on flowering crops that are visited by pollinators. Pyrethrins, from which they were derived, occur naturally in the nectar of some flowering plant species. We know relatively little about how such compounds--i.e., compounds that target sodium channels--influence pollinators at low or sub-lethal doses. Here, we exposed individual adult forager honeybees to several compounds that bind to sodium channels to identify whether these compounds affect motor function. Using an assay previously developed to identify the effect of drugs and toxins on individual bees, we investigated how acute exposure to 10 ng doses (1 ppm of the pyrethroid insecticides (cyfluthrin, tau-fluvalinate, allethrin and permethrin and the nectar toxins (aconitine and grayanotoxin I affected honeybee locomotion, grooming and wing fanning behaviour. Bees exposed to these compounds spent more time upside down and fanning their wings. They also had longer bouts of standing still. Bees exposed to the nectar toxin, aconitine, and the pyrethroid, allethrin, also spent less time grooming their antennae. We also found that the concentration of the nectar toxin, grayanotoxin I (GTX, fed to bees affected the time spent upside down (i.e., failure to perform the righting reflex. Our data show that low doses of pyrethroids and other nectar toxins that target sodium channels mainly influence motor function through their effect on the righting reflex of adult worker honeybees.

  3. Antisecretory and antimotility activity of Aconitum heterophyllum and its significance in treatment of diarrhea

    Satyendra K Prasad


    Full Text Available Aim: The roots of the plant Aconitum heterophyllum (EAH are traditionally used for curing hysteria, throat infection, dyspepsia, abdominal pain, diabetes, and diarrhea. Therefore, the present study was undertaken to determine the mechanism involved in the anti-diarrheal activity of roots of A. heterophyllum. Materials and Methods: Ant-diarrheal activity of ethanol extract at 50, 100, and 200 mg/kg p.o. was evaluated using fecal excretion and castor oil-induced diarrhea models, while optimized dose, that is, 100 mg/kg p.o. was further subjected to small intestinal transit, intestinal fluids accumulation, PGE 2 -induced enteropooling and gastric emptying test. To elucidate the probable mechanism, various biochemical parameters and Na + , K + concentration in intestinal fluids were also determined. Further, antibacterial activity of extract along with its standardization using aconitine as a marker with the help of HPLC was carried out. Results: The results depicted a significant (P < 0.05 reduction in normal fecal output at 100 and 200 mg/kg p.o. of extract after 5 th and 7 th h of treatment. Castor oil-induced diarrhea model demonstrated a ceiling effect at 100 mg/kg p.o. with a protection of 60.185% from diarrhea. EAH at 100 mg/kg p.o. also showed significant activity in small intestinal transit, fluid accumulation, and PGE 2 -induced enteropooling models, which also restored the altered biochemical parameters and prevented Na + and K + loss. The extract with 0.0833% w/w of aconitine depicted a potential antibacterial activity of extract against microbes implicated in diarrhea. Conclusion: The study concluded antisecretory and antimotility effect of A. heterophyllum, which mediates through nitric oxide path way.

  4. Pyrethroids and Nectar Toxins Have Subtle Effects on the Motor Function, Grooming and Wing Fanning Behaviour of Honeybees (Apis mellifera).

    Oliver, Caitlin J; Softley, Samantha; Williamson, Sally M; Stevenson, Philip C; Wright, Geraldine A


    Sodium channels, found ubiquitously in animal muscle cells and neurons, are one of the main target sites of many naturally-occurring, insecticidal plant compounds and agricultural pesticides. Pyrethroids, derived from compounds found only in the Asteraceae, are particularly toxic to insects and have been successfully used as pesticides including on flowering crops that are visited by pollinators. Pyrethrins, from which they were derived, occur naturally in the nectar of some flowering plant species. We know relatively little about how such compounds--i.e., compounds that target sodium channels--influence pollinators at low or sub-lethal doses. Here, we exposed individual adult forager honeybees to several compounds that bind to sodium channels to identify whether these compounds affect motor function. Using an assay previously developed to identify the effect of drugs and toxins on individual bees, we investigated how acute exposure to 10 ng doses (1 ppm) of the pyrethroid insecticides (cyfluthrin, tau-fluvalinate, allethrin and permethrin) and the nectar toxins (aconitine and grayanotoxin I) affected honeybee locomotion, grooming and wing fanning behaviour. Bees exposed to these compounds spent more time upside down and fanning their wings. They also had longer bouts of standing still. Bees exposed to the nectar toxin, aconitine, and the pyrethroid, allethrin, also spent less time grooming their antennae. We also found that the concentration of the nectar toxin, grayanotoxin I (GTX), fed to bees affected the time spent upside down (i.e., failure to perform the righting reflex). Our data show that low doses of pyrethroids and other nectar toxins that target sodium channels mainly influence motor function through their effect on the righting reflex of adult worker honeybees.

  5. Detection and validated quantification of toxic alkaloids in human blood plasma--comparison of LC-APCI-MS with LC-ESI-MS/MS.

    Beyer, Jochen; Peters, Frank T; Kraemer, Thomas; Maurer, Hans H


    Poisonings with toxic plants may occur after abuse, intentional or accidental ingestion of plants. For diagnosis of such poisonings, multianalyte procedures were developed for detection and validated quantification of the toxic alkaloids aconitine, atropine, colchicine, coniine, cytisine, nicotine and its metabolite cotinine, physostigmine, and scopolamine in plasma using LC-APCI-MS and LC-ESI-MS/MS. After mixed-mode solid-phase extraction of 1 ml of plasma, the analytes were separated using a C8 base select separation column and gradient elution (acetonitrile/ammonium formate, pH 3.5). Calibration curves were used for quantification with cotinine-d(3), benzoylecgonine-d(3), and trimipramine-d(3) as internal standards. The method was validated according to international guidelines. Both assays were selective for the tested compounds. No instability was observed after repeated freezing and thawing or in processed samples. The assays were linear for coniine, cytisine, nicotine and its metabolite cotinine, from 50 to 1000 ng/ml using LC-APCI-MS and 1 to 1000 ng/ml using LC-ESI-MS/MS, respectively, and for aconitine, atropine, colchicine, physostigmine, and scopolamine from 5 to 100 ng/ml for LC-APCI-MS and 0.1 to 100 ng/ml for LC-ESI-MS/MS, respectively. Accuracy ranged from -38.6 to 14.0%, repeatability from 2.5 to 13.5%, and intermediate precision from 4.8 to 13.5% using LC-APCI-MS and from -38.3 to 8.3% for accuracy, from 3.5 to 13.8%, for repeatability, and from 4.3 to 14.7% for intermediate precision using LC-ESI-MS/MS. The lower limit of quantification was fixed at the lowest calibrator in the linearity experiments. With the exception of the greater sensitivity and higher identification power, LC-ESI-MS/MS had no major advantages over LC-APCI-MS. Both presented assays were applicable for sensitive detection of all studied analytes and for accurate and precise quantification, with the exception of the rather volatile nicotine. The applicability of the assays was

