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Sample records for aconitine

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

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

    2004-01-01

    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.

  2. p-sulfonated calix[8]arene functionalized graphene as a "turn on" fluorescent sensing platform for aconitine determination.

    Yang, Long; Xie, Xiaoguang; Cai, Le; Ran, Xin; Li, Yucong; Yin, Tianpeng; Zhao, Hui; Li, Can-Peng

    2016-08-15

    This work reports a novel method for the determination of aconitine through the competitive host-guest interaction between p-sulfonated calix[8]arene (SCX8) and signal probe/target molecules by using SCX8 functionalized reduced graphene oxide (SCX8-RGO) as a receptor. Three dyes (ST, RhB, BRB) and aconitine were selected as the probe and target molecules, respectively. The formation of SCX8-RGO·ST, SCX8-RGO·RhB, and SCX8-RGO·BRB complexes greatly decreases the fluorescence emission of ST, RhB, and BRB. The aconitine/SCX8 complex possesses a higher binding constant than ST/SCX8, RhB/SCX8, and BRB/SCX8 complexes, thus the dye in the SCX8 cavity can be replaced by aconitine to revert the fluorescence emission of SCX8-RGO·dye, leading to a "switch-on" fluorescence response. The fluorescence intensity of SCX8-RGO·ST, SCX8-RGO·RhB, and SCX8-RGO·BRB complexes increased linearly with increasing concentration of aconitine ranging from 1.0 to 14.0μM, 2.0-16.0μM, and 1.0-16.0μM, respectively. Based on the competitive host-guest interaction, the proposed detection method for aconitine showed detection limits of 0.28μM, 0.60μM, and 0.37μM, respectively, and was successfully applied for the determination of aconitine in human serum samples with good recoveries from 95.1% to 104.8%. The proposed method showed high selectivity for aconitine beyond competitive binding analytes. In addition, the inclusion complex of the SCX8/aconitine was studied by the molecular docking and molecular dynamics simulation, which indicated that the phenyl ester group of the aconitine molecule was included into the SCX8 cavity. PMID:27085945

  3. Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na+ channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca2+ 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 Ca2+ handling proteins demonstrated that aconitine promoted Ca2+ overload through the expression regulation of Ca2+ 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 Ca2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca2+ overload causes arrhythmia in rats.

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

    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: ► Effect of atropine or glycyrrhizic acid on aconitine–BSA binding. ► UV–vis absorption and fluorescence spectroscopic techniques used. ► Aconitine quenched BSA fluorescence via dynamic quenching with r=2.62 nm. ► Atropine sulphate and glycyrrhizic acid decreased KA and n of aconitine–BSA. ► Support for aconitine detoxification by atropine and glycyrrhizic acid.

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

    Zhenying Zhao

    2013-11-01

    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.

  6. 3-Deoxy­aconitine from the root of Aconitum Carmichaeli Debx.

    Gao, Feng; Zhu, Shou-An; Xiong, Shi-Jun

    2010-01-01

    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 ...

  7. Calix[8]arene functionalized single-walled carbon nanohorns for dual-signalling electrochemical sensing of aconitine based on competitive host-guest recognition.

    Yang, Long; Ran, Xin; Cai, Le; Li, Yucong; Zhao, Hui; Li, Can-Peng

    2016-09-15

    A dual-signalling electrochemical approach has been developed towards aconitine based on competitive host-guest interaction by selecting methylene blue (MB) and p-sulfonated calix[8]arene functionalized single-walled carbon nanohorns (SCX8-SWCNHs) as the "reporter pair". Upon the presence of aconitine to the performed SCX8-SWCNHs·MB complex, the MB molecules are displaced by aconitine. This results in a decreased oxidation peak current of MB and the appearance of an oxidation peak of aconitine, and the changes of these signals correlate linearly with the concentration of aconitine. A linear response range of 1.00-10.00μM for aconitine with a low detection limit of 0.18μM (S/N=3) was obtained by using the proposed method. This method could be successfully utilized to detect aconitine in serum samples. This dual-signalling sensor can provide more sensitive target recognition and will have important applications in the sensitive and selective electrochemical detection of aconitine. PMID:27135940

  8. 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: xhb_6505@163.com [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Sun, Xiao-bo, E-mail: sun_xiaobo163@163.com [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)

    2014-08-15

    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

  9. 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

    2007-01-01

    @@ 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 ).

