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Sample records for pyrrolizidine alkaloid expression

  1. Pyrrolizidine alkaloids.

    Science.gov (United States)

    Robertson, Jeremy; Stevens, Kiri

    2014-12-01

    This review covers pyrrolizidine alkaloids isolated from natural sources. Topics include: aspects of structure, isolation, and biological/pharmacological studies; total syntheses of necic acids, necine bases and closely-related non-natural analogues.

  2. Single cell subtractive transcriptomics for identification of cell-specifically expressed candidate genes of pyrrolizidine alkaloid biosynthesis.

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    Sievert, Christian; Beuerle, Till; Hollmann, Julien; Ober, Dietrich

    2015-09-01

    Progress has recently been made in the elucidation of pathways of secondary metabolism. However, because of its diversity, genetic information concerning biosynthetic details is still missing for many natural products. This is also the case for the biosynthesis of pyrrolizidine alkaloids. To close this gap, we tested strategies using tissues that express this pathway in comparison to tissues in which this pathway is not expressed. As many pathways of secondary metabolism are known to be induced by jasmonates, the pyrrolizidine alkaloid-producing species Heliotropium indicum, Symphytum officinale, and Cynoglossum officinale of the Boraginales order were treated with methyl jasmonate. An effect on pyrrolizidine alkaloid levels and on transcript levels of homospermidine synthase, the first specific enzyme of pyrrolizidine alkaloid biosynthesis, was not detectable. Therefore, a method was developed by making use of the often observed cell-specific production of secondary compounds. H. indicum produces pyrrolizidine alkaloids exclusively in the shoot. Homospermidine synthase is expressed only in the cells of the lower leaf epidermis and the epidermis of the stem. Suggesting that the whole pathway of pyrrolizidine alkaloid biosynthesis might be localized in these cells, we have isolated single cells of the upper and lower epidermis by laser-capture microdissection. The resulting cDNA preparations have been used in a subtractive transcriptomic approach. Quantitative real-time polymerase chain reaction has shown that the resulting library is significantly enriched for homospermidine-synthase-coding transcripts providing a valuable source for the identification of further genes involved in pyrrolizidine alkaloid biosynthesis.

  3. Pyrrolizidine alkaloids from Heliotropium indicum

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    Souza, Joao Sammy N.; Machado, Luciana L.; Pessoa, Otilia D.L.; Lemos, Telma L.G. [Ceara Univ., Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica]. E-mail: tlemos@dqoi.ufc.br; Braz-Filho, Raimundo [Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacases, RJ (Brazil). Setor de Quimica de Produtos Naturais; Overk, Cassia R.; Ping Yao; Cordell, Geoffrey A. [University of Illinois at Chicago, IL (United States). College of Pharmacy. Dept. of Medicinal Chemistry and Pharmacognosy

    2005-11-15

    ndicine (1), a new pyrrolizidine alkaloid with unusual structural features, together with the known lycopsamine (2), were isolated from the roots of Heliotropium indicum (Boraginaceae). The structures were established by a combination of 1D and 2D NMR methods (COSY, HMQC, HMBC, and NOESY) and HREIMS. This is the first report of a lactone pyrrolizidine alkaloid in the genus Heliotropium. Compounds 1 and 2 were assayed for antioxidant activity and showed moderate activity. (author)

  4. Genotoxicity of pyrrolizidine alkaloids.

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    Chen, Tao; Mei, Nan; Fu, Peter P

    2010-04-01

    Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C --> T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs.

  5. Pyrrolizidine alkaloids from Onosma erecta.

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    Damianakos, Harilaos; Sotiroudis, Georgios; Chinou, Ioanna

    2013-10-25

    The MeOH extract of the aerial parts of Onosma erecta afforded four new pyrrolizidine alkaloids, 7-O-acetylechinatine N-oxide (1), a viridinatine N-oxide stereoisomer (2), 7-epi-echimiplatine N-oxide (3), and onosmerectine N-oxide (4), and two additional new natural products, the acid 2,3-dimethyl-2,3,4-trihydroxypentanoic acid (5) and the acyloin 4-methyl-2-hydroxypentanone (6).

  6. Pyrrolizidine alkaloids of senecio sp from Peru

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    Liliana Ruiz Vásquez and Matías Reina Artiles

    2011-01-01

    Full Text Available Six pyrrolizidine alkaloids (PAs (two saturated macrocyclic, three unsaturated macrocyclic and one unsaturated seco-macrocyclic were isolated from native Peruvian Senecio species. The structures of these alkaloids were established by a complete NMR spectroscopic analysis, chemical transformations and comparison of their NMR data with those published for similar alkaloids. Three PAs were then tested for antifungal activity against Fusarium moniliforme, F. (Sheldon, F. oxysporum fs. lycopersici (Scheldt and F. solani (Mart, no significant activity being observed.

  7. Pyrrolizidine alkaloids of senecio sp from Peru

    OpenAIRE

    2011-01-01

    Six pyrrolizidine alkaloids (PAs) (two saturated macrocyclic, three unsaturated macrocyclic and one unsaturated seco-macrocyclic) were isolated from native Peruvian Senecio species. The structures of these alkaloids were established by a complete NMR spectroscopic analysis, chemical transformations and comparison of their NMR data with those published for similar alkaloids. Three PAs were then tested for antifungal activity against Fusarium moniliforme, F. (Sheldon), F. oxysporum fs. lycopers...

  8. Pyrrolizidine alkaloids of Senecio sp from Peru

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    Ruiz Vasquez, Liliana; Reina Artiles, Matias [Instituto de Productos Naturales y Agrobiologia, CSIC, Tenerife (Spain); Gonzalez Coloma, Azucena [Instituto de Ciencias Agrarias (ICA), CSIC, Madrid (Spain); Cabrera Perez, Raimundo [Universidad de La Laguna (ULL), Tenerife (Spain). Unidad de Fitopatologia, Facultad de Biologia; Ruiz Mesia, Lastenia [Universidad Nacional de la Amazonia Peruana (LIPNAA-UNAP), AA.HH. Nuevo San Lorenzo, San Juan, Iquitos (Peru). Lab. de Investigacion en Productos Naturales Antiparasitarios de la Amazonia

    2011-07-01

    Six pyrrolizidine alkaloids (PAs) (two saturated macrocyclic, three unsaturated macrocyclic and one unsaturated seco-macrocyclic) were isolated from native Peruvian Senecio species. The structures of these alkaloids were established by a complete NMR spectroscopic analysis, chemical transformations and comparison of their NMR data with those published for similar alkaloids. Three PAs were then tested for antifungal activity against Fusarium moniliforme, F. (Sheldon), F. oxysporum fs. lycopersici (Scheldt) and F. solani (Mart), no significant activity being observed. (author)

  9. Eremophilanes and Pyrrolizidine Alkaloids of Senecioneae Species

    OpenAIRE

    2014-01-01

    The chemical study of two species of the tribe Senecioneae afforded two eremophilanes and two pyrrolizidine alkaloids from Se - necio subauriculatus and four modified eremophilanes from Roldana oaxacana . The chemistry of these species is in accord with that re - ported for species of Senecio and Roldana studied so far, and therefore, with the already described for the tribe Senecioneae.

  10. Independent recruitment of a flavin-dependent monooxygenase for safe accumulation of sequestered pyrrolizidine alkaloids in grasshoppers and moths.

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    Linzhu Wang

    Full Text Available Several insect lineages have developed diverse strategies to sequester toxic pyrrolizidine alkaloids from food-plants for their own defense. Here, we show that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the holometabolous butterflies, an almost identical strategy evolved independently for safe accumulation of pyrrolizidine alkaloids. This strategy involves a pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to their respective N-oxide, enabling the insects to avoid high concentrations of toxic pyrrolizidine alkaloids in the hemolymph. We have identified a pyrrolizidine alkaloid N-oxygenase, which is a flavin-dependent monooxygenase, of the grasshopper Zonocerus variegatus. After heterologous expression in E. coli, this enzyme shows high specificity for pyrrolizidine alkaloids of various structural types and for the tropane alkaloid atropine as substrates, a property that has been described previously for a pyrrolizidine alkaloid N-oxygenase of the arctiid moth Grammia geneura. Phylogenetic analyses of insect flavin-dependent monooxygenase sequences suggest that independent gene duplication events preceded the establishment of this specific enzyme in the lineages of the grasshoppers and of arctiid moths. Two further flavin-dependent monooxygenase sequences have been identified from Z. variegatus sharing amino acid identities of approximately 78% to the pyrrolizidine alkaloid N-oxygenase. After heterologous expression, both enzymes are also able to catalyze the N-oxygenation of pyrrolizidine alkaloids, albeit with a 400-fold lower specific activity. With respect to the high sequence identity between the three Z. variegatus sequences this ability to N-oxygenize pyrrolizidine alkaloids is interpreted as a relict of a former bifunctional ancestor gene of which one of the gene copies optimized this activity for the specific adaptation to pyrrolizidine alkaloid containing food plants.

  11. Independent recruitment of a flavin-dependent monooxygenase for safe accumulation of sequestered pyrrolizidine alkaloids in grasshoppers and moths.

    Science.gov (United States)

    Wang, Linzhu; Beuerle, Till; Timbilla, James; Ober, Dietrich

    2012-01-01

    Several insect lineages have developed diverse strategies to sequester toxic pyrrolizidine alkaloids from food-plants for their own defense. Here, we show that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the holometabolous butterflies, an almost identical strategy evolved independently for safe accumulation of pyrrolizidine alkaloids. This strategy involves a pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to their respective N-oxide, enabling the insects to avoid high concentrations of toxic pyrrolizidine alkaloids in the hemolymph. We have identified a pyrrolizidine alkaloid N-oxygenase, which is a flavin-dependent monooxygenase, of the grasshopper Zonocerus variegatus. After heterologous expression in E. coli, this enzyme shows high specificity for pyrrolizidine alkaloids of various structural types and for the tropane alkaloid atropine as substrates, a property that has been described previously for a pyrrolizidine alkaloid N-oxygenase of the arctiid moth Grammia geneura. Phylogenetic analyses of insect flavin-dependent monooxygenase sequences suggest that independent gene duplication events preceded the establishment of this specific enzyme in the lineages of the grasshoppers and of arctiid moths. Two further flavin-dependent monooxygenase sequences have been identified from Z. variegatus sharing amino acid identities of approximately 78% to the pyrrolizidine alkaloid N-oxygenase. After heterologous expression, both enzymes are also able to catalyze the N-oxygenation of pyrrolizidine alkaloids, albeit with a 400-fold lower specific activity. With respect to the high sequence identity between the three Z. variegatus sequences this ability to N-oxygenize pyrrolizidine alkaloids is interpreted as a relict of a former bifunctional ancestor gene of which one of the gene copies optimized this activity for the specific adaptation to pyrrolizidine alkaloid containing food plants.

  12. Pyrrolizidine alkaloids and diterpenes from Villasenoria orcuttii

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    Arciniegas, Amira; Perez-Castorena, Ana L.; Gonzalez, Karina; Vivar, Alfonso Romo de, E-mail: alperezc@unam.mx [Instituto de Quimica, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, Coyoacan, DF (Mexico); Reyes-Lezama, Marisol [Centro Conjunto de Investigacion en Quimica Sustentable, Universidad Autonoma del Estado de Mexico-Universidad Nacional Autonoma de Mexico (UAEM-UNAM), Carretera Toluca-Atlacomulco, Estado de Mexico (Mexico); Villasenor, Jose Luis [Instituto de Biologia, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, Coyoacan, DF, (Mexico)

    2013-07-15

    The chemical study of Villasenoria orcuttii, the only species of the genus Villasenoria, afforded three acyclic diterpenes, two of them described for the first time. Two pyrrolizidine alkaloids, florosenine and floridanine, among other known compounds were also isolated. The absolute configuration of floridanine was determined by X-ray analysis using anomalous dispersion with Cu K{sub {alpha}} radiation, and its {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) data were corrected. (author)

  13. Pyrrolizidine Alkaloids from Onosmakaheirei Teppner (Boraginaceae

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    Ioanna Maria Orfanou

    2016-03-01

    Full Text Available The new pyrrolizidine alkaloid (PA 3΄-O-acetylechinatine N-oxide (7, along with two more known PAs (5, 6, two known flavonoids (3, 4, one known alkannin (1, two known triterpenoids, one known sterol, and allantoin (2 were isolated from the aerial parts of Onosma kaheirei. In addition, the retention indeces of the reduced PAs 6 and 7 were determined in a DB-5 WCOT column, to aid their detection by GC/MS in the future.

  14. Effects of antibacterial agents on in vitro ovine ruminal biotransformation of the hepatotoxic pyrrolizidine alkaloid jacobine.

    OpenAIRE

    1992-01-01

    Ingestion of pyrrolizidine alkaloids, naturally occurring plant toxins, causes illness and death in a number of animal species. Senecio jacobaea pyrrolizidine alkaloids cause significant economic losses due to livestock poisoning, particularly in the Pacific Northwest. Some sheep are resistant to pyrrolizidine alkaloid poisoning, because ovine ruminal biotransformation detoxifies free pyrrolizidine alkaloids in digesta. Antibacterial agents modify ruminal fermentation. Pretreatment with antib...

  15. Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis.

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    Luckert, Claudia; Hessel, Stefanie; Lenze, Dido; Lampen, Alfonso

    2015-10-01

    1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 μM of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a |fold change| of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NFκB and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPARα/γ/δ were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure.

  16. [Advance on pharmacologic actions, toxicity and pharmacokinetics of pyrrolizidine alkaloids].

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    Gao, Jiangguo; Wang, Changhong; Li, Yan; Wang, Zhengtao

    2009-03-01

    Plants containing pyrrolizidine alkaloids were widely used in traditional medicine. Its hepatotoxicity is main toxicity as well known internationally. In order to providing some foundation for the future studies, the advancement on the pharmacologic actions, toxicity, and pharmacokinetics or toxicokinetics of pyrrolizidine alkaloids was reviewed.

  17. TOXIC PYRROLIZIDINE ALKALOIDS OF ECHIUM AMOENUM FISCH. & MEY.

    OpenAIRE

    2006-01-01

    Toxic pyrrolizidine alkaloids are present in some species of Echium (Boraginaceae). In this study petals of Echium amoenum Fisch. & Mey. (Gol-e-Gavzaban) as a popular herbal medicine in Iran, were investigated for pyrrolizidine alkaloids (PAs). The alkaloids were separated and purified by preparative TLC and characterized by IR, one and two dimensional 1H and 13C-NMR and Mass spectroscopy. Four toxic alkaloids namely: echimidine I, echimidine isomer II, 7-angeloyl retronecine III and 7-ti...

  18. Genotoxic and tumorigenic pyrrolizidine alkaloids in Chinese herbal plants

    Institute of Scientific and Technical Information of China (English)

    P.P. Fu; Q. Xia; M.W. Chou; G. Lin

    2005-01-01

    Pyrrolizidine alkaloids are a class of hepatotoxic and tumorigenic compounds detected in Chinese herbal plants,contaminated foods, and dietary supplements. In this review, the sources, toxicity, genotoxicity, tumorigenicity, and the metabolic pathways,particular the activation pathways leading to hepatotoxicity and tumorigenicity, of pyrrolizidine alkaloids are briefly discussed, with a focus on the most recent important findings concerning the genotoxic mechanism by which riddelliine liver tumors. This mechanism involves the formation of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and may be general to most carcinogenic pyrrolizidine alkaloids.

  19. Pyrrolizidine alkaloids in honey: comparison of analytical methods

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    Kempf, M.; Wittig, M.; Reinhard, A.; Ohe, von der K.; Blacquière, T.; Raezke, K.P.; Michel, R.; Schreier, P.; Beuerle, T.

    2011-01-01

    Pyrrolizidine alkaloids (PAs) are a structurally diverse group of toxicologically relevant secondary plant metabolites. Currently, two analytical methods are used to determine PA content in honey. To achieve reasonably high sensitivity and selectivity, mass spectrometry detection is demanded. One me

  20. Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids

    DEFF Research Database (Denmark)

    Schimming, Olivia; Challinor, Victoria L; Tobias, Nicholas J;

    2015-01-01

    Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis...

  1. Activity of pyrrolizidine alkaloids against biofilm formation and Trichomonas vaginalis

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    Crotalaria genus belongs to the subfamily Papilionoideae comprising about 600 species spread throughout tropical, neotropical and subtropical regions. In this study, seeds of Crolatalaria pallida were used to the isolation of usaramine, a pyrrolizidine alkaloid. Thus, Pseudomonas aeruginosa and Stap...

  2. Detection and quantification of pyrrolizidine alkaloids in antibacterial medical honeys.

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    Cramer, Luise; Beuerle, Till

    2012-12-01

    In recent years, there has been an increasing interest in antibacterial honey for wound care ranging from minor abrasions and burns to leg ulcers and surgical wounds. On the other hand, several recent studies demonstrated that honey for human consumption was contaminated with natural occurring, plant derived pyrrolizidine alkaloids.1,2-Unsaturated pyrrolizidine alkaloids are a group of secondary plant metabolites that show developmental, hepato-, and geno-toxicity as well as carcinogenic effects in animal models and in in vitro test systems. Hence, it was of particular interest to analyze the pyrrolizidine alkaloid content of medical honeys intended for wound care.19 different medical honey samples and/or batches were analyzed by applying a recently established pyrrolizidine alkaloid sum parameter method. 1,2-Unsaturated pyrrolizidine alkaloids were converted into the common necin backbone structures and were analyzed and quantified by GC-MS in the selected ion monitoring mode.All but one medical honey analyzed were pyrrolizidine alkaloid positive. The results ranged from 10.6 µg retronecine equivalents per kg to 494.5 µg retronecine equivalents/kg medical honey. The average pyrrolizidine alkaloid content of all positive samples was 83.6 µg retronecine equivalents/kg medical honey (average of all samples was 79.3 µg retronecine equivalents/kg medical honey). The limit of detection was 2.0 µg retronecine equivalents/kg medical honey, while the limit of quantification was 6.0 µg retronecine equivalents/kg medical honey (S/N > 7/1).Based on the data presented here and considering the fact that medical honeys can be applied to open wounds, it seems reasonable to discuss the monitoring of 1,2-unsaturated pyrrolizidine alkaloids in honey intended for wound treatment.

  3. TOXIC PYRROLIZIDINE ALKALOIDS OF ECHIUM AMOENUM FISCH. & MEY.

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    MITRA MEHRABANI

    2006-06-01

    Full Text Available Toxic pyrrolizidine alkaloids are present in some species of Echium (Boraginaceae. In this study petals of Echium amoenum Fisch. & Mey. (Gol-e-Gavzaban as a popular herbal medicine in Iran, were investigated for pyrrolizidine alkaloids (PAs. The alkaloids were separated and purified by preparative TLC and characterized by IR, one and two dimensional 1H and 13C-NMR and Mass spectroscopy. Four toxic alkaloids namely: echimidine I, echimidine isomer II, 7-angeloyl retronecine III and 7-tigloyl retronecine IV were identified.

  4. Pyrrolizidine alkaloids from Bulgarian species of the genus Senecio

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    NADEZHDA KOSTOVA

    2006-12-01

    Full Text Available Nine Bulgarian species from the genus Senecio were studied phytochemically and/or by GC-MS analysis. Senecivernine-N-oxide was isolated and identified by spectral data for the first time. Different types of pyrrolizidine alkaloids were tested for cytotoxicity on murine lymphocytes. At a concentration of 100 µg/ml, the alkaloid retroisosenine showed immunosuppressive effect.

  5. Pyrrolizidine alkaloid-derived DNA adducts as a common biological biomarker of pyrrolizidine alkaloid-induced tumorigenicity.

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    Xia, Qingsu; Zhao, Yuewei; Von Tungeln, Linda S; Doerge, Daniel R; Lin, Ge; Cai, Lining; Fu, Peter P

    2013-09-16

    Pyrrolizidine alkaloid-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. The U.S. National Toxicology Program (NTP) classified riddelliine, a tumorigenic pyrrolizidine alkaloid, as "reasonably anticipated to be a human carcinogen" in the NTP 12th Report on Carcinogens in 2011. We previously determined that four DNA adducts were formed in rats dosed with riddelliine. The structures of the four DNA adducts were elucidated as (i) a pair of epimers of 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine adducts (termed as DHP-dG-3 and DHP-dG-4) as the predominant adducts; and (ii) a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl)dehydrosupinidine adducts (termed as DHP-dA-3 and DHP-dA-4 adducts). In this study, we selected a nontumorigenic pyrrolizidine alkaloid, platyphylliine, a pyrrolizidine alkaloid N-oxide, riddelliine N-oxide, and nine tumorigenic pyrrolizidine alkaloids (riddelliine, retrorsine, monocrotaline, lycopsamine, retronecine, lasiocarpine, heliotrine, clivorine, and senkirkine) for study in animals. Seven of the nine tumorigenic pyrrolizidine alkaloids, with the exception of lycopsamine and retronecine, are liver carcinogens. At 8-10 weeks of age, female F344 rats were orally gavaged for 3 consecutive days with 4.5 and 24 μmol/kg body weight test article in 0.5 mL of 10% DMSO in water. Twenty-four hours after the last dose, the rats were sacrificed, livers were removed, and liver DNA was isolated for DNA adduct analysis. DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts were formed in the liver of rats treated with the individual seven hepatocarcinogenic pyrrolizidine alkaloids and riddelliine N-oxide. These DNA adducts were not formed in the liver of rats administered retronecine, the nontumorigenic pyrrolizidine alkaloid, platyphylliine, or vehicle control. These results indicate that this set of DNA adducts, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, is a common biological biomarker of

  6. Pyrrolizidine alkaloids in honey and bee pollen.

    Science.gov (United States)

    Dübecke, A; Beckh, G; Lüllmann, C

    2011-03-01

    A total of 3917 honey samples and 119 'bee pollen' samples (pollen collected by honeybees) were analysed for pyrrolizidine alkaloids (PAs). Some 0.05 M sulphuric acid was used for extraction followed by a clean-up step by means of solid-phase extraction. Separation and detection was achieved by target analysis using an LC-MS/MS system. PAs were found in 66% of the raw honeys (bulk honey not yet packaged in containers for sale in retail outlets) and in 94% of honeys available in supermarkets (retail honey). A total of 60% of the bee pollen samples were PA positive. The PA pattern was used to identify the potential origin of the PAs in honey, which was verified for the genus Echium by relative pollen analysis. The results give an estimate of the impact of PA-containing plants belonging to the genera Echium, Senecio and, to a certain extent, Eupatorium on PA levels in honey and can serve as a decision basis for beekeepers in order to find the most suitable location for the production of honey and bee pollen low in PAs.

  7. Pyrrolizidine alkaloids from Heliotropium transoxanum Bunge

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    M. R. Delnavazi

    2016-02-01

    Full Text Available Background and objectives: The plants belonging to the genus Heliotropium L. (Boraginaceae are the main sources of toxic pyrrolizidine alkaloids (PAs. In the present study, we have investigated the PAs of the aerial parts of Heliotropium transoxanum Bunge, a perennial species native to Iran. Methods: Silica gel column chromatography and silica gel PTLC were applied for the isolation of PAs present in the total methanol extract of H. transoxanum. The structures of the isolated compounds were identified using 1H-NMR, 13C-NMR and EIMS spectral analyses. Results: Three PAs, heliotrine (1, lasiocarpine (2 and heliotrine N-oxide (3,with known mutagenic and genotoxic properties, were isolated from the aerial parts of H. transoxanum. Conclusion: The results of this study on the presence of toxic PAs in H. transoxanum introduce this herb as a poisonous species and also suggest it as an appropriate source for the isolation of heliotrine and lasiocarpine for further toxicological and pharmacological studies.

  8. Pyrrolizidine alkaloids from seven wild-growing Senecio species in Serbia and Montenegro

    OpenAIRE

    2009-01-01

    The genus Senecio (family Asteraceae) is one of the largest in the world. It comprises about 1100 species which are the rich source of pyrrolizidine alkaloids. Plants containing pyrrolizidine alkaloids are among the most important sources of human and animal exposure to plant toxins and carcinogens. The pyrrolizidine alkaloids of seven Senecio species (S. erucifolius, S. othonnae, S. wagneri, S. subalpinus, S. carpathicus, S. paludosus and S. rupestris) were studied. Fourteen alkaloids were i...

  9. Pyrrolizidine alkaloids in medicinal tea of Ageratum conyzoides

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    Cristiane F. Bosi

    2013-06-01

    Full Text Available It is now widely-recognized that the view that herbal remedies have no adverse effects and/or toxicity is incorrect; some traditionally-used plants can present toxicity. The well-established popular use of Ageratum conyzoides has led to its inclusion in a category of medicinal crude drugs created by the Brazilian Health Surveillance Agency. Ageratum belongs to the Eupatorieae tribe, Asteraceae, and is described as containing toxic pyrrolizidine alkaloids. Aqueous extracts of Ageratum conyzoides L. harvested in Brazil (commercial, flowering and non-flowering samples were prepared according to the prescribed method and analyzed by HPLC-HRMS. The pyrrolizidine alkaloids lycopsamine, dihydrolycopsamine, and acetyl-lycopsamine and their N-oxides, were detected in the analyzed extracts, lycopsamine and its N-oxide being known hepatotoxins and tumorigens. Together with the pyrrolizidine alkaloids identified by HPLC-HRMS, thirteen phenolic compounds were identified, notably, methoxylated flavonoids and chromenes. Toxicological studies on A. conyzoides are necessary, as is monitoring of its clinical use. To date, there are no established safety guidelines on pyrrolizidine alkaloids-containing plants, and their use in Brazil.

  10. Evolution through time of Pyrrolizidine Alkaloids detection and quantification

    OpenAIRE

    Monteiro-Silva, Filipe; González-Aguilar, Gerardo

    2013-01-01

    Pyrrolizidine Alkaloids (PAs) are a group of naturally occurring alkaloids that are produced by plants as a defense mechanism against insect herbivores. The analytical methodologies employed for their detection have come a long way since the first analytical experiment and in the last 30 years had an enormous development, both technological and experimental. It is notorious that before the generalization of certain technologies, especially in a post-war atmosphere, most scientific researches ...

  11. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

    OpenAIRE

    2002-01-01

    Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP)-derived DNA adduct formation. This mechanism may ...

  12. Independent Recruitment of a Flavin-Dependent Monooxygenase for Safe Accumulation of Sequestered Pyrrolizidine Alkaloids in Grasshoppers and Moths

    OpenAIRE

    2012-01-01

    Several insect lineages have developed diverse strategies to sequester toxic pyrrolizidine alkaloids from food-plants for their own defense. Here, we show that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the holometabolous butterflies, an almost identical strategy evolved independently for safe accumulation of pyrrolizidine alkaloids. This strategy involves a pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to their respective N-oxide,...

  13. Molekulare Identifizierung und Charakterisierung der Flavin-abhängigen Monooxygenasen in verschiedenen Pyrrolizidin-Alkaloid-adaptierten Insekten

    OpenAIRE

    2013-01-01

    Several insect lineages have developed diverse strategies to sequester toxic pyrrolizidine alkaloids from food-plants for their own defense. Here, we show that in two highly divergent insect taxa, the hemimetabolous grasshoppers and the holometabolous butterflies, an almost identical strategy evolved independently for safe accumulation of pyrrolizidine alkaloids. This strategy involves a pyrrolizidine alkaloid N-oxygenase that transfers the pyrrolizidine alkaloids to their respect...

  14. Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides.

    Science.gov (United States)

    He, Xiaobo; Xia, Qingsu; Woodling, Kellie; Lin, Ge; Fu, Peter P

    2017-10-01

    There are 660 pyrrolizidine alkaloids (PAs) and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation. Copyright © 2017. Published by Elsevier B.V.

  15. Acetylcholinesterase inhibitory activity of pyrrolizidine alkaloids from Echium confusum Coincy.

    Science.gov (United States)

    Benamar, Houari; Tomassini, Lamberto; Venditti, Alessandro; Marouf, Abderrazak; Bennaceur, Malika; Serafini, Mauro; Nicoletti, Marcello

    2017-06-01

    Four pyrrolizidine alkaloids, namely 7-O-angeloyllycopsamine N-oxide 1, echimidine N-oxide 2, echimidine 3 and 7-O-angeloylretronecine 4, were isolated for the first time from the whole plant ethanolic extract of Echium confusum Coincy, through bioassay-guided approach. Their structures were determined by spectroscopic means. All the isolates compounds showed moderate activities in inhibiting AChE, with IC50 0.276-0.769.

  16. Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids.

    Science.gov (United States)

    Schimming, Olivia; Challinor, Victoria L; Tobias, Nicholas J; Adihou, Hélène; Grün, Peter; Pöschel, Laura; Richter, Christian; Schwalbe, Harald; Bode, Helge B

    2015-10-19

    Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non-ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram-negative and Gram-positive bacteria indicates an important biological function in bacteria.

  17. Soil-borne microorganisms and soil-type affect pyrrolizidine alkaloids in Jacobaea vulgaris

    NARCIS (Netherlands)

    Joosten, L.; Mulder, P.P.J.; Klinkhamer, P.G.L.; Veen, van J.A.

    2009-01-01

    Secondary metabolites like pyrrolizidine alkaloids (PAs) play a crucial part in plant defense. We studied the effects of soil-borne microorganisms and soil-type on pyrrolizidine alkaloids in roots and shoots of Jacobaea vulgaris. We used clones of two genotypes from a dune area (Meijendel), propagat

  18. Soil-borne microorganisms and soil-type affect pyrrolizidine alkaloids in Jacobaea vulgaris

    NARCIS (Netherlands)

    Joosten, L.; Mulder, P.P.J.; Klinkhamer, P.G.L.; Veen, van J.A.

    2009-01-01

    Secondary metabolites like pyrrolizidine alkaloids (PAs) play a crucial part in plant defense. We studied the effects of soil-borne microorganisms and soil-type on pyrrolizidine alkaloids in roots and shoots of Jacobaea vulgaris. We used clones of two genotypes from a dune area (Meijendel),

  19. Carry-over of pyrrolizidine alkaloids from feed to milk in dairy cows

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.; Mulder, P.P.J.; Zeilmaker, M.J.; Top, van den H.J.; Remmelink, G.J.; Brandon, E.A.; Klijnstra, M.; Meijer, G.A.L.; Schothorst, R.; Egmond, van H.J.

    2011-01-01

    Pyrrolizidine alkaloids are toxins present in many plants belonging to the families of Asteraceae, Boraginaceae and Fabaceae. Particularly notorious are pyrrolizidine alkaloids present in ragwort species (Senecio), which are held responsible for hepatic disease in horses and cows and may lead to the

  20. Recognition of pyrrolizidine alkaloid esters in the invasive aquatic plant Gymnocoronis spilanthoides (Asteraceae)

    Science.gov (United States)

    Introduction – The freshwater aquatic plant Gymnocoronis spilanthoides (Senegal tea plant, jazmín del bañado, Falscher Wasserfreund) is an invasive plant in many countries. Behavioural observations of pyrrolizidine alkaloid-pharmacophagous butterflies suggested the presence of pyrrolizidine alkaloid...

  1. Mass-spectrometry-directed analysis and purification of pyrrolizidine alkaloid cis/trans isomers in Gynura japonica.

    Science.gov (United States)

    Fang, Lianxiang; Xiong, Aizhen; Yang, Xiao; Cheng, Wenzhi; Yang, Li; Wang, Zhengtao

    2014-08-01

    Pyrrolizidine alkaloids are highly hepatotoxic natural chemicals that produce irreversible chronic and acute hepatotoxic effects on human beings. Purification of large amounts of pyrrolizidine alkaloids is necessary for toxicity studies. In this study, an efficient method for targeted analysis and purification of pyrrolizidine alkaloid cis/trans isomers from herbal materials was developed for the first time. Targeted analysis of the hepatotoxic pyrrolizidine alkaloids was performed by liquid chromatography with tandem mass spectrometry (precursor ion scan and daughter ion scan), and the purification of pyrrolizidine alkaloids was achieved with a mass-directed auto purification system. The extraction and preparative liquid chromatography conditions were optimized. The developed method was applied to analysis of Gynura japonica (Thunb.) Juel., a herbal medicine traditionally used for detumescence and relieving pain but is potentially hepatotoxic as it contains pyrrolizidine alkaloids. Twelve pyrrolizidine alkaloids (six cis/trans isomer pairs) were identified with reference compounds or characterized by liquid chromatography with tandem mass spectrometry, and five individual pyrrolizidine alkaloids, including (E)-seneciphylline, seneciphylline, integerrimine, senecionine, and seneciphyllinine, were prepared from G. japonica roots with high efficiency. The results of this work provide a new technique for the preparation of large amounts of pyrrolizidine alkaloid reference substances, which will also benefit toxicological studies of pyrrolizidine alkaloids and treatments for pyrrolizidine alkaloid-induced toxicity.

  2. Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties

    Directory of Open Access Journals (Sweden)

    Assem El-Shazly

    2014-04-01

    Full Text Available Among the diversity of secondary metabolites which are produced by plants as means of defence against herbivores and microbes, pyrrolizidine alkaloids (PAs are common in Boraginaceae, Asteraceae and some other plant families. Pyrrolizidine alkaloids are infamous as toxic compounds which can alkylate DNA und thus cause mutations and even cancer in herbivores and humans. Almost all genera of the family Boraginaceae synthesize and store this type of alkaloids. This review reports the available information on the present status (literature up to early 2014 of the pyrrolizidine alkaloids in the Boraginaceae and summarizes the topics structure, distribution, chemistry, chemotaxonomic significance, and biological properties.

  3. Pyrrolizidine alkaloids from seven wild-growing Senecio species in Serbia and Montenegro

    Directory of Open Access Journals (Sweden)

    BORIS M. MANDIC

    2009-01-01

    Full Text Available The genus Senecio (family Asteraceae is one of the largest in the world. It comprises about 1100 species which are the rich source of pyrrolizidine alkaloids. Plants containing pyrrolizidine alkaloids are among the most important sources of human and animal exposure to plant toxins and carcinogens. The pyrrolizidine alkaloids of seven Senecio species (S. erucifolius, S. othonnae, S. wagneri, S. subalpinus, S. carpathicus, S. paludosus and S. rupestris were studied. Fourteen alkaloids were isolated and their structures determined from spectroscopic data (1H- and 13C-NMR, IR and MS. Five of them were identified in S. erucifolius, four in S. othonnae, two in S. wagneri, four in S. subalpinus, two in S. carpathicus, three in S. paludosus and three in S. rupestris. Seven pyrrolizidine alkaloids were found for the first time in particular species. The results have chemotaxonomic importance. The cytotoxic activity and antimicrobial activity of some alkaloids were also studied.