  6. Enrichment and Purification of Alkaloids from Aconitum carmichaelii with D101 Macroporous Resin%D101型大孔树脂纯化附子生物碱

    彭拓华; 张少俊; 钟世顺; 杨毅达; 杨彤


    Objective; To resarch chemical composition change after enrichment and purification of alkaloids from Aconitum carmichaelii with D101 macroporous resin. Method: Taking transfer rate of total alkaloids, diester diterpenoid alkaloids, aconitine, hypaconitine and mesaconitine as indexes, before and after purification, the content of alkaloids from extracts of A. carmichaelii was determined by UV and HPLC, ingredients of alkaloids differentiated by TLC. Result; Alkaloids from A. carmichaelii was enriched by D101 macroporous resin, transfer rate and purity of total alkaloids were 83. 70% , 67. 34% , respectively; Transfer rate of aconitine, hypaconitine and mesaconitine were 77.78% , 94. 12% , 52.63% ; It showed 6 similar biological spots by TLC comparison, this indicated that there was no significant difference before and after enrichment of alkaloids composition. Conclusion; D101 type macroporous resin could effectively enhance purity of total alkaloids from A. carmichaelii with high transfer rate of alkaloids, it could be used for production promotion.%目的:研究附子生物碱经D101型大孔树脂富集后化学成分的变化.方法:以附子中总生物碱、酯型生物碱、乌头碱、次乌头碱及新乌头碱的转移率为指标,采用UV,HPLC,TLC分别对富集前后附子提取物中的生物碱进行含量测定及其成分鉴别.结果:采用D101型大孔树脂富集附子生物碱,总生物碱转移率83.70%,纯度67.34%;乌头碱转移率77.78%,次乌头碱转移率94.12%,新乌头碱转移率52.63%;TLC比较发现显示6个相似的生物斑点,说明富集前后生物碱化学成分无明显差异.结论:D101型大孔树脂能有效提高附子中总生物碱的纯度,且各生物碱转移率较高,可用于大生产推广.

  7. Modern toxic antipersonnel projectiles.

    Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent


    In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

  8. Clinical and Experimental Study on Effect of Yangxin Fumai Oral Liquid (


    Objective: To evaluate the therapeutic effect of Yangxin Fumai Oral Liquid (YFOL,养心复脉口服液), a Chinese herbal medicine for nourishing Heart and restoring pulse, in treating patients with extrasystole. Methods: The effect of YFOL was observed in treating 30 patients with different kinds of extrasystole and compared with that in 30 patients treated by propafenone. The effect of YFOL on experimental arrhythmia was studied in animals as well. Results: Clinical observation showed that the effect of treatment against extrasystole in the two groups was similar, but the YFOL group showed better results in symptom improvement (P<0.01) with no marked side-effect. Experimental study showed that YFOL could reduce the chloroform induced ventricular fibrillation occurrence in mice, delay the initiating time of ventricular extrasystole, tachycardia and fibrillation induced by aconitine, BaCl2 and coronary artery ligation in rats, or shorten the lasting time of arrhythmia, reduce the attacking frequency of ventricular extrasystole. There was significant difference in comparing with the control group (P<0.05, P<0.01). Conclusion:YFOL is a good and convenient Chinese herbal preparation for different kinds of extrasystole with few toxic and side-effect in clinical practice.

  9. Clinical and Experimental Study on Effect of Yangxin Fumai Oral Liquid (养心复脉口服液) in Treating Patients with Extrasystole

    樊巧玲; 许惠琴; 李飞; 祁晓华; 汤粉英


    Objective: To evaluate the therapeutic effect of Yangxin Fumai Oral Liquid (YFOL,养心复脉口服液), a Chinese herbal medicine for nourishing Heart and restoring pulse, in treating patients with extrasystole. Methods: The effect of YFOL was observed in treating 30 patients with different kinds of extrasystole and compared with that in 30 patients treated by propafenone. The effect of YFOL on experimental arrhythmia was studied in animals as well. Results: Clinical observation showed that the effect of treatment against extrasystole in the two groups was similar, but the YFOL group showed better results in symptom improvement (P<0.01) with no marked side-effect. Experimental study showed that YFOL could reduce the chloroform induced ventricular fibrillation occurrence in mice, delay the initiating time of ventricular extrasystole, tachycardia and fibrillation induced by aconitine, BaCl2 and coronary artery ligation in rats, or shorten the lasting time of arrhythmia, reduce the attacking frequency of ventricular extrasystole. There was significant difference in comparing with the control group (P<0.05, P<0.01). Conclusion:YFOL is a good and convenient Chinese herbal preparation for different kinds of extrasystole with few toxic and side-effect in clinical practice.

  10. Quantitative and Qualitative Analysis of Aconitum Alkaloids in Raw and Processed Chuanwu and Caowu by HPLC in Combination with Automated Analytical System and ESI/MS/MS

    Aimin Sun


    Full Text Available HPLC in combination with automated analytical system and ESI/MS/MS was used to analyze aconitine (A, mesaconitine (MA, hypaconitine (HA, and their benzoyl analogs in the Chinese herbs Caowu and Chuanwu. First, an HPLC method was developed and validated to determine A, MA, and HA in raw and processed Caowu and Chuanwu. Then an automated analytical system and ESI/MS/MS were applied to analyze these alkaloids and their semihydrolyzed products. The results obtained from automated analytical system are identical to those from ESI/MS/MS, which indicated that the method is a convenient and rapid tool for the qualitative analysis of herbal preparations. Furthermore, HA was little hydrolyzed by heating processes and thus it might account more for the toxicity of processed aconites. Hence, HA could be used as an indicator when one alkaloid is required as a reference to monitor the quality of raw and processed Chuanwu and Caowu. In addition, the raw and processed Chuanwu and Caowu can be distinguished by monitoring the ratio of A and MA to HA.

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

    Jiang, Zhi-Hong; Xie, Ying; Zhou, Hua; Wang, Jing-Rong; Liu, Zhong-Qiu; Wong, Yuen-Fan; Cai, Xiong; Xu, Hong-Xi; Liu, Liang


    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.

  12. Enrichment and purification of six Aconitum alkaloids from Aconiti kusnezoffii radix by macroporous resins and quantification by HPLC-MS.

    Liu, Jingjing; Li, Qing; Liu, Ran; Yin, Yidi; Chen, Xiaohui; Bi, Kaishun


    Aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine are six main Aconitum alkaloids from traditional Chinese medicine, Aconiti kusnezoffii radix, which possess highly bioactive as well as highly toxic character for medicinal use. In the present study, for the purpose of better utilizing the toxic herbal material, the performance characteristics of NKA-II, D101, X-5, AB-8, S-8, HPD722 and HPD750 macroporous resins for the enrichment and purification of these six Aconitum alkaloids were critically evaluated. Results showed that NKA-II offered the best adsorption and desorption capacities for six Aconitum alkaloids among the seven macroporous resins tested, which were affected significantly by the pH value. Subsequently, dynamic adsorption and desorption experiments had been carried out with the column packed by NKA-II resin to optimize the separation process of six Aconitum alkaloids. After one run treatment with NKA-II resin, the content of total six Aconitum alkaloids were increased from 5.87% to 60.3%, the recovery was 75.8%. Meanwhile, a validated HPLC-MS method had been developed to qualitative and quantitative these six Aconitum alkaloids. This method would provide scientific references to the large-scale production of six Aconitum alkaloids from Aconiti kusnezoffii radix or other plants and might also expand the secure application of these highly toxic components for pharmacy.