  10. Comparative study on effects of single and multiple oral administration of mungbean (Phaseolus radiatus L.) seed extract on the pharmacokinetics of aconitine by UHPLC-MS.

    Gao, Enze; Yu, Xiaohan; Liu, Ting; Li, Hualing; Wang, Pei; Wei, Yingqing; Zhao, Yunli; Yu, Zhiguo

    2014-10-01

    The study was aimed to investigate the effects of single and multiple oral administration of mungbean (Phaseolus radiatus L.) seed extract (ME) on the pharmacokinetics of aconitine in rats. The Sprague-Dawley rats were randomly divided into three groups (six rats each group). In group 1, rats were orally administered 500 µg/kg aconitine after receiving a single oral dose of 1 g/kg ME. In group 2, rats were orally administered with 500 µg/kg aconitine at day 7 of treatment with 1 g/kg/day ME. In group 3, rats were orally administered with 500 µg/kg aconitine. Blood samples were collected at different time points (0.083, 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0 h). The concentration of aconitine in rats plasma was determined by a fully validated ultra-high-performance liquid chromatography coupled with mass spectrometry method. The results showed that single and multiple oral co-administration of ME significantly altered the pharmacokinetic parameters of aconitine. PMID:24590733

  11. 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: yangsophia76@hotmail.com; Zhang, Tianhong, E-mail: wdzth@sina.com; Li, Zheng, E-mail: lizh2524@126.com; Xu, Liang, E-mail: wj24998@163.com; Liu, Fei, E-mail: liufeipharm@163.com; Ruan, Jinxiu, E-mail: ruanjx1936@yahoo.com.cn; Liu, Keliang, E-mail: keliangliu55@126.com; Zhang, Zhenqing, E-mail: zhangzhenqingpharm@163.com

    2013-12-15

    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

  12. 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

    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 × 10−5 to 2.85 × 10−5 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 (Cmax) 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 (AUC0–12h) 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 Cmax and AUC of aconitine. • P

  13. 新乌头碱、乌头碱与次乌头碱在附子不同炮制法中含量变化的实验研究%Experimental study of the content of new aconitine,aconitine and hypoaconitine in different processing method of aconite

    赵永堂

    2012-01-01

    目的 探讨不同炮制方法的炮制品中新乌头碱、乌头碱与次乌头碱含量变化.方法 分别采用江西建昌帮法、樟树帮法与2005年版法制备附子炮制品,通过HPLC色谱法测定其中新乌头碱、乌头碱与次乌头碱含量.结果 3种炮制方法的炮制品中新乌头碱、乌头碱与次乌头碱的平均质量分数分别为:建昌帮法:(2.13±0.26),(6.78±0.18),(11.26±0.97)μg/g;樟树帮法:(2.35±0.39),(3.23±0.88),(8.09±0.92)μg/g;中国药典法:(1.43±0.18),0,(1.68±0.23)μg/g.结论 建昌帮煨制附子中新乌头碱、乌头碱与次乌头碱总含量比另外两种方法的总含量要高,这为建昌帮炮制技术的研究提供了科学根据.%Objective To explore the content of new aconitinc. Aconitine and hypoaconitine in products processed by different approaches. Methods Aconite processed products were prepared with Jiangxi Jianchangbang method, Zhangshubang method and method provided in Chinese Pharmacopeia (2005 edition). And the content of new aconitine, aconitine and hypoaconitine in the products were detenrimed with chromatography (HPLC) method. Results Average quality scores of new aconitine, aconitine and hypoaconitine processed with the three methods were as follows: With jianchangbang method, the contents were (2.13±0.26), (6.78±0.18), fll.26±0.97)μg/g, respectively; with Zhangshubang method, the contents were (2.35±0.39), (3.23±0.S8), (S.09±0.92)μg/g, respectively; with method provided In Chinese Pharmacopeia, the contents were (1.43±0.18), 0, (1.68±0.23)μg/g, respectively. Conclusion Contents of new aconitine, aconitine and hypaconitine are higher when processed with Jianebang method than processed with the other two methods, which provides scientific evidence for further Investigation of Jianchangbang method.