  4. Phytotoxicity Assessment of Certain Phytochemical Products Containing Pyrrolizidine Alkaloids

    Directory of Open Access Journals (Sweden)

    Cristina Șeremet Oana

    2013-10-01

    Full Text Available Introduction: Tussilago farfara (coltsfoot, Petasites hybridus (common butterbur, Senecio vernalis (eastern groundsel and Symphytum officinale (comfrey are species traditionally used in phytotherapy that besides the therapeutic compounds contain toxic pyrrolizidine alkaloids (PAs. The aim of the paper is to determine the total PAs content and the phytotoxicity of the above species. Material and methods: The quantitative determination of pyrrolizidine alkaloids is based on the stoichiometric reaction of protonated alkaloids with methyl orange. In acidic conditions the dye is released from the complex and its color is assessed spectrophotometrically using a linear regression curve of senecionine as a standard. The phytotoxicity was assessed by Triticum bioassay that studies the effect of the extracts (0.001-5.00%, w/v upon root elongation (inhibitory concentration - IC50 and on the karyokinetic film. Results: The highest amount of total PAs was found in Senecio vernalis (654.8 ± 35.96 μg/g dry plant and the lowest in Petasites hybridus. The lowest IC50 was found for Tussilago farfara followed by Petasites hybridus, Senecio vernalis, and Symphytum officinale. The results were supported by microscopic examination. Conclusions: The results of the spectrophotometric assay are consistent with the ones found in the literature. All extracts inhibited the elongation of the main root of wheat caryopses, however, no correlation between phytotoxicity and the PAs concentration could be emphasized

  5. Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties

    OpenAIRE

    2014-01-01

    Among the diversity of secondary metabolites which are produced by plants as means of defence against herbivores and microbes, pyrrolizidine alkaloids (PAs) are common in Boraginaceae, Asteraceae and some other plant families. Pyrrolizidine alkaloids are infamous as toxic compounds which can alkylate DNA und thus cause mutations and even cancer in herbivores and humans. Almost all genera of the family Boraginaceae synthesize and store this type of alkaloids. This review reports the available ...

  6. Carry-over of pyrrolizidine alkaloids from feed to milk in dairy cows.

    Science.gov (United States)

    Hoogenboom, L A P; Mulder, P P J; Zeilmaker, M J; van den Top, H J; Remmelink, G J; Brandon, E F A; Klijnstra, M; Meijer, G A L; Schothorst, R; Van Egmond, H P

    2011-03-01

    Pyrrolizidine alkaloids are toxins present in many plants belonging to the families of Asteraceae, Boraginaceae and Fabaceae. Particularly notorious are pyrrolizidine alkaloids present in ragwort species (Senecio), which are held responsible for hepatic disease in horses and cows and may lead to the death of the affected animals. In addition, these compounds may be transferred to edible products of animal origin and as such be a threat for the health of consumers. To investigate the possible transfer of pyrrolizidine alkaloids from contaminated feed to milk, cows were put on a ration for 3 weeks with increasing amounts (50-200 g day(-1)) of dried ragwort. Milk was collected and sampled twice a day; faeces and urine twice a week. For milk, a dose-related appearance of pyrrolizidine alkaloids was found. Jacoline was the major component in milk despite being a minor component in the ragwort material. Practically no N-oxides were observed in milk, notwithstanding the fact that they constituted over 80% of the pyrrolizidine alkaloids in ragwort. The overall carry-over of the pyrrolizidine alkaloids was estimated to be only around 0.1%, but for jacoline 4%. Notwithstanding the low overall carry-over, this may be relevant for consumer health considering the genotoxic and carcinogenic properties demonstrated for some of these compounds. Analysis of the faeces and urine samples indicated that substantial metabolism of pyrrolizidine alkaloids is taking place. The toxicity and potential transfer of metabolites to milk is unknown and remains to be investigated.

  7. Pyrrolizidine alkaloids in food and feed on the Belgian market.

    Science.gov (United States)

    Huybrechts, Bart; Callebaut, Alfons

    2015-01-01

    Pyrrolizidine alkaloids (PAs) are widely distributed plant toxins with species dependent hepatotoxic, carcinogenic, genotoxic and pneumotoxic risks. In a recent European Food Safety Authority (EFSA) opinion, only two data sets from one European country were received for honey, while one feed data set was included. No data are available for food or feed samples from the Belgian market. We developed an LC-MS/MS method, which allowed the detection and quantification of 16 PAs in a broad range of matrices in the sub ng g(-1) range. The method was validated in milk, honey and hay and applied to honey, tea (Camellia sinensis), scented tea, herbal tea, milk and feed samples bought on the Belgian market. The results confirmed that tea, scented tea, herbal tea and honey are important food sources of pyrrolizidine alkaloid contamination in Belgium. Furthermore, we detected PAs in 4 of 63 commercial milk samples. A high incidence rate of PAs in lucerne (alfalfa)-based horse feed and in rabbit feed was detected, while bird feed samples were less contaminated. We report for the first time the presence of monocrotaline, intermedine, lycopsamine, heliotrine and echimidine in cat food.

  8. A concise route to pyrrolizidine alkaloids bearing the 1,2-amino alcohol functionality

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, C.; Aizpurua, J.M.; Roman, P.; Luque, A.; Martinez-Ripoll, M. [Facultad de Quimica, Departamento de Quimica Organica, Universidad del Pais Vascom San Sebastian (Spain)

    1996-10-01

    The first entry to optically pure 4-amino-3-hydroxy-pyrrolizidine and 4-amino-pyrrolizidine alkaloid frameworks is provided by a highly diastereoselective [2+2] cycloaddition of alkoxyketenes to N-Boc-prolinal imines as the key reaction.

  9. The analysis of pyrrolizidine alkaloids in Jacobaea vulgaris; a comparison of extraction and detection methods

    NARCIS (Netherlands)

    Joosten, L.; Mulder, P.P.J.; Vrieling, K.; Van Veen, J.A.; Klinkhamer, P.G.L.

    2010-01-01

    Introduction - Pyrrolizidine alkaloids (PAs) serve an important function in plant defence. Objective - To compare different extraction methods and detection techniques, namely gas chromatography with nitrogen phosphorus detection (GC-NPD) and liquid chromatography tandem mass spectrometry (LC-MS/MS)

  10. New records of pyrrolizidine alkaloid-feeding insects. Hemiptera and Coleoptera on Senecio brasiliensis.

    Science.gov (United States)

    Klitzke; Trigo

    2000-04-01

    New records are reported for a Hemipteran (Largus rufipennis) and a Coleopteran (Chauliognathus fallax) feeding on Senecio brasiliensis (Asteraceae) and sequestering pyrrolizidine alkaloids (PAs). Both insects are warningly colored and rejected by predators.

  11. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2002-09-01

    Full Text Available Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP-derived DNA adduct formation. This mechanism may be general to most carcinogenic pyrrolizidine alkaloids, including the retronecine-, heliotridine-, and otonecinetype pyrrolizidine alkaloids. It is hypothesized that these DHP-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. The mechanisms that involve the formation of DNA cross-linking and endogenous DNA adducts are also discussed.

  12. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    Energy Technology Data Exchange (ETDEWEB)

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D. (Univ. of Texas Health Science Center, San Antonio (USA))

    1989-03-07

    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the {alpha}-glucosidase amyloglucosidase (50% inhibition at 5.8 {mu}M), but it did not inhibit {beta}-glucosidase, {alpha}- or {beta}-mannosidase, or {alpha}- or {beta}-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc{sub 3}Man{sub 7-9}(GlcNAc){sub 2}-oligosaccharides.

  13. [Pyrrolizidine alkaloids and seneciosis in farm animals. Part 1: occurrence, chemistry and toxicology].

    Science.gov (United States)

    Petzinger, E

    2011-01-01

    Pyrrolizidine alkaloids belong to a class of phytotoxins which are present in more than 6000 plant species. The disease seneciosis in farm animals represents the severe poisoning by pyrrolizidine alkaloids from plants of the genus Senecio. This form of poisoning has been known since the end of the 19th century in Germany, the USA, Canada and New Zealand, and is mainly caused by Senecio jacobaea and related Senecio spp. in farm animals, including poultry. Animal poisoning by pyrrolizidine alkaloids is of worldwide importance. In Germany poisoning of horses and cattle by Senecio jacobaea, which was earlier named Schweinsberg disease, is of renewed relevance for veterinary medicine. The disease occurs almost entirely as a consequence of chronic poisoning and in general ends fatally. The ultimate cause is the formation of toxic metabolites of pyrrolizidine alkaloids in the liver, and their covalent binding to nucleic acids and proteins leading to liver cirrhosis. Because many pyrrolizidine alkaloids possess mutagenic, and a few also carcinogenic properties, European and international authorities are concerned about possible residue levels in food of animal origin. The review addresses in its first part several aspects, being the occurrence, the chemistry, and the toxicology of pyrrolizidine alkaloids as well as animal intoxications by poisonous plants. In the second part (46) clinical characteristics of animal seneciosis, the therapeutic interventions, the significant species differences and a critical assessment of so-called nontoxic amounts of Senecio plants in animal fodder with reference to cumulative lethal toxin doses are presented.

  14. Pyrrolizidine alkaloids in medicinal plants from North America.

    Science.gov (United States)

    Roeder, E; Wiedenfeld, H; Edgar, J A

    2015-06-01

    Pyrrolizidine alkaloids (PAs) are mutagenic, carcinogenic, pneumotoxic, teratogenic and fetotoxic. Plants containing PAs commonly poison livestock in many countries, including the USA and Canada. In some regions of the world PA-producing plants sometimes grow in grain crops and items of food made with PA contaminated grain, such as bread baked using contaminated flour, have been, and continue to be, responsible for large incidents of acute, often fatal human poisoning. Herbal medicines and food supplements containing PAs are also recognized as a significant cause of human poisoning and it is desirable that such medications are identified and subjected to strict regulation. In this review we consider the PAs known to be, or likely to be, present in both the traditionally used medicinal plants of North America and also medicinal plants that have been introduced from other countries and are being recommended and used as phytopharmaceuticals in the USA and Canada.

  15. Determination of pyrrolizidine alkaloids in tea, herbal drugs and honey.

    Science.gov (United States)

    Bodi, Dorina; Ronczka, Stefan; Gottschalk, Christoph; Behr, Nastassja; Skibba, Anne; Wagner, Matthias; Lahrssen-Wiederholt, Monika; Preiss-Weigert, Angelika; These, Anja

    2014-01-01

    Honey was previously considered to be one of the main food sources of human pyrrolizidine alkaloid (PA) exposure in Europe. However, comprehensive analyses of honey and tea sampled in the Berlin retail market revealed unexpected high PA amounts in teas. This study comprised the analysis of 87 honey as well as 274 tea samples including black, green, rooibos, melissa, peppermint, chamomile, fennel, nettle, and mixed herbal tea or fruit tea. Total PA concentrations in tea ranged from < LOD to 5647 µg kg(-1), while a mean value of about 10 µg kg(-1) was found in honey samples. Additionally, herbal drugs were investigated to identify the source of PA in teas. Results suggest that PA in tea samples are most likely a contamination caused by co-harvesting of PA-producing plants. In some cases such as fennel, anise or caraway, it cannot be excluded that these plants are able to produce PA themselves.

  16. Pyrrolizidine alkaloids in the food chain: development, validation, and application of a new HPLC-ESI-MS/MS sum parameter method.

    Science.gov (United States)

    Cramer, Luise; Schiebel, Hans-Martin; Ernst, Ludger; Beuerle, Till

    2013-11-27

    Contamination of food and feed with pyrrolizidine alkaloids is currently discussed as a potential health risk. Here, we report the development of a new HPLC-ESI-MS/MS sum parameter method to quantitate the pyrrolizidine alkaloid content in complex food matrices. The procedure was validated for honey and culinary herbs. Isotopically labeled 7-O-9-O-dibutyroyl-[9,9-(2)H2]-retronecine was synthesized and utilized as an internal standard for validation and quantitation. The total pyrrolizidine alkaloid content of a sample is expressed as a single sum parameter: retronecine equivalents (RE). Ld/Lq for honey was 0.1 μg RE/kg/0.3 μg RE/kg. For culinary herbs, 1.0 μg RE/kg/3.0 μg RE/kg (dry weight, dw) and 0.1 μg RE/kg/0.3 μg RE/kg (fresh weight, fw) were determined, respectively. The new method was applied to analyze 21 herbal convenience products. Fifteen products (71%) were pyrrolizidine alkaloid positive showing pyrrolizidine alkaloid concentrations ranging from 0.9 to 74 μg RE/kg fw.

  17. Changes in plant defense chemistry (pyrrolizidine alkaloids) revealed through high-resolution spectroscopy

    Science.gov (United States)

    Carvalho, Sabrina; Macel, Mirka; Schlerf, Martin; Moghaddam, Fatemeh Eghbali; Mulder, Patrick P. J.; Skidmore, Andrew K.; van der Putten, Wim H.

    2013-06-01

    Plant toxic biochemicals play an important role in defense against natural enemies and often are toxic to humans and livestock. Hyperspectral reflectance is an established method for primary chemical detection and could be further used to determine plant toxicity in the field. In order to make a first step for pyrrolizidine alkaloids detection (toxic defense compound against mammals and many insects) we studied how such spectral data can estimate plant defense chemistry under controlled conditions. In a greenhouse, we grew three related plant species that defend against generalist herbivores through pyrrolizidine alkaloids: Jacobaea vulgaris, Jacobaea erucifolia and Senecio inaequidens, and analyzed the relation between spectral measurements and chemical concentrations using multivariate statistics. Nutrient addition enhanced tertiary-amine pyrrolizidine alkaloids contents of J. vulgaris and J. erucifolia and decreased N-oxide contents in S. inaequidens and J. vulgaris. Pyrrolizidine alkaloids could be predicted with a moderate accuracy. Pyrrolizidine alkaloid forms tertiary-amines and epoxides were predicted with 63% and 56% of the variation explained, respectively. The most relevant spectral regions selected for prediction were associated with electron transitions and Csbnd H, Osbnd H, and Nsbnd H bonds in the 1530 and 2100 nm regions. Given the relatively low concentration in pyrrolizidine alkaloids concentration (in the order of mg g-1) and resultant predictions, it is promising that pyrrolizidine alkaloids interact with incident light. Further studies should be considered to determine if such a non-destructive method may predict changes in PA concentration in relation to plant natural enemies. Spectroscopy may be used to study plant defenses in intact plant tissues, and may provide managers of toxic plants, food industry and multitrophic-interaction researchers with faster and larger monitoring possibilities.

  18. Livestock Poisoning with Pyrrolizidine Alkaloid Containing Plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium and Echium spp.)

    Science.gov (United States)

    Pyrrolizidine alkaloids (PAs) are potent liver toxins that have been identified in over 6,000 plants throughout the world. Alkaloids are nitrogen-based compounds with potent biological activity. About half of the identified PAs are toxic and several cause cancer (carcinogenic). PA-containing plants...

  19. Evolutionary recruitment of a flavin-dependent monooxygenase for stabilization of sequestered pyrrolizidine alkaloids in arctiids.

    Science.gov (United States)

    Langel, Dorothee; Ober, Dietrich

    2011-09-01

    Pyrrolizidine alkaloids are secondary metabolites that are produced by certain plants as a chemical defense against herbivores. They represent a promising system to study the evolution of pathways in plant secondary metabolism. Recently, a specific gene of this pathway has been shown to have originated by duplication of a gene involved in primary metabolism followed by diversification and optimization for its specific function in the defense machinery of these plants. Furthermore, pyrrolizidine alkaloids are one of the best-studied examples of a plant defense system that has been recruited by several insect lineages for their own chemical defense. In each case, this recruitment requires sophisticated mechanisms of adaptations, e.g., efficient excretion, transport, suppression of toxification, or detoxification. In this review, we briefly summarize detoxification mechanism known for pyrrolizidine alkaloids and focus on pyrrolizidine alkaloid N-oxidation as one of the mechanisms allowing insects to accumulate the sequestered toxins in an inactivated protoxic form. Recent research into the evolution of pyrrolizidine alkaloid N-oxygenases of adapted arctiid moths (Lepidoptera) has shown that this enzyme originated by the duplication of a gene encoding a flavin-dependent monooxygenase of unknown function early in the arctiid lineage. The available data suggest several similarities in the molecular evolution of this adaptation strategy of insects to the mechanisms described previously for the evolution of the respective pathway in plants.

  20. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

    Science.gov (United States)

    Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

    2016-03-07

    Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  1. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

    Directory of Open Access Journals (Sweden)

    Xinmiao Yan

    2016-03-01

    Full Text Available Pyrrolizidine Alkaloids (PAs are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1 and glutathione peroxidase 1 (GPX1 targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  2. Soil-borne microorganisms and soil-type affect pyrrolizidine alkaloids in Jacobaea vulgaris

    OpenAIRE

    2009-01-01

    Secondary metabolites like pyrrolizidine alkaloids (PAs) play a crucial part in plant defense. We studied the effects of soil-borne microorganisms and soil-type on pyrrolizidine alkaloids in roots and shoots of Jacobaea vulgaris. We used clones of two genotypes from a dune area (Meijendel), propagated by tissue culture and grown on two sterilized soils and sterilized soils inoculated with 5% of non-sterilized soil of either of the two soil-types. Soil-borne microorganisms and soil-type affect...

  3. Pyrrolizidine Alkaloids in Adenostyles alliariae and A. glabra from the Austrian Alps.

    Science.gov (United States)

    Chizzola, Remigius

    2015-07-01

    The alkaloid content of Adenostyles alliariae and A. glabra (Asteraceae) has been evaluated. Both species contain toxic macrocyclic unsaturated pyrrolizidine alkaloids with seneciphylline as the main compound accounting for more than 90% of the alkaloid fraction in all above ground plant parts. Further alkaloids were spartioidine, acetyl-senciphylline and senecionine. Inflorescences showed the highest alkaloid contents with 21.1 and 13.4 mg/g in A. alliariae and A. glabra, respectively. Stems and leaves had 2-3 times lower contents. Therefore, these Adenostyles species must be considered as highly toxic plants.

  4. Pyrrolizidine alkaloids in herbal teas for infants, pregnant or lactating women.

    Science.gov (United States)

    Mädge, Inga; Cramer, Luise; Rahaus, Ines; Jerz, Gerold; Winterhalter, Peter; Beuerle, Till

    2015-11-15

    A general contamination of tea with pyrrolizidine alkaloids (PA) has just become known. Here, we report the application and modification of a new HPLC-ESI-MS/MS sum parameter method to quantitate PA content of herbal teas intended for infants, pregnant and lactating women. Using p-toluenesulfonyl isocyanate for derivatization and a stable isotope labeled internal standard, the total retronecine-/heliotridine-type PA content of the samples is expressed in form of a single sum parameter (retronecine equivalents: RE). The new methods were applied to analyze 44 tea samples for such consumer groups. Thirty eight products (86%) were tested PA positive showing PA concentrations ranging from 0 to 391 μg RE/kg (average: 50 μg RE/kg). The dataset is discussed in the view of the current discussion on PA in the food chain with special focus on those particular vulnerable consumer groups.

  5. Effect of certain elicitors on production of pyrrolizidine alkaloids in hairy root cultures of Echium rauwolfii.

    Science.gov (United States)

    Abd El-Mawla, A M A

    2010-03-01

    Hairy root cultures of Echium rauwolfii were obtained by infection of sterile apical shoots with Agrobacterium rhizogenes. The linear increase in fresh weight was found to be parallel to the alkaloids production. The transformed cultures were exposed to different elicitors, such as methyl jasmonate (MJ), quercetin and salicylic acid in order to increase their productivity. Pyrrolizidine alkaloids were quantitatively determined by HPLC. Estimation of total alkaloids was achieved by peak area calculations. MJ at a concentration of 100 microM induced the accumulation of total alkaloids about 19-fold compared to the untreated control. The flavonoid quercetin (Q) at a concentration of 50 microM enhanced the pyrrolizidine accumulation approximately 6-fold. The induction effect of both MJ and Q can be suppressed by pre-incubation of hairy root cultures with salicylic acid.

  6. Inter-laboratory comparison study for pyrrolizidine alkaloids in animal feed using spiked and incurred material

    NARCIS (Netherlands)

    Nijs, de W.C.M.; Elbers, I.J.W.; Mulder, P.P.J.

    2014-01-01

    Pyrrolizidine alkaloids (PAs) are hepatotoxic metabolites produced by plants. PAs in animal feed can cause acute or chronic intoxications in animals and can be transferred to milk. An inter-laboratory comparison study among 12 laboratories, using their own methods of analysis, was conducted for the

  7. Pyrrolizidine alkaloid-containing toxic plants (Scenecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.)

    Science.gov (United States)

    Pyrrolizidine alkaloid (PA) containing plants are found throughout the world and are probably the most common plant cause of poisoning of livestock, wildlife and humans. PAs are potent liver toxins that under some conditions can be carcinogenic. The objective of this paper is to briefly introduce hi...

  8. Pyrrolizidine alkaloid variation in Jacobaea plants : from plant organ to cell level

    NARCIS (Netherlands)

    Nuringtyas, Tri Rini

    2013-01-01

    The aim of this thesis is to understand the diversity of pyrrolizidine alkaloids (PAs) in Jacobaea plants with respect to their spatial distribution and its consequences for generalist insects. Chapter 2 reports on the role of endophytes in the production of PAs in Jacobaea. Plants were treated with

  9. Anti-inflammatory Activity of Pyrrolizidine Alkaloids from the Leaves of Madhuca pasquieri (Dubard).

    Science.gov (United States)

    Hoang, Le Son; Tran, Manh Hung; Lee, Joo Sang; To, Dao Cuong; Nguyen, Van Thu; Kim, Jeong Ah; Lee, Jeong Hyung; Woo, Mi Hee; Min, Byung Sun

    2015-01-01

    A novel pyrrolizidine alkaloids, madhumidine A (1), and two known alkaloids, lindelofidine benzoic acid ester (2) and minalobine B (3) were isolated from the leaves of Madhuca pasquieri (Dubard) H. J. LAM. The chemical structures of these alkaloids were established mainly by NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against lipopolysaccharide-induced nitric oxide production in macrophage RAW264.7 cell. In addition, the cytotoxic activity of all isolated compounds was tested against a panel of cancer cell lines.

  10. Sensitive determination of pyrrolizidine alkaloids in Tussilago farfara L. by field-amplified, sample-stacking, sweeping micellar electrokinetic chromatography.

    Science.gov (United States)

    Cao, Kun; Xu, Yi; Mu, Xiuni; Zhang, Qing; Wang, Renjie; Lv, Junjiang

    2016-11-01

    Pyrrolizidine alkaloids are the toxic components in Tussilago farfara L. Due to the lack of standard substances for quantitative analysis and traces of pyrrolizidine alkaloids in total alkaloids, the full quality control of Tussilago farfara L has been limited. In this study, we aimed to solve the difficulty of determination of pyrrolizidine alkaloids and identify more components in the total alkaloids. An on-line preconcentration method has been applied to improve determining sensitivity of pyrrolizidine alkaloids in Tussilago farfara L. in which included field-amplified sample stacking and sweeping in micellar electrokinetic capillary chromatography. The main parameters that affected separation and stacking efficiency were investigated in details. Under the optimal conditions, the sensitivity enhancement factors obtained by the developed method for the analytes were from 15- to 12-fold, the limits of detection of senkirkine and senecionine were 2∼5 μg/L. Senkirkine and senecionine have been detected in alkaloids (c) of Tussilago farfara L, along ferulic acid methyl ester and methyl caffeate. The developed method was also applied to the analysis of acid extraction (a) of Tussilago farfara L, and senkirkine could be detected directly. The results indicated that the developed method is feasible for the analysis of pyrrolizidine alkaloids in Tussilago farfara L with good recoveries.

  11. Crotalaria medicaginea associated with horse deaths in northern Australia: new pyrrolizidine alkaloids.

    Science.gov (United States)

    Fletcher, Mary T; Hayes, Patricia Y; Somerville, Michael J; De Voss, James J

    2011-11-09

    Crotalaria medicaginea has been implicated in horse poisoning in grazing regions of central-west Queensland, which resulted in the deaths of more than 35 horses from hepatotoxicosis in 2010. Liver pathology was suggestive of pyrrolizidine alkaloidosis, and we report here the isolation of two previously uncharacterized pyrrolizidine alkaloids from C. medicaginea plant specimens collected from pastures where the horses died. The first alkaloid was shown by mass spectometric and NMR analyses to be 1β,2β-epoxy-7β-hydroxy-1α-methoxymethyl-8α-pyrrolizidine, which, like other alkaloids previously isolated from C. medicaginea, lacks the requisite functionality for hepatotoxcity. The second alkaloid isolated in this investigation was a new macrocyclic diester of otonecine, which we have named cromedine. The (1)H and (13)C NMR spectra of cromedine were fully assigned by 2D NMR techniques and allowed the constitution of the macrocyclic diester to be assigned unambiguously. C. medicaginea specimens implicated in this investigation do not belong to any of the three recognized Australian varieties (C. medicaginea var. neglecta, C. medicaginea var. medicaginea, and C. medicaginea var. linearis) and appear to be a local variant or form, referred to here as C. medicaginea (chemotype cromedine).

  12. Identification and quantification of hepatotoxic pyrrolizidine alkaloids in the Ethiopian medicinal plant Solanecio gigas (Asteraceae).

    Science.gov (United States)

    Asres, K; Sporer, F; Wink, M

    2007-09-01

    The pyrrolizidine alkaloid content of Solanecio gigas (Vatke) C. Jeffrey (Asteraceae), an Ethiopian medicinal plant widely used for the treatment of colic, diarrhea, gout, otitis media, typhoid fever, and noted for its wound dressing and antiabortifacient activities was studied. The flower and leaf extracts contained 0.19% and 0.14% alkaloids (dry weight), respectively. GLC-MS analysis indicated that all the alkaloids in the flowers are pyrrolizidine alkaloids (PAs), whereas the leaves contain other type of alkaloids with PAs occurring in low concentrations. Roughly, 80% and 90% of the total PAs in the flowers and the leaves, respectively, were shown to occur as N-oxides. Eighteen alkaloids were detected in the flower extract with the retronecine type twelve-membered macrocyclic diesters integerrimine, senecionine and usaramine comprising 82% of the total PA content. Analysis of the PA profile of the leaves indicated that it has a simpler pattern than the one observed for the flowers. Only five PAs were detected in the leaves with integerrimine making up about 50% of the total PAs. Quantification of the PA content by GLC showed that the flowers and leaves contain 3321.21 and 84.84 microg per 10 g of dried plant material, respectively. These results indicate that users of this herb are at high risk of poisoning since the most toxic twelve membered macrocyclics of the retronecine type are the dominant PAs in the plant.

  13. Pyrrolizidine alkaloid-containing toxic plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.).

    Science.gov (United States)

    Stegelmeier, Bryan L

    2011-07-01

    Pyrrolizidine alkaloid (PA)-containing plants are found throughout the world and are probably the most common plant cause of poisoning of livestock, wildlife, and humans. PAs are potent liver toxins that under some conditions can be carcinogenic. This article briefly introduces high-risk North American PA-containing plants, summarizing their toxicity and subsequent pathology. Current diagnostic techniques, treatments, and strategies to avoid losses to PA poisoning are also reviewed. Published by Elsevier Inc.

  14. A free lunch? No cost for acquiring defensive plant pyrrolizidine alkaloids in a specialist arctiid moth (Utetheisa ornatrix).

    Science.gov (United States)

    Cogni, Rodrigo; Trigo, José R; Futuyma, Douglas J

    2012-12-01

    Many herbivorous insects sequester defensive chemicals from their host plants. We tested sequestration fitness costs in the specialist moth Utetheisa ornatrix (Lepidoptera: Arctiidae). We added pyrrolizidine alkaloids (PAs) to an artificial diet at different concentrations. Of all the larval and adult fitness components measured, only development time was negatively affected by PA concentration. These results were repeated under stressful laboratory conditions. On the other hand, the amount of PAs sequestered greatly increased with the diet PA concentration. Absence of a detectable negative effect does not necessarily imply a lack of costs if all individuals express the biochemical machinery of detoxification and sequestration constitutively. Therefore, we used qPCR to show that expression of the gene used to detoxify PAs, pyrrolizidine-alkaloid-N-oxygenase (pno), increased 41-fold in our highest PA treatment. Nevertheless, fitness components were affected only slightly or not at all, suggesting that sequestration in this species does not incur a strong cost. The apparent lack of costs has important implications for our understanding of the evolution of ecological interactions; for example, it implies that selection by specialist herbivores may decrease the levels of certain chemical defences in plant populations.

  15. Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Retrorsine, Leading to DNA Adduct Formation In Vivo

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2005-04-01

    Full Text Available Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. The high toxicity of many pyrrolizidine alkaloids has caused considerable loss of free-ranging livestock due to liver and pulmonary lesions. Chronic exposure of toxic pyrrolizidine alkaloids to laboratory animals induces cancer. This investigation studies the metabolic activation of retrorsine, a representative naturally occurring tumorigenic pyrrolizidine alkaloid, and shows that a genotoxic mechanism is correlated to the tumorigenicity of retrorsine. Metabolism of retrorsine by liver microsomes of F344 female rats produced two metabolites, 6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, at a rate of 4.8 ± 0.1 nmol/mg/min, and retrorsine-N-oxide, at a rate of 17.6±0.5 nmol/mg/min. Metabolism was enhanced 1.7-fold by using liver microsomes prepared from dexamethasone-treated rats. DHP formation was inhibited 77% and retrorsine N-oxide formation was inhibited 29% by troleandomycin, a P450 3A enzyme inhibitor. Metabolism of retrorsine with lung, kidney, and spleen microsomes from dexamethasone-treated rats also generated DHP and the N-oxide derivative. When rat liver microsomal metabolism of retrorsine occurred in the presence of calf thymus DNA, a set of DHP-derived DNA adducts was formed; these adducts were detected and quantified by using a previously developed 32P-postlabeling/HPLC method. These same DNA adducts were also found in liver DNA of rats gavaged with retrorsine. Since DHP-derived DNA adducts are suggested to be potential biomarkers of riddelliine-induced tumorigenicity, our results indicate that (i similar to the metabolic activation of riddelliine, the mechanism of retrorsine-induced carcinogenicity in rats is also through a genotoxic mechanism involving DHP; and (ii the set of DHP-derived DNA adducts found in liver DNA of rats gavaged with retrorsine or riddelliine can serve as biomarkers for the

  16. Metabolic activation of pyrrolizidine alkaloids leading to phototoxicity and photogenotoxicity in human HaCaT keratinocytes.

    Science.gov (United States)

    Wang, Chia-Chi; Xia, Qingsu; Li, Meng; Wang, Shuguang; Zhao, Yuewei; Tolleson, William H; Yin, Jun-Jie; Fu, Peter P

    2014-01-01

    Pyrrolizidine alkaloids, produced by a large number of poisonous plants with wide global distribution, are associated with genotoxicity, tumorigenicity, and hepatotoxicity in animals and humans. Mammalian metabolism converts pyrrolizidine alkaloids to reactive pyrrolic metabolites (dehydropyrrolizidine alkaloids) that form covalent protein and DNA adducts. Although a mechanistic understanding is currently unclear, pyrrolizidine alkaloids can cause secondary (hepatogenous) photosensitization and induce skin cancer. In this study, the phototoxicity of monocrotaline, riddelliine, dehydromonocrotaline, dehydroriddelliine, and dehydroretronecine (DHR) in human HaCaT keratinocytes under ultraviolet A (UVA) irradiation was determined. UVA irradiation of HaCaT cells treated with dehydromonocrotaline, dehydroriddelline, and DHR resulted in increased release of lactate dehydrogenase and enhanced photocytotoxicity proportional to the UVA doses. UVA-induced photochemical DNA damage also increased proportionally with dehydromonocrotaline and dehydroriddelline. UVA treatment potentiated the formation of 8-hydroxy-2'-deoxyguanosine DNA adducts induced by dehydromonocrotaline in HaCaT skin keratinocytes. Using electron spin resistance trapping, we found that UVA irradiation of dehydromonocrotaline and dehydroriddelliine generates reactive oxygen species (ROS), including hydroxyl radical, singlet oxygen, and superoxide, and electron transfer reactions, indicating that cytotoxicity and genotoxicity of these compounds could be mediated by ROS. Our results suggest that dehydropyrrolizidine alkaloids formed or delivered to the skin cause pyrrolizidine alkaloid-induced secondary photosensitization and possible skin cancer.

  17. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome

    Directory of Open Access Journals (Sweden)

    Gao H

    2015-08-01

    Full Text Available Hong Gao,1,* Jianqing Q Ruan,2,* Jie Chen,1 Na Li,2 Changqiang Q Ke,3 Yang Ye,3–5 Ge Lin,2,4,5 Jiyao Y Wang1,61Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong; 3Shanghai Institute of Materia Medica, Shanghai, People’s Republic of China; 4Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines, Shanghai Institute of Materia Medica, 5Chinese University of Hong Kong, Hong Kong; 6Center of Evidence-Based Medicine Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this work and share first authorship Background: The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS.Methods: Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients’ age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis.Results: Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23

  18. Pyrrolizidine alkaloids in plants used in the traditional medicine of Madagascar and the Mascarene islands.

    Science.gov (United States)

    Roeder, E; Wiedenfeld, H

    2011-09-01

    Pyrrolizidine alkaloids (PAs) can be hazardous to the health of humans and animals. Although their toxicity has been known for a long time, PA containing plants are still in use in many traditional medicines. Traditional healing systems have become of increasing interest as many people believe that they can be used without any risk and side effects. This also applies to the traditional medicine of Madagascar and the Mascarene island (Mauritius, Reunion, Rodriguez). Recent literature reports have recommended this traditional medicine because of its good efficacy and pharmacological properties. However, several plants are listed there which have already been described to contain toxic PAs or are suspected of containing them.

  19. Plants containing pyrrolizidine alkaloids used in the traditional Indian medicine--including ayurveda.

    Science.gov (United States)

    Roeder, E; Wiedenfeld, H

    2013-02-01

    Pyrrolizidine alkaloids (PAs) show a hazardous potential for humans and animals. They can possess mutagenic, teratogenic, cancerogenic and fetotoxic properties. One pathway of a human intoxication can be the use of medicinal plants which contain toxic PAs. The Traditional Indian medicine--in particular Ayurveda--is a popular and well-known healing system. Within this system several PA-containing plants are used which, on account of their PA level, represent a severe health risk. In general, it is not recommended to use plants containing those toxic compounds.

  20. Sesquiterpenes, flavonoids, shikimic acid derivatives and pyrrolizidine alkaloids from Senecio kingii Hook.

    Science.gov (United States)

    Ruiz-Vásquez, Liliana; Reina, Matías; López-Rodríguez, M; Giménez, Cristina; Cabrera, Raimundo; Cuadra, Pedro; Fajardo, Víctor; González-Coloma, Azucena

    2015-09-01

    Twenty-four compounds including eleven eremophilanolides (1-11), one eremophilane (13), five shikimic acid derivatives (14-18), six flavonoids (19-24), and the macrocyclic unsaturated pyrrolizidine alkaloid integerrimine (25) were isolated from Senecio kingii, an endemic species from the Magallanes Region (Chile). Compounds 3, 5, 6, 8-11 and 13-18 have not been previously reported as natural products. Their molecular structures were determined by NMR spectroscopic analysis and comparison with published NMR data. An X-ray-analysis of compound 3 has been performed. Their insecticidal and antifungal activities were tested, being compound 3 the strongest insect antifeedant. Compounds 6, 9 and 18 were moderate antifungals.