  13. The Optimization of HPLC Determination for Three Kinds of Alkaloids in Aconitum kongboense L .%工布乌头中三种生物碱HPLC法测定优化

    王若丁; 王超; 孟凡娟; 彭光华; 兰小中


    In order to optimize the extracting method of alkaloids in Aconitum kongboense L .,the content of mesaconitine ,talatisamine and aconitine were determined by HPLC .The results showed that 10% ammonia 1 mL ,ether 20 mL ,soak for 24 h ,30 min after ultrasonic treatment could be used to the quantitative analysis of the alkaloids of A conitum kongboense L ..%为优化工布乌头中生物碱的测定方法,采用 H PLC法测定工布乌头中新乌头碱、塔拉萨敏和乌头碱的含量。结果表明:采用10%氨水1 mL、乙醚20 mL ,浸泡24 h后超声处理30 min可有效地对工布乌头中生物碱进行定量分析。

  14. Characterization of in vivo and in vitro electrophysiological and antiarrhythmic effects of a novel IKACh blocker, NIP-151: a comparison with an IKr-blocker dofetilide.

    Hashimoto, Norio; Yamashita, Toru; Tsuruzoe, Nobutomo


    We investigated the electrophysiological and antiarrhythmic effects of a novel antiarrhythmic agent, NIP-151, and compared these effects with those of an IKr-blocker dofetilide. NIP-151 potently inhibited acetylcholine-activated K current (IKACh) with an IC50, with 1.6 nM in HEK293 cells expressing the GIRK1/4 channel, but it had little effect on IKr (IC50 = 57.6 microM). NIP-151 dose-dependently terminated AF both in vagal nerve stimulation-induced AF (at 5 and 15 microg/kg per minute) and aconitine-induced AF (at 30 and 100 microg/kg) models. This compound significantly prolonged the atrial effective refractory period (ERP), but it had no significant effects on ventricular ERP. There were no significant changes on electrocardiographic variables with NIP-151 (up to 1,000 microg/kg per minute) administration. In contrast, dofetilide had little effect in either AF model, even though this compound potently prolonged atrial ERP. Dofetilide also significantly prolonged ventricular ERP and the QT interval in anesthetized dogs, which are related to proarrhythmic risk. In conclusion, a novel antiarrhythmic agent NIP-151, which potently blocked IKACh, was highly effective in the two types of canine AF models with an atrial-specific ERP-prolonging profile. Therefore, NIP-151 might be useful for the treatment of AF with lower risk of proarrhythmia, compared with IKr blockers.

  15. Characteristics of Early Afterdepolarization in Mouse Atrial Fibers

    刘泰槰; 陈希娟


    Early afterdepolarization (EAD) in mouse atrial fibers was investigated under the treatment with aconitine, 3. 0 mmol/L K+ ,quinidine, ryanodine or Bay k 8644. All of these EADs possessed the following common characteristics j all the parameters of EAD showed cycle length-dependence; take-off potential of the first triggered burst played an important role in the generation of the other parameters ; hyper-polarization of the triggered brust enhanced the end of EAD; and the second plateau response might be used as an indicator of the capability of EAD generation of myocardiac cell. All those EADs were inhibited or abolished by nifedipine, tetrodotoxin or lidocaine. Potassium channel activators, lemakalim, thalium ion, acetyl-choline or high potassium could also inhibit or abolish the EADs. It is suggested that the EADs induced by different agents may base on a common mechanism ; all currents contributing to the plateau phase of the action potential play an important role in the generation of EAD.

  16. Separation and purification of five alkaloids from Aconitum duclouxii by counter-current chromatography.

    Wang, Yarong; Cai, Shining; Chen, Yang; Deng, Liang; Zhou, Xumei; Liu, Jia; Xu, Xin; Xia, Qiang; Lin, Mao; Zhang, Jili; Huang, Weili; Wang, Wenjun; Xiang, Canhui; Cui, Guozhen; Du, Lianfeng; He, Huan; Qi, Baohui


    C19 -diterpenoid alkaloids are the main components of Aconitum duclouxii Levl. The process of separation and purification of these compounds in previous studies was tedious and time consuming, requiring multiple chromatographic steps, thus resulted in low recovery and high cost. In the present work, five C19 -diterpenoid alkaloids, namely, benzoylaconine (1), N-deethylaconitine (2), aconitine (3), deoxyaconitine (4), and ducloudine A (5), were efficiently prepared from A. duclouxii Levl (Aconitum L.) by ethyl acetate extraction followed with counter-current chromatography. In the process of separation, the critical conditions of counter-current chromatography were optimized. The two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water/NH3 ·H2 O (25%) (1:1:1:1:0.1, v/v) was selected and 148.2 mg of 1, 24.1 mg of 2, 250.6 mg of 3, 73.9 mg of 4, and 31.4 mg of 5 were obtained from 1 g total Aconitum alkaloids extract, respectively, in a single run within 4 h. Their purities were found to be 98.4, 97.2, 98.2, 96.8, and 96.6%, respectively, by ultra-high performance liquid chromatography analysis. The presented separation and purification method was simple, fast, and efficient, and the obtained highly pure alkaloids are suitable for biochemical and toxicological investigation.

  17. Further Studies on Structure-Cardiac Activity Relationships of Diterpenoid Alkaloids.

    Zhang, Zhong-Tang; Jian, Xi-Xian; Ding, Jia-Yu; Deng, Hong-Ying; Chao, Ruo-Bing; Chen, Qiao-Hong; Chen, Dong-Lin; Wang, Feng-Peng


    The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.

  18. The risk of life-threatening ventricular arrhythmias in presence of high-intensity endurance exercise along with chronic administration of nandrolone decanoate.

    Abdollahi, Farzane; Joukar, Siyavash; Najafipour, Hamid; Karimi, Abdolah; Masumi, Yaser; Binayi, Fateme


    Anabolic steroids used to improve muscular strength and performance in athletics. Its long-term consumption may induce cardiovascular adverse effects. We assessed the risk of ventricular arrhythmias in rats which subjected to chronic nandrolone plus high-intensity endurance exercise. Animals were grouped as; control (CTL), exercise (Ex): 8 weeks under exercise, vehicle group (Arach): received arachis oil, and Nan group: received nandrolone decanoate 5 mg/kg twice a week for 8 weeks, Arach+Ex group, and Nan+Ex. Finally, under anesthesia, arrhythmia was induced by infusion of 1.5 μg/0.1 mL/min of aconitine IV and ventricular arrhythmias were recorded for 15 min. Then, animals' hearts were excised and tissue samples were taken. Nandrolone plus exercise had no significant effect on blood pressure but decreased the heart rate (Pventricular fibrillation (VF) frequency and also decreased the VF latency (P<0.05 versus CTL group). Combination of exercise and nandrolone could not recover the decreasing effects of nandrolone on animals weight gain but, it enhanced the heart hypertrophy index (P<0.05). In addition, nandrolone increased the level of hydroxyproline (HYP) and malondialdehyde (MDA) but had not significant effect on glutathione peroxidase of heart. Exercise only prevented the effect of nandrolone on HYP. Nandrolone plus severe exercise increases the risk of VF that cannot be explained only by the changes in redox system. The intensification of cardiac hypertrophy and prolongation of JT interval may be a part of involved mechanisms.