  14. 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

    2011-01-01

    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.

  15. 中药提取物配伍对乳腺癌MDA-MB-231BO细胞侵袭作用的影响及其机制%Inhibitory effects of osthole, psoralen and aconitine on invasive activities of breast cancer MDA-MB-231BO cell line and the mechanisms

    郭保凤; 刘胜; 叶依依; 韩向晖

    2011-01-01

    Objective: To explore the inhibitory effects and to investigate the mechanisms of combined treatment of osthole, psoralen with aconitine on human breast cancer cell line MDA-MB-231BO.Methods: The best inhibitory concentration of osthole, psoralen combined with aconitine on MDA-MB-231BO cells was obtained by stepwise regression analysis after adopting a uniform experiment design. The invasive activities were observed by transwell assays, and expressions of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, Smad4, Smad7, nuclear factor-icB (NF-kB) and receptor activator of NF-kB ligand (RANK)mRNAs were analyzed by real-time quantitative polymerase chain reaction.Results; The optimal combination concentrations of osthol, psoralen and aconitine were 6.44, 8.89 and 9.44 βg/mL, respectively. Cell invasion was significantly inhibited after 24 hours of treatment using the combination drugs and zoledronic acid. TGF-01, Smad2, Smad3, Smad4, Smad7, NF-kB and RANK mRNA expressions of the optimal combination group and zoledronic acid group were significantly reduced compared with the control group (P<0.01). Furthermore, TGF-pi, Smad2, Smad3, Smad4, Smad7, NF-kB and RANK mRNA expressions of the optimal combination group were significantly lower than those of the weak combination group (P<0.01).Conclusion; Combination treatment of osthole, psoralen with aconitine can inhibit cancer cell invasion, which is a result of alteration of the TGF-β/Smad signaling pathway and down-regulation of NF-kB and RANK expressions.%目的:探讨中药蛇床子、补骨脂、附子有效成分蛇床子素、补骨脂素、乌头碱对乳腺癌细胞株MDA-MB-231BO的侵袭抑制作用及其机制.方法:采用均匀设计实验方案进行组方设计,逐步回归分析拟合蛇床子素、补骨脂素配伍乌头碱的回归方程;采用人乳腺癌骨高转移细胞(MDA-MB-231BO)体外侵袭实验,实时荧光定量聚合酶链反应检测,观察药物处理MDA-MB-231 BO细胞后,细胞

  16. 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...

  17. Determination of Aconitine, Hypaconitine and Mesaconitine in Xiaotong Patches by HPLC%消痛膏中乌头碱、次乌头碱和新乌头碱的HPLC法测定

    梅馨; 潘金火; 杨菁

    2014-01-01

    建立了高效液相色谱法测定消痛膏中的乌头碱、次乌头碱和新乌头碱.使用Hedera ODS-2柱,以乙腈∶四氢呋喃(25∶15)为流动相A,以0.1 mol/L乙酸铵溶液(每1L加冰乙酸0.5 ml)为流动相B,梯度洗脱,检测波长235 nm.乌头碱、次乌头碱和新乌头碱分别在0.07~0.42μg、0.15~0.88 μg和0.05~0.32 μg范围内线性关系良好,回收率分别为92.7%、92.1%和93.0%,RSD分别为3.37%、2.09%和3.14%.

  18. Total Synthesis of (-)-Cardiopetaline.

    Nishiyama, Yoshitake; Yokoshima, Satoshi; Fukuyama, Tohru

    2016-05-20

    The total synthesis of (-)-cardiopetaline, an aconitine-type natural product, has been accomplished. Our synthesis involved a Wagner-Meerwein rearrangement of a sulfonyloxirane that enabled, in a single step, the construction of the bicyclo[3.2.1] system in the aconitine skeleton and effective introduction of oxygen functional groups at the appropriate positions. PMID:27166640

  19. Study on Metabolites of Aconitum Alkaloids in Human Urine

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

    2003-01-01

    @@ 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.

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

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

    2007-01-01

    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.

  1. 3-Deoxyaconitine from the root of Aconitum Carmichaeli Debx.

    Feng Gao

    2010-06-01

    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.