  1. 2,6-Lutidine-isatinecate, a semi-synthetic pyrrolizidine alkaloid: X-ray and N. M. R. studies

    Energy Technology Data Exchange (ETDEWEB)

    Drewes, S.E.; Field, J.S.; Pitchford, A.T.; Van Rooyen, P.H.; Dillen, J.L.M.

    1985-09-01

    A semi-synthetic pyrrolizidine alkaloid has been prepared from a necic acid and a pyridine base moiety. N.M.R. and X-ray analyses of this compound were carried out in order to establish the relationship between the structure and chemical shift.

  2. Interspecific transfer of pyrrolizidine alkaloids: An unconsidered source of contaminations of phytopharmaceuticals and plant derived commodities.

    Science.gov (United States)

    Nowak, Melanie; Wittke, Carina; Lederer, Ines; Klier, Bernhard; Kleinwächter, Maik; Selmar, Dirk

    2016-12-15

    Many plant derived commodities contain traces of toxic pyrrolizidine alkaloids (PAs). The main source of these contaminations seems to be the accidental co-harvest of PA-containing weeds. Yet, based on the insights of the newly described phenomenon of the horizontal transfer of natural products, it is very likely that the PA-contaminations may also be due to an uptake of the alkaloids from the soil, previously being leached out from rotting PA-plants. The transfer of PAs was investigated using various herbs, which had been mulched with dried plant material from Senecio jacobaea. All of the acceptor plants exhibited marked concentrations of PAs. The extent and the composition of the imported PAs was dependent on the acceptor plant species. These results demonstrate that PAs indeed are leached out from dried Senecio material into the soil and confirm their uptake by the roots of the acceptor plants and the translocation into the leaves.

  3. UPLC-MS/MS method for determination of selected pyrrolizidine alkaloids in feed.

    Science.gov (United States)

    Bolechová, Martina; Cáslavský, Josef; Pospíchalová, Markéta; Kosubová, Petra

    2015-03-01

    Alkaloids known as secondary metabolites are grouped by typical structural characteristics into large families such as pyrrolizidine alkaloids (PAs) comprising more than 350 individual heterocyclic compounds. The PAs present a serious health risk to human and livestock; hence there is a need for methods that allow these dangerous plant toxins to be determined. In this study, a fast, reliable and sensitive approach is proposed to identify and quantify PAs in feed samples. PAs including monocrotaline, senkirkine, senecionine, seneciphylline and retrorsine were determined by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Sample preparation was based on a modified QuEChERS approach. The mean recovery, precision, matrix effects and limits of quantification were assessed for three matrices within the method validation. The presented method was used to inspect 41 various feed samples, where the presence of PAs was expected. Roughages and feed for rabbits contained the highest levels of PAs, in general.

  4. Metabolic activation of pyrrolizidine alkaloids: insights into the structural and enzymatic basis.

    Science.gov (United States)

    Ruan, Jianqing; Yang, Mengbi; Fu, Peter; Ye, Yang; Lin, Ge

    2014-06-16

    Pyrrolizidine alkaloids (PAs) are natural toxins widely distributed in plants. The toxic potencies of different PAs vary significantly. PAs are mono- or diesters of necine acids with a necine base. On the basis of the necine bases, PAs are classified into three types: retronecine-type, otonecine-type, and platynecine-type. Hepatotoxic PAs contain an unsaturated necine base. PAs exert hepatotoxicity through metabolic activation by hepatic cytochromes P450s (CYPs) to generate reactive intermediates which form pyrrole-protein adducts. These adducts provide a mechanism-based biomarker to assess PA toxicity. In the present study, metabolic activation of 12 PAs from three structural types was investigated first in mice to demonstrate significant variations in hepatic metabolic activation of different PAs. Subsequently, the structural and enzymatic factors affecting metabolic activation of these PAs were further investigated by using human liver microsomes and recombinant human CYPs. Pyrrole-protein adducts were detected in the liver and blood of mice and the in vitro systems treated with toxic retronecine-type and otonecine-type PAs having unsaturated necine bases but not with a platynecine-type PA containing a saturated necine base. Retronecine-type PAs produced more pyrrole-protein adducts than otonecine-type PAs with similar necine acids, demonstrating that the structure of necine base affected PA toxic potency. Among retronecine-type PAs, open-ring diesters generated the highest amount of pyrrole-protein adducts, followed by macrocyclic diesters, while monoesters produced the least. Only CYP3A4 and CYP3A5 activated otonecine-type PAs, while all 10 CYPs studied showed the ability to activate retronecine-type PAs. Moreover, the contribution of major CYPs involved also varied significantly among retronecine-type PAs. In conclusion, our findings provide a scientific basis for predicting the toxicities of individual PAs in biological systems based on PA structural

  5. Analysis of pyrrolizidine alkaloids and evaluation of some biological activities of Algerian Senecio delphinifolius (Asteraceae).

    Science.gov (United States)

    Tidjani, Soukaina; Okusa, Philippe N; Zellagui, Amar; Banuls, Laetitia Moreno Y; Stévigny, Caroline; Duez, Pierre; Rhouati, Salah

    2013-04-01

    Although Senecio species are known as sources of potentially toxic pyrrolizidine alkaloids (PAs), some species of this genus are traditionally used as remedies, notably in Algeria. In this paper, the evaluation of biological activities and the analysis of PAs of Algerian specimens of Senecio delphinifolius Vahl are reported. The n-butanolic extract of the herb showed a weak antibacterial effect against Escherichia coli with a MIC of 1 mg/mL, but was inactive against Staphylococcus aureus and Pseudomonas aeruginosa. The n-butanolic extracts of the roots, stems and herb showed a modest antioxidant activity, scavenging the free radical DPPH with respective IC50 values of 55.3, 50.2 and 13.3 microg/mL. A cytotoxic effect against a series of human tumor cell lines was observed with the n-butanolic extract from stems (IC50 ranging between 34 and 88 microg/mL). The herb of the evaluated sample contains 140 ppm of PAs (senecionine, seneciphylline, integerrimine, senkirkine) and PA-related alkaloids (dehydrosenkirkine and neosenkirkine). As the major PAs belong to the toxic series (1,2-unsaturation in the pyrrolizidine cycle and macrocyclic diester), the use of S. delphinifolius should be discouraged in traditional medicine.

  6. Pyrrolizidine alkaloids in food: a spectrum of potential health consequences.

    Science.gov (United States)

    Edgar, J A; Colegate, S M; Boppré, M; Molyneux, R J

    2011-03-01

    Contamination of grain with 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs) and their N-oxides is responsible for large incidents of acute and subacute food poisoning, with high morbidity and mortality, in Africa and in central and south Asia. Herbal medicines and teas containing dehydroPAs have also caused fatalities in both developed and developing countries. There is now increasing recognition that some staple and widely consumed foods are sometimes contaminated by dehydroPAs and their N-oxides at levels that, while insufficient to cause acute poisoning, greatly exceed maximum tolerable daily intakes and/or maximum levels determined by a number of independent risk assessment authorities. This suggests that there may have been cases of disease in the past not recognised as resulting from dietary exposure to dehydroPAs. A review of the literature shows that there are a number of reports of liver disease where either exposure to dehydroPAs was suspected but no source was identified or a dehydroPA-aetiology was not considered but the symptoms and pathology suggests their involvement. DehydroPAs also cause progressive, chronic diseases such as cancer and pulmonary arterial hypertension but proof of their involvement in human cases of these chronic diseases, including sources of exposure to dehydroPAs, has generally been lacking. Growing recognition of hazardous levels of dehydroPAs in a range of common foods suggests that physicians and clinicians need to be alert to the possibility that these contaminants may, in some cases, be a possible cause of chronic diseases such as cirrhosis, pulmonary hypertension and cancer in humans.

  7. Cytotoxicity of pyrrolizidine alkaloid in human hepatic parenchymal and sinusoidal endothelial cells: Firm evidence for the reactive metabolites mediated pyrrolizidine alkaloid-induced hepatotoxicity.

    Science.gov (United States)

    Yang, Mengbi; Ruan, Jianqing; Fu, Peter P; Lin, Ge

    2016-01-05

    Pyrrolizidine alkaloids (PAs) widely distribute in plants and can cause hepatic sinusoidal obstruction syndrome (HSOS), which typically presents as a primary sinusoidal endothelial cell damage. It is well-recognized that after ingestion, PAs undergo hepatic cytochromes P450 (CYPs)-mediated metabolic activation to generate dehydropyrrolizidine alkaloids (DHPAs), which are hydrolyzed to dehydroretronecine (DHR). DHPAs and DHR are reactive metabolites having same core pyrrole moiety, and can bind proteins to form pyrrole-protein adducts, which are believed as the primary cause for PA-induced HSOS. However, to date, the direct evidences supporting the toxicity of DHPAs and DHR in the liver, in particular in the sinusoidal endothelial cells, are lacking. Using human hepatic sinusoidal endothelial cells (HSEC) and HepG2 (representing hepatic parenchymal cells), cells that lack CYPs activity, this study determined the direct cytotoxicity of dehydromonocrotaline, a representative DHPA, and DHR, but no cytotoxicity of the intact PA (monocrotaline) in both cell lines, confirming that reactive metabolites mediate PA intoxication. Comparing with HepG2, HSEC had significantly lower basal glutathione (GSH) level, and was significantly more susceptible to the reactive metabolites with severer GSH depletion and pyrrole-protein adducts formation. The toxic potency of two reactive metabolites was also compared. DHPA was more reactive than DHR, leading to severer toxicity. In conclusion, our results unambiguously provided the first direct evidence for the critical role of DHPA and DHR in the reactive metabolites-mediated PA-induced hepatotoxicity, which occurs predominantly in HSEC due to severe GSH depletion and the significant formation of pyrrole-protein adducts in HSEC.

  8. 7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.

    Science.gov (United States)

    He, Xiaobo; Xia, Qingsu; Fu, Peter P

    2017-04-03

    Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.

  9. Senecio brasiliensis and pyrrolizidine alkaloids: toxicity to animals and human health

    Directory of Open Access Journals (Sweden)

    Helenice de Souza Spinosa

    2013-06-01

    Full Text Available Most economic losses in Brazilian livestock production, especially in horses and cattle, are due to poison plants, such as those of the genus Senecio. Senecio brasiliensis Lessing is the main cause of death in cattle in the state of Rio Grande do Sul. The toxicity of this genus is attributed to their content of pyrrolizidine alkaloids, which undergo liver biotransformation creating toxic metabolites, namely pyrroles. These compounds can be transferred to humans through contaminated animal products or by the use of this plant in folk medicine. Thus, the present article is a review of the species S. brasiliensis, its toxic active principles and the mechanism by which pathogenesis occurs. Other plants with the same toxic principles that are harmful to human health are covered as well.

  10. 7-cysteine-pyrrole conjugate: A new potential DNA reactive metabolite of pyrrolizidine alkaloids.

    Science.gov (United States)

    He, Xiaobo; Xia, Qingsu; Ma, Liang; Fu, Peter P

    2016-01-01

    Pyrrolizidine alkaloids (PAs) require metabolic activation to exert cytotoxicity, genotoxicity, and tumorigenicity. We previously reported that (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts are responsible for PA-induced liver tumor formation in rats. In this study, we determined that metabolism of riddelliine and monocrotaline by human or rat liver microsomes produced 7-cysteine-DHP and DHP. The metabolism of 7-glutathionyl-DHP by human and rat liver microsomes also generated 7-cysteine-DHP. Further, reaction of 7-cysteine-DHP with calf thymus DNA in aqueous solution yielded the described DHP-derived DNA adducts. This study represents the first report that 7-cysteine-DHP is a new PA metabolite that can lead to DNA adduct formation.

  11. EFSA (European Food Safety Authority), 2016. Dietary exposure assessment to pyrrolizidine alkaloids in the European population

    DEFF Research Database (Denmark)

    Petersen, Annette

    Chronic and acute dietary exposure to pyrrolizidine alkaloids (PAs) was estimated in the European population via the consumption of plant-derived foods. This resulted in highest estimates of mean chronic dietary exposure of 34.5–48.4 ng/kg body weight (bw) per day in ‘Toddlers’ (LB–UB) and 154...... consumers. Ad hoc exposure scenarios for food supplements via consumption of pollen-based supplements showed chronic exposure to PAs that ranged between 0.7 and 12 ng/kg bw per day (minimum LB–maximum UB), while acute exposure was between 2.8 and 44 ng/kg bw per day (minimum LB–maximum UB), in both cases...

  12. Pyrrolizidine Alkaloids from Echium vulgare in Honey Originate Primarily from Floral Nectar.

    Science.gov (United States)

    Lucchetti, Matteo A; Glauser, Gaetan; Kilchenmann, Verena; Dübecke, Arne; Beckh, Gudrun; Praz, Christophe; Kast, Christina

    2016-06-29

    Pyrrolizidine alkaloids (PAs) in honey can be a potential human health risk. So far, it has remained unclear whether PAs in honey originate from pollen or floral nectar. We obtained honey, nectar, and plant pollen from two observation sites where Echium vulgare L. was naturally abundant. The PA concentration of honey was determined by targeted analysis using a high pressure liquid chromatography-mass spectrometry system (HPLC-MS/MS), allowing the quantification of six different PAs and PA-N-oxides present in E. vulgare. Echium-type PAs were detected up to 0.153 μg/g in honey. Nectar and plant pollen were analyzed by nontargeted analysis using ultrahigh pressure liquid chromatography-high resolution-mass spectrometry (UHPLC-HR-MS), allowing the detection of 10 alkaloids in small size samples. Echium-type PAs were detected between 0.3-95.1 μg/g in nectar and 500-35000 μg/g in plant pollen. The PA composition in nectar and plant pollen was compared to the composition in honey. Echimidine (+N-oxide) was the main alkaloid detected in honey and nectar samples, while echivulgarine (+N-oxide) was the main PA found in plant pollen. These results suggest that nectar contributes more significantly to PA contamination in honey than plant pollen.

  13. Loss of pyrrolizidine alkaloids on decomposition of ragwort (Senecio jacobaea) as measured by LC-TOF-MS.

    Science.gov (United States)

    Crews, Colin; Driffield, Malcolm; Berthiller, Franz; Krska, Rudolf

    2009-05-13

    The decomposition of toxic pyrrolizidine alkaloids in ragwort (Senecio jacobaea) on storage in waste bags has been evaluated by a new time-of-flight mass spectrometric detection method. The method makes progress in meeting the clear need for modern analytical methods for pyrrolizidine alkaloids and for studies into factors affecting the stability of the toxins in the uprooted plant, which might still be accessible to animals. The experiments demonstrated a rapid decomposition of the toxins in ragwort stored in bags, from 340 mg/kg to less than 40 mg/kg in four weeks and virtually complete loss after 10 weeks. The information obtained can guide effective ragwort removal procedures to safeguard grazing animals.

  14. 1,3-Oxazin-6-one Derivatives and Bohemamine-Type Pyrrolizidine Alkaloids from a Marine-Derived Streptomyces spinoverrucosus.

    Science.gov (United States)

    Fu, Peng; La, Scott; MacMillan, John B

    2016-03-25

    Two new 1,3-oxazin-6-one derivatives (1 and 2) and six new bohemamine-type pyrrolizidine alkaloids (3-8) were isolated from the marine-derived Streptomyces spinoverrucosus strain SNB-048. Their structures including the absolute configurations were fully elucidated on the basis of spectroscopic analysis, ECD spectra, quantum chemical calculations, and chemical methods. Compounds 1 and 2 possess a γ-lactam moiety and a 1,3-oxazin-6-one system.

  15. Quantification of pyrrolizidine alkaloids in North American plants and honey by LC-MS: single laboratory validation.

    Science.gov (United States)

    Mudge, Elizabeth M; Jones, A Maxwell P; Brown, Paula N

    2015-01-01

    Pyrrolizidine alkaloids (PAs) are a class of naturally occurring compounds produced by many flowering plants around the World. Their presence as contaminants in food systems has become a significant concern in recent years. For example, PAs are often found as contaminants in honey through pollen transfer. A validated method was developed for the quantification of four pyrrolizidine alkaloids and one pyrrolizidine alkaloid N-oxide in plants and honey grown and produced in British Columbia. The method was optimised for extraction efficiency from the plant materials and then subjected to a single-laboratory validation to assess repeatability, accuracy, selectivity, LOD, LOQ and method linearity. The PA content in plants ranged from1.0 to 307.8 µg/g with repeatability precision between 3.8 and 20.8% RSD. HorRat values were within acceptable limits and ranged from 0.62 to 1.63 for plant material and 0.56-1.82 for honey samples. Method accuracy was determined through spike studies with recoveries ranging from 84.6 to 108.2% from the raw material negative control and from 82.1-106.0 % for the pyrrolizidine alkaloids in corn syrup. Based on the findings in this single-laboratory validation, this method is suitable for the quantitation of lycopsamine, senecionine, senecionine N-oxide, heliosupine and echimidine in common comfrey (Symphytum officinale), tansy ragwort (Senecio jacobaea), blueweed (Echium vulgare) and hound's tongue (Cynoglossum officinale) and for PA quantitation in honey and found that PA contaminants were present at low levels in BC honey.

  16. Chemical Diversity Investigation of Hepatotoxic Pyrrolizidine Alkaloids in Qianliguang (Senecio scandens and Related Species by UHPLC-QTOF-MS

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    Lin Zhu

    2015-04-01

    Full Text Available Objective: Qianliguang (Senecio scandens is a common Chinese medicinal herb. Qianliguang-containing herbal proprietary products are registered as over-the-counter remedies in China and exported to Western countries. The presence of hepatotoxic pyrrolizidine alkaloids (PAs has raised concerns about the safety of using Qianliguang and its products. The present study aims at investigation of different types of PAs present in Qianliguang collected from representative locations in China.

  17. 7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids

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    Xiaobo He

    2016-10-01

    Full Text Available Plants containing pyrrolizidine alkaloids (PAs are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs that are capable of alkylating cellular DNA and proteins, form (±-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP and DHP. Reactions of 7-NAC-DHP with 2′-deoxyguanosine (dG, 2′-deoxyadenosine (dA, and calf thymus DNA in aqueous solution followed by enzymatic hydrolysis yielded DHP-dG and/or DHP-dA adducts. These results indicate that 7-NAC-DHP is a reactive metabolite that can lead to DNA adduct formation.

  18. Hepatotoxicity associated with pyrrolizidine alkaloid (Crotalaria spp) ingestion in a horse on Easter Island.

    Science.gov (United States)

    Arzt, J; Mount, M E

    1999-04-01

    Since 1984, a significant number of privately owned and feral horses on Easter Island have died of a syndrome consisting of progressive anorexia, weight loss, obtundation, and other central nervous system abnormalities. A single horse experiencing clinical signs of the reported syndrome was identified, examined and necropsied. Clinical signs included inappetence, emaciation, ataxia and icterus. Gross necropsy findings included hepatic enlargement and mottling, ascites and gastric impaction. Histopathological lesions included hepatic hemorrhage and necrosis, periportal megalocytosis, portal fibrosis, bile duct hyperplasia and multinucleate hepatocytes. Crotalaria grahamiana and C pallida, were identified in the pasture of the presenting horse, and found to be widespread on the island. Alkaloid fingerprinting identified grahamine, monocrotalin, and a grahamine analog in C grahamiana. A retrorsine analog and a senecionine analog were identified in C pallida. The highly characteristic lesions and the identification of pyrrolizidine alkaloids in the 2 plants strongly suggest that ingestion of 1 or both of the Crotalaria species led to chronic liver damage and hepatic encephalopathy in the presenting horse. Widespread distribution of C grahamiana on the island and reported temporal and seasonal trends in incidence among horses and cattle suggest that C grahamiana may be responsible for extensive morbidity and mortality among horses and cattle on Easter Island.

  19. Quantitative analysis of total retronecine esters-type pyrrolizidine alkaloids in plant by high performance liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Fang; Wang Changhong; Xiong Aizhen; Wang Wan; Yang Li [Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Road, Zhangjiang Hi-Tech Park, Shanghai 201203 (China); Branford-White, Christopher J. [Institute for Health Research and Policy, London Metropolitan University, 166-220 Holloway Road, London N7 8DB (United Kingdom); Wang Zhengtao [Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Road, Zhangjiang Hi-Tech Park, Shanghai 201203 (China); School of Chinese Pharmacy, China Pharmaceutical University, Nanjing 210038 (China)], E-mail: wangzt@shutcm.edu.cn; Bligh, S.W. Annie [Institute for Health Research and Policy, London Metropolitan University, 166-220 Holloway Road, London N7 8DB (United Kingdom)], E-mail: a.bligh@londonmet.ac.uk

    2007-12-12

    Pyrrolizidine alkaloids (PAs) are alkaloids which typically contain a necine (7-hydroxy-1-hydroxymethyl-6,7-dihydro-5H-pyrrolizidine) base unit, and they can be found in one third of the higher plants around the world. They are hepatotoxic, mutagenic and carcinogenic and pose a threat to human health and safety. A specific, quick and sensitive method is therefore needed to detect and quantify the PAs sometimes in trace amount in herbs, tea or food products. Based on high performance liquid chromatography with prior derivatization of the alkaloids using o-chloranil and Ehrlich's reagent, we report an improved method for quantitative analysis of the total amount of retronecine esters-type pyrrolizidine alkaloids (RET-PAs) in a plant extract. The total quantitation of RET-PAs is achieved because of a common colored retronecine marker, a 7-ethoxy-1-ethoxylmethyl retronecine derivative, is produced with all the different RET-PAs during the derivatization reaction. The chemical identity of the common retronecine marker was characterized on-line by positive mode electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. The limit of detection using the improved method is 0.26 nmol mL{sup -1} and the limit of quantitation is 0.79 nmol mL{sup -1}. The advantages of this method are much enhanced sensitivity in detection and quantitation, and, no restriction on the choice of RET-PA as a calibration standard. Application of the developed method to the quantitation of total RET esters-type PAs in Senecio scandens from different regions of China is also reported.

  20. Optimisation of isolation procedure for pyrrolizidine alkaloids from Rindera umbellata Bunge.

    Science.gov (United States)

    Mandić, Boris M; Vlajić, Marina D; Trifunović, Snežana S; Simić, Milena R; Vujisić, Ljubodrag V; VuČković, Ivan M; Novaković, Miroslav M; Nikolić-Mandić, Snežana D; Tešević, Vele V; Vajs, Vlatka V; Milosavljević, Slobodan M

    2015-01-01

    Procedure for isolation of pyrrolizidine alkaloids (PAs) from Rindera umbellata Bunge plant species was optimised. Different extraction media (methanol, ethanol and sulphuric acid), concentration and volume of sulphuric acid, pH of PA solution for alkaline extraction, extraction time and techniques (maceration, ultrasonic and overhead rotary mixer assisted extraction) were investigated. The yields of six PAs (7-angeloyl heliotridane, 7-angeloyl heliotridine, lindelofine, 7-angeloyl rinderine, punctanecine and heliosupine) were monitored by GC-MS/FID. The best results for the isolation all of six PAs were obtained when the extraction was performed with 1 M sulphuric acid (30 mL per 1.00 g of dried sample) by overhead rotary mixer during three days. Optimal pH value for alkaline extraction of PAs with CH₂Cl₂ was 9, and the extraction should be performed with four portions of 30 mL of CH₂Cl₂. This procedure could be also useful for a plant sample preparation for GC and LC analyses of PAs.

  1. Toxicity of pyrrolizidine alkaloids to Spodoptera exigua using insect cell lines and injection bioassays.

    Science.gov (United States)

    Nuringtyas, Tri R; Verpoorte, Robert; Klinkhamer, Peter G L; van Oers, Monique M; Leiss, Kirsten A

    2014-06-01

    Pyrrolizidine alkaloids (PAs) are feeding deterrents and toxic compounds to generalist herbivores. Among the PAs of Jacobaea vulgaris Gaertn, jacobine and erucifoline are the most effective against insect herbivores as indicated by correlative studies. Because little is known about the effect of jacobine and erucifoline as individual PAs, we isolated these compounds from their respective Jacobaea chemotypes. These PAs and other commercially available senecionine-like PAs, including senecionine, seneciphylline, retrorsine, and senkirkine, were tested as free base and N-oxide forms at a range of 0-70 ppm. Feeding bioassays using live insects are closer to the natural pattern but require relatively large amounts of test compounds. We, therefore, compared the toxicity of PAs using both Spodoptera exigua cell line and larval injection bioassays. Both bioassays led to similar results in the order of PA toxicity, indicating that the cell lines are a valuable tool for a first toxicity screen. Testing individual PAs, jacobine and erucifoline were the most toxic PAs, suggesting their major role in plant defense against generalist herbivores. Senkirkine and seneciphylline were less toxic than jacobine and erucifoline but more toxic than retrorsine. Senecionine was not toxic at the tested concentrations. For all toxic PAs, the free base form was more toxic than the N-oxide form. Our results demonstrate that structural variation of PAs influences their effectiveness in plant defense.

  2. Risk assessment on the use of herbal medicinal products containing pyrrolizidine alkaloids.

    Science.gov (United States)

    Allgaier, Clemens; Franz, Stephanie

    2015-11-01

    Pyrrolizidine alkaloids (PA) are common plantal toxins directed against insect herbivores. Unsaturated PAs are known to be hepatotoxic. Many of the PAs are in addition mutagenic and some may possibly be carcinogenic for humans. The risk of an exposure to PAs associated with their occurrence in herbal medicinal products and in foodstuff is under current discussion. The present risk assessment for herbal medicinal products containing PAs is based on a margin of safety derivation for foodstuff indicating that a life-long exposure to maximally 0.007 μg/kg bw/day is not expected to be associated with safety concerns. This approach offers a possibility to estimate the potential risk of PA-containing herbal medicinal products irrespective of the route of administration. It assumes PA levels in the final herbal medicinal product below 0.01 ppm and considers for dermal administration a 100% skin penetration of the PAs reflecting a worst-case scenario. As a result, the calculated margins of safety show a potential exposure using herbal medicinal products 70-, 45.5-, and 19.3-fold lower on a one-day base and 608-, 396-, and 168- fold lower on a one-year base for adults, children aged 12 years, and children aged 4 years, respectively, than the thresholds considered acceptable for foodstuff.

  3. Are effects of common ragwort in the Ames test caused by pyrrolizidine alkaloids?

    Science.gov (United States)

    Bovee, Toine F H; Helsdingen, Richard J R; Hoogenboom, Ron L A P; de Nijs, Monique W C M; Liu, Xiaojie; Vrieling, Klaas; Klinkhamer, Peter G L; Peijnenburg, Ad A C M; Mulder, Patrick P J

    2015-08-01

    It has previously been demonstrated by others that acetone extracts of Senecio jacobaea (syn. Jacobaea vulgaris, common or tansy ragwort) test positive in the Salmonella/microsome mutagenicity test (Ames test). Pyrrolizidine alkaloids (PAs) are thought to be responsible for these mutagenic effects. However, it was also observed that the major PA present in common ragwort, jacobine, produced a negative response (with and without the addition of rat liver S9) in Salmonella test strains TA98, TA100, TA1535 and TA1537. To investigate which compounds in the plant extracts were responsible for the positive outcome, the present study investigated the contents and mutagenic effects of methanol and acetone extracts prepared from dried ground S. jacobaea and Senecio inaequidens (narrow-leafed ragwort). Subsequently, a fractionation approach was set up in combination with LC-MS/MS analysis of the fractions. It was shown that the positive Ames test outcomes of S. jacobaea extracts are unlikely to be caused by PAs, but rather by the flavonoid quercetin. This study also demonstrates the importance of identifying compounds responsible for positive test results in bioassays.

  4. Pyrrolizidine alkaloids: their occurrence in Spanish honey collected from purple viper's bugloss (Echium spp.).

    Science.gov (United States)

    Orantes-Bermejo, F J; Serra Bonvehí, J; Gómez-Pajuelo, A; Megías, M; Torres, C

    2013-01-01

    The incidence and concentration of pyrrolizidine alkaloids (PAs) from Echium spp. plant have been defined in 103 Spanish honey samples. Each sample was examined to determine total pollen content, the percentage of Echium spp. pollen, and simultaneous measurements of PAs and their N-oxides concentrations by the HPLC-ESI/MS method to identify the potential origin of PAs in honey. PAs were found in 94.2% of the raw honey samples analysed, in the range of 1-237 µg kg(-1) (average concentration = 48 µg kg(-1)). The PA pattern was clearly dominated by echimidine, lycopsamine and their N-oxides, representing the 97.8% of total ∑PAs, and only echimidine and echimidine-N-oxide surpassed the 87% of total ∑PA content. Others PAs, seneciphylline and heliotrine-N-oxide, appear to be reported in a lower incidence and concentration (average of 3 and 1 µg kg(-1), respectively). The Pearson Chi-squared test (p ≤ 0.01) confirms the non-correspondence between pollen plants and PA content. This study was also realised to generate a dataset in order to evaluate the potential risk of Spanish honeys containing PA plants belonging to the genera Echium.

  5. Synergistic effects of pyrrolizidine alkaloids and lipopolysaccharide on preterm delivery and intrauterine fetal death in mice.

    Science.gov (United States)

    Guo, Yu; Ma, Zhenguo; Kou, Hao; Sun, Rongze; Yang, Hanxiao; Smith, Charles Vincent; Zheng, Jiang; Wang, Hui

    2013-08-29

    Preterm birth is the leading cause of death for newborn infants, and lipopolysaccharide (LPS) is commonly used to induce preterm delivery in experimental animals. Pyrrolizidine alkaloids (PAs) are widespread and occur in foods, herbs, and other plants. This study was to investigate the synergistic effects of LPS and two representative PAs, retrorsine (RTS) and monocrotaline (MCT), on preterm delivery and fetal death. Pregnant Kunming mice were divided into seven groups: control, RTS, MCT, LPS, RTS+LPS and two MCT+LPS groups. Animals in PAs and PAs+LPS groups were dosed intragastrically with RTS (10mg/kg) or MCT (20 mg/kg or 60 mg/kg) from gestational day (GD) 9 to GD16; mice given LPS were injected intraperitoneally with 150 μg/kg on GD15.5. Latencies to delivery, numbers of pups live and dead at birth were recorded, and livers of live neonates were collected. The incidence of LPS-induced preterm birth was enhanced in dams pretreated with MCT, and combination of PAs and LPS increased fetal mortality from PAs. The enhancement of LPS-induced preterm delivery and fetal demise in animals exposed chronically to PAs and other substances found in foods and beverages consumed widely by humans merits further focused investigation.

  6. Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline

    Energy Technology Data Exchange (ETDEWEB)

    Petry, T.W.; Bowden, G.T.; Huxtable, R.J.; Sipes, I.G.

    1984-04-01

    Hepatic DNA damage induced by the pyrrolizidine alkaloid monocrotaline was evaluated following i.p. administration to adult male Sprague-Dawley rats. Animals were treated with various doses ranging upward from 5 mg/kg, and hepatic nuclei were isolated 4 hr later. Hepatic nuclei were used as the DNA source in all experiments. DNA damage was characterized by the alkaline elution technique. A mixture of DNA-DNA interstrand cross-links and DNA-protein cross-links was induced. Following an injection of monocrotaline, 30 mg/kg i.p., DNA-DNA interstrand cross-linking reached a maximum within 12 hr or less and thereafter decreased over a protracted period of time. By 96 hr postadministration, the calculated cross-linking factor was no longer statistically different from zero. No evidence for the induction of DNA single-strand breaks was observed, although the presence of small numbers of DNA single-strand breaks could have been masked by the overwhelming predominance of DNA cross-links. These DNA cross-links may be related to the hepatocarcinogenic, hepatotoxic, and/or antimitotic effects of monocrotaline.

  7. Diagnostic performance of Contrast-enhanced CT in Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstructive Syndrome

    Science.gov (United States)

    Kan, Xuefeng; Ye, Jin; Rong, Xinxin; Lu, Zhiwen; Li, Xin; Wang, Yong; Yang, Ling; Xu, Keshu; Song, Yuhu; Hou, Xiaohua

    2016-01-01

    Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS. PMID:27897243

  8. Heliotropium europaeum poisoning in cattle and analysis of its pyrrolizidine alkaloid profile.

    Science.gov (United States)

    Shimshoni, Jakob Avi; Mulder, Patrick P J; Bouznach, Arieli; Edery, Nir; Pasval, Israel; Barel, Shimon; Abd-El Khaliq, Mohammed; Perl, Samuel

    2015-02-11

    Pyrrolizidine alkaloids (PAs) are carcinogenic and genotoxic phytochemicals found exclusively in angiosperms. The ingestion of PA-containing plants often results in acute and chronic toxicities in man and livestock, targeting mainly the liver. During February 2014, a herd of 15-18-month-old mixed-breed beef cattle (n = 73) from the Galilee region in Israel was accidently fed hay contaminated with 12% Heliotropium europaeum (average total PA intake was 33 mg PA/kg body weight/d). After 42 d of feed ingestion, sudden death occurred over a time period of 63 d with a mortality rate of 33%. Necropsy and histopathological examination revealed fibrotic livers and moderate ascites, as well as various degrees of hyperplasia and fibrosis of bile duct epithelial cells. Elevated γ-glutamyl-transferase and alkaline phosphatase levels were indicative of severe liver damage. Comprehensive PA profile determination of the contaminated hay and of native H. europaeum by LC-MS/MS revealed the presence of 30 PAs and PA-N-oxides, including several newly reported PAs and PA-N-oxides of the rinderine and heliosupine class. Heliotrine- and lasiocarpine-type PAs constituted 80% and 18% of the total PAs, respectively, with the N-oxides being the most abundant form (92%). The PA profile of the contaminated hay showed very strong resemblance to that of H. europaeum.

  9. Diversity of pyrrolizidine alkaloids in native and invasive Senecio pterophorus (Asteraceae): implications for toxicity.

    Science.gov (United States)

    Castells, Eva; Mulder, Patrick P J; Pérez-Trujillo, Míriam

    2014-12-01

    Changes in plant chemical defenses after invasion could have consequences on the invaded ecosystems by modifying the interactions between plants and herbivores and facilitating invasion success. However, no comprehensive biogeographical studies have yet determined the phenotypic levels of plant chemical defenses, as consumed by local herbivores, covering large distributional areas of a species. Senecio pterophorus is a perennial shrub native to Eastern South Africa, expanded into Western South Africa and introduced into Australia and Europe. As other Asteraceae, S. pterophorus contains pyrrolizidine alkaloids (PAs) toxic to vertebrate and invertebrate herbivores. Here we analyzed S. pterophorus PAs by LC-MS/MS on foliage sampled across its entire distributional range, including the native and all non-native areas. PA concentrations and diversity was very high: we found 57 compounds belonging to 6 distinct necine base-types, including the highly toxic 1,2-unsaturated PAs (retronecine and otonecines) and the less toxic 1,2-saturated PAs (platynecine and rosmarinecines). Plants from different origins diverged in their PA absolute and relative concentrations. Rosmarinine was the most abundant compound in Australia and South Africa, but it was nearly absent in Europe. We characterized three plant chemotypes: retrorsine-senkirkine chemotype in Eastern South Africa, rosmarinine chemotype in Australia and Western South Africa, and acetylseneciphylline chemotype in Europe. PA absolute concentrations were highest in Australia. The increased absolute and relative concentrations of retronecine PAs from Australia and Europe, respectively, indicate that S. pterophorus is potentially more toxic in the invasive range than in the native range.