  19. Cardiac Characteristics of Transgenic Mice Overexpressing Refsum Disease Gene-Associated Protein within the Heart.

    Koh, J T; Choi, H H; Ahn, K Y; Kim, J U; Kim, J H; Chun, J Y; Baik, Y H; Kim, K K


    Arrhythmia is a common cardiac symptom of Refsum disease. Recently, we identified a novel neuron-specific PAHX-associated protein (PAHX-AP1), which binds to the Refsum disease gene (PAHX). In this report, we developed heart-targeted transgenic (TG) mice under the control of alpha-myosin heavy chain promoter to determine whether cardiac overexpression of PAHX-AP1 provokes cardiac involvement symptoms. Northern and in situ hybridization analyses revealed PAHX-AP1 transcript was overexpressed in TG atrium, especially in the sinoatrial node. TG mice showed tachycardia, and tachyarrhythmia was observed in 20% of TG mice. Isolated TG atria showed higher frequency beating and were more sensitive to aconitine-induced tachyarrhythmia than the wild-type, and 40% of the TG atria showed irregular beating. Action potential duration in TG atrial fiber was shortened much more than the wild-type. Systemic administration of arrhythmogenic agents induced arrhythmia in TG mice, while no arrhythmia with the same dose in nonTG mice. Our results indicate that the chronic atrial tachycardia by overexpressed neuron-specific PAHX-AP1 transgene in atrium may be responsible for the increased susceptibility to arrhythmia.

  20. Toluene and benzene inhalation influences on ventricular arrhythmias in the rat.

    Magos, G A; Lorenzana-Jiménez, M; Vidrio, H


    We have previously found that toluene did not share the capacity of benzene for increasing the arrhythmogenic action of epinephrine in the rat, but appeared to elicit the opposite effect. The present experiments were carried out to verify this observation in rats subjected to more severe ventricular arrhythmias. In animals previously inhaling either air, toluene or benzene and anesthetized with pentobarbital, arrhythmias were produced by coronary ligation or aconitine. In both models, toluene decreased and benzene increased the number of ectopic ventricular beats in the 30 min following induction of arrhythmia. Gas chromatographic measurement of toluene levels in the heart during and after inhalation revealed essentially constant concentrations at the time of arrhythmia evaluation, equivalent to approximately one-third the peak levels observed at the end of inhalation. Although the mechanism of the effect of toluene on arrhythmia could not be ascertained, nonspecific membrane stabilization or central serotonergic stimulation were considered as possible explanations. Since both mechanisms could be operant also in the case of benzene, the opposite effects of the solvents on arrhythmia could not be readily accounted for.

  1. Study on the Metabolic Characteristics of Aconite Alkaloids in the Extract of Radix aconiti under Intestinal Bacteria of Rat by UPLC/MSn Technique

    辛杨; 皮子凤; 宋凤瑞; 刘志强; 刘淑莹


    The extract of Radix aconiti was incubated with rat intestinal bacteria in vitro. Further, aconitine and hypaconitine standard were incubated at the same condition as the extract of Radix aconiti, respectively. Ultra Performance Liquid Chromatography/Multi-Mass Spectrometry (UPLC/MSn) was used for detecting and identifying all the aco- nite alkaloids. Results showed that there were four metabolites which were identified as 8-butyryl-14-benzoylmesa- conine (m/z 660), 8-propionyl-14-benzoylaconine (m/z 660), 8-butyryl-14-benzoylaconine (m/z 674) and 8-valeryl-14-benzoylmesaconine (m/z 674) in the metabolized sample of the extract of Radix aconiti. The relative area ratio of them presented increasing trend during 6 d. On the basis of all results, we could concluded that substi- tution at N atom mainly influenced the metabolizing rate of diester-diterpenoid alkaloids (DDAs), C-8 substitute was active metabolized site, intestinal bacterial metabolites of the aconite alkaloids in the extract of Radix aconiti were mainly the substitute with propionyl group, butyl group or valeryl group at C-8. This paper illustrated holistic metabolizing profile of the extract of Radix aconiti in vitro and possible metabolizing reaction type of main DDAs, which could provide reference for finding out potential bioactive components in the extract and the prescription of Chinese Medicine.

  2. Morpho-phenological and Antibacterial Characteristics of Aconitum spp.

    Yoirentomba Meetei SINAM


    Full Text Available Aconitum species have been traditionally used as ethnomedicine to cure various ailments. The present study reveals the morpho-phenology and antibacterial property of alkaloid extracts of the two Aconitum species. The morpho-phenological characteristics will be helpful for determining the resource availability. Aconitum nagarum is erect type, whereas, Aconitum elwesii is a climber. Aconitum elwesii grows in advance of A. nagarum in terms of growth, flowering and senescence. Towards the end of the year, when the fruits have ripened, the parent tuber dies off. As a result, the daughter tuber becomes independent and in the following spring, takes over the function of the parent tuber. Aconitum nagarum and A. elwesii were found to contain 4-5 aconitine equivalent (AE mg/g of alkaloid. These alkaloids showed antibacterial activity against different bacterial species including human pathogens, namely, Staphylococcus aureus, Salmonella typhimurium, Bordetella bronchiseptica, Escherichia coli, Bacillus subtilis, Pseudomonas putida, Pseudomonas fluorescence and Xanthomonas campestris. However, the extent of antibacterial activity varied among different bacterial species. The antibacterial activity against S. aureus, B. bronchiseptica, and B. subtilis was bactericidal in nature, whereas, against other tested bacterial species was bacteriostatic. Efficacy of the antibacterial activity of these alkaloids was evaluated by comparing with that of standard antibiotics. Differential localization of the antibacterial principle was observed among the Aconitum species studied.

  3. Toxicity assessment of nine types of decoction pieces from the daughter root of Aconitum carmichaeli (Fuzi) based on the chemical analysis of their diester diterpenoid alkaloids.

    Lu, Guanghua; Dong, Zhengqi; Wang, Qing; Qian, Guangsheng; Huang, Wenhua; Jiang, Zhihong; Leung, Kelvin Sze-Yin; Zhao, Zhongzhen


    Various processed types of FUZI (the daughter roots of the highly toxic plant Aconitum carmichaeli Debx, FZ) decoction pieces (the herbal materials processed according to the specifications of Chinese medicine manuals; " YINPIAN" in Chinese transliteration) are widely used in traditional medicine to treat various diseases, but their toxicities are not known. Nine types of FZ decoction pieces, including one raw slice and eight processed forms, were therefore prepared, each in 7 to 10 batches, to assess for their toxicity. Altogether 84 FZ samples were quantified on the amount of highly toxic diester diterpenoid alkaloids, i.e., aconitine, mesaconitine and hypaconitine by a newly developed HPLC method with HPLC-DAD and LC-MS techniques. The comparison of the processed FZ to raw slices of the root showed that the amount of each analyte in the processed FZ was drastically decreased. The sum of the three toxic compounds in the 8 types of processed FZ was only 3.91-34.80 % of this value in the FZ raw slice. This implies that the toxicity of processed FZ was decreased significantly. The amounts of toxic components in the 8 types of processed FZ varied significantly, often by a power of ten, indicating that the dosage of these herbs, when prescribed for clinical uses, should be cautiously set in order to avoid poisoning incidents.

  4. Qualitative and Quantitative Assessments of Aconiti Lateralis Radix Praeparata Using High-Performance Liquid Chromatography Coupled with Diode Array Detection and Hybrid Ion Trap-Time-of-Flight Mass Spectrometry.