  2. 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; Bo Gao; Xueqing Ding; Chi-Ming Huang; Paul Pui-Hay But

    2012-01-01

    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 sy...

  3. Indikation und Anwendung psychotroper Arzneimittel unter besonderer Berücksichtigung der Benzodiazepine in der Stomatologie in der DDR von 1949-1990

    Mielke, Renate

    2013-01-01

    To summarise, it can be stated that many psychotropic substances or drugs were used in the field of dentistry in East Germany (GDR). During the 1950s the most commonly used psychotropic drugs used in dentistry in the GDR were herbal medizines, bromides, and bromid-urea derivatives, methyl pentinol Pentinol®), aconitine, caffeine, codeine, reserpine, numerous barbituric acid derivatives Lepinal® and Kalypnon®, the guaiacol glycerine ether Neuroton®, the benactyzine product Procalm®, the hydant...

  4. Non-targeted metabolomics identified a common metabolic signature of lethal ventricular tachyarrhythmia (LVTA) in two rat models.

    Wang, Xingxing; Wang, Dian; Yu, Xiaojun; Zhang, Guohong; Wu, Jiayan; Zhu, Guanghui; Su, Ruibing; Lv, Junyao

    2016-06-21

    Lethal ventricular tachyarrhythmia (LVTA) is the predominant underlying mechanism of sudden cardiac death (SCD). The aim of this study is to characterize the metabolic features of myocardia following LVTA, and identify potential biomarkers to diagnose LVTA. We developed two LVTA rat models induced by aconitine injection or coronary artery ligation, which represent cardiac ion channel disease-related and cardiac ischemia-related SCD, respectively. The myocardial metabolic profile was investigated by gas chromatography-mass spectrometry and proton nuclear magnetic resonance-based metabolomics. Twenty-three aconitine-injected and 14 coronary artery ligation-treated rats developed LVTA SCD. A total of 38 differential metabolites of myocardia were identified in aconitine-induced LVTA rats, of which 31 metabolites showed a similar change in coronary artery ligation-related LVTA rats. Fatty acids (stearic, palmitic, linoleic, elaidic, and myristic) and branched-chain amino acids (valine, leucine, and isoleucine) were the most down-regulated metabolites. Furthermore, elevated ADP, phosphate, lactate, glutamate, aspartate, threonine, choline and arginine were also observed. Major pathways regarding these dysregulated metabolites post LVTA are energy excessive consumption and deficit, ionic imbalance, oxidative stress, cardiac cytotoxicity and membrane injury. Valine, stearic acid and leucine collectively enable a precision of 92.9% to distinguish LVTA from its control, and are correlated with several arrhythmia indices. Our results uncovered a common metabolic feature of LVTA in myocardia in two rat models, which represent cardiac ion channel disease and cardiac ischemia, respectively. l-Valine, l-leucine and stearic acid jointly confer good potential for distinguishing LVTA, which might be potential biomarkers of LVTA-related SCD. PMID:27138062

  5. Drug: D06784 [KEGG MEDICUS

    Full Text Available D06784 Crude, Drug Processed aconite root (JP16); Powdered processed aconite root (...JP16); Processed aconite root (fibrous root); Powdered processed aconite root (fibrous root) Aconitine [CPD:...nd Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs D06784 Processed aconite root (JP16); Powdered...hinese medicine formulations D06784 Processed aconite root (JP16); Powdered processed aconite root (JP16) Tr...g the interior D06784 Processed aconite root; Processed aconite root (fibrous root); Powdered

  6. Important Poisonous Plants in Tibetan Ethnomedicine

    Lijuan Ma

    2015-01-01

    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.