  10. Pyrrolizidine alkaloids from Liparis nervosa with inhibitory activities against LPS-induced NO production in RAW264.7 macrophages.

    Science.gov (United States)

    Huang, Shuai; Zhou, Xian-li; Wang, Cui-juan; Wang, You-song; Xiao, Feng; Shan, Lian-hai; Guo, Zhi-yun; Weng, Jie

    2013-09-01

    Six pyrrolizidine alkaloids were isolated from the whole herb of Liparis nervosa together with two previously known ones. Their structures were elucidated by extensive spectroscopic analyses and chemical reactions. The cytotoxicity of the isolates was evaluated against A549, HepG2, and MCF-7 human cancer cell lines; however, no significant growth inhibition was observed. All compounds were evaluated for the inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, and most significantly inhibited NO production with IC50 values in the range of 2.16-38.25 μM.

  11. 7-glutathione pyrrole adduct: a potential DNA reactive metabolite of pyrrolizidine alkaloids.

    Science.gov (United States)

    Xia, Qingsu; Ma, Liang; He, Xiaobo; Cai, Lining; Fu, Peter P

    2015-04-20

    Pyrrolizidine alkaloid (PA)-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form pyrrolic metabolites to exert cytotoxicity and tumorigenicity. We previously determined that metabolism of tumorigenic PAs produced four DNA adducts, designated as DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, that are responsible for liver tumor initiation. 7-Glutathione-(±)-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (7-GS-DHP), formed in vivo and in vitro, and 7,9-di-GS-DHP, formed in vitro, are both considered detoxified metabolites. However, in this study we determined that incubation of 7-GS-DHP with 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) yields DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts as well as the reactive metabolite DHP. Furthermore, reaction of 7-GS-DHP with calf thymus DNA in aqueous solution at 37 °C for 4, 8, 16, 24, 48, or 72 h, followed by enzymatic hydrolysis yielded DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts. Under our current experimental conditions, DHP-dA-3 and DHP-dA-4 adducts were formed in a trace amount from the reaction of 7,9-di-GS-DHP with dA. No DHP-dG-3 or DHP-dG-4 adducts were detected from the reaction of 7,9-di-GS-DHP with dG. This study represents the first report that the 7-GS-DHP adduct can be a potential reactive metabolite of PAs leading to DNA adduct formation.

  12. Southern Monarchs do not Develop Learned Preferences for Flowers With Pyrrolizidine Alkaloids.

    Science.gov (United States)

    de Oliveira, Marina Vasconcelos; Trigo, José Roberto; Rodrigues, Daniela

    2015-07-01

    Danaus butterflies sequester pyrrolizidine alkaloids (PAs) from nectar and leaves of various plant species for defense and reproduction. We tested the hypothesis that the southern monarch butterfly Danaus erippus shows innate preferences for certain flower colors and has the capacity to develop learned preferences for artificial flowers presenting advantageous floral rewards such as PAs. We predicted that orange and yellow flowers would be innately preferred by southern monarchs. Another prediction is that flowers with both sucrose and PAs would be preferred over those having sucrose only, regardless of flower color. In nature, males of Danaus generally visit PA sources more often than females, so we expected that males of D. erippus would exhibit a stronger learned preference for PA sources than the females. In the innate preference tests, adults were offered artificial non-rewarding yellow, orange, blue, red, green, and violet flowers. Orange and yellow artificial flowers were most visited by southern monarchs, followed by blue and red ones. No individual visited either green or violet flowers. For assessing learned preferences for PA flowers over flowers with no PAs, southern monarchs were trained to associate orange flowers with sucrose plus the PA monocrotaline vs. yellow flowers with sucrose only; the opposite combination was used to train another set of butterflies. In the tests, empty flowers were offered to trained butterflies. Neither males nor females showed learned preferences for flower colors associated with PAs in the training set. Thus, southern monarchs resemble the sister species Danaus plexippus in their innate preferences for orange and yellow flowers. Southern monarchs, similarly to temperate monarchs, might not be as PA-demanding as are other danaine species.

  13. Inter-laboratory comparison study for pyrrolizidine alkaloids in animal feed using spiked and incurred material.

    Science.gov (United States)

    de Nijs, Monique; Elbers, Ingrid J W; Mulder, Patrick P J

    2014-01-01

    Pyrrolizidine alkaloids (PAs) are hepatotoxic metabolites produced by plants. PAs in animal feed can cause acute or chronic intoxications in animals and can be transferred to milk. An inter-laboratory comparison study among 12 laboratories, using their own methods of analysis, was conducted for the detection and quantification of PAs in animal feed. The participants were asked to quantify PAs in a blank test sample, a blank test sample to be spiked with a provided spiking mixture of seven PA standards, and a test sample contaminated with common groundsel (Senecio vulgaris). Ten of the participating laboratories used an LC-MS/MS method, one used an LC-ToF-MS method, and one used a GC-MS method. None of the laboratories reported false-negative samples, while two laboratories reported false-positive results in the blank sample. z-scores were calculated for each laboratory for seven PAs in test samples B and C. z-scores varied considerably between laboratories for the concentrations of the free bases and less for the N-oxides, probably due to the lower levels of the free bases as compared with the N-oxides in the contaminated feed. Questionable or unsatisfactory results for the z-scores were obtained for 8% of the cases for the spiked sample and for 12% of the incurred sample. Three laboratories scored consequently positive or negative results. No preferred method for quantification of PAs in feed could be identified within the methods used for this study due to the relatively small number of participants. It was concluded that this inter-laboratory study shows that the methods used for PA detection need further development for accurate estimation of PAs in contaminated feed.

  14. [Determination of five pyrrolizidine alkaloids in honey by liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Lü, Chen; Ding, Tao; Ma, Xin; Chen, Guosong; Yuan, Fang; Wu, Bin; Shen, Chongyu; Zhang, Rui; Fei, Xiaoqing; Zhang, Xiaoyan; Chen, Lei; Li, Li

    2013-11-01

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of five pyrrolizidine alkaloids (PAs) (monocrotaline, senkirkine, retrorsine, seneciphylline and senecionine) in honey. The honey samples were dissolved in 0.1 mol/L hydrochloric acid solution and a strong-cation exchange column was used to purify and concentrate the target analytes. The separation of the analytes was carried out on a Phenomenex C18 column (100 mm x 4.6 mm, 2.6 microm) using the mobile phases of acetonitrile and 5 mmol/L ammonium acetate-0.1% (volume percentage) formic acid aqueous solution with gradient elution. The separated compounds were detected in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI+). The calibration curves were of good linearity in the range of 1-100 microg/L (r > 0.99). The limit of quantification of the method was 1.0 microg/kg. The average recoveries were between 73.1% to 107.1% at three spiked levels (1, 20 and 50 microg/kg) with the relative standard deviations (RSDs) in the range of 4.1% to 17.0%. The proposed method was applied to different kinds of honey from China, New Zealand, Spain and Australia. The samples included rape, vitex, sunflower, cotton, tilia tree, date, acacia, buckwheat, manuka and eucalyptus honey. Monocrotaline, senkirkine and retrorsine were not detected in the collected honey samples. However, seneciphylline and senecionine were found in most of the honey samples. The concentrations of seneciphylline and senecionine were 11.0 -31.1 microg/kg and 8.3-29.1 microg/kg, respectively.

  15. Characterization and screening of pyrrolizidine alkaloids and N-oxides from various parts of many botanicals and dietary supplements using liquid chromatography high resolution mass spectrometry

    Science.gov (United States)

    The UHPLC-QToF-MS analysis of pyrrolizidine alkaloids from various parts of 37 botanicals and 7 dietary supplements was performed. A separation by LC was achieved using a reversed-phase column and a gradient of water/acetonitrile each containing formic acid as the mobile phase. MS-MS detection was u...

  16. Content of pyrrolizidine alkaloids in the leaves of coltsfoot (Tussilago farfara L. in Poland

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    Artur Adamczak

    2013-11-01

    Full Text Available Coltsfoot (Tussilago farfara L. is a common species, widely used in European and Chinese traditional medicine for the treatment of respiratory diseases. However, raw material from this plant contains hepatotoxic pyrrolizidine alkaloids (PAs. The aim of the study was to determine the variability of the level of PAs (senkirkine and senecionine in leaves of coltsfoot originated from natural populations in Poland. In the phytochemical analysis, 20 samples of T. farfara were used. This plant material was obtained from the Garden of Medicinal Plants in Plewiska near Poznań and originated from different regions of Poland. Coltsfoot leaves were harvested in the middle of July of 2010 and then dried at room temperature. The alkaloid content was detected using the HPLC-DAD method. The amount of PAs in leaves of T. farfara changed in a wide range from 0.06 to 1.04 μg g−1 of dry matter (DM. The content of senkirkine and senecionine was positively correlated (r = 0.68, P = 0.001. There was no statistically significant correlation between the amount of PAs as well as leaf weight and water content in leaves of T. farfara. Our results showed that a medium-sized leaf of coltsfoot (0.33 g DM may contain from 0.02 to 0.34 μg of PAs (on average 0.14 μg. The level of PAs was not associated with the region of Poland, but phytochemical similarity of samples was usually visible at the local scale. Coltsfoot leaves are characterized by a high variability of the content of toxic PAs, much higher than in the case of the main active compounds, especially flavonoids and mucilage. This phytochemical variability is mainly genetically determined (samples came from a garden collection, and it can be increased by environmental factors. Our investigations indicate that Polish natural populations of T. farfara may provide raw material with a low level of toxic PAs.

  17. Stereochemical inversion of pyrrolizidine alkaloids byMechanitis polymnia (Lepidoptera: Nymphalidae: Ithomiinae): Specificity and evolutionary significance.

    Science.gov (United States)

    Trigo, J R; Barata, L E; Brown, K S

    1994-11-01

    Pyrrolizidine alkaloids (PAs), acquired by adults or larvae of Danainae and Ithomiinae butterflies and Arctiidae moths from plants, protect these lepidopterans against predators and are biosynthetic precursors of male sex pheromones. The investigation of PAs in many species of wild-caught adults of Ithomiinae showed lycopsamine (1) [(7R)-OH, (2'S)-OH, (3'S)-OH] as the main alkaloid. In incorporation experiments, PA-free (freshly emerged) adults of the ithomiineMechanitis polymnia were fed seven PAs: lycopsamine and four of its known natural stereoisomers-indicine (2) [(7R)-OH, (2'R)-OH, (3'S)-OH], intermedine (3) [(7R)-OH, (2'S)-OH, (3'R)-OH], rinderine (4) [(7S)-OH, (2'S)-OH, (3'R)-OH], and echinatine (5) [(7S)-OH, (2'S)-OH, (3'S)-OH], and two PAs without the 7-OH: supinine (6) [(2'S)-OH, (3'R)-OH] and amabiline (7) [(2'S)-OH, (3'S)-OH]. Males epimerized PAs 3, 4, and 5 mainly to lycopsamine (1). Females fed these same three PAs changed a smaller proportion to lycopsamine; their lesser capacity to modify PAs corresponds to their normal acquisition of already transformed PAs from males during mating rather than through visits of adults to plant sources of PAs. The alkaloids1 and2, both 7R and 3'S, were incorporated without or with minimum change by males and females. Feeding experiments with6 and7 (males only) showed an inversion at the 3' center of6 and no change in7. The inversion from 7S to 7R (probably via oxyreduction) may be closely related to the evolution of acquisition of PAs by butterflies and moths. Two hypotheses are discussed: (1) The ancestral butterflies are probably adapted to tolerate, assimilate, and use (7R)-PAs (most common in plants; all widespread 1,2-unsaturated macrocyclic PA diesters show this configuration). The development of (7R)-PA receptors in the butterflies could lead to a specialization on this configuration in two ways: to help find PA plants and to utilize these components in sexual chemical communication. A later appearance of (7

  18. The chemical profile of pyrrolizidine alkaloids from selected greek endemic boraginaceae plants determined by gas chromatography/mass spectrometry.

    Science.gov (United States)

    Damianakos, Harilaos; Jeziorek, Malgorzata; Pietrosiuk, Agnieszka; Chinou, Ioanna

    2014-01-01

    Four Greek endemic Boraginaceae plants, Onosma erecta Sibth. & Sm., Onosma kaheirei Teppner, Onosma leptantha Heldr., and Cynoglossum columnae L. (aerial parts), were screened for their content of pyrrolizidine alkaloids (PAs). TLC with the Mattocks-Molyneux visualization reagent was used as a preliminary qualitative test for PA or PA N-oxide detection. The extracts of the species found to contain PAs and their N-oxides were further analyzed by GC/MS, so as to identify their structures by means of the mass spectra and retention index values of known PAs already published in the literature. Twenty-three PAs were identified. For additional peaks, recognized as possible PAs by their MS pattern, no exact structures were tentatively suggested, as a result of lack of matching literature data. Furthermore, a quantitative PA profile of the species was obtained.

  19. Pyrrolizidine alkaloids (PAs) in honey and pollen-legal regulation of PA levels in food and animal feed required.

    Science.gov (United States)

    Kempf, Michael; Reinhard, Annika; Beuerle, Till

    2010-01-01

    Pyrrolizidine alkaloids (PAs) are secondary plant constituents that comprise about 400 different structures and occur in two major forms, a tertiary form and the corresponding N-oxide. PAs containing a 1,2-double bond are pre-toxins and metabolically activated by the action of hepatic P-450 enzymes to toxic pyrroles. Besides the acute toxic effects, the genotoxic and tumorigenicity potential of PAs was demonstrated in some eukaryotic model systems. Recently, the potential PA contamination of food and feeding stuff attracted recurrent great deals of attention. Humans are exposed to these toxins by consumption of herbal medicine, herbal teas, dietary supplements or food containing PA plant material. In numerous studies the potential threat to human health by PAs is stated. In pharmaceuticals, the use of these plants is regulated. Considering the PA concentrations observed especially in authentic honey from PA producing plants and pollen products, the results provoke an international regulation of PAs in food.

  20. Case Report. The first report of pyrrolizidine alkaloid poisoning in a gazelle (Gazella Subgutturosa – histopathologic diagnosis

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    Khordadmehr Monireh

    2016-03-01

    Full Text Available Pyrrolizidine alkaloids (PAs are natural phytotoxins found in thousands of plant species around the world. They are probably the most common poisonous plants affecting livestock, wildlife and humans. The disease occurs almost entirely as a consequence of chronic poisoning and in general ends fatally. In the present study, PAs poisoning was investigated in a gazelle with hepatic encephalopathy associated with severe neurologic signs. The main clinical signs included head pressing, progressive depression and weakness, ataxia and reluctance to move, turn the head to the left and to paddle, hyperesthesia and decreased food intake. Histopathological examination revealed major lesions in the liver consisting of severe hepatocyte megalocytosis and hypertrophy with nuclei enlargement, mild bile duct hyperplasia, centriacinar fatty change and hepatocellular necrosis. Moreover, pulmonary congestion and edema with endothelium necrosis and alveolar septa thickening, severe congestion in vessels of the brain and meninges, and myocardial necrosis were observed.

  1. Pyrrolizidine Alkaloids and Fatty Acids from the Endemic Plant Species Rindera umbellata and the Effect of Lindelofine-N-oxide on Tubulin Polymerization

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    Vlatka V. Vajs

    2013-09-01

    Full Text Available The examination of the aerial parts, roots, and seeds of the endemic plant Rindera umbellata is reported in this paper for the first time. Phytochemical investigation of R. umbellata led to the isolation and characterization of ten pyrrolizidine alkaloids and eleven fatty acids in the form of triglycerides. Pyrrolizidine alkaloids 1–9 were found in the aerial parts, 7 and 8 in the roots, and 6–10, together with eleven fatty acids, in the seeds of this plant species. The structures of compounds 1–10 were established based on spectroscopic studies (1H- and 13C-NMR, 2D NMR, IR and CI-MS. After trans-esterification, methyl esters of the fatty acids were analyzed using GC-MS. The effect of lindelofine-N-oxide (7 on tubulin polymerization was determined.

  2. Pyrrolizidine alkaloids and fatty acids from the endemic plant species Rindera umbellata and the effect of lindelofine-N-oxide on tubulin polymerization.

    Science.gov (United States)

    Mandić, Boris M; Simić, Milena R; Vučković, Ivan M; Vujisić, Ljubodrag V; Novaković, Miroslav M; Trifunović, Snežana S; Nikolić-Mandić, Snežana D; Tešević, Vele V; Vajs, Vlatka V; Milosavljević, Slobodan M

    2013-09-03

    The examination of the aerial parts, roots, and seeds of the endemic plant Rindera umbellata is reported in this paper for the first time. Phytochemical investigation of R. umbellata led to the isolation and characterization of ten pyrrolizidine alkaloids and eleven fatty acids in the form of triglycerides. Pyrrolizidine alkaloids 1-9 were found in the aerial parts, 7 and 8 in the roots, and 6-10, together with eleven fatty acids, in the seeds of this plant species. The structures of compounds 1-10 were established based on spectroscopic studies (¹H- and ¹³C-NMR, 2D NMR, IR and CI-MS). After trans-esterification, methyl esters of the fatty acids were analyzed using GC-MS. The effect of lindelofine-N-oxide (7) on tubulin polymerization was determined.

  3. Further evidence on the intramolecular lactonization in rat liver microsomal metabolism of 12-O-acetylated retronecine-type pyrrolizidine alkaloids.

    Science.gov (United States)

    Tang, Jun; Wang, Zhengtao; Akao, Teruaki; Hattori, Masao

    2013-11-01

    We have previously found evidence of intramolecular lactonization in rat liver microsomal metabolism of isoline, a 12-O-acetylated pyrrolizidine alkaloid. In this study, the metabolism of another 12-O-acetylated pyrrolizidine alkaloid, acetylduciformine, by the proposed transformation pathway was investigated under the same incubation conditions. Two deacetylated metabolites from acetylduciformine were isolated and purified by chromatographic methods, and further characterized based on their physical properties and spectral data. One metabolite (lankongensisine A) was the lactone of another one (duciformine). Both compounds were first obtained as hydrolyzed metabolites from acetylduciformine by rat liver microsomes. More importantly, the present study provided further evidence for the intramolecular lactonization in the microsomal metabolism of 12-O-acetylated retronecine-type PAs.

  4. Stereocontrolled cyclic nitrone cycloaddition strategy for the synthesis of pyrrolizidine and indolizidine alkaloids.

    Science.gov (United States)

    Brandi, Alberto; Cardona, Francesca; Cicchi, Stefano; Cordero, Franca M; Goti, Andrea

    2009-08-10

    The synthesis of polyhydroxylated indolizidines and pyrrolizidines belonging to the class of iminosugars, endowed with a vast and assorted biological activity, can be achieved in a straightforward manner by a general strategy consisting of a highly stereoselective 1,3-dipolar cycloaddition of polyhydroxylated pyrroline-N-oxides followed by simple transformations of the isoxazolidine adducts. The strategy allows the complete control of the relative and absolute stereochemistry of the numerous stereogenic centers decorating these compounds.

  5. Multi-analyte high performance liquid chromatography coupled to high resolution tandem mass spectrometry method for control of pesticide residues, mycotoxins, and pyrrolizidine alkaloids.

    Science.gov (United States)

    Dzuman, Zbynek; Zachariasova, Milena; Veprikova, Zdenka; Godula, Michal; Hajslova, Jana

    2015-03-10

    A new reliable and highly sensitive method based on high performance liquid chromatographic (HPLC) separation and high resolution tandem mass spectrometric detection (HRMS/MS) has been developed and validated for determination of 323 pesticide residues, 55 mycotoxins, and 11 plant toxins represented by pyrrolizidine alkaloids. The method was validated for three matrices, leek, wheat, and tea differing in nature/amount of co-extracts that may cause various matrix effects. For target analytes isolation, optimized QuEChERS-based (quick, easy, cheap, effective, rugged, and safe) extraction procedure was employed. Spectral HRMS/MS library has been established providing an entire spectrum of fragment ions for each analyte, which allows unbiased identification and confirmation of target compounds. The limits of quantification (LOQs) of target analytes were below 10 μg kg(-1) for 82%, 81%, and 61% for matrices leek, wheat, and tea, respectively. Recoveries were in the acceptable range (70-120%) according to SANCO/12571/2013 for most of target analytes, except for highly polar 'masked' mycotoxin deoxynivalenol-3-glucoside with recoveries 35%, 47%, and 42% for matrices leek, wheat, and tea, respectively. The linearities of calibration curves expressed as coefficients of determination were in the range of 0.9661-1.000, and repeatabilities expressed as relative standard deviations (RSDs) at LOQs lied in the range of 0.25-13.51%. The trueness of the method was verified using several certified reference materials (CRMs) and proficiency test samples.

  6. A new approach for simultaneous screening and quantification of toxic pyrrolizidine alkaloids in some potential pyrrolizidine alkaloid-containing plants by using ultra performance liquid chromatography-tandem quadrupole mass spectrometry.

    Science.gov (United States)

    Zhou, Yan; Li, Na; Choi, Franky Fung-Kei; Qiao, Chun-Feng; Song, Jing-Zheng; Li, Song-Lin; Liu, Xin; Cai, Zong-Wei; Fu, Peter P; Lin, Ge; Xu, Hong-Xi

    2010-11-29

    A rapid, but sensitive and selective method for simultaneous screening and quantification of toxic pyrrolizidine alkaloids (PAs) by ultra performance liquid-chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) on a tandem quadrupole mass spectrometer (TQ-MS) is described. This was accomplished by incorporating the precursor ion scan (PIS) acquisition and multiple reaction monitoring (MRM) acquisition in the same UPLC-MS/MS run. Notably, the developed PIS approach for detecting two pairs of characteristic product ions at m/z 120/138 or 168/150, allowed specific identification of toxic retronecine and otonecine types PAs. This PIS method is highly sensitive with over 10-fold sensitivity improvement upon previously published LC-MS method. Moreover, this new approach is suitable for high sample throughput and was applied to the screening and quantifying toxic PAs in 22 samples collected from seven Parasenecio species and four Senecio species. In addition, coupling the MRM with PIS approach generated quantitative results equivalent to those obtained by conventional MRM-only approach. This coupled MRM with PIS approach could provide both qualitative and quantitative results without the need of repetitive analyses.

  7. Pyrrolizidine Alkaloids: Potential Role in the Etiology of Cancers, Pulmonary Hypertension, Congenital Anomalies, and Liver Disease.

    Science.gov (United States)

    Edgar, John A; Molyneux, Russell J; Colegate, Steven M

    2015-01-20

    Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute poisoning can also result from deliberate or accidental consumption of 1,2-dehydropyrrolizidine alkaloid-containing herbal medicines, teas, and spices. In recent years, it has been confirmed that there is also significant, low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids in many countries due to consumption of common foods such as honey, milk, eggs, salads, and meat. The level of 1,2-dehydropyrrolizidine alkaloids in these foods is generally too low and too intermittent to cause acute toxicity. However, these alkaloids are genotoxic and can cause slowly developing chronic diseases such as pulmonary arterial hypertension, cancers, cirrhosis, and congenital anomalies, conditions unlikely to be easily linked with dietary exposure to 1,2-dehydropyrrolizidine alkaloids, especially if clinicians are unaware that such dietary exposure is occurring. This Perspective provides a comprehensive review of the acute and chronic toxicity of 1,2-dehydropyrrolizidine alkaloids and their potential to initiate certain chronic diseases, and suggests some associative considerations or indicators to assist in recognizing specific cases of diseases that may have resulted from dietary exposure to these hazardous natural substances. If it can be established that low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids is a significant cause of some of these costly and debilitating diseases, then this should lead to initiatives to reduce the level of these alkaloids in the food chain.

  8. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia—A Case of Novel Weapons?

    Science.gov (United States)

    Skoneczny, Dominik; Weston, Paul A.; Zhu, Xiaocheng; Gurr, Geoff M.; Callaway, Ragan M.; Weston, Leslie A.

    2015-01-01

    Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant’s capacity to deter natural enemies in its invaded range through production of novel weapons. PMID:26561809

  9. Survey of pyrrolizidine alkaloids in teas and herbal teas on the Swiss market using HPLC-MS/MS.

    Science.gov (United States)

    Mathon, Caroline; Edder, Patrick; Bieri, Stefan; Christen, Philippe

    2014-11-01

    Pyrrolizidine alkaloids (PAs) are a large class of natural compounds amongst which the esterified 1,2-unsaturated necine base is toxic for humans and livestock. In the present study, a method was developed and validated for the screening and quantification of nine PAs and one PA N-oxide in teas (Camellia sinensis (L.) O. Kuntze) and herbal teas (camomile, fennel, linden, mint, rooibos, verbena). Samples were analysed by HPLC on a RP-column, packed with sub-2 μm core-shell particles, and quantified using tandem mass spectrometry operating in the positive electrospray ionisation mode. These PAs and some of their isomers were detected in a majority of the analysed beverages (50/70 samples). In 24 samples, PA concentrations were above the limit of quantification and the sum of the nine targeted PAs was between 0.021 and 0.954 μg per cup of tea. Thus, in some cases, total concentrations exceed the maximum daily intake recommended by the German Federal Institute for Risk Assessment and the UK's Committee On Toxicity (i.e. 0.007 μg kg(-1) bw).

  10. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia--A Case of Novel Weapons?

    Science.gov (United States)

    Skoneczny, Dominik; Weston, Paul A; Zhu, Xiaocheng; Gurr, Geoff M; Callaway, Ragan M; Weston, Leslie A

    2015-11-06

    Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant's capacity to deter natural enemies in its invaded range through production of novel weapons.

  11. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia—A Case of Novel Weapons?

    Directory of Open Access Journals (Sweden)

    Dominik Skoneczny

    2015-11-01

    Full Text Available Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs and their N-oxides (PANOs was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17 by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant’s capacity to deter natural enemies in its invaded range through production of novel weapons.

  12. UPLC TOF MS for sensitive quantification of naturally occurring pyrrolizidine alkaloids in Petasites hybridus extract (Ze 339).

    Science.gov (United States)

    Schenk, Alexander; Siewert, Beate; Toff, Stephan; Drewe, Jürgen

    2015-08-01

    Due to increasing regulatory awareness of their hepatotoxic, genotoxic and possibly carcinogenic potential, pyrrolizidine alkaloid (PA) content has to be thoroughly monitored in herbal medicinal preparations. Recently, new very low PA regulatory threshold concentrations have been requested by the authorities. Therefore, a highly sensitive and reproducible UPLC TOF MS method for the quantification of the PAs senkirkine, senecionine, seneciphylline, senecionine-N-oxide and seneciphylline-N-oxide in a CO2-extract of Petasites hybridus leaves (Ze 339) has been developed. The limit of quantification (LOQ) was 2ppb for all PAs. Recovery at the LOQ was between 88.9 and 141.9%, the repeatability precision between 3.5 and 13.6%. Linearity of the five PAs showed correlation coefficients between 0.9995 and 0.9998 and coefficients of variation between 7.44 and 8.56%. A working range between 2 ppb and 200 ppb could be fixed. In the tested batches of the P. hybridus extract Ze 339, the absence of PAs could be demonstrated. In conclusion, this assay allows to determine trace PA concentrations in P. hybridus extract Ze 339, making it suitable for analytical PA monitoring in accordance with regulatory requirements.

  13. Chemical Diversity Investigation of Hepatotoxic Pyrrolizidine Alkaloids in Qianliguang (Senecio scandens) and Related Species by UHPLC-QTOF-MS1

    Institute of Scientific and Technical Information of China (English)

    Lin Zhua; Na Li; Jian-Qing Ruan; Peter P. Fu; Zhong-Zhen Zhao; Ge Lina

    2015-01-01

    Objective: Qianliguang (Senecio scandens) is a common Chinese medicinal herb. Qianliguang-containing herbal proprietary products are registered as over-the-counter remedies in China and exported to Western countries. The presence of hepatotoxic pyrrolizidine alkaloids (PAs) has raised concerns about the safety of using Qianliguang and its products. The present study aims at investigation of different types of PAs present in Qianliguang collected from representative locations in China. Methods: In this study, a simple but specific UHPLC-QTOF-MS method for the determination of toxic PAs was developed, based on the characteristic fragment ions specific to different types of PAs. It was successfully applied for the identification and distinguishing of PAs present in Qianliguang and related Senecio species growing in different locations of China. Results: Significant diversity of the PA types and quantities were revealed among the samples tested. The estimated total amounts of toxic PAs in three of the samples exceed the toxic limits of PA intake restricted by WHO, demonstrating the timely and highly demand for regulating both types and quantities of PAs present in Qianliguang. Conclusions: This study provides the methodology for simultaneous identification and quantification of PAs present in herbs without requiring corresponding standards, which could be further used for more systematic investigations of the PA distribution in Qianliguang and other PA-containing herbs.

  14. Pyrrolizidine and tropane alkaloids in teas and the herbal teas peppermint, rooibos and chamomile in the Israeli market.

    Science.gov (United States)

    Shimshoni, Jakob Avi; Duebecke, Arne; Mulder, Patrick P J; Cuneah, Olga; Barel, Shimon

    2015-01-01

    Dehydro pyrrolizidine alkaloids (dehydro PAs) are carcinogenic phytotoxins prevalent in the Boraginaceae, Asteraceae and Fabaceae families. Dehydro PAs enter the food and feed chain by co-harvesting of crops intended for human and animal consumption as well as by carry-over into animal-based products such as milk, eggs and honey. Recently the occurrence of dehydro PAs in teas and herbal teas has gained increasing attention from the EU, due to the high levels of dehydro PAs found in commercially available teas and herbal teas in Germany and Switzerland. Furthermore, several tropane alkaloids (TAs, e.g. scopolamine and hyoscyamine) intoxications due to the consumption of contaminated herbal teas were reported in the literature. The aim of the present study was to determine the dehydro PAs and TAs levels in 70 pre-packed teabags of herbal and non-herbal tea types sold in supermarkets in Israel. Chamomile, peppermint and rooibos teas contained high dehydro PAs levels in almost all samples analysed. Lower amounts were detected in black and green teas, while no dehydro PAs were found in fennel and melissa herbal teas. Total dehydro PAs concentrations in chamomile, peppermint and rooibos teas ranged from 20 to 1729 μg/kg. Except for black tea containing only mono-ester retrorsine-type dehydro PAs, all other teas and herbal teas showed mixed patterns of dehydro PA ester types, indicating a contamination by various weed species during harvesting and/or production. The TA levels per teabag were below the recommended acute reference dose; however, the positive findings of TAs in all peppermint tea samples warrant a more extensive survey. The partially high levels of dehydro PAs found in teas and herbal teas present an urgent warning letter to the regulatory authorities to perform routine quality control analysis and implement maximum residual levels for dehydro PAs.

  15. Development and validation of a rapid multiplex ELISA for pyrrolizidine alkaloids and their N-oxides in honey and feed.

    Science.gov (United States)

    Oplatowska, Michalina; Elliott, Christopher T; Huet, Anne-Catherine; McCarthy, Mark; Mulder, Patrick P J; von Holst, Christoph; Delahaut, Philippe; Van Egmond, Hans P; Campbell, Katrina

    2014-01-01

    Pyrrolizidine alkaloids (PAs) are a group of plant secondary metabolites with carcinogenic and hepatotoxic properties. When PA-producing plants contaminate crops, toxins can be transferred through the food chain and cause illness in humans and animals, most notably hepatic veno-occlusive disease. Honey has been identified as a direct risk of human exposure. The European Food Safety Authority has recently identified four groups of PAs that are of particular importance for food and feed: senecionine-type, lycopsamine-type, heliotrine-type and monocrotaline-type. Liquid or gas chromatography methods are currently used to detect PAs but there are no rapid screening assays available commercially. Therefore, the aim of this study was to develop a rapid multiplex ELISA test for the representatives of three groups of alkaloids (senecionine, lycopsamine and heliotrine types) that would be used as a risk-management tool for the screening of these toxic compounds in food and feed. The method was validated for honey and feed matrices and was demonstrated to have a detection capability less than 25 μg/kg for jacobine, lycopsamine, heliotrine and senecionine. The zinc reduction step introduced to the extraction procedure allows for the additional detection of the presence of N-oxides of PAs. This first multiplex immunoassay for PA detection with N-oxide reduction can be used for the simultaneous screening of 21 samples for >12 PA analytes. Honey samples (n = 146) from various origins were analysed for PA determination. Six samples were determined to contain measurable PAs >25 μg/kg by ELISA which correlated to >10 μg/kg by LC-MS/MS.

  16. Complete 1H NMR assignments of pyrrolizidine alkaloids and a new eudesmanoid from Senecio polypodioides.

    Science.gov (United States)

    Villanueva-Cañongo, Claudia; Pérez-Hernández, Nury; Hernández-Carlos, Beatriz; Cedillo-Portugal, Ernestina; Joseph-Nathan, Pedro; Burgueño-Tapia, Eleuterio

    2014-05-01

    Chemical investigation of the aerial parts of Senecio polypodioides lead to the isolation of the new eudesmanoid 1β-angeloyloxyeudesm-7-ene-4β,9α-diol (1) and the known dirhamnosyl flavonoid lespidin (3), while from roots, the known 7β-angeloyloxy-1-methylene-8α-pyrrolizidine (5) and sarracine N-oxide (6), as well as the new neosarracine N-oxide (8), were obtained. The structure of 1 and 8 was elucidated by spectral means. Complete assignments of the (1)H NMR data for 5, 6, sarracine (7), and 8 were made using one-dimensional and two-dimensional NMR experiments and by application of the iterative full spin analysis of the PERCH NMR software.

  17. Pyrrolizidine alkaloids: Potential role in the etiology of cancers, pulmonary hypertension, congenital anomalies, and liver disease

    Science.gov (United States)

    Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute...

  18. Persistence of echimidine, a hepatotoxic pyrrolizidine alkaloid, from honey into mead

    Science.gov (United States)

    Honey produced by bees foraging on Echium plantagineum is known to contain dehydropyrrolizidine alkaloids characteristic of the plant. Following a prolific growth of E. plantagineum in the wake of Australian bushfires, two samples of mead, a fermented drink made from honey, and the honey used to pre...

  19. A rapid and highly specific method to evaluate the presence of pyrrolizidine alkaloids in Borago officinalis seed oil.