    Zhang, Na; Song, Yuelin; Song, Qingqing; Shi, Shepo; Zhang, Qian; Zhao, Yunfang; Li, Jun; Tu, Pengfei


    Dual roles have been widely disclosed for Aconiti Lateralis Radix Praeparata (Chinese name: Fuzi) by acting as an effective herbal medicine accompanied with high toxicity risk and narrow therapeutic range. Aconite alkaloids, also known as diterpenoid alkaloids (DAs), have been proved to be primary therapeutic as well as toxic material basis of Fuzi. In the present study, we aim to characterize qualitative profile along with quantitative features of DAs in Fuzi, which could benefit the quality control of Fuzi as well as its safe medication in clinic. Chromatographic fingerprinting was achieved using 12 batches of crude materials collected from different habitats (similarities >0.9) by hyphenating liquid chromatography (LC) with diode array detection. Simultaneous determination of six primary DAs, namely benzoylmesaconine, benzoylaconine, benzoylhypaconine, mesaconine, aconitine and hypaconitine, was also carried out. The developed method was systematically validated and successfully applied for quantitative characterization. Significant variations were observed regarding the contents of those six analytes among different raw materials. A total of 99 DAs were detected and characterized, including 9 unambiguous identities and 77 putative assignments, as well as 13 unknown compounds, from the representative extract by LC coupled with hybrid ion trap-time-of-flight mass spectrometry. The findings obtained herein could favor in-depth understanding of the chemical composition of DAs and the quality control of Fuzi.

  5. Restraint stress changes heart sensitivity to arrhythmogenic drugs%制动应激改变心脏对致心律失常药物的敏感性

    孙安阳; 李德兴; 王幼林; 李庆平


    AIM: To study the effects of acute restraint stress on ventricular electric stability (VES)and its mechanisms of action. METHODS:VES was evaluated both in vivo and in vitro by the changes of arrhythmogenic responses to icv or ip aconitine in rats and iv BaCl2 or adrenaline in rabbits following restraint stress for different durations. Pretreatments and the assay of heart-specific enzymes were made. RESULTS: The heart sensitivity to these drugs was promoted after stress for 2 h,but obtunded after stress for 8 h (the latency of ventricular arrhythmia to icv aconitine was shortened from 4. 1± 0. 9 min in control rats to 2.9±0. 9 min after stress for 2 h, P<0.05; but prolonged to 9.3± 3.8 min after stress for 8 h, P < 0.05). In Langendorff heart, the changes of VES induced by stress were similar to those in vivo, but to lesser degree. Pretreatment with adrenalectomy inhibited the descending phase of VES, while pretreatment with both aminophylline and vagotomy remarkably depressed the ascending phase at 8 h. In addition, the serum activities of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase and their isozymes, LDH1 and CK-MB, were elevated at 2 h, and rose continuously at 8 h.CONCLUSION: Acute restraint stress causes biphasic changes of VES. The initial decrease of VES was related to adrenal catecholamine release, whereasthe following increase of VES was ascribed to adaptive decrease of cAMP and vagal activation. The changes of VES did not always parallel the injury of heart.%目的:研究急性制动应激对心脏电稳定性的作用及机制.方法:应激后用icv或ip乌头碱及iv氯化钡或肾上腺素致心律失常反应的改变来评价在体及离体心脏电稳定性,施予预处理初步分析机制.结果:应激2 h促进药物性心律失常;应激8 h反而抑制之.icy乌头碱致心律失常的潜伏期在正常大鼠为4.1±0.9 min,但应激2 h后缩短至2.9±0.9 min,应激8 h后延长至9.3±3.8 min.该双

  6. Experimental studies on the antiarrhythmic effect of Xintaiping%心泰平抗实验性心律失常作用的研究

    陈庆文; 孙建平; 张永春; 罗大力; 何树庄; 杨宝峰


    目的 观察心泰平对多种实验性心律失常的拮抗作用以及对大鼠血流动力学和心电图(ECG)的影响。方法 采用乌头碱、BaCl2、电刺激和冠脉结扎诱发大鼠及家兔心律失常的4种实验动物模型,观察心泰平口服给药对心律失常的防治作用;大鼠左心室内插管,多道生理记录仪检测血流动力学指标和ECG。结果 心泰平生药4g/kg与8g/kg明显延迟大鼠乌头碱性心律失常的出现时间(P<0.01),降低室颤发生率,提高窦性节律恢复率,并显著提高家兔电刺激的室颤阈(P<0.01),对大鼠BaCl2和冠脉结扎性心律失常也有一定的对抗作用;生药8g/kg可降低大鼠左室收缩压(LVSP)和-dp/dtmax(P<0.05),延长Q-T间期(P<0.05),无负性频率和传导作用。结论 心泰平可防治多种心律失常,尤以功能性为佳,且对心脏抑制作用小。%Objective To study the effects of Xintaiping(XTP) on experimentalarrhythmias,hemodynamics and ECG.Methods Using the animal arrhythmic models induced by aconitine,BaCl2,electric stimulation and coronary artery ligation,hemodynamics and ECG were assessed by means of left ventricular catheterization using a polygraph system in rats.Results XTP 4g/kg and 8g/kg prolonged significantly the onset time of aconitineinduced arrhythmias in rats(P<0.01),decreased the incidence of VF,and increased the threshold of electric stimulation-induced VF in rabbits (P<0.01).XTP could also counteract arrhythmias induced by BaCl2 and coronary occlusion in rats.XTP 8g/kg decreased LVSP and -dp/dtmax in rats(P<0.05),prolonged Q-T interval(P<0.05),but didn't affect dp/dtmax,SAP,heart beat and A-V.Conclusion XTP is a traditional Chinese herb with little heart inhibition,protectes the animals well from experimental arrhythmias,especially induced by aconitine and electric stimulation.

  7. Establishment of a bioassay for the toxicity evaluation and quality control of Aconitum herbs

    Qin, Yi [Integrative Medicine Center, 302 Military Hospital, Beijing 100039 (China); Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500 (China); Wang, Jia-bo, E-mail: [China Military Institute of Chinese Materia Medica, 302 Military Hospital, Beijing 100039 (China); Zhao, Yan-ling; Shan, Li-mei [Integrative Medicine Center, 302 Military Hospital, Beijing 100039 (China); Li, Bao-cai [Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500 (China); Fang, Fang; Jin, Cheng [Integrative Medicine Center, 302 Military Hospital, Beijing 100039 (China); Xiao, Xiao-he, E-mail: [Integrative Medicine Center, 302 Military Hospital, Beijing 100039 (China)


    Highlights: Black-Right-Pointing-Pointer A new bioassay was optimized to evaluate the toxicity of Aconitum herbs. Black-Right-Pointing-Pointer Characterizing total toxicity is its unique advantage over chemical analysis methods. Black-Right-Pointing-Pointer The application of this bioassay promotes the safe use of Aconitum herbs in clinic. - Abstract: Currently, no bioassay is available for evaluating the toxicity of Aconitum herbs, which are well known for their lethal cardiotoxicity and neurotoxicity. In this study, we established a bioassay to evaluate the toxicity of Aconitum herbs. Test sample and standard solutions were administered to rats by intravenous infusion to determine their minimum lethal doses (MLD). Toxic potency was calculated by comparing the MLD. The experimental conditions of the method were optimized and standardized to ensure the precision and reliability of the bioassay. The application of the standardized bioassay was then tested by analyzing 18 samples of Aconitum herbs. Additionally, three major toxic alkaloids (aconitine, mesaconitine, and hypaconitine) in Aconitum herbs were analyzed using a liquid chromatographic method, which is the current method of choice for evaluating the toxicity of Aconitum herbs. We found that for all Aconitum herbs, the total toxicity of the extract was greater than the toxicity of the three alkaloids. Therefore, these three alkaloids failed to account for the total toxicity of Aconitum herbs. Compared with individual chemical analysis methods, the chief advantage of the bioassay is that it characterizes the total toxicity of Aconitum herbs. An incorrect toxicity evaluation caused by quantitative analysis of the three alkaloids might be effectively avoided by performing this bioassay. This study revealed that the bioassay is a powerful method for the safety assessment of Aconitum herbs.