  7. Important poisonous plants in tibetan ethnomedicine.

    Ma, Lijuan; Gu, Ronghui; Tang, Li; Chen, Ze-E; Di, Rong; Long, Chunlin

    2015-01-01

    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. PMID:25594733

  8. Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

    The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using [3H]batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of [3H]BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of [3H]BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizations indicate that [3H]BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations

  9. Quantitative Enhancement of Active Content and Biomass of Two Aconitum Species Through Suitable Cultivation Technology

    Raman BAHUGUNA

    2013-03-01

    Full Text Available High altitude medicinal plants are facing problem due to their unsustainable utilization. So, the cultivation of these plants with appropriate technology may fulfill the demand of pharmaceutical industry and may also promote the conservation at their natural habitat. Highly important two species of Aconitum were studied for the enhancement of net profit by applying protected farming system. Both the experimental species were grown under natural and greenhouse conditions. Very positive results were obtained in plants of both Aconitum species grown under greenhouse as compared to natural conditions. Enhancement in yield was 12 and 9 times high in Aconitum heterophyllum Wall. ex Royle and Aconitum balfourii Stapf. respectively grown under greenhouse as compared to natural condition. Pseudoaconitine and aconitine were also observed high in greenhouse grown (0.51% and 0.42% respectively than naturally grown plants (0.49% and 0.40% respectively. The quantity of atisine and aconitine was also found high (0.35% & 0.27% respectively in greenhouse than naturally grown plants (0.19% & 0.16% respectively. It was noticed that plant height, leaf number, and average length of tubers were high in plants grown inside greenhouse in contrast to natural habitat. Almost five and two folds more tubers were found in A. balfourii and A. heterophyllum respectively in plants grown under greenhouse in comparison to natural conditions.

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

    Chang-Kil Yoo

    2001-06-01

    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.

  11. Analysis of toxic alkaloids in body samples.

    Beyer, Jochen; Drummer, Olaf H; Maurer, Hans H

    2009-03-10

    Many plants contain toxic alkaloids which may be dangerous to humans. Despite the large number of poisonous plants, cases of fatal plant poisonings are relatively rare. The frequencies of poisonings and the plants involved are often regionally specific. Plant poisonings can be aggregated into three categories: unintended ingestions, intended ingestions, and poisoning due to abuse of plant material. Unintended ingestions often occur in children or from a mix-up of plants and mushrooms in adults. Intended ingestions are common in homicides and suicides. Increasingly common is the abuse of plants for hallucinogenic reasons. Toxicological analysis of such alkaloids may help in diagnosis of poisoning or abuse cases. This review describes the toxic alkaloids aconitine, atropine, coniine, colchicine, cytisine, dimethyltryptamine, harmine, harmaline, ibogaine, kawain, mescaline, scopolamine, and taxine, which are often involved in fatal and non-fatal poisonings. The paper summarizes the symptoms of the intoxications and reviews the methods of detection of their toxic constituents in biological fluids. PMID:19147309

  12. Human organic cation transporter 2 (hOCT2): Inhibitor studies using S2-hOCT2 cells

    Highly expressed in kidney and located on the basolateral membrane, human organic cation transporter 2 (hOCT2) can transport various compounds (i.e. drugs and toxins) into the proximal tubular cell. Using cultured proximal tubule cells stably expressing hOCT2 (i.e. S2-hOCT2 cells), we sought to probe different compound classes (e.g. analgesics, anti-depressants, anti-psychotics, disinfectant, herbicides, insecticides, local anesthetic, muscarinic acetylcholine receptor antagonist, sedatives, steroid hormone, stimulants and toxins) for their ability to inhibit 14C-TEA uptake, a prototypical OCT2 substrate. Aconitine, amitriptyline, atropine, chlorpyrifos, diazepam, fenitrothion, haloperidol, lidocaine, malathion, mianserin, nicotine and triazolam significantly inhibited 14C-TEA uptake; IC50 values were 59.2, 2.4, 2.0, 20.7, 32.3, 13.2, 32.5, 104.6, 71.1, 17.7, 52.8 and 65.5 μM, respectively. In addition, aconitine, amitriptyline, atropine, chlorpyrifos, fenitrothion, haloperidol, lidocaine, and nicotine displayed competitive inhibition with Ki values of 145.6, 2.5, 2.4, 24.8, 16.9, 51.6, 86.8 and 57.7 μM, respectively. These in vitro data support the notion that compounds pertaining to a wide variety of different drug classes have the potential to decrease renal clearance of drugs transported via hOCT2. Consequently, these data warrant additional studies to probe hOCT2 and its role to influence drug pharmacokinetics

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

    Satyendra K Prasad

    2014-01-01

    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.

  14. 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

    2012-01-01

    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.

  15. 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

    1995-01-01

    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

  16. 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.