    Science.gov (United States)

    Vacillotto, Giulio; Favretto, Donata; Seraglia, Roberta; Pagiotti, Rita; Traldi, Pietro; Mattoli, Luisa

    2013-10-01

    Pyrrolizidine alkaloids (PAs) are complex molecules, present in plants as free bases and N-oxides. They are known for their hepatotoxicity, and consequently there is a health risk associated with the use of medicinal herbs that contain PAs. Unfortunately, there is no international regulation of PAs in foods, unlike those for herbs and medicines: in particular, for herbal preparation or herbal extracts, the total PA content must not exceed 1 µg/kg or 1 µg/l, respectively. Borago officinalis seed oil is a source of γ-linolenic acid, and its use is increased in both pharmaceutical and health food industries. Even if studies based on gas chromatography and TLC methods showed that PAs are not co-extracted with oil, the development of a rapid and sensitive method able to evaluate the presence of PAs in commercially available products is surely of interest. The presence of PAs in a commercially available Borago officinalis seed oil was tested either in the oil sample diluted with tetrahydrofuran/methanol (MeOH)/H2 O (85/10/5 v:v:v) or after extraction with MeOH/H2 O (50/50 v:v) solution The samples were analysed by electrospray ionization in positive ion mode and in high mass resolution (60,000) conditions. In both cases to evaluate the effectiveness of the method, spiking experiments were performed adding known amount of two PA standards to the borage seed oil. A limit of detection in the order of 200 ppt was determined for these two compounds, strongly analogous to Borago officinalis seed oil PAs. Consequently, if present, PAs level in Borago officinalis seed oil must lower than 200 ppt.

  20. Lack of metabolic activation and predominant formation of an excreted metabolite of nontoxic platynecine-type pyrrolizidine alkaloids.

    Science.gov (United States)

    Ruan, Jianqing; Liao, Cangsong; Ye, Yang; Lin, Ge

    2014-01-21

    Pyrrolizidine alkaloid (PA) poisoning is well-known because of the intake of PA-containing plant-derived natural products and PA-contaminated foodstuffs. Based on different structures of the necine bases, PAs are classified into three types: retronecine, otonecine, and platynecine type. The former two type PAs possessing an unsaturated necine base with a 1,2-double bond are hepatotoxic due to the P450-mediated metabolic activation to generate reactive pyrrolic ester, which interacts with cellular macromolecules leading to toxicity. With a saturated necine base, platynecine-type PAs are reported to be nontoxic and their nontoxicity was hypothesized to be due to the absence of metabolic activation; however, the metabolic pathway responsible for their nontoxic nature is largely unknown. In the present study, to prove the absence of metabolic activation in nontoxic platynecine-type PAs, hepatic metabolism of platyphylline (PLA), a representative platynecine-type PA, was investigated and directly compared with the representatives of two toxic types of PAs in parallel. By determining the pyrrolic ester-derived glutathione conjugate, our results confirmed that the major metabolic pathway of PLA did not lead to formation of the reactive pyrrolic ester. More interestingly, having a metabolic rate similar to that of toxic PAs, PLA also underwent oxidative metabolisms mediated by P450s, especially P450 3A4, the same enzyme that catalyzes metabolic activation of two toxic types of PAs. However, the predominant oxidative dehydrogenation pathway of PLA formed a novel metabolite, dehydroplatyphylline carboxylic acid, which was water-soluble, readily excreted, and could not interact with cellular macromolecules. In conclusion, our study confirmed that the saturated necine bases determine the absence of metabolic activation and thus govern the metabolic pathway responsible for the nontoxic nature of platynecine-type PAs.

  1. Testing the generalist-specialist dilemma: the role of pyrrolizidine alkaloids in resistance to invertebrate herbivores in Jacobaea species.

    Science.gov (United States)

    Wei, Xianqin; Vrieling, Klaas; Mulder, Patrick P J; Klinkhamer, Peter G L

    2015-02-01

    Plants produce a diversity of secondary metabolites (SMs) to protect them from generalist herbivores. On the other hand, specialist herbivores use SMs for host plant recognition, feeding and oviposition cues, and even sequester SMs for their own defense. Therefore, plants are assumed to face an evolutionary dilemma stemming from the contrasting effects of generalist and specialist herbivores on SMs. To test this hypothesis, bioassays were performed with F2 hybrids from Jacobaea species segregating for their pyrrolizidine alkaloids (PAs), using a specialist flea beetle (Longitarsus jacobaeae) and a generalist slug (Deroceras invadens). Our study demonstrated that while slug feeding damage was negatively correlated with the concentration of total PAs and that of senecionine-like PAs, flea beetle feeding damage was not affected by PAs. It was positively correlated though, with leaf fresh weight. The generalist slug was deterred by senecionine-like PAs but the specialist flea beetle was adapted to PAs in its host plant. Testing other herbivores in the same plant system, it was observed that the egg number of the specialist cinnabar moth was positively correlated with jacobine-like PAs, while the silver damage of generalist thrips was negatively correlated with senecionine- and jacobine-like PAs, and the pupae number of generalist leaf miner was negatively correlated with otosenine-like PAs. Therefore, while the specialist herbivores showed no correlation whatsoever with PA concentration, the generalist herbivores all showed a negative correlation with at least one type of PA. We concluded that the generalist herbivores were deterred by different structural groups of PAs while the specialist herbivores were attracted or adapted to PAs in its host plants.

  2. 白背三七叶中吡咯里西啶生物碱的LC-MSn检测%Detection of pyrrolizidine alkaloids from leaf of Gynura divaricata by LC-MSn

    Institute of Scientific and Technical Information of China (English)

    李丽梅; 张涵庆; 吕寒; 李维林; 徐德然; 郭巧生

    2008-01-01

    @@ 广泛分布于植物中的吡咯里西啶生物碱(pyrrolizidine alkaloids,PAs)由具有双稠吡咯啶环的氨基醇与不同有机酸缩合而成,醇部分为裂碱(necine),酸部分为裂酸(necic acid).

  3. Simultaneous determination of sesquiterpenes and pyrrolizidine alkaloids from the rhizomes of Petasites hybridus (L.) G.M. et Sch. and dietary supplements using UPLC-UV and HPLC-TOF-MS methods.

    Science.gov (United States)

    Avula, Bharathi; Wang, Yan-Hong; Wang, Mei; Smillie, Troy J; Khan, Ikhlas A

    2012-11-01

    UPLC-UV and HPLC-TOF-MS methods have been developed for the analysis of major sesquiterpenes and pyrrolizidine alkaloids from rhizomes of Petasites hybridus (L.) G.M. et Sch. (Family, Asteracea) and dietary supplements claiming to contain P. hybridus. The best results were obtained with Acquity UPLC™ HSS T3 (100 mm × 2.1 mm, I.D., 1.8 μm) column system using a gradient elution with a mobile phase consisting of ammonium formate (50mM) and acetonitrile (0.05% formic acid) at a constant flow rate of 0.25 mL/min via UPLC-UV. The newly developed method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy and precision. The limits of detection were found to be 5 μg/mL and 0.1 μg/mL for pyrrolizidine alkaloids and sesquiterpenes, respectively by UPLC-UV and 0.001 and 0.01 μg/mL, respectively using HPLC-TOF-MS. The methods were successfully used to analyze different P. hybridus market products, as well as to distinguish between two other Petasites species. The total content of petasins was found to be in the range of 0.02-11.6 mg/dosage form for 15 dietary supplements and no petasins were detected in an additional six dietary supplements. Additionally, pyrrolizidine alkaloids, which are considered to be toxic for the liver, were detected in seven dietary supplements. The amount of petasin in seven dietary supplements was found to be within limits of label claim and no pyrrolizidine alkaloids were detected. HPLC-mass spectrometry coupled with electrospray ionization (ESI) interface method is described for the identification and confirmation of sesquiterpenes and pyrrolizidine alkaloids from plant extracts and dietary supplements that claim to contain P. hybridus as well as different species of Petasites.

  4. Structure-activity relationships of pyrrolizidine alkaloids in insect chemical defense against the orb-weaving spider Nephila clavipes.

    Science.gov (United States)

    Silva, Karina Lucas; Trigo, José Roberto

    2002-04-01

    Pyrrolizidine alkaloids (PAs) are known to protect Arctiidae moths and Danainae and Ithomiinae butterflies against the orb-weaving spider Nephila clavipes (Araneae, Araneidae, Tetragnathinae), which liberates adults of these insects unharmed from its web. We tested against this spider the role of eight PAs and one derived structure [an 89:11 mixture of the 12-membered macrocyclic diester free base integerrimine and senecionine and the respective N-oxide; two hydrolysis products from this mixture (the necine base retronecine, its respective N-oxide, and a mixture of integerriminic and senecionic necic acids); the 12-membered macrocyclic senkirkine; the 9-O-monoester free base senecioylretronecine and its respective N-oxide; and the 9-O-monoester free base callimorphine (a PA biosynthesized only by insects from retronecine)]. The mixture integerrimine-senecionine N-oxide seems to be more active than the respective free base [LibD50 (liberation dose 50) = 0.042 and 0.153 microg/dry weight of prey, respectively], but the difference in activity between the N-oxide and free base of the 9-O-monoester senecioylretronecine was slight (LibD50 = 0.167 and 0.104, respectively). Senkirkine, an otonecine base PA that does not form N-oxide and is not found in insects, was the less active, showing the highest LibD50 (0.354). The difference in antipredator activity between N-oxides and free bases from macrocyclic diesters and monoesters may be correlated with physicochemical properties of these molecules in interaction with the Nephila receptors. For the active structures, there was a significant correlation between dosage and antipredator activity. Both forms of retronecine and a necic acid mixture were inactive, supporting the hypothesis that PAs biosynthesized by insects from retronecine were originally produced and stored in order to optimize chemical defense. Comparison of dose/activity data with reported amounts of PAs in butterflies suggested that, in general, PA

  5. The ecological context of pyrrolizidine alkaloids in food, feed and forage: an overview.

    Science.gov (United States)

    Boppré, Michael

    2011-03-01

    Plant-produced 1,2-dehydropyrrolizidine ester alkaloids and their N-oxides (PAs) not only cause acute poisoning of humans and livestock, but also the likely harmful cryptic effects of chronic exposure pose particular food safety risks that need to be addressed for consumer protection. In natural contexts, however, PAs cause few or no problems. Rather, these plant secondary metabolites are important elements of ecosystems and plant-animal relationships; the existence and persistence of many PA-adapted organisms, in various ways, depends on the presence of PA-containing plants or even on PAs as such. PA plants are widely distributed among unrelated families of the plant kingdom; there is great structural diversity of PAs, and the amounts of PAs produced are subject to great variation due to multiple causes. These realities, coupled with many deficiencies in our scientific understanding, make the presence and roles of PAs in nature a subject with limited potential for valid generalisations and predictions, and complex and difficult to summarise. PAs, their producer plants and their users are integral parts of ecosystems worldwide, and we have to learn to live with these allelochemicals by accepting the presence of some harmful natural chemicals in the environment and by taking regulatory action to reduce health risks to humans. Regulations for consumer protection are long overdue. However, any such measures must be flexible enough to accommodate the findings of future research. Transdisciplinary efforts are required to fill gaps in the knowledge and to come up with additional means to monitor the presence of PAs in food and feed.

  6. Statement on the risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements

    DEFF Research Database (Denmark)

    Petersen, Annette

    that there was a possible health concern for those toddlers and children who are high consumers of honey. A new exposure assessment including new occurrence data was published by EFSA in 2016 and was used to update the risk characterisation. The CONTAM Panel established a new Reference Point of 237 μg/kg body weight per......EFSA was asked by the European Commission to deliver a scientific opinion on the risks for human health related to the presence of pyrrolizidine alkaloids (PAs) in honey, tea, herbal infusions and food supplements and to identify the PAs of relevance in the aforementioned food commodities...... day to assess the carcinogenic risks of PAs, and concluded that there is a possible concern for human health related to the exposure to PAs, in particular for frequent and high consumers of tea and herbal infusions. The Panel noted that consumption of food supplements based on PA-producing plants...

  7. Pyrrolizidine alkaloids pyrrolams A-D: A survey of synthetic efforts, biological activity, and studies on their stability

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Tilve, S.G.

    as new drugs paradigm for the treatment of many diseases such as cancer, viral infections, diabetes, and so-forth. 10 N N R 2 H OH N OH H OH Pyrrolizidine Crotanecine R 1 =H, R 2 = H Supinidine R 1 =H, R 2 =OH Retronecine R 1 =OH,R 2 =H Heliotridine N...

  8. A stereoselective approach to indolizidine and pyrrolizidine alkaloids: total synthesis of (-)-lentiginosine, (-)-epi-lentiginosine and (-)-dihydroxypyrrolizidine.

    Science.gov (United States)

    Kauloorkar, Shruti Vandana; Jha, Vishwajeet; Jogdand, Ganesh; Kumar, Pradeep

    2014-07-07

    A simple and highly efficient approach to hydroxylated pyrrolizidine and indolizidine is developed from an aldehyde as a starting material using organocatalytic and asymmetric dihydroxylation reactions as key steps. Its application to the total synthesis of (-)-lentiginosine, (-)-epi-1,2-lentiginosine and (-)-dihydroxypyrrolizidine is also reported.

  9. 吡咯里西啶生物碱的药理作用、毒性及药(毒)物代谢动力学研究进展%Advance on pharmacologic actions, toxicity and pharmacokinetics of pyrrolizidine alkaloids

    Institute of Scientific and Technical Information of China (English)

    高江国; 王长虹; 李岩; 王峥涛

    2009-01-01

    含有吡咯里西啶生物碱的植物在传统医药中有广泛使用,其肝毒性引起广泛关注.作者综述了吡咯里西啶生物碱的药理作用、毒性和药(毒)物代谢动力学等方面的研究进展,以便为后期研究提供基础.%Plants containing pyrrolizidine alkaloids were widely used in traditional medicine. Its hepatotoxicity is main toxicity as well known internationally.In order to providing some foundation for the future studies, the advancement on the pharmacologic actions,toxicity, and pharmacokinetics or toxicokinetics of pyrrolizidine alkaloids was reviewed.

  10. In silico prediction of the site of oxidation by cytochrome P450 3A4 that leads to the formation of the toxic metabolites of pyrrolizidine alkaloids.

    Science.gov (United States)

    Fashe, Muluneh M; Juvonen, Risto O; Petsalo, Aleksanteri; Vepsäläinen, Jouko; Pasanen, Markku; Rahnasto-Rilla, Minna

    2015-04-20

    In humans, the metabolic bioactivation of pyrrolizidine alkaloids (PAs) is mediated mainly by cytochrome P450 3A4 (CYP3A4) via the hydroxylation of their necine bases at C3 or C8 of heliotridine- and retronecine-type PAs or at the N atom of the methyl substituent of otonecine-type PAs. However, no attempts have been made to identify which C atom is the most favorable site for hydroxylation in silico. Here, in order to determine the site of hydroxylation that eventually leads to the formation of the toxic metabolites produced from lasiocarpine, retrorsine, and senkirkin, we utilized the ligand-based electrophilic Fukui function f(-)(r) and hydrogen-bond dissociation energies (BDEs) as well as structure-based molecular docking. The ligand-based computations revealed that the C3 and C8 atoms of lasiocarpine and retrorsine and the C26 atom of senkirkin were chemically the most susceptible locations for electrophilic oxidizing reactions. Similarly, according to the predicted binding orientation in the active site of the crystal structure of human CYP3A4 (PDB code: 4I4G ), the alkaloids were positioned in such a way that the C3 atom of lasiocarpine and retrorsine and the C26 of senkirkin were closest to the catalytic heme Fe. Thus, it is concluded that the C3 atom of lasiocarpine and retrorsine and C26 of senkirkin are the most favored sites of hydroxylation that lead to the production of their toxic metabolites.

  11. Detection of pyrrolizidine alkaloids using flow analysis with both acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Gorman, Bree A. [School of Biological and Chemical Sciences, Deakin University, Geelong, Vic. 3217 (Australia); Barnett, Neil W. [School of Biological and Chemical Sciences, Deakin University, Geelong, Vic. 3217 (Australia)]. E-mail: barnie@deakin.edu.au; Bos, Richard [School of Biological and Chemical Sciences, Deakin University, Geelong, Vic. 3217 (Australia)

    2005-06-13

    For the first time, analytically useful chemiluminescence was elicited from the reactions of the pyrrolizidine alkaloids. Heliotrine, retronecine, supinine, monocrotaline and echinatine N-oxide yielded chemiluminescence upon reaction with tris(2,2'-bipyridyl)ruthenium(II) whilst lasiocarpine, its N-oxide and supinine elicited light upon reaction with acidic potassium permanganate. Detection limits for heliotrine were 1.25 x 10{sup -7} M and 9 x 10{sup -9} M for tris(2,2'-bipyridyl)ruthenium(III) perchlorate with flow injection analysis (FIA) and the silica-immobilised reagent (4-[4-(dichloromethylsilanyl)-butyl]-4'-methyl-2,2'-bipyridine)bis (2,2'-bipyridyl)ruthenium(II) with sequential injection analysis (SIA), respectively. Lasiocarpine was detectable at 1.4 x 10{sup -7} M using acidic potassium permanganate with FIA. Additionally, the silica-immobilised reagent was optimised with respect to the oxidant (ammonium ceric nitrate) concentration and the aspiration times which afforded a detection limit for codeine of 5 x 10{sup -10} M using SIA.

  12. Characterization and screening of pyrrolizidine alkaloids and N-oxides from botanicals and dietary supplements using UHPLC-high resolution mass spectrometry.

    Science.gov (United States)

    Avula, Bharathi; Sagi, Satyanarayanaraju; Wang, Yan-Hong; Zweigenbaum, Jerry; Wang, Mei; Khan, Ikhlas A

    2015-07-01

    The UHPLC-QToF-MS analysis of pyrrolizidine alkaloids (PAs) from various parts of 37 botanicals and 7 products was performed. A separation by LC was achieved using a reversed-phase column and a gradient of water/acetonitrile each containing formic acid as the mobile phase. MS-MS detection was used because of its high selectivity, and ability to provide structural information. Free base and N-oxides were observed by this method. PAs were analyzed and detected in plants from three different families, viz., Asteraceae, Boraginaceae and Fabaceae. The Asteraceae family was found to contain senecionine and lycopsamine type PAs. The Boraginaceae family contained lycopsamine and heliotrine type PAs and the Fabaceae family contained senecionine and monocrotaline type PAs. These PAs may serve as important markers for the detection of these plant materials in food and dietary supplements. PAs were identified in 44 samples by comparing their retention times, accurate mass and mass fragmentation patterns with those of 25 reference standards.

  13. Comparison of the anti-inflammatory active constituents and hepatotoxic pyrrolizidine alkaloids in two Senecio plants and their preparations by LC-UV and LC-MS.

    Science.gov (United States)

    Chen, Pinghong; Wang, Yi; Chen, Lulin; Jiang, Wei; Niu, Yan; Shao, Qing; Gao, Lu; Zhao, Quancheng; Yan, Licheng; Wang, Shufang

    2015-11-10

    Two Senecio plants, Senecio cannabifolius Less. and its variety S. cannabifolius Less. var. integrifolius (Kiodz.) Kidam., were both used as the raw material of Feining granule, a traditional Chinese medicine product for treating respiratory diseases. In this study, the chemical profiles of these two plants were investigated and compared by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). A total number of 83 constituents, including 55 organic acids, 11 flavonoids, 4 alkaloids, 3 terpenes and 10 other types of compounds, were characterized. The results indicated that the levels of most flavonoids were higher in S. cannabifolius than in S. cannabifolius var. integrifolius, however, the levels of hepatotoxic pyrrolizidine alkaloids (PAs) were higher in S. cannabifolius var. integrifolius than in S. cannabifolius. Fifteen constituents were evaluated on lipopolysaccharides (LPS) induced RAW 264.7 cells, and eleven of them showed inhibition effect against nitric oxide (NO) production. Finally, the levels of ten major constituents (including seven anti-inflammatory active ones) and two PAs in Feining granule from two Senecio plants were determined and compared by the LC-UV and LC-MS methods, respectively. It was found that one organic acid (homogentisic acid) and two PAs (seneciphylline and senecionine) had higher contents in the preparation of S. cannabifolius var. integrifolius than in that of S. cannabifolius, however, the situations were inverse for the levels of four organic acids and flavonoids (chlorogenic acid, hyperoside, isoquercitrin, and isochlorogenic acid B). Based on the above results, S. cannabifolius might be a better raw material for Feining granule than S. cannabifolius var. integrifolius, because it contained more anti-inflammatory constituents and less hepatotoxic PAs than the latter. However, more pharmacological evaluations should be carried out to support the selection. The results in this study were helpful

  14. The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey-derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus)

    Science.gov (United States)

    Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids (DHPAs) that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recomm...

  15. Clivorine, an otonecine pyrrolizidine alkaloid from Ligularia species, impairs neuronal differentiation via NGF-induced signaling pathway in cultured PC12 cells.

    Science.gov (United States)

    Xiong, Aizhen; Yan, Artemis Lu; Bi, Cathy W C; Lam, Kelly Y C; Chan, Gallant K L; Lau, Kitty K M; Dong, Tina T X; Lin, Huangquan; Yang, Li; Wang, Zhengtao; Tsim, Karl W K

    2016-08-15

    Pyrrolizidine alkaloids (PAs) are commonly found in many plants including those used in medical therapeutics. The hepatotoxicities of PAs have been demonstrated both in vivo and in vitro; however, the neurotoxicities of PAs are rarely mentioned. In this study, we aimed to investigate in vitro neurotoxicities of clivorine, one of the PAs found in various Ligularia species, in cultured PC12 cells. PC12 cell line was employed to first elucidate the neurotoxicity and the underlying mechanism of clivorine, including cell viability and morphology change, neuronal differentiation marker and signaling pathway. PC12 cells were challenged with series concentrations of clivorine and/or nerve growth factor (NGF). The cell lysates were collected for MTT assay, trypan blue staining, immunocytofluorescent staining, qRT-PCR and western blotting. Clivorine inhibited cell proliferation and neuronal differentiation evidenced by MTT assay and dose-dependently reducing neurite outgrowth, respectively. In addition, clivorine decreased the level of mRNAs encoding for neuronal differentiation markers, e.g. neurofilaments and TrkA (NGF receptor). Furthermore, clivorine reduced the NGF-induced the phosphorylations of TrkA, protein kinase B and cAMP response element-binding protein in cultured PC12 cells. Taken together, our results suggest that clivorine might possess neurotoxicities in PC12 cells via down-regulating the NGF/TrkA/Akt signaling pathway. PAs not only damage the liver, but also possess neurotoxicities, which could possibly result in brain disorders, such as depression. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. Investigation of targeted pyrrolizidine alkaloids in traditional Chinese medicines and selected herbal teas sourced in Ireland using LC-ESI-MS/MS.

    Science.gov (United States)

    Griffin, Caroline T; Gosetto, Francesca; Danaher, Martin; Sabatini, Stefano; Furey, Ambrose

    2014-01-01

    Publications linking hepatotoxicity to the use of herbal preparations are escalating. Herbal teas, traditional Chinese medicines (TCMs) and dietary supplements have been shown to contain pyrrolizidine alkaloids (PAs). Acute PA toxicosis of the liver can result in sinusoidal-obstruction syndrome, also known as veno-occlusive disease (VOD). This paper describes a sensitive and robust method for the detection of targeted PAs and their N-oxides (PANOs) in herbal products (selected herbal teas and TCMs) sourced within Ireland. The sample preparation includes a simple acidic extraction with clean-up via solid-phase extraction (SPE). Sample extracts were accurately analysed by using LC-ESI-MS/MS applying for the first time a pentafluorophenyl (PFP) core-shell column to the chromatographic separation of PAs and PANOs. The method was validated for selectivity, taking into consideration matrix effects, specificity, linearity, precision and trueness. Limits of detection (LOD) and limits of quantitation (LOQ) were quantified for all PAs and PANOs ranging from 0.4 to 1.9 µg kg⁻¹ and from 1.3 to 6.3 µg kg⁻¹, respectively. In this study 10 PAs and four PANOs were targeted because they are commercially available as reference standards. Therefore, this study can only report the levels of these PAs and PANOs analysed in the herbal teas and TCMs. The results reported represent the minimum levels of PAs and PANOs present in the samples analysed; commercially available herbal teas (n = 18) and TCMs (n = 54). A total of 50% herbal teas and 78% Chinese medicines tested positive for one or more PAs and/or PANOs included within this study, ranging from 10 to 1733 and from 13 to 3668 µg kg⁻¹, respectively.

  17. The comparative pharmacokinetics of two pyrrolizidine alkaloids, senecionine and adonifoline, and their main metabolites in rats after intravenous and oral administration by UPLC/ESIMS.

    Science.gov (United States)

    Wang, Changhong; Li, Yan; Gao, Jiangguo; He, Yuqi; Xiong, Aizhen; Yang, Li; Cheng, Xuemei; Ma, Yueming; Wang, Zhengtao

    2011-07-01

    Pyrrolizidine alkaloids (PAs) are considered to be one of the most hepatotoxic groups of compounds of plant origin and are present in about 3% of the world's flowering plants. Most PAs represent a considerable health hazard to both livestock and humans through the consumption of plants and PA-contaminated products such as milk, honey, herbal teas, and medicines. This study determined the differences in the in vivo pharmacokinetic behavior of senecionine (SEN), adonifoline (ADO), and their main metabolites in rats after intravenous administration and oral administration by ultraperformance liquid chromatography/electrospray ionization mass spectrometry. Upon intravenous administration and oral administration of SEN and ADO, significant differences in pharmacokinetics were observed, with the SEN and ADO being absorbed fast with lower bioavailability and being quickly metabolized to PA N-oxides and hydroxylation products of PAs or their N-oxides. It could be seen that the plasma concentration ratio of senecionine N-oxide (SEN-NO) to SEN (C (SEN-NO)/C (SEN)) was significantly larger than that for adonifoline N-oxide (ADO-NO) and ADO (C (ADO-NO)/C (ADO)) (P < 0.001) for both dosing routes in rats. The high N-oxygenation activity and extensive toxicity of SEN, compared with ADO, in rats raised the question of whether or not the higher metabolic rate of SEN in rats in vivo was related to its potent toxicity. The toxicity of SEN-NO and ADO-NO needs to be evaluated further and compared in vitro/in vivo. This study was most helpful for interpreting the metabolism of metabolic bioactivation and detoxication, and toxicity differences among SEN, ADO and other PAs.

  18. Feeding on Host Plants with Different Concentrations and Structures of Pyrrolizidine Alkaloids Impacts the Chemical-Defense Effectiveness of a Specialist Herbivore.

    Science.gov (United States)

    Martins, Carlos H Z; Cunha, Beatriz P; Solferini, Vera N; Trigo, José R

    2015-01-01

    Sequestration of chemical defenses from host plants is a strategy widely used by herbivorous insects to avoid predation. Larvae of the arctiine moth Utetheisa ornatrix feeding on unripe seeds and leaves of many species of Crotalaria (Leguminosae) sequester N-oxides of pyrrolizidine alkaloids (PAs) from these host plants, and transfer them to adults through the pupal stage. PAs confer protection against predation on all life stages of U. ornatrix. As U. ornatrix also uses other Crotalaria species as host plants, we evaluated whether the PA chemical defense against predation is independent of host plant use. We fed larvae from hatching to pupation with either leaves or seeds of one of eight Crotalaria species (C. incana, C. juncea, C. micans, C. ochroleuca, C. pallida, C. paulina, C. spectabilis, and C. vitellina), and tested if adults were preyed upon or released by the orb-weaving spider Nephila clavipes. We found that the protection against the spider was more effective in adults whose larvae fed on seeds, which had a higher PA concentration than leaves. The exceptions were adults from larvae fed on C. paulina, C. spectabilis and C. vitellina leaves, which showed high PA concentrations. With respect to the PA profile, we describe for the first time insect-PAs in U. ornatrix. These PAs, biosynthesized from the necine base retronecine of plant origin, or monocrotaline- and senecionine-type PAs sequestered from host plants, were equally active in moth chemical defense, in a dose-dependent manner. These results are also partially explained by host plant phylogeny, since PAs of the host plants do have a phylogenetic signal (clades with high and low PA concentrations in leaves) which is reflected in the adult defense.

  19. The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice.

    Science.gov (United States)

    Zhu, Lin; Xue, Junyi; Xia, Qingsu; Fu, Peter P; Lin, Ge

    2017-02-01

    Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and the most common poisonous plants affecting livestock, wildlife, and humans. Our previous studies demonstrated that PA-derived DNA adducts can potentially be a common biological biomarker of PA-induced liver tumor formation. In order to validate the use of these PA-derived DNA adducts as a biomarker, it is necessary to understand the basic kinetics of the PA-derived DNA adducts formed in vivo. In this study, we studied the dose-dependent response and kinetics of PA-derived DNA adduct formation and removal in male ICR mice orally administered with a single dose (40 mg/kg) or multiple doses (10 mg/kg/day) of retrorsine, a representative carcinogenic PA. In the single-dose exposure, the PA-derived DNA adducts exhibited dose-dependent linearity and persisted for up to 4 weeks. The removal of the adducts following a single-dose exposure to retrorsine was biphasic with half-lives of 9 h (t 1/2α) and 301 h (~12.5 days, t 1/2β). In the 8-week multiple exposure study, a marked accumulation of PA-derived DNA adducts without attaining a steady state was observed. The removal of adducts after the multiple exposure also demonstrated a biphasic pattern but with much extended half-lives of 176 h (~7.33 days, t 1/2α) and 1736 h (~72.3 days, t 1/2β). The lifetime of PA-derived DNA adducts was more than 8 weeks following the multiple-dose treatment. The significant persistence of PA-derived DNA adducts in vivo supports their role in serving as a biomarker of PA exposure.

  20. Feeding on Host Plants with Different Concentrations and Structures of Pyrrolizidine Alkaloids Impacts the Chemical-Defense Effectiveness of a Specialist Herbivore

    Science.gov (United States)

    Cunha, Beatriz P.; Solferini, Vera N.

    2015-01-01

    Sequestration of chemical defenses from host plants is a strategy widely used by herbivorous insects to avoid predation. Larvae of the arctiine moth Utetheisa ornatrix feeding on unripe seeds and leaves of many species of Crotalaria (Leguminosae) sequester N-oxides of pyrrolizidine alkaloids (PAs) from these host plants, and transfer them to adults through the pupal stage. PAs confer protection against predation on all life stages of U. ornatrix. As U. ornatrix also uses other Crotalaria species as host plants, we evaluated whether the PA chemical defense against predation is independent of host plant use. We fed larvae from hatching to pupation with either leaves or seeds of one of eight Crotalaria species (C. incana, C. juncea, C. micans, C. ochroleuca, C. pallida, C. paulina, C. spectabilis, and C. vitellina), and tested if adults were preyed upon or released by the orb-weaving spider Nephila clavipes. We found that the protection against the spider was more effective in adults whose larvae fed on seeds, which had a higher PA concentration than leaves. The exceptions were adults from larvae fed on C. paulina, C. spectabilis and C. vitellina leaves, which showed high PA concentrations. With respect to the PA profile, we describe for the first time insect-PAs in U. ornatrix. These PAs, biosynthesized from the necine base retronecine of plant origin, or monocrotaline- and senecionine-type PAs sequestered from host plants, were equally active in moth chemical defense, in a dose-dependent manner. These results are also partially explained by host plant phylogeny, since PAs of the host plants do have a phylogenetic signal (clades with high and low PA concentrations in leaves) which is reflected in the adult defense. PMID:26517873

  1. Feeding on Host Plants with Different Concentrations and Structures of Pyrrolizidine Alkaloids Impacts the Chemical-Defense Effectiveness of a Specialist Herbivore.

    Directory of Open Access Journals (Sweden)

    Carlos H Z Martins

    Full Text Available Sequestration of chemical defenses from host plants is a strategy widely used by herbivorous insects to avoid predation. Larvae of the arctiine moth Utetheisa ornatrix feeding on unripe seeds and leaves of many species of Crotalaria (Leguminosae sequester N-oxides of pyrrolizidine alkaloids (PAs from these host plants, and transfer them to adults through the pupal stage. PAs confer protection against predation on all life stages of U. ornatrix. As U. ornatrix also uses other Crotalaria species as host plants, we evaluated whether the PA chemical defense against predation is independent of host plant use. We fed larvae from hatching to pupation with either leaves or seeds of one of eight Crotalaria species (C. incana, C. juncea, C. micans, C. ochroleuca, C. pallida, C. paulina, C. spectabilis, and C. vitellina, and tested if adults were preyed upon or released by the orb-weaving spider Nephila clavipes. We found that the protection against the spider was more effective in adults whose larvae fed on seeds, which had a higher PA concentration than leaves. The exceptions were adults from larvae fed on C. paulina, C. spectabilis and C. vitellina leaves, which showed high PA concentrations. With respect to the PA profile, we describe for the first time insect-PAs in U. ornatrix. These PAs, biosynthesized from the necine base retronecine of plant origin, or monocrotaline- and senecionine-type PAs sequestered from host plants, were equally active in moth chemical defense, in a dose-dependent manner. These results are also partially explained by host plant phylogeny, since PAs of the host plants do have a phylogenetic signal (clades with high and low PA concentrations in leaves which is reflected in the adult defense.

  2. Investigation of pyrrolizidine alkaloids including their respective N-oxides in selected food products available in Hong Kong by liquid chromatography electrospray ionisation mass spectrometry.

    Science.gov (United States)

    Chung, Stephen W C; Lam, Aaron C H

    2017-07-01

    This study determined the levels of pyrrolizidine alkaloids (PAs), including their respective N-oxides, in foodstuffs available in Hong Kong by liquid chromatography-electrospray ionisation tandem mass spectrometry. A total of 234 samples (48 food items) were collected randomly from a local market and analysed. About 50% of samples were found to contain detectable amount of PAs. Amongst the 48 food items, PAs were not detected in 11 food items, including barley flour, beef, cattle liver, pork, pig liver, chicken meat, chicken liver, milk, non-fermented tea, Melissa tea and linden tea. For those found to contain detectable PAs, the summed PA content ranged up to 11,000 µg kg(-1). The highest sum of PA content among the 37 food items calculated with lower bound was cumin seed, then followed by oregano, tarragon and herbs de Provence with ranges of 2.5-11,000, 1.5-5100, 8.0-3300 and 18-1300 µg kg(-1) respectively. Among the samples, the highest sum of PA content was detected in a cumin seed sample (11,000 µg kg(-1)), followed by an oregano (5100 µg kg(-1)), a tarragon (3300 µg kg(-1)) and a herbs de Provence (1300 µg kg(-1)). In general, the results of this study agreed well with other published results in peer-reviewed journals, except that the total PAs in honey and specific tea infusion in this study were comparatively lower.

  3. The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey-derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus).