  8. Simultaneous quantification and pharmacokinetics of alkaloids in Herba Ephedrae-Radix Aconiti Lateralis extracts.

    Song, Shuai; Tang, Qingfa; Huo, Huiling; Li, Hancheng; Xing, Xuefeng; Luo, Jiabo


    The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 μm) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination.

  9. A multiple ion channel blocker, NIP-142, for the treatment of atrial fibrillation.

    Tanaka, Hikaru; Hashimoto, Norio


    Atrial fibrillation (AF) is one of the most frequent cardiac arrhythmia and is associated with increased cardiovascular morbidity and mortality, and the risk of stroke. Although currently available antiarrhythmic drugs are moderately effective in restoring normal sinus rhythm in patients with AF, excessive delay of ventricular repolarization by these agents may be associated with increased risk of proarrhythmia. Therefore, selective blockers of cardiac ion channel(s) that are exclusively present in the atria are highly desirable. NIP-142 is a novel benzopyrane derivative, which blocks potassium, calcium, and sodium channels and shows atrial specific action potential duration prolongation. NIP-142 preferentially blocks the ultrarapid delayed rectifier potassium current (I Kur) and the acetylcholine-activated potassium current (I KACh). Since I Kur and I KACh have been shown to be expressed more abundantly in the atrial than in the ventricular myocardium, the atrial-specific repolarization prolonging effect of NIP-142 is considered to be due to the blockade of these potassium currents. In canine models, NIP-142 was shown to terminate the microreentry type AF induced by vagal nerve stimulation and the macroreentry type atrial flutter induced by an intercaval crush. These effects of NIP-142 have been attributed to the prolongation of atrial effective refractory period (ERP), because this compound prolonged atrial ERP without affecting intraatrial and interatrial conduction times in these models. The ERP prolongation by NIP-142 was greater in the atrium than in the ventricle. NIP-142 also terminated the focal activity type AF induced by aconitine. In addition, NIP-142 reversed the atrial ERP shortening and the loss of rate adaptation induced by short-term rapid atrial pacing in anesthetized dogs. Thus, although clinical trials are required to provide evidence for its efficacy and safety, the novel multiple ion channel blocker, NIP-142, appears to be a useful agent for

  10. Establishment of one-step approach to detoxification of hypertoxic aconite based on the evaluation of alkaloids contents and quality.

    Zhang, Ding-Kun; Han, Xue; Tan, Peng; Li, Rui-Yu; Niu, Ming; Zhang, Cong-En; Wang, Jia-Bo; Yang, Ming; Xiao, Xiao-He


    Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.

  11. The Combination of Three Natural Compounds Effectively Prevented Lung Carcinogenesis by Optimal Wound Healing.

    Linxin Liu

    Full Text Available The tumor stroma has been described as "normal wound healing gone awry". We explored whether the restoration of a wound healing-like microenvironment may facilitate tumor healing. Firstly, we screened three natural compounds (shikonin, notoginsenoside R1 and aconitine from wound healing agents and evaluated the efficacies of wound healing microenvironment for limiting single agent-elicited carcinogenesis and two-stage carcinogenesis. The results showed that three compounds used alone could promote wound healing but had unfavorable efficacy to exert wound healing, and that the combination of three compounds made up treatment disadvantage of a single compound in wound healing and led to optimal wound healing. Although individual treatment with these agents may prevent cancer, they were not effective for the treatment of established tumors. However, combination treatment with these three compounds almost completely prevented urethane-induced lung carcinogenesis and reduced tumor burden. Different from previous studies, we found that urethane-induced lung carcinogenesis was associated with lung injury independent of pulmonary inflammation. LPS-induced pulmonary inflammation did not increase lung carcinogenesis, whereas decreased pulmonary inflammation by macrophage depletion promoted lung carcinogenesis. In addition, urethane damaged wound healing in skin excision wound model, reversed lung carcinogenic efficacy by the combination of three compounds was consistent with skin wound healing. Further, the combination of these three agents reduced the number of lung cancer stem cells (CSCs by inducing cell differentiation, restoration of gap junction intercellular communication (GJIC and blockade of the epithelial-to-mesenchymal transition (EMT. Our results suggest that restoration of a wound healing microenvironment represents an effective strategy for cancer prevention.

  12. Induction of rat hepatic cytochromes P450 by toxic ingredients in plants: lack of correlation between toxicity and inductive activity.

    Yamada, H; Nakamura, T; Oguri, K


    "Animal-Plant Warfare" is one of the hypotheses for the evolution of drug-metabolizing P450s. To address the validity of this hypothesis, we examined the induction of xenobiotic-metabolizing P450s by 12 plant toxins in rats, using hepatic activity for testosterone metabolism as the index. The compounds tested were aconitine, morphine, tubocurarine, physostigmine, pilocarpine, muscarine, cocaine, atropine, amygdalin, digitonin, nicotine and solanine. Drinking water containing a test compound was given to rats for 4 days, and the hepatic activity of testosterone metabolism was determined together with monitoring body weight gain and liver weight as the indices of toxicity. The results showed that while cocaine and nicotine have a minor ability to increase testosterone 16 beta-hydroxylase activity, a marker activity for the CYP2B1 and 2, all other compounds did not have any such effect. No correlation was observed between a change in 16 beta-hydroxylase and toxicity caused by toxins. Therefore, these results did not support the idea that the inducibility of the CYP2B subfamily in animals is acquired through "Animal-Plant Warfare". Several compounds examined here increased or decreased hepatic activities of testosterone 2 alpha-, 6 beta-, 7 alpha- and 16 alpha-hydroxylation and 17-oxidation, indicating a possible effect on the CYP2A, 2C and 3A subfamily. Of these effects, a moderate correlation (r toxicity. It is therefore suggested that inhibition or suppression of the expression of CYP2C11 is one of the mechanisms in the toxicity of plant toxins for rats, although it comes from an examination using limited numbers of compounds.