  17. Simultaneous determination of thirteen major active compounds in Guanjiekang preparation by UHPLC-QQQ-MS/MS.

    Wang, Canjian; Xie, Ying; Xiang, Zheng; Zhou, Hua; Liu, Liang

    2016-01-25

    An ultra high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method has been developed to evaluate the quality of a pharmaceutical herbal preparation, Guanjiekang (GJK), through a simultaneous determination of 13 major active compounds with a huge difference in level of content. Chromatographic separation was achieved on a Waters Acquilty UPLC C18 column (2.1 × 100 mm, 1.7 μm) with a mobile phase consisting of acetonitrile and buffer solution (10mM ammonium acetate containing 0.1% acetic acid) under a gradient elution manner. A triple quadrupole mass spectrometer was operated in positive ionization mode with multiple reaction monitoring for the detection of the 13 compounds. All calibration curves showed excellent linear regressions (R(2)>0.999) within the test range. The precision, repeatability and stability of the 13 compounds were below 5.0% in terms of RSD. The recoveries were 99.2-103.9% with RSD of 0.23-3.30% for GJK samples. The method was successfully used for the analysis of samples of GJK preparation and showed that the lowest level was in aconitine (0.582 ± 0.143 ng/g) and the highest was in paeoniflorin (16.80 ± 0.886 mg/g), with a 41800 folds of difference. In conclusion, a rapid, sensitive, precise, accurate, and reliable UHPLC-QQQ-MS/MS method has been developed for the simultaneous detection of 13 active compounds with massive difference in level of content in the pharmaceutical samples of GJK preparation, which can be applied for the quality control of GJK product. PMID:26588049

  18. Screening approach by ultra-high performance liquid chromatography-tandem mass spectrometry for the blood quantification of thirty-four toxic principles of plant origin. Application to forensic toxicology.

    Carlier, Jérémy; Guitton, Jérôme; Romeuf, Ludovic; Bévalot, Fabien; Boyer, Baptiste; Fanton, Laurent; Gaillard, Yvan

    2015-01-15

    Plant poisonings have left their mark on history and still cause many deaths, whether intentional or accidental. The means to show toxicological evidence of such poisonings should be implemented with great care. This article presents a technique for measuring thirty-nine toxic principles of plant origin in the blood, covering a large amount of toxins from local or exotic plants: α-lobeline, α-solanine, aconitine, ajmaline, atropine, brucine, cephalomannine, colchicine, convallatoxin, cymarine, cytisine, digitoxin, digoxin, emetine, gelsemine, ibogaine, jervine, kavain, lanatoside C, lupanine, mitragynine, neriifolin, oleandrin, ouabain, paclitaxel, physostigmine, pilocarpine, podophyllotoxin, proscillaridin A, reserpine, retrorsine, ricinine, scopolamine, senecionine, sparteine, strophanthidin, strychnine, veratridine and yohimbine. Analysis was carried out using an original ultra-high performance liquid chromatography separation coupled with tandem mass spectrometry detection. Extraction was a standard solid phase extraction performed on Oasis(®) HLB cartridge. Thirty-four of the thirty-nine compounds were put through a validation procedure. The assay was linear in the calibration curve range from 0.5 or 5 μg/L to 1000 μg/L according to the compounds. The method is sensitive (LOD from 0.1 to 1.6 μg/L). The within-day precision of the assay was less than 22.5% at the LLOQ, and the between-day precision was less than 21.5% for 10 μg/L for all the compounds included. The assay accuracy was in the range of 87.4 to 119.8% for the LLOQ. The extraction recovery and matrix effect ranged from 30 to 106% and from -30 to 14%, respectively. It has proven useful and effective in several difficult forensic cases. PMID:25438245