    Science.gov (United States)

    Brown, Ammon W; Stegelmeier, Bryan L; Colegate, Steven M; Gardner, Dale R; Panter, Kip E; Knoppel, Edward L; Hall, Jeffery O

    2016-05-01

    Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a tisane or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52 and 1.04 mmol lycopsamine, intermedine or reduced comfrey extract per kg bodyweight (BW) for 10 days. After another 7 days chicks were euthanized. Based on clinical signs of poisoning, serum biochemistry, and histopathological analysis the reduced comfrey extract was more toxic than lycopsamine and intermedine. This work suggests a greater than additive effect of the individual alkaloids and/or a more potent toxicity of the acetylated derivatives in the reduced comfrey extract. It also suggests that safety recommendations based on purified compounds may underestimate the potential toxicity of comfrey.

  4. Development of a fast isocratic LC-MS/MS method for the high-throughput analysis of pyrrolizidine alkaloids in Australian honey.

    Science.gov (United States)

    Griffin, Caroline T; Mitrovic, Simon M; Danaher, Martin; Furey, Ambrose

    2015-01-01

    Honey samples originating from Australia were purchased and analysed for targeted pyrrolizidine alkaloids (PAs) using a new and rapid isocratic LC-MS/MS method. This isocratic method was developed from, and is comparable with, a gradient elution method and resulted in no loss of sensitivity or reduction in chromatographic peak shape. Isocratic elution allows for significantly shorter run times (6 min), eliminates the requirement for column equilibration periods and, thus, has the advantage of facilitating a high-throughput analysis which is particularly important for regulatory testing laboratories. In excess of two hundred injections are possible, with this new isocratic methodology, within a 24-h period which is more than 50% improvement on all previously published methodologies. Good linear calibrations were obtained for all 10 PAs and four PA N-oxides (PANOs) in spiked honey samples (3.57-357.14 µg l(-1); R(2) ≥ 0.9987). Acceptable inter-day repeatability was achieved for the target analytes in honey with % RSD values (n = 4) less than 7.4%. Limits of detection (LOD) and limits of quantitation (LOQ) were achieved with spiked PAs and PANOs samples; giving an average LOD of 1.6 µg kg(-1) and LOQ of 5.4 µg kg(-1). This method was successfully applied to Australian and New Zealand honey samples sourced from supermarkets in Australia. Analysis showed that 41 of the 59 honey samples were contaminated by PAs with the mean total sum of PAs being 153 µg kg(-1). Echimidine and lycopsamine were predominant and found in 76% and 88%, respectively, of the positive samples. The average daily exposure, based on the results presented in this study, were 0.051 µg kg(-1) bw day(-1) for adults and 0.204 µg kg(-1) bw day(-1) for children. These results are a cause for concern when compared with the proposed European Food Safety Authority (EFSA), Committee on Toxicity (COT) and Bundesinstitut für Risikobewertung (BfR - Federal Institute of Risk Assessment Germany) maximum

  5. Intoxicação por alcaloides pirrolizidínicos em ruminantes e equinos no Brasil Poisoning by pyrrolizidine alkaloids in ruminants and horses in Brazil

    Directory of Open Access Journals (Sweden)

    Ricardo B. Lucena

    2010-05-01

    Full Text Available Casos de intoxicação por alcaloides pirrolizidínicos (APs em ruminantes e equinos foram investigados retrospectivamente através do acesso aos arquivos de dois laboratórios de diagnóstico veterinário no Sul e Nordeste brasileiro. Os dados obtidos foram comparados com aqueles retirados da literatura concernentes a surtos dessa toxicose no Brasil, onde ela é associada com a ingestão de plantas que contêm APs dos gêneros Senecio, Crotalaria e Echium. Formas aguda e crônica da toxicose foram encontradas. A doença aguda foi observada em associação com a ingestão de Crotalaria retusa em ovinos e caprinos. C. retusa e Senecio spp. também foram responsáveis pela intoxicação crônica em bovinos, equinos e ovinos. A intoxicação por APs é uma importante causa de morte em animais pecuários no Brasil. Essa é a principal causa de morte em bovinos na região Central do Rio Grande do Sul e uma das principais causas de morte em equinos na Paraíba. A epidemiologia, os sinais clínicos, a patologia e a importância da intoxicação por APs são descritos e discutidos.Cases of poisoning by pyrrolizidine alkaloids (PAs in ruminants and horses were surveilled retrospectively by accessing the files of two veterinary diagnostic laboratories in southern and northeastern Brazil. The data obtained were compared with those withdrawn from the literature and pertaining to outbreaks of the toxicosis in Brazil where it is associated with the ingestion of PAs-containing plants from the genera Senecio, Crotalaria and Echium. Acute and chronic forms of the toxicosis were encountered. Acute disease was observed in association with the ingestion of Crotalaria retusa in sheep and goats. C. retusa and Senecio spp. were also responsible for chronic poisoning in cattle, horses and sheep. PAs poisoning is an important cause of death in livestock in Brazil. It is the major cause of death in cattle in the Central region of Rio Grande do Sul and one of the major

  6. Effective application of freezing lipid precipitation and SCX-SPE for determination of pyrrolizidine alkaloids in high lipid foodstuffs by LC-ESI-MS/MS.

    Science.gov (United States)

    Yoon, Soo Hwan; Kim, Min-Sun; Kim, Sang Hoon; Park, Hyun Mee; Pyo, Heesoo; Lee, Yong Moon; Lee, Kyung-Tae; Hong, Jongki

    2015-06-15

    Pyrrolizidine alkaloids (PAs) are naturally occurring plant toxins associated with serious hepatic disease in humans and animals. In this study, rapid and sensitive analytical method was developed for the determination of 9 toxic PAs in popularly high lipid foodstuffs by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). PAs in lipid foodstuff were effectively purified by freezing lipid precipitation (FLP) and strong cation exchange (SCX)-solid-phase extraction (SPE). Especially, FLP could easily remove the large amounts of triacylglycerols in the lipid sample extract and effectively combine with SPE cleanup. During the FLP procedure, over 77% of the lipids in the foodstuff extracts were rapidly eliminated without any significant loss of the PAs with over 81% recovery. The elimination efficiency of lipids by FLP was tested with LC-atmospheric chemical ionization (APCI)-MS. For further purification, SCX-SPE cartridge could successfully purify PAs from the remaining interfering substances by the variation pH with 5% NH4OH in methanol. For precise quantification and confirmation of PAs in complicate sample matrices, appropriate transition ions in LC-MS/MS-multiple-ion reaction monitoring (MRM) mode were selected on the basis of MS/MS fragmentation pathways of PAs. The established analytical method was validated in terms of the linearity, limits of detection (LOD), and quantification (LOQ), precision, and accuracy. The method was deemed satisfactory by inter- and intra-day validation and exhibited both high accuracy and precision (relative standard deviation<11.06%). Overall limits of detection and quantitation of PAs were approximately 0.06-0.60ng/mL at a signal-to-noise ratio (S/N) of 3 and were about 0.20-1.99ng/mL at a S/N of 10 for all foodstuffs. The established method was successfully applied for the monitoring of toxic PAs in several types of high lipid foodstuffs such as soybeans, seed oil, milk, and margarine.

  7. Polyhydroxylated pyrrolizidine alkaloids from transannular iodoaminations: application to the asymmetric syntheses of (-)-hyacinthacine A1, (-)-7a-epi-hyacinthacine A1, (-)-hyacinthacine A2, and (-)-1-epi-alexine.

    Science.gov (United States)

    Brock, E Anne; Davies, Stephen G; Lee, James A; Roberts, Paul M; Thomson, James E

    2013-05-21

    The transannular iodoamination of substituted 1,2,3,4,7,8-hexahydroazocine scaffolds has been developed into a versatile, diastereodivergent route to enable the synthesis of a range of pyrrolizidine alkaloids, as demonstrated by the syntheses of (-)-hyacinthacine A1, (-)-7a-epi-hyacinthacine A1, (-)-hyacinthacine A2, and (-)-1-epi-alexine. The requisite 1,2,3,4,7,8-hexahydroazocines (bearing either an N-α-methyl-p-methoxybenzyl group or no N-substituent) were readily prepared via conjugate addition of lithium (R)-N-but-3-enyl-N-(α-methyl-p-methoxybenzyl)amide to either tert-butyl (4S,5R,E)-4,5-dihydroxy-4,5-O-isopropylidene-2,7-dienoate (derived from d-ribose) or tert-butyl (S,S,E)-4,5-dihydroxy-4,5-O-isopropylidene-2,7-dienoate (derived from l-tartaric acid) coupled with in situ enolate oxidation with (-)-camphorsulfonyloxaziridine, followed by ring-closing metathesis with Grubbs I catalyst. Subsequent reaction with I2 resulted in transannular iodoamination (accompanied by concomitant loss of the N-α-methyl-p-methoxybenzyl group for tertiary amine substrates) to give the corresponding pyrrolizidine scaffolds.

  8. Research progress of especial toxicity and of pyrrolizidine alkaloids%含吡咯里西啶生物碱植物的特殊毒性及致毒机制研究进展

    Institute of Scientific and Technical Information of China (English)

    韩佳寅; 梁爱华; 高双荣

    2011-01-01

    Pyrrolizidine alkaloids(PAs) are widely distributed in many plants including medicinal herbs. The hepatotoxicity of PAs has been known academically for a long time, however, their reproductive toxicity, mutagenesis and carcinogenicity have been less researched. This article is an overview of the clinical and experimental reports of the reproductive toxicity, mutagenesis and carcinogenicity of PAs, the effective factors and generating mechanism of the toxicity.%吡咯里西啶类生物碱(pyrrolizidine alkaloids,PAs)是一类在植物中广泛分布的成分,含有吡咯里西啶类生物碱的植物在民间被作为草药和植物茶饮品应用的现象极为普遍.然而,研究发现吡咯里西啶类生物碱具有明确的毒性作用,其中的肝毒性早已引起人们的关注,而生殖毒性、致突变和致癌性方面的毒性却研究较少.本文主要就PAs的生殖毒性、致突变和致癌方面的特殊毒性进行综述,主要总结了20世纪50年代以来关于PAs特殊毒性的临床报道及动物实验研究,并对现有研究所认为的影响PAs特殊毒性的因素及PAs特殊毒性产生的机制进行了归纳.

  9. 9-Glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine Is the Major Pyrrolic Glutathione Conjugate of Retronecine-Type Pyrrolizidine Alkaloids in Liver Microsomes and in Rats.

    Science.gov (United States)

    Chen, Meixia; Li, Liang; Zhong, Dafang; Shen, Shuijie; Zheng, Jiang; Chen, Xiaoyan

    2016-02-15

    Retronecine-, otonecine-, and heliotridine-type pyrrolizidine alkaloids (PAs) are all reported to be hepatotoxic. These PAs are suggested to be metabolized to the corresponding electrophilic dehydropyrrolizidine alkaloids (dehydro-PAs) and subsequently conjugated with macromolecules, such as glutathione (GSH). In the present study, a total of five glutathione conjugates, named M1-M5, were detected in rat and human liver microsomal incubations with three retrornecine-type PAs (isoline, retrorsine, or monocrotaline) in the presence of glutathione, and were chemically synthesized. M1 and M3 were unambiguously identified as a pair of epimers of 7-glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (7-GSH-DHP), and M4 and M5 were epimers of 7,9-diglutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (7,9-diGSH-DHP). M2, an extremely unstable conjugate, was proposed to be 9-glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (9-GSH-DHP). It was the most abundant among the five GSH conjugates, and the finding corrects the mistake that 7-GSH-DHP is the predominant GSH conjugate derived from dehydro-PAs. Similar patterns in glutathione conjugate profile were observed in the bile of rats treated with the PAs. This is the first study to describe 9-GSH-DHP as a major pyrrolic GSH conjugate of retronecine-type PAs, providing insight into the interactions of dehydro-PAs with biomolecules.

  10. A novel ultra-performance liquid chromatography hyphenated with quadrupole time of flight mass spectrometry method for rapid estimation of total toxic retronecine-type of pyrrolizidine alkaloids in herbs without requiring corresponding standards.

    Science.gov (United States)

    Zhu, Lin; Ruan, Jian-Qing; Li, Na; Fu, Peter P; Ye, Yang; Lin, Ge

    2016-03-01

    Nearly 50% of naturally-occurring pyrrolizidine alkaloids (PAs) are hepatotoxic, and the majority of hepatotoxic PAs are retronecine-type PAs (RET-PAs). However, quantitative measurement of PAs in herbs/foodstuffs is often difficult because most of reference PAs are unavailable. In this study, a rapid, selective, and sensitive UHPLC-QTOF-MS method was developed for the estimation of RET-PAs in herbs without requiring corresponding standards. This method is based on our previously established characteristic and diagnostic mass fragmentation patterns and the use of retrorsine for calibration. The use of a single RET-PA (i.e. retrorsine) for construction of calibration was based on high similarities with no significant differences demonstrated by the calibration curves constructed by peak areas of extract ion chromatograms of fragment ion at m/z 120.0813 or 138.0919 versus concentrations of five representative RET-PAs. The developed method was successfully applied to measure a total content of toxic RET-PAs of diversified structures in fifteen potential PA-containing herbs.

  11. Pyrrolizidine alkaloids of Senecio cannabifolius var.integrilifolius%单麻叶千里光中肝毒吡咯里西啶生物碱的分离与鉴定

    Institute of Scientific and Technical Information of China (English)

    马鸿雁; 杨莉; 王长虹; 王峥涛

    2011-01-01

    Objective: To study the pyrrolizidine alkaloids of Senecio cannabifolius var. integrilifolius. Method: Variouschromatographic methods were used for the isolation and purification of chemical constitutents of the plant and their structures were elucidated on the basis of spectral analysis. Result: Four compounds were determinated as jacobine( 1 ) ,jacoline(2 ), jaconine(3), senecicannabine(4). Conclusion: All compounds were isolated from this plant for the first time.%目的:研究菊科千里光属植物单麻叶千里光Senecio cannabifolius var.integrilifolius的肝毒性吡咯里西啶生物碱.方法:运用多种色谱方法进行分离纯化,应用现代波谱学分析方法进行结构鉴定.结果:从单麻叶千里光的总碱部位中分离得到4个吡咯里西啶生物碱,分别鉴定为:jacobine(1),jacoline(2),jaconine(3),senecicannabine(4).结论:化合物1~4均为首次从该植物中分离得到.

  12. 吡咯里西啶类生物碱小鼠腹腔注射急性毒性的QSAR研究%QSAR Study on Pyrrolizidine Alkaloids of Acute Toxicity in Mouse by Intraperitoneal Injection

    Institute of Scientific and Technical Information of China (English)

    彭静; 闫心丽; 王琳; 李佐静; 孙也之; 孟繁浩

    2012-01-01

    吡咯里西啶类生物碱(Pyrrolizidine alkaloids,PAs)是一类分布广泛的天然有毒生物碱,主要分布在菊科、紫草科、豆科、兰科等植物中.采用偏最小二乘回归方法(PLS)进行降维,研究了11种吡咯里西啶类化合物的各种量化参数对其小鼠腹腔注射急性毒性的影响,并建立了毒性预测模型.预测模型为:Log(toxi)= -0.184303×LogP+0.02999×SAA+0.0251521×SAG+0.050163×Volume+0.142551×MR+0.108834×Polar+0.00161785×TE-0.137259×BE+0.0103498×IAE-0.0460575×EE+0.0506026×CCI+0.171899×HoF-0.555739×Dipole,结果表明该模型具有较好的毒性预测能力.

  13. 含双稠吡咯啶生物碱的植物及其对畜牧业的危害%Plants Containing Pyrrolizidine Alkaloids and Their Hazards to Animal Husbandry

    Institute of Scientific and Technical Information of China (English)

    王跃虎; 司红丽; 王建华

    2002-01-01

    @@ 双稠吡咯啶生物碱(Pyrrolizidine alkaloids,PA)广泛存在于多种植物中,据统计,世界上约有3%的有花植物即6000余种植物含有PAs.迄今为止,PAs已在13个科的植物中检出,多数属于紫草科(聚合草属和天芥菜属)、菊科(千里光属、狗舌草属、橐吾属及泽兰属)和豆科(野百合属).人们把含有PAs的植称为PA植物.PAs是植物的次生代谢产物,对植物来说具有化学防卫的功能,在一定程度上可抵御草食动物、昆虫和植物病原的侵害.

  14. Comparison of metabolism-mediated effects of pyrrolizidine alkaloids in a HepG2/C3A cell-S9 co-incubation system and quantification of their glutathione conjugates.

    Science.gov (United States)

    Tamta, Hemlata; Pawar, Rahul S; Wamer, Wayne G; Grundel, Erich; Krynitsky, Alexander J; Rader, Jeanne I

    2012-10-01

    1. Toxicity of pyrrolizidine alkaloids (PAs) largely depends on their metabolic activation by hepatic enzymes, including cytochrome P450s, to become chemically reactive pyrrolic derivatives. These then spontaneously release the esterifying acids to generate carbonium ions that form covalent adducts with cellular nucleophiles to exhibit toxicity. 2. In our investigation, metabolism-mediated toxicity of monocrotaline, retrorsine, lycopsamine, echimidine (retronecine-type PAs), heliotrine (a heliotridine-type PA) and senkirkine (an otonecine-type PA) was studied using an in vitro co-incubation assay. 3. Human hepatocarcinoma (HepG2/C3A) cells were incubated with PAs in the presence and absence of rat liver S9 fraction and the toxicity was assessed as lowered mitochondrial activity. 4. Bioactivation potential was measured by incubating PAs with rat liver S9 fraction, NADPH and GSH in a cell free system. Pyrrolic metabolites generated were entrapped as glutathione conjugates (7-GSH-DHP and 7,9-di-GSHDHP) which were quantified using LC-MS-MS analysis. 5. Our results indicated that PAs were metabolized by rat liver S9 fraction into reactive pyrrolic derivatives which were toxic to HepG2/C3A cells. This approach can be used to determine and compare bioactivation potential and metabolism-mediated toxicity of various PAs.

  15. Simultaneous investigation of sesquiterpenes, pyrrolizidine alkaloids and N-oxides in Butterbur (Petasites hybridus) with an offline 2D-combination of HPLC-UV and LC-MMI-ToF-MS.

    Science.gov (United States)

    Aydın, Ahmet Alper; Letzel, Thomas

    2013-11-01

    With the worldwide rapid increasing interest in the use of natural products as dietary supplements, medical remedies and functional foods, it has been accepted that omitting the plant constituents with potential adverse effects was a huge fault of the past. Several countries developed regulations to limit the consumption of such products in the markets. Among these natural products, butterbur (Petasites) has been used for years as herbal supplement for its anti-spasmodic and anti-inflammatory effects. However, its hepatotoxic alkaloid content limits the direct usage. In this study, investigation of sesquiterpenes and pyrrolizidine alkaloids (PAs) together with their N-oxide forms has been conducted with an offline 2D-combination using high-performance liquid chromatography with UV detection (HPLC-UV) and liquid chromatography - multi mode ionization - time-of-flight mass spectrometry (LC-MMI-ToF-MS) for plant screening. The content has been qualitatively investigated to provide information on the constituents of the plant rhizomes extracted using ethanol. Besides the reported hepatotoxic and medically bio-active plant constituents, a strategy has been suggested for estimating the retention order and retention times with respect to calculated logD (distribution coefficient) and hydrophobicity distributions on C18 reversed-phase column when all standard compounds are not available in laboratory. In this sense, the influence of calculated logD and hydrophobicity distributions on retention time has been clarified via available PA and PA-N-oxide standards. The ethanolic extract of Petasites hybridus has been used for examination of the strategy in a real-sample model. Additionally, the advantages of the developed HPLC-UV and LC-MMI-ToF-MS combination have been discussed with respect to the presented results.

  16. 中药毒性的代谢组学研究(Ⅱ):吡咯里西啶类生物碱的肝肾毒性%Metabonomic Study on the Toxicity of Chinese Medicine (Ⅱ) : Hepato-nephrotoxicity of Pyrrolizidine Alkaloids

    Institute of Scientific and Technical Information of China (English)

    祁乃喜; 刘玉梅; 何翠翠; 华嘉; 李建新

    2012-01-01

    目的 分析经中药千里光中吡咯里西啶类生物碱染毒后大鼠尿液内源性代谢产物的变化,研究该类生物碱的肝肾毒性,为中药毒性评价提供简单可靠的方法.方法 利用生物核磁共振技术分析对照组,吡咯里西啶类生物碱口服给药组的大鼠7d的尿液、结合模式识别技术和主成分分析法评价吡咯里西啶类生物碱对大鼠尿液内源性代谢物的影响,探讨吡咯里西啶类生物碱的肝肾毒性.结果 与对照组相比,口服吡咯里西啶类生物碱引起大鼠尿中牛磺酸,氧化三甲胺以及二甲基甘氨酸含量的持续增高,说明对肝脏及肾脏造成了损伤,提示吡咯里西啶类生物碱存在肝肾毒性.结论 从代谢组学的角度可以诠释中药千里光的肝肾毒性,提示代谢组学方法可为传统中药毒性研究提供新的手段.%OBJECTIVE To study the hepato-nephrotoxicity of pyrrolizidine alkaloids isolated from Herba Senecionis Scan-dentis via analyzing changes of endogenous metabolites in rat urines after administration of the alkaloids,and provide a simple and reliable method for toxicity evaluation of traditional Chinese medicine(TCM). METHODS The hepato-nephrotoxicity of the alkaloids was explored through analyzing urines collected from rats in both the control and pyrrolizidine alkaloids orally administrated groups in 7 days by bio-nuclear magnetic resonance(bio-NMR),and evaluating pyrrolizidine alkaloids' influences on endogenous metabolites in urine by pattern recognition technique and principal component analysis(PCA). RESULTS Compared with the control group,the continuous increase of taurine,trimethylamine-N-oxide(TMAO)and dimethylglycine(DMG)in urines of pyrrolizidine alkaloids orally administrated group proved that alkaloids had caused damages to the liver and kidney,which indicated the hepato-nephrotoxicity of pyrrolizidine alkaloids.CONCLUSION The hepato-nephrotoxicity of Herba Senecionis Scandentis could be

  17. An Outbreak of Hepatic Veno-Occlusive Disease in Western Afghanistan Associated with Exposure to Wheat Flour Contaminated with Pyrrolizidine Alkaloids

    Directory of Open Access Journals (Sweden)

    Faizullah Kakar

    2010-01-01

    Full Text Available Pyrrolizidine alakloids (PAs are known to cause hepatic veno-occlusive disease (VOD. Outbreaks have occurred in Western Afghanistan since 1974, the latest in February 2008. We conducted an outbreak investigation using a case-control design. Sixty-seven cases of VOD were compared with 199 community controls. Consumption of bread was strongly associated with disease (adjusted odds ratio: 35.8 [95%CI: 7.6–168.2]. Toxic doses of PA were found in plant extracts and in samples of wheat flour taken from the study area. Compared to wheat flour there was 1000 times less PA in milk and whey and in water samples the PA content was zero. Although direct analysis was not possible, contaminated wheat flour used to make bread was the likely source of PA causing the outbreak. Eating a more varied diet including meat and fruit may be protective. Prevention and control measures will rely on community awareness and agricultural interventions to ensure safety of the food supply.

  18. An outbreak of hepatic veno-occlusive disease in Western afghanistan associated with exposure to wheat flour contaminated with pyrrolizidine alkaloids.

    Science.gov (United States)

    Kakar, Faizullah; Akbarian, Zarif; Leslie, Toby; Mustafa, Mir Lais; Watson, John; van Egmond, Hans P; Omar, Mohammad Fahim; Mofleh, Jawad

    2010-01-01

    Pyrrolizidine alakloids (PAs) are known to cause hepatic veno-occlusive disease (VOD). Outbreaks have occurred in Western Afghanistan since 1974, the latest in February 2008. We conducted an outbreak investigation using a case-control design. Sixty-seven cases of VOD were compared with 199 community controls. Consumption of bread was strongly associated with disease (adjusted odds ratio: 35.8 [95%CI: 7.6-168.2]). Toxic doses of PA were found in plant extracts and in samples of wheat flour taken from the study area. Compared to wheat flour there was 1000 times less PA in milk and whey and in water samples the PA content was zero. Although direct analysis was not possible, contaminated wheat flour used to make bread was the likely source of PA causing the outbreak. Eating a more varied diet including meat and fruit may be protective. Prevention and control measures will rely on community awareness and agricultural interventions to ensure safety of the food supply.

  19. 《中国药典》含吡咯里西啶生物碱的中药品种与用药安全%Pyrrolizidine alkaloids-containing Chinese medicines in the Chinese Pharmacopoeia and related safety concerns

    Institute of Scientific and Technical Information of China (English)

    汤俊; 服部征雄

    2011-01-01

    吡咯里西啶类生物碱是一类分布广泛的天然有毒生物碱,存在于许多中草药中,一些品种还被历版所收载.为了掌握(2010版)中含这类生物碱的中药品种的收载情况,本文进行了系统的整理和分析;同时,结合该类生物碱的研究现状及本实验室一些最新研究数据,探讨安全性问题与对策.结果发现新版药典一部现存9种药材品种(不包括饮片)含有肝毒吡咯里西啶类生物碱,并涉及数十种成方制剂;由于大多数品种缺乏该类成分的安全限量检查,其潜在的用药风险可能被忽视.建议开展相关基础研究和进行毒性评价,从而进一步提升相关品种的安全性控制水平,为临床安全用药提供保障.%It has been well-known that many medicinal plants used in traditional Chinese medicine contain hepatotoxic pyrrolizidine alkaloids (HPAs), and some even have been recorded in many editions of the Chinese Pharmacopoeia (ChP). In order to clarify the current status of these PAs-containing Chinese materia medica and proprietary Chinese formulae, the ChP 2010, the newest version, and the related safety issues were thoroughly investigated and analyzed on the current advances in research. Total nine crude drugs (not including the processed slices) were found to contain HPAs, which may be present in tens of Chinese proprietary drugs prepared with these crude drugs. Because of the lack of the alkaloid limitation in most monographs, their potential threats to human health may be underestimated. For this reason, attention should be drawn to the importance of the issue. The key point is to conduct the basic studies immediately on these PA-containing herbal plants or products, whose possible hazards need to be carefully assessed. Further efforts should also be made to elevate the criteria for quality control and ensure the drugs' safety in clinic for human health.

  20. Pyrrolizidine alkaloids-containing plants and hepatic veno-occlusive disease%含吡咯里西啶类生物碱植物与肝小静脉闭塞病

    Institute of Scientific and Technical Information of China (English)

    蔡皓东; 孙凤霞

    2007-01-01

    植物中的吡咯里西啶类生物碱(pyrrolizidine alkaloids,PAs)是引致肝小静脉闭塞病的主要原因之一.美国、英国和我国等许多国家都有与含PAs植物或草药相关的肝小静脉闭塞病或肝损害的报道.全球约有6 000余种植物含PAs,主要为4个科某些属的植物,即(1)菊科的千里光属、橐吾属、泽兰属、菊三七属和蜂斗菜属;(2)紫草科的所有属;(3)豆科的猪屎豆属;(4)兰科的羊耳蒜属.我国有38种中草药含PAs,常用的有12种:千里光、狗舌草、菊三七、款冬、佩兰、泽兰、山紫菀、紫草、天芥菜、野百合、猪屎豆、羊耳蒜.PAs本身的毒性极低,但其代谢物有肝毒性.PAs致肝毒性的摄入量,成人通常为每日数毫克至数百毫克,但WHO认为致肝小静脉闭塞病的每日最低摄入量为0.015 mg/kg,即相当于70 kg体重成人每天1 mg.肝小静脉闭塞病的主要临床表现为顽固性腹水、黄疸、肝大.肝小静脉闭塞病尚无特效疗法,主要为对症、支持治疗.近年有报道用糖皮质激素或肝素治疗,但疗效和安全性尚待研究.作者认为,我国应加强含PAs植物致中毒的教育和监测.

  1. E/Z-Thesinine-O-4'-alpha-rhamnoside, pyrrolizidine conjugates produced by grasses (Poaceae).

    Science.gov (United States)

    Koulman, Albert; Seeliger, Claudine; Edwards, Patrick J B; Fraser, Karl; Simpson, Wayne; Johnson, Linda; Cao, Mingshu; Rasmussen, Susanne; Lane, Geoffrey A

    2008-06-01

    Based on direct infusion mass spectrometry we identified a novel alkaloid as a major component of perennial ryegrass (Lolium perenne). Initial mass spectral data suggested it to be a pyrrolizidine conjugate. As this class of alkaloids has not been described before from grasses, we isolated it to elucidate its structure. The isolated alkaloid proved to be a mixture of two stereoisomers. The structures of the two compounds as determined by 1D and 2D NMR spectroscopy, were E-thesinine-O-4'-alpha-rhamnoside (1) and Z-thesinine-O-4'-alpha-rhamnoside (2). These identifications were supported by the characterisation by GC-MS and optical rotation of (+)-isoretronecanol as the necine base released on alkaline hydrolysis of these alkaloids. 1 and 2 together with the aglycone and a hexoside were also detected in tall fescue (Festuca arundinacea). This is the first report of pyrrolizidine alkaloids produced by grasses (Poaceae).

  2. Pyrrolizidine alkaloid clivorine on GSH and its related enzymes in human embryonic kidney cell 293%山冈橐吾碱对HEK293细胞谷胱甘肽含量及相关酶活力的影响

    Institute of Scientific and Technical Information of China (English)

    季莉莉; 陈莹; 王峥涛

    2007-01-01

    吡咯里西啶生物碱(pyrrolizidine alkaloids,PAs)是一类天然的植物性毒素,广泛存在于6000多种高等植物中。山冈橐吾碱(clivorine)是从菊科橐吾属药用植物鹿蹄橐吾(Ligularia hodgsonii)中分离得到的otonecine型吡咯里西啶生物碱,橐吾属部分药用植物的根及根茎在民间习称为山紫菀或川紫菀,常用来代替紫菀(Radix Asteris),治疗咳嗽、肝炎和其他炎症,

  3. Identification and developmental expression profiling of putative alkaloid biosynthetic genes in Corydalis yanhusuo bulbs.

    Science.gov (United States)

    Liao, Dengqun; Wang, Pengfei; Jia, Chan; Sun, Peng; Qi, Jianjun; Zhou, Lili; Li, Xian'en

    2016-01-18

    Alkaloids in bulbs of Corydalis (C.) yanhusuo are the major pharmacologically active compounds in treatment of blood vessel diseases, tumors and various pains. However, due to the absence of gene sequences in C. yanhusuo, the genes involved in alkaloid biosynthesis and their expression during bulb development remain unknown. We therefore established the first transcriptome database of C. yanhusuo via Illumina mRNA-Sequencing of a RNA composite sample collected at Bulb initiation (Day 0), early enlargement (Day 10) and maturation (Day 30). 25,013,630 clean 90 bp paired-end reads were de novo assembled into 47,081 unigenes with an average length of 489 bp, among which 30,868 unigenes (65.56%) were annotated in four protein databases. Of 526 putative unigenes involved in biosynthesis o f various alkaloids, 187 were identified as the candidate genes involved in the biosynthesis of benzylisoquinoline alkaloids (BIAs), the only alkaloid type reported in C. yanhusuo untill now. BIAs biosynthetic genes were highly upregulated in the overall pathway during bulb development. Identification of alkaloid biosynthetic genes in C. yanhusuo provide insights on pathways and molecular regulation of alkaloid biosynthesis, to initiate metabolic engineering in order to improve the yield of interesting alkaloids and to identify potentially new alkaloids predicted from the transcriptomic information.

  4. Pro-toxic 1,2-Dehydropyrrolizidine alkaloid esters, including unprecedented 10-membered macrocyclic diesters, in the medicinally-used Alafia cf. caudata and Amphineurion marginatum (Apocynaceae: Apocynoideae: Nerieae and Apoc

    Science.gov (United States)

    The attraction of pyrrolizidine alkaloid-pharmacophagous insects indicated the presence of pro-toxic dehydropyrrolizidine alkaloids in Alafia cf. caudata Stapf (Nerieae: Alafinae) and Amphineurion marginatum (Roxb.) D.J. Middleton (Apocyneae: Amphineuriinae). Subsequently, monoesters of retronecine ...

  5. Alkaloids in the human food chain - Natural occurrence and possible adverse effects

    NARCIS (Netherlands)

    Koleva, I.; Beek, van T.A.; Soffers, A.E.M.F.; Dusemund, B.; Rietjens, I.

    2012-01-01

    Alkaloid-containing plants are an intrinsic part of the regular Western diet. The present paper summarizes the occurrence of alkaloids in the food chain, their mode of action and possible adverse effects including a safety assessment. Pyrrolizidine alkaloids are a reason for concern because of their

  6. Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

    Science.gov (United States)

    Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metab...

  7. Variation in the expression of ergot alkaloids between individual tillers of perennial ryegrass

    Science.gov (United States)

    Mace, Wade; Lunn, Kristy; Lloyd-West, Catherine

    2014-11-01

    Epichloë fungal endophytes of cool season grasses are well known to produce a range of alkaloids of benefit to the host. Some of these compounds are advantageous to agriculture due to qualities that promote pasture persistence (e.g. the loline class of alkaloids confer insect protection) while others are detrimental to the wellbeing of grazing livestock. The ergot alkaloids (e.g. ergovaline), produced in ryegrass and tall fescue associations, causes poor animal health in farming regions in many countries around the world and further study is required to improve our knowledge on this class of compounds. Here we present the application of a quantitative LC-MS/MS (liquid chromatography coupled to mass spectrometry) method measuring eight ergot alkaloids (chanoclavine, agroclavine, elymoclavine, lysergol, lysergic acid, ergine, lysergyl alanine, ergovaline) produced by endophyte infected grasses, to monitor levels in individual tillers from multiple plants of a single cultivar of perennial ryegrass (Lolium perenne cv. ‘Grasslands Samson’) infected with a common toxic endophyte strain (Epichloë festucae var. lolii). Monitoring the expression in individual tillers allows an estimation of the variability within a plant (between tillers) as well as between plants. The study showed that there is significant variation in the concentration of the ergot alkaloids between tillers of a single plant, at or exceeding the level of variation observed between individual plants of a population. This result emphasizes the fundamental importance of robust experimental design and sampling procedures when alkaloid expression assessment is required and these need to be rigorously tailored to the hypothesis being tested.