  13. Effects of hemoperfusion on toxic ingredients in plasma and histopathology in acute rabbits with acute intoxication of Radix Aconiti Kusmezoffii Monkshood%血液灌流对急性草乌中毒兔血浆毒性成分及组织病理学的影响

    邱俏檬; 刘刚; 卢中秋; 王志翊; 梁欢


    Objective To explore effects of hcmoperfusion on toxic ingredients in plasma of rabbiis with a-cute intoxication of Radix Aconiti Kusmezoffii Monkshood.Method Sixteen male Japanese Giant Ear Rabbits were randomly divided into acute poisoning(AP)group and acute poisoning + hemoperfusion(AH)group(8 an-hnals in each group).Acute poisoning models were established in rabbits of both groups with intragastric adminis-tration of Radix Aconiti Kusmezoffii Monkshood liquid in dose of 1 mL/kg in order to produce arrhythm which oc-curred within ode hour after intragastric administration was regarded as the criteria of successful animal model.and then hemoperfusion with active carbon was performed for 2 hours in AH group.The pathological chanses of brain,myocardium and hepatic tissues were observed.The plasma concentrations of toxicants including mesaconitine,a-conitine and hypaconitine were measured by using HPLC-MS at 1 h,2 h,3 h,and 6 h after poisoning.Student's T test was used to identify the significance.Results The brain.myocardium and hepatic tissues of the rabbits in AP group showed hyperemia and edema which were attenuated after hemoperfusion.The plasma concentrations of mesaconitine,aconitine and hypaconitine revealed no significant differences between AP group and AH group with-in one hour after poisoning(P>0.05),while at 2 h and 3 h after poisoning,the plasma concentrations of mesaconitine were(2.11±1.08)ng/mL,(2.02±1.46)ng/mL,respectively,aconitine(39.70±9.31)ng/mL,(19.71±16.06)ng/mL,respectively,and hypaconitine(1.70±0.71)ng/mL,(2.12±1.33)ng/mL,respec-fively in AH group,and they were significantly lower than those in AP group(P<0.05).Conclusions The the plasma concentrations of mesaconitine,aconitine and hypaconitine were lower and the histopathological changes were attenuated after hemoperfusion.Hemoperfusion is a good intervention for acute intoxication of Radix Aconiti Kusmezoffii Monkshood.%目的 探讨血液灌流对急性草乌中毒兔血浆毒

  14. 乌头属植物中毒事件的病因判定%An etiological judgment of a poisoning event caused by Acontium plant

    谢立璟; 王效俊; 侯小平; 刘全儒; 王英伟; 龙鑫; 马沛滨; 孙承业


    Disease Control and Prevention (CDC) hastened to the scene to conduct epidemiological investigation,to obtain the clinical features of the poisoning patients,and to collect the specimen of blood and vomitus of patients and the fresh sample of suspicious poisonous plants.Chinese Center for Disease Control and Prevention organized the relevant institutes to conduct morphological and DNA molecular identification of the poisonous plant,toxin detection of the blood and vomitus specimen.The above-mentioned results were synthesized to determine the poisoning reason and provide guidance for clinical diagnosis and treatment.Results On May 30,2010,13 staffs in a metal company in Tacheng District picked and ate the "wild celery" which grew in nearby mountain.Within 15 to 30 minutes after eating the "wild celery",they successively developed numbness in mouth,lips,and limbs,as well as asthenia,nausea and vomiting.They were sent to a local hospital,4 patients died on the way to the hospital,other 9 patients received rescue therapy in the hospital,2 of them died about 4 hours after poisoning despite resuscitation attemempts.The morphological identification of fresh sample of suspected poisonous plants was demonstrated as Aconitum,Raunnculaceae.Aconitine was detected in a vomitus specimen and 3 blood specimens.The aconitine content in blood specimens were 0.17,0.25 and 0.48 μg/L,respectively.The result of DNA molecular identification showed that the fresh leaves of suspected poisonous plants collected from the scene belonged to the same species of Acontium.This event was determined as a sudden poisoning event caused by picking and eating Acontium stems and leaves by mistaken.Conclusion The etiological judgment model for poisoning event might play an important guiding role in the determination of the cause of poisoning events.

  15. Study of Compatibility of Liquiritin, Glycyrrhetinic Acid and Hypaconitine%甘草苷、甘草次酸与次乌头碱配伍的研究

    刘巧云; 张宇燕; 万海同; 杨洁红; 周天梅; 杨珍


    目的:探讨甘草苷、甘草次酸与次乌头碱(HA)配伍对心肌细胞MDA含量及心肌连接蛋白43(Cx43)表达水平的影响.方法:以新生SD乳鼠心肌细胞为研究对象,HA分别单独作用,与甘草苷、甘草次酸、甘草苷+甘草次酸不同浓度按1∶1、1∶2、1∶4比例配伍作用于心肌细胞,检测其MDA活性,根据结果选取配伍效果理想的配伍组,采用RT-PCR测定心肌连接蛋白43(Cx43)基因表达.结果:HA与甘草苷、甘草次酸、甘草苷和甘草次酸配伍组比HA单独作用可以提高Cx43基因的表达,减少MDA含量,其中1∶1次乌头碱甘草次酸组、1∶4次乌头碱甘草苷组、1∶1∶1次乌头碱和甘草次酸、甘草苷组作用可以增加Cx43基因的表达水平.结论:适宜浓度比例的甘草苷、甘草次酸与HA配伍可以减少HA对心肌细胞的氧化损伤及增加43(Cx43)基因表达水平.%Objective: To explore the compatibility of liquiritin, glycyrrhetinic acid and hypaconitine which can affect content of MDA and expression level of connexin43 ( Cx43 ) gene to myocardial cells. Methods: The primary cultured myo-cardial cells were as reseach subjects, hypaconitine and the proportions of aconitine to liquiritin and glycyrrhetinic acid were 1 : 1,1 : 2,1 :4 respectively to myocardial cells. The content of MDA was tested and then according to this result, selecting the best compatibility. The level of connexin43 (Cx43) gene was tested by RT - PCR. Results: Compatibilities of hypaconitine and liquiritin, hypaconitine and glycyrrhetinic acid, hypaconitine and liquiritin and glycyrrhetinic acid can reduce the content of MDA and elevate the level of connexin43 (Cx43) gene than single hypaconitine. The compatibility of hypaconitine and liquiritin(1 :4) ,the compatibility of hypaconitine and glycyrrhetinic acid (1 : 1) ,the compatibility of hypaconitine and liquiritin and glycyrrhetinic acid(l : 1 : 1) can increase the connexin43(Cx43) gene level. Conclusion: The

  16. Determination of 3 kinds of Aconitum alkaloids in human urine and whole blood using ultra-pressure liquid chromatography-mass spectrometry%超高压液相色谱-串联质谱法快速测定人尿液和全血中3种乌头生物碱

    张秀尧; 蔡欣欣; 林学尧; 陈端秀


      Objective To establish a rapid ultra-pressure liquid chromatography-tandem mass spectrome-try (UPLC-MS/MS) method for detection of aconitine, mesaconitine and hypaconitine in human urine and whole blood. Methods Urine sample was directly injected into the separation system and plasma sample was initially prepared by precipitation of proteins with acetonitrile–methanol (9:1, v/v). The analysis of the alkaloids was performed on an ACQUITY UPLC BEH C18 column using gradient elution with methanol and 5.0 mmol/L ammonium bicarbonate in water, and then detected by the positive electrospray ionization-MS/MS (ESI-MS/MS) method under MRM mode, and quantified by matrix internal standard method using noscapine as internal standard. Results The average recoveries were 93.9%~108%and 89.7%~109%for the three alkaloids in urine and whole blood, with relative standard deviation (RSD) of 1.3%~11%and 1.1%~18%(n=6), respec-tively. The quantitative limits (S/N=10) of the alkaloids in both of urine and whole blood were 0.05μg/L and 0.1μg/L. Conclusion This method is sensitive and accurate, and has been successfully applied to determine the 3 alkaloids in one case of food poisoning.%  目的建立快速检测人尿液和全血中乌头碱、新乌头碱和次乌头碱的超高压液相色谱-串联质谱分析方法。方法尿液样品直接进样,全血样品经乙腈-甲醇(9:1, v/v)沉淀蛋白,以甲醇和5.0 mmol/L碳酸氢铵水溶液作为流动相进行梯度洗脱,在BEH C18色谱柱上实现分离,电喷雾正离子多反应监测方式检测,以那可丁作为内标的基质标准内标法定量。结果尿液和全血中3种乌头生物碱的平均加标回收率分别为93.9%~108%和89.7%~109%,相对标准偏差为1.3%~11%和1.1%∼18%(n=6),定量限(S/N =10)分别为0.05μg/L 和0.1μg/L。结论此方法灵敏、准确,已成功应用于一起中毒事件的检测。