  19. Aconitum Alkaloid Poisoning Related to the Culinary Uses of Aconite Roots

    Thomas Y. K. Chan

    2014-09-01

    Full Text Available Aconite roots (roots or root tubers of the Aconitum species are eaten as root vegetables and used to prepare herbal soups and meals, mainly for their purported health benefits. Aconite roots contain aconitine and other Aconitum alkaloids, which are well known cardiotoxins and neurotoxins. To better understand why Aconitum alkaloid poisoning related to the culinary uses of aconite roots can occur and characterize the risks posed by these “food supplements”, relevant published reports were reviewed. From 1995 to 2013, there were eight reports of aconite poisoning after consumption of these herbal soups and meals, including two reports of large clusters of cases (n = 19–45 and two reports of cases (n = 15–156 managed by two hospitals over a period of 4.5 to 5 years. The herbal formulae used did not adhere to the suggested guidelines, with regarding to the doses (50–500 g instead of 3–30 g per person and types (raw instead of processed of aconite roots used. The quantities of Aconitum alkaloids involved were huge, taking into consideration the doses of aconite roots used to prepare herbal soups/meals and the amounts of aconite roots and herbal soups/meals consumed. In a large cluster of cases, despite simmering raw “caowu” (the root tuber of A. kusnezoffii in pork broth for 24 h, all 19 family members who consumed this soup and boiled “caowu” developed poisoning. Severe or even fatal aconite poisoning can occur after consumption of herbal soups and foods prepared from aconite roots. Even prolonged boiling may not be protective if raw preparations and large quantities of aconite roots are used. The public should be warned of the risk of severe poisoning related to the culinary and traditional medicinal uses of aconite roots.

  20. Toxic Constituents Index: A Toxicity-Calibrated Quantitative Evaluation Approach for the Precise Toxicity Prediction of the Hypertoxic Phytomedicine—Aconite

    Zhang, Ding-kun; Li, Rui-sheng; Han, Xue; Li, Chun-yu; Zhao, Zhi-hao; Zhang, Hai-zhu; Yang, Ming; Wang, Jia-bo; Xiao, Xiao-he

    2016-01-01

    Complex chemical composition is an important reason for restricting herbal quality evaluation. Despite the multi-components determination method significantly promoted the progress of herbal quality evaluation, however, which mainly concerned the total amount of multiple components and ignored the activity variation between each one, and did not accurately reflect the biological activity of botanical medicines. In this manuscript, we proposed a toxicity calibrated contents determination method for hyper toxic aconite, called toxic constituents index (TCI). Initially, we determined the minimum lethal dose value of mesaconitine (MA), aconitine (AC), and hypaconitine (HA), and established the equation TCI = 100 × (0.3387 ×XMA + 0.4778 ×XAC + 0.1835 ×XHA). Then, 10 batches of aconite were selected and their evaluation results of toxic potency (TP), diester diterpenoid alkaloids (DDAs), and TCI were compared. Linear regression analysis result suggested that the relevance between TCI and TP was the highest and the correlation coefficient R was 0.954. Prediction error values study also indicated that the evaluation results of TCI was highly consistent with that of TP. Moreover, TCI and DDAs were both applied to evaluate 14 batches of aconite samples oriented different origins; from the different evaluation results, we found when the proportion of HA was reached 25% in DDAs, the pharmacopeia method could generate false positive results. All these results testified the accuracy and universality of TCI method. We believe that this study method is rather accurate, simple, and easy operation and it will be of great utility in studies of other foods and herbs. PMID:27378926

  1. Toxic Constituents Index: A Toxicity-Calibrated Quantitative Evaluation Approach for the Precise Toxicity Prediction of the Hypertoxic Phytomedicine-Aconite.

    Zhang, Ding-Kun; Li, Rui-Sheng; Han, Xue; Li, Chun-Yu; Zhao, Zhi-Hao; Zhang, Hai-Zhu; Yang, Ming; Wang, Jia-Bo; Xiao, Xiao-He