  8. Variation in the expression of ergot alkaloids between individual tillers of perennial ryegrass

    Directory of Open Access Journals (Sweden)

    Wade Jeffray Mace

    2014-11-01

    Full Text Available Epichloë fungal endophytes of cool season grasses are well known to produce a range of alkaloids of benefit to the host. Some of these compounds are advantageous to agriculture due to qualities that promote pasture persistence (e.g. the loline class of alkaloids confer insect protection while others are detrimental to the wellbeing of grazing livestock. The ergot alkaloids (e.g. ergovaline, produced in ryegrass and tall fescue associations, causes poor animal health in farming regions in many countries around the world and further study is required to improve our knowledge on this class of compounds. Here we present the application of a quantitative LC-MS/MS (liquid chromatography coupled to mass spectrometry method measuring eight ergot alkaloids (chanoclavine, agroclavine, elymoclavine, lysergol, lysergic acid, ergine, lysergyl alanine, ergovaline produced by endophyte infected grasses, to monitor levels in individual tillers from multiple plants of a single cultivar of perennial ryegrass (Lolium perenne cv. ‘Grasslands Samson’ infected with a common toxic endophyte strain (Epichloë festucae var. lolii. Monitoring the expression in individual tillers allows an estimation of the variability within a plant (between tillers as well as between plants.The study showed that there is significant variation in the concentration of the ergot alkaloids between tillers of a single plant, at or exceeding the level of variation observed between individual plants of a population. This result emphasizes the fundamental importance of robust experimental design and sampling procedures when alkaloid expression assessment is required and these need to be rigorously tailored to the hypothesis being tested.

  9. Gene expression profiling provides insights into pathways of oxaliplatin-related sinusoidal obstruction syndrome in humans

    OpenAIRE

    Rubbia-Brandt, Laura; Tauzin, Sébastien; Brezault, Catherine; Delucinge-Vivier, Céline; Descombes, Patrick; Dousset, Bertand; Majno, Pietro; Mentha, Gilles; Terris, Benoit

    2011-01-01

    Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human l...

  10. Detection of high levels of pyrrolizidine-N-oxides in the endangered plant cryptantha crassipes (Terlingua creek cat's-eye)using HPLC-ESI-MS

    Science.gov (United States)

    Chemical investigation of nine species of Cryptantha identified at least two chemotypes within the genus. It was determined that under especially harsh and dry growing conditions of the Chihuahuah desert of Texas, the N-oxides of two major pyrrolizidine alkaloids, lycopsamine and intermedine, foun...

  11. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    XU MaoJun; DONG JuFang

    2007-01-01

    Bax, a mammalian pro-apoptotic member of the Bcl-2 family, triggers hypersensitive reactions when expressed in plants. To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells, we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter. The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied. Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0- and 5.5-fold of the control cells. Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str, two key genes in terpenoid indole alkaloid biosynthetic pathway of Catharanthus roseus cells, and stimulates the accumulation of defense-related protein PR1 in the cells, showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway. Thus, our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  12. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Bax,a mammalian pro-apoptotic member of the Bcl-2 family,triggers hypersensitive reactions when expressed in plants.To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells,we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter.The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied.Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0-and 5.5-fold of the control cells.Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str,two key genes in terpenoid indole alkaloid bio-synthetic pathway of Catharanthus roseus cells,and stimulates the accumulation of defense-related protein PR1 in the cells,showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway.Thus,our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  13. Dendrobium nobile Lindl. alkaloids regulate metabolism gene expression in livers of mice.

    Science.gov (United States)

    Xu, Yun-Yan; Xu, Ya-Sha; Wang, Yuan; Wu, Qin; Lu, Yuan-Fu; Liu, Jie; Shi, Jing-Shan

    2017-07-19

    In our previous studies, Dendrobium nobile Lindl. alkaloids (DNLA) has been shown to have glucose-lowering and antihyperlipidaemia effects in diabetic rats, in rats fed with high-fat diets, and in mice challenged with adrenaline. This study aimed to examine the effects of DNLA on the expression of glucose and lipid metabolism genes in livers of mice. Mice were given DNLA at doses of 10-80 mg/kg, po for 8 days, and livers were removed for total RNA and protein isolation to perform real-time RT-PCR and Western blot analysis. Dendrobium nobile Lindl. alkaloids increased PGC1α at mRNA and protein levels and increased glucose metabolism gene Glut2 and FoxO1 expression. DNLA also increased the expression of fatty acid β-oxidation genes Acox1 and Cpt1a. The lipid synthesis regulator Srebp1 (sterol regulatory element-binding protein-1) was decreased, while the lipolysis gene ATGL was increased. Interestingly, DNLA increased the expression of antioxidant gene metallothionein-1 and NADPH quinone oxidoreductase-1 (Nqo1) in livers of mice. Western blot on selected proteins confirmed these changes including the increased expression of GLUT4 and PPARα. DNLA has beneficial effects on liver glucose and lipid metabolism gene expressions, and enhances the Nrf2-antioxidant pathway gene expressions, which could play integrated roles in regulating metabolic disorders. © 2017 Royal Pharmaceutical Society.

  14. Toxicosis by Plant Alkaloids in Humans and Animals in Colombia

    Directory of Open Access Journals (Sweden)

    Gonzalo J. Diaz

    2015-12-01

    Full Text Available Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and γ-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia.

  15. Toxicosis by Plant Alkaloids in Humans and Animals in Colombia

    Science.gov (United States)

    Diaz, Gonzalo J.

    2015-01-01

    Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and γ-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia. PMID:26690479

  16. Toxicosis by Plant Alkaloids in Humans and Animals in Colombia.

    Science.gov (United States)

    Diaz, Gonzalo J

    2015-12-11

    Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and γ-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia.

  17. Digital Gene Expression Analysis Provides Insight into the Transcript Profile of the Genes Involved in Aporphine Alkaloid Biosynthesis in Lotus (Nelumbo nucifera)

    Science.gov (United States)

    Yang, Mei; Zhu, Lingping; Li, Ling; Li, Juanjuan; Xu, Liming; Feng, Ji; Liu, Yanling

    2017-01-01

    The predominant alkaloids in lotus leaves are aporphine alkaloids. These are the most important active components and have many pharmacological properties, but little is known about their biosynthesis. We used digital gene expression (DGE) technology to identify differentially-expressed genes (DEGs) between two lotus cultivars with different alkaloid contents at four leaf development stages. We also predicted potential genes involved in aporphine alkaloid biosynthesis by weighted gene co-expression network analysis (WGCNA). Approximately 335 billion nucleotides were generated; and 94% of which were aligned against the reference genome. Of 22 thousand expressed genes, 19,000 were differentially expressed between the two cultivars at the four stages. Gene Ontology (GO) enrichment analysis revealed that catalytic activity and oxidoreductase activity were enriched significantly in most pairwise comparisons. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, dozens of DEGs were assigned to the categories of biosynthesis of secondary metabolites, isoquinoline alkaloid biosynthesis, and flavonoid biosynthesis. The genes encoding norcoclaurine synthase (NCS), norcoclaurine 6-O-methyltransferase (6OMT), coclaurine N-methyltransferase (CNMT), N-methylcoclaurine 3′-hydroxylase (NMCH), and 3′-hydroxy-N-methylcoclaurine 4′-O-methyltransferase (4′OMT) in the common pathways of benzylisoquinoline alkaloid biosynthesis and the ones encoding corytuberine synthase (CTS) in aporphine alkaloid biosynthetic pathway, which have been characterized in other plants, were identified in lotus. These genes had positive effects on alkaloid content, albeit with phenotypic lag. The WGCNA of DEGs revealed that one network module was associated with the dynamic change of alkaloid content. Eleven genes encoding proteins with methyltransferase, oxidoreductase and CYP450 activities were identified. These were surmised to be genes involved in aporphine alkaloid biosynthesis. This

  18. Pyrrolizidine Alkaloids: Testing for Toxic Constituents of Comfrey.

    Science.gov (United States)

    Vollmer, John J.; And Others

    1987-01-01

    Discusses the possibilities of toxins present in medicinal herbs. Describes an experiment in which toxic constituents can be selectively detected by thin-layer chromatography and NMR spectroscopy. (TW)

  19. The aporphine alkaloid boldine induces adiponectin expression and regulation in 3T3-L1 cells.

    Science.gov (United States)

    Yu, Bangning; Cook, Carla; Santanam, Nalini

    2009-10-01

    Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor (PPAR)-gamma, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H(2)O(2)) (100 microM) or tumor necrosis factor-alpha (TNFalpha) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5-100 microM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARgamma, and C/EBPalpha to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H(2)O(2) or TNFalpha and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5-25 microM) having a larger inductive effect compared to higher concentrations (50-100 microM). Boldine treatment alone in the absence of H(2)O(2) or TNFalpha was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease.

  20. Improved expression of His(6)-tagged strictosidine synthase cDNA for chemo-enzymatic alkaloid diversification.

    Science.gov (United States)

    Yang, Liuqing; Zou, Hongbin; Zhu, Huajian; Ruppert, Martin; Gong, Jingxu; Stöckigt, Joachim

    2010-04-01

    Strictosidine synthase (STR1) catalyzes the stereoselective formation of 3alpha(S)-strictosidine from tryptamine and secologanin. Strictosidine is the key intermediate in the biosynthesis of 2,000 plant monoterpenoid indole alkaloids, and it is a key precursor of enzyme-mediated synthesis of alkaloids. An improved expression system is described which leads to optimized His(6)-STR1 synthesis in Escherichia coli. Optimal production of STR1 was achieved by determining the impact of co-expression of chaperones pG-Tf2 and pG-LJE8. The amount and activity of STR1 was doubled in the presence of chaperone pG-Tf2 alone. His(6)-STR1 immobilized on Ni-NTA can be used for enzymatic synthesis of strictosidines on a preparative scale. With the newly co-expressed His(6)-STR1, novel 3alpha(S)-12-azastrictosidine was obtained by enzymatic catalysis of 7-azatryptamine and secologanin. The results obtained are of significant importance for application to chemo-enzymatic approaches leading to diversification of alkaloids with novel improved structures.

  1. An in vitro comparison of the cytotoxic potential of selected dehydropyrrolizidine alkaloids and some N-oxides

    Science.gov (United States)

    Plants containing dehydro-pyrrolizidine alkaloids (PAs) can be found throughout the world and their invasive, weedy nature often results in PA contamination of feed and food. Other PA-containing plants may be purposefully or accidentally included in food or herbal preparations. Poisoning can be acu...

  2. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.

    Science.gov (United States)

    Bacher, Nicole; Tiefenthaler, Martin; Sturm, Sonja; Stuppner, Hermann; Ausserlechner, Michael J; Kofler, Reinhard; Konwalinka, Günther

    2006-03-01

    Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.

  3. Early changes in gene expression induced by acute UV exposure in leaves of Psychotria brachyceras, a bioactive alkaloid accumulating plant.

    Science.gov (United States)

    do Nascimento, Naíla Cannes; Menguer, Paloma Koprovski; Sperotto, Raul Antonio; de Almeida, Márcia Rodrigues; Fett-Neto, Arthur Germano

    2013-05-01

    UV-B radiation can damage biomolecules, such as DNA, RNA, and proteins, halting essential cellular processes; this damage is partly due to ROS generation. Plant secondary metabolites may protect against UV-B. Psychotria brachyceras Müll. Arg. (Rubiaceae), a subtropical shrub, produces brachycerine, a monoterpene indole alkaloid mainly accumulated in leaf tissues, which displays antioxidant and antimutagenic activities. Exposure of P. brachyceras cuttings to UV-B radiation significantly increases leaf brachycerine concentration. It has been suggested that this alkaloid might contribute to protection against UV-B damage both through its quenching activity on ROS and as UV shield. To identify differentially expressed genes of P. brachyceras in response to UV-B and investigate a possible influence of this stimulus on putative brachycerine-related genes, suppressive subtractive hybridization was applied. Complementary DNA from UV-B-treated leaves for 24 h was used as tester, and cDNA from untreated leaves, as driver. After BLASTX alignments, 134 sequences matched plant genes. Using quantitative RT-PCR, selected genes potentially related to brachycerine showed significant increases in transcription after UV-B exposure: tryptophan decarboxylase, ACC oxidase, UDP-glucose glucosyltransferase, lipase, and serine/threonine kinase. Results suggest a possible involvement of brachycerine in acute UV-B responses and show that alkaloid accumulation seems at least partly regulated at transcriptional level.

  4. A Straightforward Route to Enantiopure Pyrrolizidines and Indolizidines by Cycloaddition to Pyrroline N-Oxides Derived from the Chiral Pool

    Directory of Open Access Journals (Sweden)

    Alberto Brandi

    1998-12-01

    Full Text Available Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D- and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and g-crotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (–-hastanecine, as well as to indolizidine alkaloids, i.e. (+- lentiginosine.

  5. Vinca alkaloids.

    Science.gov (United States)

    Moudi, Maryam; Go, Rusea; Yien, Christina Yong Seok; Nazre, Mohd

    2013-11-01

    Vinca alkaloids are a subset of drugs obtained from the Madagascar periwinkle plant. They are naturally extracted from the pink periwinkle plant, Catharanthus roseus G. Don and have a hypoglycemic as well as cytotoxic effects. They have been used to treat diabetes, high blood pressure and have been used as disinfectants. The vinca alkaloids are also important for being cancer fighters. There are four major vinca alkaloids in clinical use: Vinblastine (VBL), vinorelbine (VRL), vincristine (VCR) and vindesine (VDS). VCR, VBL and VRL have been approved for use in the United States. Vinflunine is also a new synthetic vinca alkaloid, which has been approved in Europe for the treatment of second-line transitional cell carcinoma of the urothelium is being developed for other malignancies. Vinca alkaloids are the second-most-used class of cancer drugs and will stay among the original cancer therapies. Different researches and studies for new vinca alkaloid applications will be carried out in this regard.

  6. Pro-toxic dehydropyrrolizidine alkaloids in the traditional Andean herbal medicine “asmachilca”

    Science.gov (United States)

    Colegate, Steven M.; Boppré, Michael; Monzón, Julio; Betz, Joseph M.

    2015-01-01

    Ethnopharmacological relevance Asmachilca is a Peruvian medicinal herb preparation ostensibly derived from Eupatorium gayanum Wedd. = Aristeguietia gayana (Wedd.) R.M. King & H. Rob. (Asteraceae: Eupatorieae). Decoctions of the plant have a reported bronchodilation effect that is purported to be useful in the treatment of respiratory allergies, common cold and bronchial asthma. However, its attractiveness to pyrrolizidine alkaloid-pharmacophagous insects indicated a potential for toxicity for human consumers. Aim of the study To determine if commercial asmachilca samples, including fully processed herbal teas, contain potentially toxic 1,2-dehydropyrrolizidine alkaloids. Materials and methods Two brands of “Asmachilca” herbal tea bags and four other commercial samples of botanical materials for preparing asmachilca medicine were extracted and analyzed using HPLC-esi(+)MS and MS/MS for the characteristic retention times and mass spectra of known dehydropyrrolizidine alkaloids. Other suspected dehydropyrrolizidine alkaloids were tentatively identified based on MS/MS profiles and high resolution molecular weight determinations. Further structure elucidation of isolated alkaloids was based on 1D and 2D NMR spectroscopy. Results Asmachilca attracted many species of moths which are known to pharmacophagously gather dehydropyrrolizidine alkaloids. Analysis of 5 of the asmachilca samples revealed the major presence of the dehydropyrrolizidine alkaloid monoesters rinderine and supinine, and their N-oxides. The 6th sample was very similar but did not contain supinine or its N-oxide. Small quantities of other dehydropyrrolizidine alkaloid monoesters, including echinatine and intermedine, were also detected. In addition, two major metabolites, previously undescribed, were isolated and identified as dehydropyrrolizidine alkaloid monoesters with two “head-to-tail” linked viridifloric and/or trachelanthic acids. Estimates of total pyrrolizidine alkaloid and N

  7. Increased chal enge in traditional Chinese medicine containing pyrrolizidine alkaloids-induced hepatic sinusoidal ob-struction syndrome%含吡咯烷生物碱的中草药致肝窦阻塞综合征研究进展

    Institute of Scientific and Technical Information of China (English)

    张骏飞(综述); 刘波; 陈从新(审校)

    2014-01-01

    Hepatic sinusoidal obstruction syndrome is rare clinically,but the incidence is recently increased. The clinical manifestations are mainly refractory ascites,jaundice and hepatomegaly.The main causes is the ingestion of pyrrolizidine alka-loids-containing herbs or plants. The early diagnosis is currently difficult. There is no specific therapy for patients with hepatic sinusoidal obstruction syndrome,except for symptomatic and supportive therapy. This review mainly discuss the mechanism,pathol-ogy,early diagnosis,and therapy of this entity.%在临床上,肝窦阻塞综合征比较少见,近年来发病率逐年升高。其主要临床表现为顽固性腹水、黄疸、肝肿大。主要病因是摄入含吡咯烷生物碱的中草药或植物。目前早期诊断困难,无特效治疗方法,主要为对症和支持治疗。本文主要介绍摄入含吡咯烷生物碱的中草药导致的肝窦阻塞综合征的发病机制、病理学和临床表现,以及诊断和治疗方面的进展。

  8. Dietary alkaloids and the development of androconial organs in Estigmene acrea

    Directory of Open Access Journals (Sweden)

    Jason W. Davenport

    2003-01-01

    Full Text Available Male salt marsh moths, Estigmene acrea (Lepidoptera: Arctiidae, possess inflatable androconial organs called coremata. Prior to mating males form aggregations and inflate their coremata en masse. The communal display attracts additional males and females for the purpose of mating. The coremata are known to carry the plant-derived dihydropyrrolizine, hydroxydanaidal. This pheromonal substance is derived from secondary plant chemicals called pyrrolizidine alkaloids found in the larval diet.

  9. Occurrence of halogenated alkaloids.

    Science.gov (United States)

    Gribble, Gordon W

    2012-01-01

    Once considered to be isolation artifacts or chemical "mistakes" of nature, the number of naturally occurring organohalogen compounds has grown from a dozen in 1954 to >5000 today. Of these, at least 25% are halogenated alkaloids. This is not surprising since nitrogen-containing pyrroles, indoles, carbolines, tryptamines, tyrosines, and tyramines are excellent platforms for biohalogenation, particularly in the marine environment where both chloride and bromide are plentiful for biooxidation and subsequent incorporation into these electron-rich substrates. This review presents the occurrence of all halogenated alkaloids, with the exception of marine bromotyrosines where coverage begins where it left off in volume 61 of The Alkaloids. Whereas the biological activity of these extraordinary compounds is briefly cited for some examples, a future volume of The Alkaloids will present full coverage of this topic and will also include selected syntheses of halogenated alkaloids. Natural organohalogens of all types, especially marine and terrestrial halogenated alkaloids, comprise a rapidly expanding class of natural products, in many cases expressing powerful biological activity. This enormous proliferation has several origins: (1) a revitalization of natural product research in a search for new drugs, (2) improved compound characterization methods (multidimensional NMR, high-resolution mass spectrometry), (3) specific enzyme-based and other biological assays, (4) sophisticated collection methods (SCUBA and remote submersibles for deep ocean marine collections), (5) new separation and purification techniques (HPLC and countercurrent separation), (6) a greater appreciation of traditional folk medicine and ethobotany, and (7) marine bacteria and fungi as novel sources of natural products. Halogenated alkaloids are truly omnipresent in the environment. Indeed, one compound, Q1 (234), is ubiquitous in the marine food web and is found in the Inuit from their diet of whale

  10. Alkaloids from single skins of the Argentinian toad Melanophryniscus rubriventris (ANURA, BUFONIDAE): An unexpected variability in alkaloid profiles and a profusion of new structures.

    Science.gov (United States)

    Garraffo, H Martin; Andriamaharavo, Nirina R; Vaira, Marcos; Quiroga, María F; Heit, Cecilia; Spande, Thomas F

    2012-12-01

    GC-MS analysis of single-skins of ten Melanophryniscus rubriventris toads (five collections of two toads each) captured during their breeding season in NW Argentina has revealed a total of 127 alkaloids of which 56 had not been previously detected in any frog or toad. Included among these new alkaloids are 23 new diastereomers of previously reported alkaloids. What is particularly distinguishing about the alkaloid profiles of these ten collections is the occurrence of many of the alkaloids, whether known or new to us, in only one of the ten skins sampled, despite two skins being obtained from each breeding site of the five populations. Many of the alkaloids are of classes known to have structures with branched-chains (e.g. pumiliotoxins and tricyclic structures) that are considered to derive from dietary mites. A large number of previously reported and new alkaloids are also of unclassified structures. Only a very few 3,5-disubstituted-indolizidine or -pyrrolizidine alkaloids are observed that have a straight-chain carbon skeleton and are likely derived from ant prey. The possible relationship of these collections made during the toad's brief breeding episodes to sequestration of dietary arthropods and individual alkaloid profiles is discussed.

  11. Genotoxicity and morphological changes induced by the alkaloid monocrotaline, extracted from Crotalaria retusa, in a model of glial cells.

    Science.gov (United States)

    Silva-Neto, J P; Barreto, R A; Pitanga, B P S; Souza, C S; Silva, V D; Silva, A R; Velozo, E S; Cunha, S D; Batatinha, M J M; Tardy, M; Ribeiro, C S O; Costa, M F D; El-Bachá, R S; Costa, S L

    2010-01-01

    Plants of Crotalaria genus (Leguminosae) present large amounts of the pyrrolizidine alkaloid monocrotaline (MCT) and cause intoxication to animals and humans. Therefore, we investigated the MCT-induced cytotoxicity, morphological changes, and oxidative and genotoxic damages to glial cells, using the human glioblastoma cell line GL-15 as a model. The comet test showed that 24h exposure to 1-500microM MCT and 500microM dehydromonocrotaline (DHMC) caused significant increases in cell DNA damage index, which reached 42-64% and 53%, respectively. Cells exposed to 100-500microM MCT also featured a contracted cytoplasm presenting thin cellular processes and vimentin destabilisation. Conversely, exposure of GL-15 cells to low concentrations of MCT (1-10microM) clearly induced megalocytosis. Moreover, MCT also induced down regulation of MAPs, especially at the lower concentrations adopted (1-10microM). Apoptosis was also evidenced in cells treated with 100-500microM MCT, and a later cytotoxicity was only observed after 6 days of exposure to 500microM MCT. The data obtained provide support for heterogenic and multipotential effects of MCT on GL-15 cells, either interfering on cell growth and cytoskeletal protein expression, or inducing DNA damage and apoptosis and suggest that the response of glial cells to this alkaloid might be related to the neurological signs observed after Crotalaria intoxication.

  12. Cross-resistance patterns and antigen expression in Vinca alkaloid- and other multiple drug-resistant human leukemic cell lines.

    Science.gov (United States)

    Beck, W T; Danks, M K; Cirtain, M C; van Heiningen, J N

    1986-01-01

    The studies presented in this report demonstrate that Vinca alkaloid-resistant human leukemic lymphoblasts display patterns of cross-resistance to other drugs that differ from those of cell lines selected for primary resistance to anthracyclines or epipodophyllotoxins. These various drug-resistant cell lines also showed differential expression of an antigen recognized by an antibody that distinguishes VLB-resistant from VLB-sensitive cells. Furthermore, comparable levels of resistance or cross-resistance to one drug are not predictive of cross-resistance to other drugs. Our data suggest, then, that the MDR phenotype is complex and may be the result of many and different biochemical lesions. Thus, in order to predict MDR, it may be necessary to document more than one of these changes with specific reagents.

  13. Vinca Alkaloids

    Directory of Open Access Journals (Sweden)

    Maryam Moudi

    2013-01-01

    Full Text Available Vinca alkaloids are a subset of drugs obtained from the Madagascar periwinkle plant. They are naturally extracted from the pink periwinkle plant, Catharanthus roseus G. Don and have a hypoglycemic as well as cytotoxic effects. They have been used to treat diabetes, high blood pressure and have been used as disinfectants. The vinca alkaloids are also important for being cancer fighters. There are four major vinca alkaloids in clinical use: Vinblastine (VBL, vinorelbine (VRL, vincristine (VCR and vindesine (VDS. VCR, VBL and VRL have been approved for use in the United States. Vinflunine is also a new synthetic vinca alkaloid, which has been approved in Europe for the treatment of second-line transitional cell carcinoma of the urothelium is being developed for other malignancies. Vinca alkaloids are the second-most-used class of cancer drugs and will stay among the original cancer therapies. Different researches and studies for new vinca alkaloid applications will be carried out in this regard.

  14. Cellular distribution of alkaloids and their translocation via phloem and xylem: the importance of compartment pH.

    Science.gov (United States)

    Nowak, M; Selmar, D

    2016-11-01

    The physico-chemical background of alkaloid allocation within plants is outlined and discussed exemplarily for pyrrolizidine alkaloids (PAs) and nicotine. The trigger for this discourse is the finding that, for example, PAs, which are taken up from the soil, are translocated in the xylem, whereas - when genuinely present in plants - they are allocated as N-oxides via phloem. Special emphasis is put on the impact of different pH values in certain compartments, as this entails significant changes in the relative lipophilic character of alkaloids: tertiary alkaloids diffuse readily through biomembranes, while the corresponding protonated alkaloids are retained in acidic compartments, i.e. vacuoles or xylem. Therefore, this phenomenon, well known as the 'ion trap mechanism', is also relevant for long-distance transport of alkaloids. Any efficient allocation of typical tertiary alkaloids within the phloem can thus be excluded. In contrast, due to their strongly increased hydrophilic properties, alkaloid-N-oxides or quarternary alkaloids cannot diffuse through biomembranes and, consequently, would be retained in the acidic xylem during translocation. The major aim of this paper is to sharpen the mind for the chemical peculiarities of alkaloids and to consider them adequately in forthcoming investigations on allocation of alkaloids.

  15. Inhibition of Corydalis decumbens Alkaloids on Hydrogen Peroxideinduced Apoptosis of PC12 Cells through Down-regulating Caspase-3 Expression

    Institute of Scientific and Technical Information of China (English)

    YAN Ren-jie; YANG Yi-fang; LUO Yong-ming; WU Chun-zhen

    2011-01-01

    Objective To extract alkaloids from Corydalis decumbens (AsCD) by supercritical CO2 fluid extraction (SFE) and to evaluate protective effects of AsCD against hydrogen peroxide (H2O2)-induced apoptosis in rat PC12 cells.Methods AsCD were extracted by SFE and oxidative damage PC12 cells model was induced by H2O2.The survival rate of the cells was determined by MTT assay; Lactate dehydrogenase release was determined by ultraviolet spectrophotometry; Flow cytometry was used to detect apoptosis; Caspase-3 mRNA and protein were determined by real-time PCR and Western blotting assay,respectively.Results AsCD remarkably reduced the cytotoxicity,prevented membrane damage,and inhibited cell apoptosis.AsCD inhibited Caspase-3 mRNA and protein expression induced by H2O2 in PC12 cells.Conclusion AsCD possess protective effects against H2O2-induced apoptosis in PC12 cells,and the mechanism of AsCD responsible to the inhibition of apoptosis is possibly attributed to thedown-regulating Caspase-3 expression.AsCD might be useful in the treatment of oxidative stress-related neurodegenerative diseases.

  16. Dendrobium alkaloids prevent Aβ25–35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice

    Directory of Open Access Journals (Sweden)

    Jing Nie

    2016-12-01

    Full Text Available Background Neuronal and synaptic loss is the most important risk factor for cognitive impairment. Inhibiting neuronal apoptosis and preventing synaptic loss are promising therapeutic approaches for Alzheimer’s disease (AD. In this study, we investigate the protective effects of Dendrobium alkaloids (DNLA, a Chinese medicinal herb extract, on β-amyloid peptide segment 25–35 (Aβ25-35-induced neuron and synaptic loss in mice. Method Aβ25–35(10 µg was injected into the bilateral ventricles of male mice followed by an oral administration of DNLA (40 mg/kg for 19 days. The Morris water maze was used for evaluating the ability of spatial learning and memory function of mice. The morphological changes were examined via H&E staining and Nissl staining. TUNEL staining was used to check the neuronal apoptosis. The ultrastructure changes of neurons were observed under electron microscope. Western blot was used to evaluate the protein expression levels of ciliary neurotrophic factor (CNTF, glial cell line-derived neurotrophic factor (GDNF, and brain-derived neurotrophic factor (BDNF in the hippocampus and cortex. Results DNLA significantly attenuated Aβ25–35-induced spatial learning and memory impairments in mice. DNLA prevented Aβ25–35-induced neuronal loss in the hippocampus and cortex, increased the number of Nissl bodies, improved the ultrastructural injury of neurons and increased the number of synapses in neurons. Furthermore, DNLA increased the protein expression of neurotrophic factors BDNF, CNTF and GDNF in the hippocampus and cortex. Conclusions DNLA can prevent neuronal apoptosis and synaptic loss. This effect is mediated at least in part via increasing the expression of BDNF, GDNF and CNTF in the hippocampus and cortex; improving Aβ-induced spatial learning and memory impairment in mice.

  17. Dendrobium alkaloids prevent Aβ25–35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice

    Science.gov (United States)

    Nie, Jing; Tian, Yong; Zhang, Yu; Lu, Yan-Liu; Li, Li-Sheng

    2016-01-01

    Background Neuronal and synaptic loss is the most important risk factor for cognitive impairment. Inhibiting neuronal apoptosis and preventing synaptic loss are promising therapeutic approaches for Alzheimer’s disease (AD). In this study, we investigate the protective effects of Dendrobium alkaloids (DNLA), a Chinese medicinal herb extract, on β-amyloid peptide segment 25–35 (Aβ25-35)-induced neuron and synaptic loss in mice. Method Aβ25–35(10 µg) was injected into the bilateral ventricles of male mice followed by an oral administration of DNLA (40 mg/kg) for 19 days. The Morris water maze was used for evaluating the ability of spatial learning and memory function of mice. The morphological changes were examined via H&E staining and Nissl staining. TUNEL staining was used to check the neuronal apoptosis. The ultrastructure changes of neurons were observed under electron microscope. Western blot was used to evaluate the protein expression levels of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex. Results DNLA significantly attenuated Aβ25–35-induced spatial learning and memory impairments in mice. DNLA prevented Aβ25–35-induced neuronal loss in the hippocampus and cortex, increased the number of Nissl bodies, improved the ultrastructural injury of neurons and increased the number of synapses in neurons. Furthermore, DNLA increased the protein expression of neurotrophic factors BDNF, CNTF and GDNF in the hippocampus and cortex. Conclusions DNLA can prevent neuronal apoptosis and synaptic loss. This effect is mediated at least in part via increasing the expression of BDNF, GDNF and CNTF in the hippocampus and cortex; improving Aβ-induced spatial learning and memory impairment in mice. PMID:27994964

  18. Dendrobium alkaloids prevent Aβ25-35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice.

    Science.gov (United States)

    Nie, Jing; Tian, Yong; Zhang, Yu; Lu, Yan-Liu; Li, Li-Sheng; Shi, Jing-Shan

    2016-01-01

    Neuronal and synaptic loss is the most important risk factor for cognitive impairment. Inhibiting neuronal apoptosis and preventing synaptic loss are promising therapeutic approaches for Alzheimer's disease (AD). In this study, we investigate the protective effects of Dendrobium alkaloids (DNLA), a Chinese medicinal herb extract, on β-amyloid peptide segment 25-35 (Aβ25-35)-induced neuron and synaptic loss in mice. Aβ25-35(10 µg) was injected into the bilateral ventricles of male mice followed by an oral administration of DNLA (40 mg/kg) for 19 days. The Morris water maze was used for evaluating the ability of spatial learning and memory function of mice. The morphological changes were examined via H&E staining and Nissl staining. TUNEL staining was used to check the neuronal apoptosis. The ultrastructure changes of neurons were observed under electron microscope. Western blot was used to evaluate the protein expression levels of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex. DNLA significantly attenuated Aβ25-35-induced spatial learning and memory impairments in mice. DNLA prevented Aβ25-35-induced neuronal loss in the hippocampus and cortex, increased the number of Nissl bodies, improved the ultrastructural injury of neurons and increased the number of synapses in neurons. Furthermore, DNLA increased the protein expression of neurotrophic factors BDNF, CNTF and GDNF in the hippocampus and cortex. DNLA can prevent neuronal apoptosis and synaptic loss. This effect is mediated at least in part via increasing the expression of BDNF, GDNF and CNTF in the hippocampus and cortex; improving Aβ-induced spatial learning and memory impairment in mice.

  19. A root-expressed L-phenylalanine:4-hydroxyphenylpyruvate aminotransferase is required for tropane alkaloid biosynthesis in Atropa belladonna.

    Science.gov (United States)

    Bedewitz, Matthew A; Góngora-Castillo, Elsa; Uebler, Joseph B; Gonzales-Vigil, Eliana; Wiegert-Rininger, Krystle E; Childs, Kevin L; Hamilton, John P; Vaillancourt, Brieanne; Yeo, Yun-Soo; Chappell, Joseph; DellaPenna, Dean; Jones, A Daniel; Buell, C Robin; Barry, Cornelius S

    2014-09-01

    The tropane alkaloids, hyoscyamine and scopolamine, are medicinal compounds that are the active components of several therapeutics. Hyoscyamine and scopolamine are synthesized in the roots of specific genera of the Solanaceae in a multistep pathway that is only partially elucidated. To facilitate greater understanding of tropane alkaloid biosynthesis, a de novo transcriptome assembly was developed for Deadly Nightshade (Atropa belladonna). Littorine is a key intermediate in hyoscyamine and scopolamine biosynthesis that is produced by the condensation of tropine and phenyllactic acid. Phenyllactic acid is derived from phenylalanine via its transamination to phenylpyruvate, and mining of the transcriptome identified a phylogenetically distinct aromatic amino acid aminotransferase (ArAT), designated Ab-ArAT4, that is coexpressed with known tropane alkaloid biosynthesis genes in the roots of A. belladonna. Silencing of Ab-ArAT4 disrupted synthesis of hyoscyamine and scopolamine through reduction of phenyllactic acid levels. Recombinant Ab-ArAT4 preferentially catalyzes the first step in phenyllactic acid synthesis, the transamination of phenylalanine to phenylpyruvate. However, rather than utilizing the typical keto-acid cosubstrates, 2-oxoglutarate, pyruvate, and oxaloacetate, Ab-ArAT4 possesses strong substrate preference and highest activity with the aromatic keto-acid, 4-hydroxyphenylpyruvate. Thus, Ab-ArAT4 operates at the interface between primary and specialized metabolism, contributing to both tropane alkaloid biosynthesis and the direct conversion of phenylalanine to tyrosine. © 2014 American Society of Plant Biologists. All rights reserved.

  20. Alkaloids from Delphinium pentagynum.

    Science.gov (United States)

    Díaz, Jesús G; Ruiz, Juan García; Herz, Werner

    2004-07-01

    Aerial parts of a collection of Delphinium pentagynum Lam. from Niebla, Southern Spain, furnished one diterpene alkaloid, 2-dehydrodeacetylheterophylloidine, two norditerpene alkaloids, 14-demethyl-14-isobutyrylanhweidelphinine and 14-demethyl-14-acetylanhweidelphinine, the known alkaloids 14-deacetylnudicauline, methyllycaconitine, 14-deacetyl-14-isobutyrylnudicauline, 14-acetylbrowniine, browniine, delcosine, lycoctonine, 18-methoxygadesine, neoline, karakoline and the aporphine alkaloid magnoflorine. Structures of the alkaloids were established by MS, 1D and 2-D NMR techniques.