  17. Simultaneous determination of the 6 kinds of aconitum alkaloid contents in Mongolian medicine Garidi-13 pill by HPLC method%HPLC法测定蒙药嘎日迪-13味丸中6种乌头类生物碱的含量

    巴图德力根; 布仁巴图; 韩志强


    Objective To establish a method for simultaneous determi-nation of 6 alkaloid in Mongolia medicine Garidi -13 pill.Methods Diamonsi I C18 column was used.The acetonitrile-tetrahydrofuran (25:15 ) and 0.1 mol? L-1 of ammonium acetate solution were used as mobile phase by gradient elution.The volume flow rate was 0.8 mL? min -1 , and column temperature was 30 ℃, wavelength was 235 nm.The speci-ficity, lower limit of quantification and standard curve , precision and re-covery rate and stability as well as the matrix effect were investigated . Results The aconitine , hypaconitine , mesaconitine , benzoylaconitine , benzoylhypacoitine and benzoylmesaconine showed a good linear relation-ship in the 3.48 ×10 -3 -0.17 ( r=0.999 5 ) ,3.24 ×10 -3 -0.16 ( r=0.999 6 ) ,6.96 ×10 -3 -0.35 ( r=0.999 5 ) ,2.06 ×10 -3 -0.10 ( r=0.999 9 ) , 2.02 ×10 -3 -0.20 ( r=0.999 9 ) and 6.66 ×10 -3 -0.33 ( r=0.999 9 ) mg? mL-1 .The RSD was 3.56%, 1.87%, 4.86%, 2.74% and 3.21%, 4.59%, respectively , and the average recovery rate was 101.11%, 98.07%, 97.81%, 9 9.24%, 104.55% and 104.84%.Conclusion The method is simple , accurate and reproduci-ble, which can simultaneously determinate the mono ester alkaloid and double ester alkaloid in the Mongolia medicine Garidi -13 pills.%目的 建立测定蒙药嘎日迪-13味丸中6种生物碱的含量的高效液相色谱法. 方法 Diamonsi I C18色谱柱,以乙腈-四氢呋喃(25:15)为流动相A,以0.1 mol? L-1醋酸铵溶液为流动相B,梯度洗脱,流速为0.8 mL? min-1 ,柱温为30 ℃,检测波长为235 nm,检测专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性. 结果 乌头碱、次乌头碱、新乌头碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、苯甲酰新乌头原碱分别在3.48 ×10 -3 ~0.17 ( r=0.999 5 ) , 3.24 ×10 -3 ~0.16 (r=0.999 6),6.96 ×10-3 ~0.35 (r=0.999 5),2.06 ×10-3 ~0.10(r =0.999 9),4.04 ×10 -3 ~0.20 (r =0.999 9),6.66 ×10 -3 ~0.33 ( r=0.999 9 ) mg? mL-1

  18. Neuroprotective effect of shenfu injection after intra-arterial thrombolysis

    Huaijun Liu; Xiuchuan Jia; Jiping Yang; Zengpin Liu; Guoshi Wang; Linfang Li


    BACKGROUND: Within 3 hours after ischemic stroke, thrombolysis can improve prognosis of patients; however, cerebral edema and cerebral hemorrhage induced by vascular recanalization at an early phase can influence on therapeutic effect of thrombolysis; therefore, thrombolysis is combined with neuroprotective agent for recently clinical treatment.OBJECTIVE: To evaluate the neuroprotective effect of shenfu injection on patients with ischemic stroke after arterial thrombolysis and compare with the controls. DESIGN: Case-controlled study. SETTING : Department of Medical Image, Second Hospital of Hebei Medical University. PARIICIPANTS: A total of 45 patients with acute stroke were selected from Emergency Department or Neurological Department of the Second Hospital of Hebei Medical University from August 2005 to May 2006. All patients were met the diagnosis criteria published by the Fourth National Stroke Conference and had middle cerebral arterial embolism with angiography. Attacked course was less than 6 hours. Patients did not have a history of stroke. Scores of the National Institutes of Health Stroke Scale (NIHSS) were not less than 4 points and patients were aged from 18 to 80 years. All subjects consented of the whole therapeutic process. METHODS: ① Intermittent perfusion was used to treat intra-arterial thrombolysis. Thirty patients with vascular recanalization or partially vascular recanalization (18 males and 12 females) were randomly divided into treatment group and control group with 15 in each group. There was no significant difference of baseline data between the two groups. After recanalization, patients in treatment group were given 20 mL shenfu injection, which consisted of ginseng saponin and aconitine (Ya'an Sanjiu Pharmaceutical Company, batch number: 041013, 10 mL/ampoule) and slowly injected into vein for longer than 5 minutes. And then, patients were intravenously dripped with 50 mL shenfu injection and 50 g/L 250 mL glucose solution once a day


    Paolo Borrione


    effects. Also, some herbs are safe in modest amounts but they may become toxic at higher doses. For example, liquorice root can be used safely for treating duodenal and gastric ulcers, but large amounts of liquorice can cause serious side effects such as hypokalemia, high blood pressure, and heart failure. Finally, other herbs, toxic by themselves: for example, germander, an herb used in some weight-loss programs, can cause fatal hepatitis. Other herbs may be toxic because of possible contaminants: the Chinese herbs caowu and chuanwu used for the management of rheumatism, arthritis, bruises, and fractures may contain highly toxic potentially fatal alkaloids such as aconitine.Therefore, despite the increased tendency to seek natural therapies, athletes have to be aware that "natural" does not equal to "safe." Herbs should not be touted as miraculous side effects-free substances, but rather as compounds that work through simple biochemistry. The effects of most herbal supplements have not been studied using rigorous scientific methodology, and the hyperbolic advertising and advocacy literature surrounding herbal products often contains untested claims, and under-reports side effects.All the preparations mentioned above exhibit hormone-like activity. Evidence in animals of reproductive disturbances associated with ingestion of feed rich in oestrogenic substances includes a lower conception rate in sheep after prolonged isoflavones consumption, infertility in cattle after consuming feed containing coumestrol, decreased fertility in captive cheetahs fed with dietary oestrogens, hyperoestrogenism in pigs fed with diets containing zearalenone, uterotropic effects in mice fed with soybean, reduced fecundity in adult males rats fed a high phytoestrogen diet for 3 days (Glover and Assinder, 2006; Srilatha, 2004 Also, in a population-based cohort study in the United Kingdom, a vegetarian diet during pregnancy was associated with a 5-fold higher risk of hypospadias, and consumption