    2016-01-01

    Complex chemical composition is an important reason for restricting herbal quality evaluation. Despite the multi-components determination method significantly promoted the progress of herbal quality evaluation, however, which mainly concerned the total amount of multiple components and ignored the activity variation between each one, and did not accurately reflect the biological activity of botanical medicines. In this manuscript, we proposed a toxicity calibrated contents determination method for hyper toxic aconite, called toxic constituents index (TCI). Initially, we determined the minimum lethal dose value of mesaconitine (MA), aconitine (AC), and hypaconitine (HA), and established the equation TCI = 100 × (0.3387 ×X MA + 0.4778 ×X AC + 0.1835 ×X HA). Then, 10 batches of aconite were selected and their evaluation results of toxic potency (TP), diester diterpenoid alkaloids (DDAs), and TCI were compared. Linear regression analysis result suggested that the relevance between TCI and TP was the highest and the correlation coefficient R was 0.954. Prediction error values study also indicated that the evaluation results of TCI was highly consistent with that of TP. Moreover, TCI and DDAs were both applied to evaluate 14 batches of aconite samples oriented different origins; from the different evaluation results, we found when the proportion of HA was reached 25% in DDAs, the pharmacopeia method could generate false positive results. All these results testified the accuracy and universality of TCI method. We believe that this study method is rather accurate, simple, and easy operation and it will be of great utility in studies of other foods and herbs. PMID:27378926

  2. 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

    2016-01-01

    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 (P<0.01) and increased the RR (P<0.01) and JT intervals (P<0.05) of electrocardiogram. Nandrolone+exercise significantly increased the ventricular 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. PMID:26686897

  3. Distribution of toxic alkaloids in tissues from three herbal medicine Aconitum species using laser micro-dissection, UHPLC-QTOF MS and LC-MS/MS techniques.

    Jaiswal, Yogini; Liang, Zhitao; Ho, Alan; Wong, LaiLai; Yong, Peng; Chen, Hubiao; Zhao, Zhongzhen

    2014-11-01

    Aconite poisoning continues to be a major type of poisoning caused by herbal drugs in many countries. Nevertheless, despite its toxic characteristics, aconite is used because of its valuable therapeutic benefits. The aim of the present study was to determine the distribution of toxic alkaloids in tissues of aconite roots through chemical profiling. Three species were studied, all being used in traditional Chinese Medicine (TCM) and traditional Indian medicine (Ayurveda), namely: Aconitum carmichaelii, Aconitum kusnezoffii and Aconitum heterophyllum. Laser micro-dissection was used for isolation of target microscopic tissues, such as the metaderm, cortex, xylem, pith, and phloem, with ultra-high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) employed for detection of metabolites. Using a multi-targeted approach through auto and targeted LC-MS/MS, 48 known compounds were identified and the presence of aconitine, mesaconitine and hypaconitine that are the biomarkers of this plant was confirmed in the tissues. These results suggest that the three selected toxic alkaloids were exclusively found in A. carmichaelii and A. kusnezoffii. The most toxic components were found in large A. carmichaelii roots with more lateral root projections, and specifically in the metaderm, cork and vascular bundle tissues. The results from metabolite profiling were correlated with morphological features to predict the tissue specific distribution of toxic components and toxicity differences among the selected species. By careful exclusion of tissues having toxic diester diterpenoid alkaloids, the beneficial effects of aconite can still be retained and the frequency of toxicity occurrences can be greatly reduced. Knowledge of tissue-specific metabolite distribution can guide users and herbal drug manufacturers in prudent selection of relatively safer and therapeutically more effective parts of the root. The information provided from

  4. 乌头属药物资源的化学和生物学研究进展%Recent advances in the chemical and biological studies of Aconitum pharmaceutical resources

    郝大程; 顾晓洁; 肖培根; 许利嘉; 彭勇

    2013-01-01

    used to summarize the global scientific effort in the phytochemical and biological studies of Aconitum.More diterpenoid alkaloids have been found in various Aconitum species,among which the aconitine type (type Ⅲ) is predominant.The versatile bioactivities of alkaloids and extracts,as well as the bioactivities of polysaccharides and other ingredients,are summarized and discussed in this review.The morphology-based 11-series classification of section Aconitum,subgenus Aconitum,is not supported by chemotaxonomy and molecular phylogeny.Molecular phylogeny based on nuclear and chloroplast DNA sequences divided the nine morphologically similar series into two clusters,which is bolstered by the chemotaxonomic data.It is essential to integrate the emerging technologies into Aconitum studies for both the sustainable utilization of Aconitum pharmaceutical resources and finding novel compounds with potential clinical utility and less toxicity.Systems biology and omics technologies will play an increasingly important role in booming pharmaceutical research involving bioactive compounds of Aconitum.

  5. HERBAL SUPPLEMENTS: CAUSE FOR CONCERN?

    Paolo Borrione

    2008-12-01

    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