  1. Reaction of dehydropyrrolizidine alkaloids with valine and hemoglobin.

    Science.gov (United States)

    Zhao, Yuewei; Wang, Shuguang; Xia, Qingsu; Gamboa da Costa, Gonçalo; Doerge, Daniel R; Cai, Lining; Fu, Peter P

    2014-10-20

    Pyrrolizidine alkaloid-containing plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids exert toxicity through metabolism to dehydropyrrolizidine alkaloids that bind to cellular protein and DNA, leading to hepatotoxicity, genotoxicity, and tumorigenicity. To date, it is not clear how dehydropyrrolizidine alkaloids bind to cellular constituents, including amino acids and proteins, resulting in toxicity. Metabolism of carcinogenic monocrotaline, riddelliine, and heliotrine produces dehydromonocrotaline, dehyroriddelliine, and dehydroheliotrine, respectively, as primary reactive metabolites. In this study, we report that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived valine (DHP-valine) adducts. For structural elucidation, DHP-valine adducts were derivatized with phenyl isothiocyanate (PITC) to DHP-valine-PITC products. After HPLC separation, their structures were characterized by mass spectrometry, UV-visible spectrophotometry, (1)H NMR, and (1)H-(1)H COSY NMR spectral analysis. Two DHP-valine-PITC adducts, designated as DHP-valine-PITC-1 and DHP-valine-PITC-3, had the amino group of valine linked to the C7 position of the necine base, and the other two DHP-valine-PITC products, DHP-valine-PITC-2 and DHP-valine-PITC-4, linked to the C9 position of the necine base. DHP-valine-PITC-1 was interconvertible with DHP-valine-PITC-3, and DHP-valine-PITC-2 was interconvertible with DHP-valine-PITC-4. Reaction of dehydroriddelliine and dehydroheliotrine with valine provided similar results. However, reaction of valine and dehydroretronecine (DHR) under similar experimental conditions did not produce DHP-valine adducts. Reaction of dehydromonocrotaline with rat hemoglobin followed by derivatization with PITC also generated the same four DHP-valine-PITC adducts. This represents the first full structural elucidation of

  2. Changes in plant defense chemistry (pyrrolizidine alkaloids) revealed through high-resolution spectroscopy

    NARCIS (Netherlands)

    Almeida De Carvalho, S.; Macel, M.; Schlerf, M.; Moghaddam, F.E.; Mulder, P.P.J.; Skidmore, A.K.; Putten, van der W.H.

    2013-01-01

    Plant toxic biochemicals play an important role in defense against natural enemies and often are toxic to humans and livestock. Hyperspectral reflectance is an established method for primary chemical detection and could be further used to determine plant toxicity in the field. In order to make a fir

  3. Diversity of pyrrolizidine alkaloids in native and invasive Senecio pterophorus (Asteraceae): Implications for toxicity

    NARCIS (Netherlands)

    Castells, E.; Mulder, P.P.J.; Perez -Trujillo, M.

    2014-01-01

    Changes in plant chemical defenses after invasion could have consequences on the invaded ecosystems by modifying the interactions between plants and herbivores and facilitating invasion success. However, no comprehensive biogeographical studies have yet determined the phenotypic levels of plant chem

  4. CHARACTERIZATION OF RUMEN BACTERIAL PYRROLIZIDINE ALKALOID BIOTRANSFORMATION IN RUMINANTS OF VARIOUS SPECIES. (R825689C006)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  5. Pyrrolizidine Alkaloid Composition Influences Cinnabar Moth Oviposition Preferences in Jacobaea Hybrids

    NARCIS (Netherlands)

    Cheng, D.; Meijden, van der E.; Mulder, P.P.J.; Vrieling, K.; Klinkhamer, P.G.L.

    2013-01-01

    Plants produce a variety of secondary metabolites (PSMs) that may be selective against herbivores. Yet, specialist herbivores may use PSMs as cues for host recognition, oviposition, and feeding stimulation, or for their own defense against parasites and predators. This summarizes a dual role of PSMs

  6. Seasonal Change of Loline Alkaloids in Endophyte-lnfected Meadow Fescue

    Institute of Scientific and Technical Information of China (English)

    TONG De-wen; WANG Jin-yi; Brain Patchett; Ravi Gooneratne

    2006-01-01

    Lolines are a group of saturated pyrrolizidine alkaloids that possess broad bioactivity against a wide array of herbivorous insects. However, they do not exhibit toxicity to ruminants such as cattle and sheep. In order to study the direct and potential physiological effects on ruminants and the mechanism of insecticide/insectifuge, the distribution of loline alkaloids in endophyte-infected meadow fescue and the seasonal change of the distribution were analyzed. The crowns,roots and leaves of endophyte-infected meadow fescue at its four different growth periods, i.e., spring, summer, early autumn and late autumn, in New Zealand were colleted. After powdering, organic solvent extraction and purification by column chromatography, all loline alkaloid samples were analyzed by capillary gas chromatography with 4-phenylmorpholine (PM) as an internal standard. The analytic results showed that the loline contents in the roots, crowns and leaves of endophyte-infected meadow fescue vary with seasons. Even within the same season, the distribution of lolines in endophyte-infected meadow fescue varies. During summer, lolines mainly existed in the leaves and roots, but in early autumn, they are produced in the crowns. It was concluded that, lolines were mainly produced in the leaves and roots of endophyte-infected meadow fescue. In gas chromatographic analysis, N-formylloline, the major component of loline alkaloid in the plant, was employed to assay the alkaloids.

  7. Exploiting plant alkaloids.

    Science.gov (United States)

    Schläger, Sabrina; Dräger, Birgit

    2016-02-01

    Alkaloid-containing plants have been used for medicine since ancient times. Modern pharmaceuticals still rely on alkaloid extraction from plants, some of which grow slowly, are difficult to cultivate and produce low alkaloid yields. Microbial cells as alternative alkaloid production systems are emerging. Before industrial application of genetically engineered bacteria and yeasts, several steps have to be taken. Original alkaloid-forming enzymes have to be elucidated from plants. Their activity in the heterologous host cells, however, may be low. The exchange of individual plant enzymes for alternative catalysts with better performance and optimal fermentation parameters appear promising. The overall aim is enhancement and stabilization of alkaloid yields from microbes in order to replace the tedious extraction of low alkaloid concentrations from intact plants.

  8. The miRNAome of Catharanthus roseus: identification, expression analysis, and potential roles of microRNAs in regulation of terpenoid indole alkaloid biosynthesis

    Science.gov (United States)

    Shen, Ethan M.; Singh, Sanjay K.; Ghosh, Jayadri S.; Patra, Barunava; Paul, Priyanka; Yuan, Ling; Pattanaik, Sitakanta

    2017-01-01

    MicroRNAs (miRNAs) regulate numerous crucial biological processes in plants. However, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including Catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (TIAs). Using small RNA-sequencing, we identified 181 conserved and 173 novel miRNAs (cro-miRNAs) in C. roseus seedlings. Genome-wide expression analysis revealed that a set of cro-miRNAs are differentially regulated in response to methyl jasmonate (MeJA). In silico target prediction identified 519 potential cro-miRNA targets that include several auxin response factors (ARFs). The presence of cleaved transcripts of miRNA-targeted ARFs in C. roseus cells was confirmed by Poly(A) Polymerase-Mediated Rapid Amplification of cDNA Ends (PPM-RACE). We showed that auxin (indole acetic acid, IAA) repressed the expression of key TIA pathway genes in C. roseus seedlings. Moreover, we demonstrated that a miRNA-regulated ARF, CrARF16, binds to the promoters of key TIA pathway genes and repress their expression. The C. roseus miRNAome reported here provides a comprehensive account of the cro-miRNA populations, as well as their abundance and expression profiles in response to MeJA. In addition, our findings underscore the importance of miRNAs in posttranscriptional control of the biosynthesis of specialized metabolites. PMID:28223695

  9. Chelidonine, a principal isoquinoline alkaloid of Chelidonium majus, attenuates eosinophilic airway inflammation by suppressing IL-4 and eotaxin-2 expression in asthmatic mice.

    Science.gov (United States)

    Kim, Seung-Hyung; Hong, Jung-Hee; Lee, Young-Cheol

    2015-12-01

    Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits anti-inflammatory and other pharmacological properties. However, its molecular mechanisms in asthma remain unclear. In this work we investigated chelidonine's effect and mechanism in airway inflammation in a mouse model of allergic asthma. The mice were sensitized to ovalbumin followed by aerosol allergen challenges and determination of chelidonine's effect on enhanced pause (Penh), pulmonary eosinophilic infiltration, eotaxin-2, interleukin-4 (IL-4), IL-13, OVA-specific IgE production, and several transcription factors. Chelidonine strongly suppressed airway eosinophilia, expression of eotaxin-2, IL-4, and IL-13 cytokine production in bronchoalveolar lavage fluid (BALF). It also attenuated lung IL-17, and eotaxin-2 mRNA expression levels. Moreover, it suppressed eotaxin-2 and IL-17 production in accordance with up- and downregulation of forkhead box p3 (Foxp3), and signal transducer and activator of transcription (STAT6) expression, respectively. Chelidonine has profound inhibitory effects on airway inflammation and this effect is caused by suppression of IL-4, eotaxin-2, and OVA-specific IgE production through the STAT6 and Foxp3 pathways. So chelidonine can improve allergic asthma in mice and be a novel anti-asthma therapeutic. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Alkaloids in Marine Algae

    OpenAIRE

    Ekrem Sezik; Aline Percot; Kasım Cemal Güven

    2010-01-01

    This paper presents the alkaloids found in green, brown and red marine algae. Algal chemistry has interested many researchers in order to develop new drugs, as algae include compounds with functional groups which are characteristic from this particular source. Among these compounds, alkaloids present special interest because of their pharmacological activities. Alkaloid chemistry has been widely studied in terrestrial plants, but the number of studies in algae is insignificant. In this review...

  11. Ergot and Its Alkaloids

    National Research Council Canada - National Science Library

    Paul L Schiff Jr

    2006-01-01

      This manuscript reviews the history and pharmacognosy of ergot, and describes the isolation/preparation, chemistry, pharmacodynamics, and pharmacotherapeutics of the major ergot alkaloids and their derivatives...

  12. Continued expression of vinca alkaloid resistance by CCRF-CEM cells after treatment with tunicamycin or pronase.

    Science.gov (United States)

    Beck, W T; Cirtain, M C

    1982-01-01

    We have shown that a glycoprotein(s) with a molecular weight of approximately 180,000 exists on the surface of cultured lymphoblasts selected for resistance to vinblastine (VLB) (CEM/VLB100). The amount of this glycoprotein, which is barely detectable on the VLB-sensitive cells (CEM), appears to be related in part to the degree of resistance, up to approximately 270-fold. Exposure of the cells to Pronase for 45 to 60 min or growth of the cells for 2 days in tunicamycin, an inhibitor of glycoprotein synthesis, resulted in the absence of the resistance-associated glycoproteins, as determined by polyacrylamide gel electrophoresis of these treated cells after labeling te cells either with sodium [3H]-borohydride or with [14C]- or [3H]glucosamine. Uptake studies with [3H]VLB revealed that CEM cells normally accumulated and retained more drug than did the CEM/VLB100 cells. While the tunicamycin or Pronase treatments slightly increased the uptake of drug by CEM cells, there was no enhanced uptake of [3H]VLB by the tunicamycin- or pronase-treated CEM/VLB100 cells, when compared with untreated controls, indicating that the loss of external surface glycoproteins did not render the resistant cells more "leaky" to drug influx. Additionally, diminished drug retention by the CEM/VLB100 cells was unaffected by these treatments. Moreover, when CEM/VLB100 cells were grown grown for 2 days in the presence of tunicamycin and several concentrations of VLB, no enhanced toxicity of VLB was noted. Other experiments with [14C]glucosamine and [3H]leucine revealed that treatment with tunicamycin did not affect the distribution of proteins in these cells. Taken together, these results permit the suggestion that the carbohydrate moiety of the cell surface resistance-associated glycoproteins does not mediate resistance to the alkaloid per se; however, a role for plasma membrane proteins cannot be ruled out at this time.

  13. Assessing the limitations to terpenoid indole alkaloid biosynthesis in Catharanthus roseus hairy root cultures through gene expression profiling and precursor feeding.

    Science.gov (United States)

    Goklany, Sheba; Loring, Ralph H; Glick, James; Lee-Parsons, Carolyn W T

    2009-01-01

    The production of pharmaceutically important terpenoid indole alkaloids (TIAs) from Catharanthus roseus is partly regulated at the transcriptional level. In this study, limitations in TIA biosynthesis from C. roseus hairy root cultures were assessed through gene expression profiling and precursor feeding. The transcript levels of key TIA pathway genes (G10h, Tdc, Str, and Sgd) and metabolite levels associated with the TIA pathway (tryptamine, loganin, secologanin, strictosidine, ajmalicine, serpentine, and tabersonine) were monitored using quantitative RT-PCR and HPLC, respectively. In cultures elicited with methyl jasmonate (250 microM MeJA on day 21), G10h, Tdc, Str, and Sgd expression increased by 9.1, 3.1, 6.7, and 8.3-fold, respectively, after 24 h. Up-regulation of gene expression was followed by a 160, 440, and 420% increase in strictosidine, ajmalicine, and tabersonine levels, respectively, after 5 days. Precursors loganin, tryptamine, or their combination were fed to noninduced and MeJA-induced cultures to complement the above studies. TIA production was not significantly enhanced in either noninduced or MeJA-induced cultures with precursor feeding. In noninduced cells, steps downstream of loganin and tryptamine were limiting (SLS, STR, or SGD) because either loganin or tryptamine accumulated in the cells with precursor feeding. These bottlenecks were partly overcome in MeJA-induced cultures as the expression of Str and Sgd genes and TIA production increased. However, secologanin accumulated in MeJA-induced cultures with precursor feeding, suggesting that STR was likely limiting under MeJA-induced conditions.

  14. Alkaloids from Menispermum dauricum.

    Science.gov (United States)

    Yu, Bing-Wu; Chen, Jian-Yong; Wang, Yan-Ping; Cheng, Kin-Fin; Li, Xiao-Yu; Qin, Guo-Wei

    2002-10-01

    The alkaloids, dechloroacutumidine and 1-epidechloroacutumine, together with three known alkaloids, acutumidine, acutumine, and dechloroacutumine, were isolated from the rhizomes of Menispermum dauricum and their structures established by spectral and chemical methods. The cytotoxicity of each compound against the growth of human cell lines was studied, and acutumine selectively inhibited T-cell growth.

  15. Effects of the Overall Alkaloid of a Traditional Chinese Medicine “Tongbiling” on the Cytokine Expression in Thl and Th2 Cells of Rheumatoid Arthritis and Their Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    陈光星; 刘清平; 王培训; 曾耀英; 刘良; 陈纪藩

    2004-01-01

    To investigate the effects of overall alkali of a traditional Chinese medicine “Tongbiling” (brucine and strychnine alkaloids in main) on the cytokines expression in Th1 and Th2 cells in the synovial fluid of patients with rheumatism arthritis and their signal pathway, the mononuclear cells in the synovial fluid (SFMC) of patients were isolated by Ficoll-Hypaque gradient centrifugation, and the CD3+ CD69+ and CD3+ HLA-DR antigen were analyzed by flow cytometry in comparison with those of the peripheral blood. The rest of cells were cultured after resuspension with RPMI 1640 culture medium. Phorbol 12, 13-dibutyrate (PDB) and ionomycin were added successively into the culture with various concentration of overall alkali Tongbiling (TBL). After 4 h of cultivation, the expression of IFN-γ and IL-4 in CD3+ cells were analyzed by flow cytometry. The influence of overall alkali TBL ( 100 mg/I,) on the intracellular calcium was investigated after Fluo-3/AM labeling and stimulation with PDB and ionomycin at 1, 2, 4 and 10 min, and the influence of TBL on the expression of CD3+ CD69+ cells were determined with stimulation of PDB for 24 h in the whole blood lymphocytes culture. It was found that the percentage of T cells bearing CD69 was significantly up-regulated (77%), while that of T cells bearing HLA-DR was 44% in the synovial mononucleated cells. After PDB and ionomycin stimulation, the expression of IFN-7 in CD3 ~ cells were up-regulated, but there was no change on the expression of IL-4 in CD3+ cells, indicating that ratio of Th1/Th2 was significantly increased and Th cells differentiate to Thl cells in mainly. Four concentrations of overall alkaloid of TBI, (200 mg/L, 100 mg/L, 50 mg/L, 25 mg/L) could down-regulated the expression of IFN-γ in CD3+ cells and the Th1/Th2 ratio obviously, but all the concentrations of the overall alkaloids had no effect on the expression of IL-4 in CD3+ cells. 100 mg/L concentration of the overall alkaloid did not down

  16. [Alkaloids of Annonaceae. XXIX. Alkaloids of Annona muricata].

    Science.gov (United States)

    Leboeuf, M; Legueut, C; Cavé, A; Desconclois, J F; Forgacs, P; Jacquemin, H

    1981-05-01

    From leaves, root - and stem - barks of Annona muricata L., seven isoquinoline alkaloids have been isolated: reticuline (main alkaloid), coclaurine, coreximine, atherosperminine, stepharine. Anomurine and anomuricine, two minor alkaloids, are new tetrahydrobenzylisoquinolines, with 5, 6, 7 substituted ring A. The phytochemical significance of these alkaloids is discussed.

  17. Genotoxic effect of alkaloids

    Directory of Open Access Journals (Sweden)

    J. A. P. Henriques

    1991-01-01

    Full Text Available Because of the increase use of alkaloids in general medical practice in recent years, it is of interest to determine genotoxic, mutagenic and recombinogenic response to different groups of alkaloids in prokaryotic and eucaryotic organisms. Reserpine, boldine and chelerythrine did not show genotoxicity response in the SOS-Chromotest whereas skimmianine showed genotixicity in the presence of a metabolic activation mixture. Voacristine isolated fromthe leaves of Ervatamia coronaria shows in vivo cytostatic and mutagenic effects in Saccharomyces cerevisiae hapioids cells. The Rauwolfia alkaloid (reserpine was not able to induce reverse mutation and recombinational mitotic events (crossing-over and gene conversion in yeast diploid strain XS2316.

  18. Alkaloids of Ocotea brachybotra.

    Science.gov (United States)

    Vecchietti, V; Casagrande, C; Ferrari, G

    1977-11-01

    Aporphine, proaporphine and morphinane alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea brachybotra (Meiss.) Mez. The known alkaloids were identified through their physico-chemical properties as: (I) (+/-)-glaziovine, (II) dicentrine, (III) ocopodine, (IV) cassynthicine, (V) predicentrine, (VI) leucoxine, (IX) sinacutine and (X) pallidine. The structure of (VI) leucoxine was confirmed by a detailed analysis of the N.M.R. spectra recorded in various conditions. New morphinane alkaloids, (XI) ocobotrine and (XII) 14-espisinomenine, having the unusual B/C-trans configuration were also isolated. Their structures were determined using spectroscopic methods and chemical correlations.

  19. Novel Euglenoid Derived Alkaloid

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Disclosed herein is a purified toxin isolated from Euglena sanguinea. More specifically the toxin, termed euglenophycin, is an alkaloid having herbicidal and...

  20. Total alkaloids of Sophora alopecuroides increases the expression of CD4+ CD25+ Tregs and IL-10 in rats with experimental colitis.

    Science.gov (United States)

    Zhou, Yi; Wang, He; Liang, Lei; Zhao, Wen-Chan; Chen, Yan; Deng, Hong-Zhu

    2010-01-01

    Previous studies have demonstrated that the total alkaloids of Sophora alopecuroides (TASA), which contains many different ingredients like sophocarpine, matrine, oxymatrine, sophoridine, sophoramine, aloperine and cytosine, were able to protect colon against ulcers caused by 2,4,6-trinitrobenze sulphonic acid (TNBS)/ethanol treated models. In order to elucidate the mechanisms by which TASA exerts its effect of anti-inflammation and immunoregulation on rats with colitis, DAI (disease activity index) and histological grading of colitis were evaluated in the animal model. Moreover, the expression of CD4(+)CD25(+) regulatory T cells (Tregs) and IL-10 in rats with experimental colitis were observed by FCM, ELISA and RT-PCR in this study. Results showed that TASA (15, 30 or 60 mg/kg/day) significantly up-regulated CD4(+)CD25(+)Tregs (P = 0.02, P = 0.02, P = 0.03) and IL-10 levels (ELISA: P = 0.03, P = 0.02, P = 0.00; RT-PCR: P = 0.04, P = 0.02, P = 0.01) respectively and decreased the DAI and histological grading of colitis in the peripheral blood (PB) and colon of rat colitis models (3.44 +/- 1.53, 4.25 +/- 1.27, 4.42 +/- 1.24 and 3.50 +/- 1.42, 4.05 +/- 1.32, 4.51 +/- 1.55 vs. 7.18 +/- 1.32 and 7.38 +/- 1.52, P Tregs and DAI (Pearson r(PB) = -0.677, P Tregs and IL-10 cytokine (IL-10 mRNA) in the colon and PB of rats (Pearson r(PB) = 0.789, P < 0.01, n = 60; Pearson r(COLON) = 0.678, P < 0.01, n = 60). These results may explain to some extent the mechanisms of TASA on treating rats with experimental colitis.

  1. Marine Indole Alkaloids

    Directory of Open Access Journals (Sweden)

    Natalie Netz

    2015-08-01

    Full Text Available Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed.

  2. Analysis of Ergot Alkaloids

    OpenAIRE

    Colin Crews

    2015-01-01

    The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS) and liquid chromatography with fluorescence detection (LC-FLD). Ot...

  3. A Root-Expressed l-Phenylalanine:4-Hydroxyphenylpyruvate Aminotransferase Is Required for Tropane Alkaloid Biosynthesis in Atropa belladonna[C][W

    Science.gov (United States)

    Bedewitz, Matthew A.; Góngora-Castillo, Elsa; Uebler, Joseph B.; Gonzales-Vigil, Eliana; Wiegert-Rininger, Krystle E.; Childs, Kevin L.; Hamilton, John P.; Vaillancourt, Brieanne; Yeo, Yun-Soo; Chappell, Joseph; DellaPenna, Dean; Jones, A. Daniel; Buell, C. Robin; Barry, Cornelius S.

    2014-01-01

    The tropane alkaloids, hyoscyamine and scopolamine, are medicinal compounds that are the active components of several therapeutics. Hyoscyamine and scopolamine are synthesized in the roots of specific genera of the Solanaceae in a multistep pathway that is only partially elucidated. To facilitate greater understanding of tropane alkaloid biosynthesis, a de novo transcriptome assembly was developed for Deadly Nightshade (Atropa belladonna). Littorine is a key intermediate in hyoscyamine and scopolamine biosynthesis that is produced by the condensation of tropine and phenyllactic acid. Phenyllactic acid is derived from phenylalanine via its transamination to phenylpyruvate, and mining of the transcriptome identified a phylogenetically distinct aromatic amino acid aminotransferase (ArAT), designated Ab-ArAT4, that is coexpressed with known tropane alkaloid biosynthesis genes in the roots of A. belladonna. Silencing of Ab-ArAT4 disrupted synthesis of hyoscyamine and scopolamine through reduction of phenyllactic acid levels. Recombinant Ab-ArAT4 preferentially catalyzes the first step in phenyllactic acid synthesis, the transamination of phenylalanine to phenylpyruvate. However, rather than utilizing the typical keto-acid cosubstrates, 2-oxoglutarate, pyruvate, and oxaloacetate, Ab-ArAT4 possesses strong substrate preference and highest activity with the aromatic keto-acid, 4-hydroxyphenylpyruvate. Thus, Ab-ArAT4 operates at the interface between primary and specialized metabolism, contributing to both tropane alkaloid biosynthesis and the direct conversion of phenylalanine to tyrosine. PMID:25228340

  4. Co-expression of AaPMT and AaTRI effectively enhances the yields of tropane alkaloids in Anisodus acutangulus hairy roots

    Science.gov (United States)

    2011-01-01

    Background Tropane alkaloids (TA) including anisodamine, anisodine, hyoscyamine and scopolamine are a group of important anticholinergic drugs with rapidly increasing market demand, so it is significant to improve TA production by biotechnological approaches. Putrescine N-methyltransferase (PMT) was considered as the first rate-limiting upstream enzyme while tropinone reductase I (TRI) was an important branch-controlling enzyme involved in TA biosynthesis. However, there is no report on simultaneous introduction of PMT and TRI genes into any TA-producing plant including Anisodus acutangulus (A. acutangulus), which is a Solanaceous perennial plant that is endemic to China and is an attractive resource plant for production of TA. Results In this study, 21 AaPMT and AaTRI double gene transformed lines (PT lines), 9 AaPMT single gene transformed lines (P lines) and 5 AaTRI single gene transformed lines (T lines) were generated. RT-PCR and real-time fluorescence quantitative analysis results revealed that total AaPMT (AaPMT T) and total AaTRI (AaTRI T) gene transcripts in transgenic PT, P and T lines showed higher expression levels than native AaPMT (AaPMT E) and AaTRI (AaTRI E) gene transcripts. As compared to the control and single gene transformed lines (P or T lines), PT transgenic hairy root lines produced significantly higher levels of TA. The highest yield of TA was detected as 8.104 mg/g dw in line PT18, which was 8.66, 4.04, and 3.11-times higher than those of the control (0.935 mg/g dw), P3 (highest in P lines, 2.004 mg/g dw) and T12 (highest in T lines, 2.604 mg/g dw), respectively. All the tested samples were found to possess strong radical scavenging capacity, which were similar to control. Conclusion In the present study, the co-expression of AaPMT and AaTRI genes in A. acutangulus hairy roots significantly improved the yields of TA and showed higher antioxidant activity than control because of higher total TA content, which is the first report on

  5. Co-expression of AaPMT and AaTRI effectively enhances the yields of tropane alkaloids in Anisodus acutangulus hairy roots

    Directory of Open Access Journals (Sweden)

    Zhang Ang

    2011-04-01

    Full Text Available Abstract Background Tropane alkaloids (TA including anisodamine, anisodine, hyoscyamine and scopolamine are a group of important anticholinergic drugs with rapidly increasing market demand, so it is significant to improve TA production by biotechnological approaches. Putrescine N-methyltransferase (PMT was considered as the first rate-limiting upstream enzyme while tropinone reductase I (TRI was an important branch-controlling enzyme involved in TA biosynthesis. However, there is no report on simultaneous introduction of PMT and TRI genes into any TA-producing plant including Anisodus acutangulus (A. acutangulus, which is a Solanaceous perennial plant that is endemic to China and is an attractive resource plant for production of TA. Results In this study, 21 AaPMT and AaTRI double gene transformed lines (PT lines, 9 AaPMT single gene transformed lines (P lines and 5 AaTRI single gene transformed lines (T lines were generated. RT-PCR and real-time fluorescence quantitative analysis results revealed that total AaPMT (AaPMT T and total AaTRI (AaTRI T gene transcripts in transgenic PT, P and T lines showed higher expression levels than native AaPMT (AaPMT E and AaTRI (AaTRI E gene transcripts. As compared to the control and single gene transformed lines (P or T lines, PT transgenic hairy root lines produced significantly higher levels of TA. The highest yield of TA was detected as 8.104 mg/g dw in line PT18, which was 8.66, 4.04, and 3.11-times higher than those of the control (0.935 mg/g dw, P3 (highest in P lines, 2.004 mg/g dw and T12 (highest in T lines, 2.604 mg/g dw, respectively. All the tested samples were found to possess strong radical scavenging capacity, which were similar to control. Conclusion In the present study, the co-expression of AaPMT and AaTRI genes in A. acutangulus hairy roots significantly improved the yields of TA and showed higher antioxidant activity than control because of higher total TA content, which is the first

  6. Alkaloids from Hippeastrum papilio

    Directory of Open Access Journals (Sweden)

    Jaume Bastida

    2011-08-01

    Full Text Available Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt (Razadyne®, Reminyl® for the treatment of Alzheimer’s disease (AD, is obtained from Amaryllidaceae plants, especially those belonging to the genera Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine has prompted searches for new sources of this compound, as well as other bioactive alkaloids for the treatment of AD. In this paper we report the isolation of the new alkaloid 11β-hydroxygalanthamine, an epimer of the previously isolated alkaloid habranthine, which was identified using NMR techniques. It has been shown that 11β-hydroxygalanthamine has an important in vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio yielded substantial quantities of galanthamine.

  7. Ergot alkaloid intoxication in perennial ryegrass (Lolium perenne): an emerging animal health concern in Ireland?

    Science.gov (United States)

    Canty, Mary J; Fogarty, Ursula; Sheridan, Michael K; Ensley, Steve M; Schrunk, Dwayne E; More, Simon J

    2014-01-01

    Four primary mycotoxicosis have been reported in livestock caused by fungal infections of grasses or cereals by members of the Clavicipitaceae family. Ergotism (generally associated with grasses, rye, triticale and other grains) and fescue toxicosis (associated with tall fescue grass, Festuca arundinacea) are both caused by ergot alkaloids, and referred to as 'ergot alkaloid intoxication'. Ryegrass staggers (associated with perennial ryegrass Lolium perenne) is due to intoxication with an indole-diperpene, Lolitrem B, and metabolites. Fescue-associated oedema, recently described in Australia, may be associated with a pyrrolizidine alkaloid, N-acetyl norloline. Ergotism, caused by the fungus Claviceps purpurea, is visible and infects the outside of the plant seed. Fescue toxicosis and ryegrass staggers are caused by Neotyphodium coenophalium and N. lolii, respectively. Fescue-associated oedema has been associated with tall fescue varieties infected with a specific strain of N. coenophialum (AR542, Max P or Max Q). The name Neotyphodium refers to asexual derivatives of Epichloë spp., which have collectively been termed the epichloë fungi. These fungi exist symbiotically within the grass and are invisible to the naked eye. The primary toxicological effect of ergot alkaloid involves vasoconstriction and/or hypoprolactinaemia. Ingestion of ergot alkaloid by livestock can cause a range of effects, including poor weight gain, reduced fertility, hyperthermia, convulsions, gangrene of the extremities, and death. To date there are no published reports, either internationally or nationally, reporting ergot alkaloid intoxication specifically associated with perennial ryegrass endophytes. However, unpublished reports from the Irish Equine Centre have identified a potential emerging problem of ergot alkaloid intoxication with respect to equines and bovines, on primarily perennial ryegrass-based diets. Ergovaline has been isolated in varying concentrations in the herbage of a

  8. Analysis of Ergot Alkaloids

    Directory of Open Access Journals (Sweden)

    Colin Crews

    2015-06-01

    Full Text Available The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS and liquid chromatography with fluorescence detection (LC-FLD. Other methods based on immunoassays are under development and variations of these and minor techniques are available for specific purposes.

  9. Spatial and temporal patterns of alkaloid variation in the poison frog Oophaga pumilio in Costa Rica and Panama over 30 years.

    Science.gov (United States)

    Saporito, Ralph A; Donnelly, Maureen A; Jain, Poonam; Martin Garraffo, H; Spande, Thomas F; Daly, John W

    2007-11-01

    A total of 232 alkaloids, representing 21 structural classes were detected in skin extracts from the dendrobatid poison frog Oophaga pumilio, collected from 53 different populations from over 30 years of research. The highly toxic pumiliotoxins and allopumiliotoxins, along with 5,8-disubstitiuted and 5,6,8-trisubstituted indolizidines, all of which are proposed to be of dietary mite origin, were common constituents in most extracts. One decahydroquinoline (DHQ), previously shown be of ant origin, occurred in many extracts often as a major alkaloid, while other DHQs occurred rather infrequently. Histrionicotoxins, thought to be of ant origin, did not appear to possess a specific pattern of occurrence among the populations, but when present, were usually found as major components. Certain 3,5-disubstituted pyrrolizidines and indolizidines, known to be of ant origin, did occur in extracts, but infrequently. Alkaloid composition differed with regard to geographic location of frog populations, and for populations that were sampled two or more times during the 30-year period significant changes in alkaloid profiles sometimes occurred. The results of this study indicate that chemical defense in a dendrobatid poison frog is dependent on geographic location and habitat type, which presumably controls the abundance and nature of alkaloid-containing arthropods.

  10. Simple Indolizidine and Quinolizidine Alkaloids.

    Science.gov (United States)

    Michael, Joseph P

    2016-01-01

    This review of simple indolizidine and quinolizidine alkaloids (i.e., those in which the parent bicyclic systems are in general not embedded in polycyclic arrays) is an update of the previous coverage in Volume 55 of this series (2001). The present survey covers the literature from mid-1999 to the end of 2013; and in addition to aspects of the isolation, characterization, and biological activity of the alkaloids, much emphasis is placed on their total synthesis. A brief introduction to the topic is followed by an overview of relevant alkaloids from fungal and microbial sources, among them slaframine, cyclizidine, Steptomyces metabolites, and the pantocins. The important iminosugar alkaloids lentiginosine, steviamine, swainsonine, castanospermine, and related hydroxyindolizidines are dealt with in the subsequent section. The fourth and fifth sections cover metabolites from terrestrial plants. Pertinent plant alkaloids bearing alkyl, functionalized alkyl or alkenyl substituents include dendroprimine, anibamine, simple alkaloids belonging to the genera Prosopis, Elaeocarpus, Lycopodium, and Poranthera, and bicyclic alkaloids of the lupin family. Plant alkaloids bearing aryl or heteroaryl substituents include ipalbidine and analogs, secophenanthroindolizidine and secophenanthroquinolizidine alkaloids (among them septicine, julandine, and analogs), ficuseptine, lasubines, and other simple quinolizidines of the Lythraceae, the simple furyl-substituted Nuphar alkaloids, and a mixed quinolizidine-quinazoline alkaloid. The penultimate section of the review deals with the sizable group of simple indolizidine and quinolizidine alkaloids isolated from, or detected in, ants, mites, and terrestrial amphibians, and includes an overview of the "dietary hypothesis" for the origin of the amphibian metabolites. The final section surveys relevant alkaloids from marine sources, and includes clathryimines and analogs, stellettamides, the clavepictines and pictamine, and bis

  11. The Securinega alkaloids.

    Science.gov (United States)

    Chirkin, Eqor; Atkatlian, William; Porée, François-Hugues

    2015-01-01

    Securinega alkaloids represent a family of plant secondary metabolites known for 50 years. Securinine (1), the most abundant and studied alkaloid of this series was isolated by Russian researchers in 1956. In the following years, French and Japanese scientists reported other Securinega compounds and extensive work was done to elucidate their intriguing structures. The homogeneity of this family relies mainly on its tetracyclic chemical backbone, which features a butenolide moiety (cycle D) and an azabicyclo[3.2.1]octane ring system (rings B and C). Interestingly, after a period of latency of 20 years, the Securinega topic reemerged as a prolific source of new natural structures and to date more than 50 compounds have been identified and characterized. The oligomeric subgroup gathering dimeric, trimeric, and tetrameric units is of particular interest. The unprecedented structure of the Securinega alkaloids was the subject of extensive synthetic efforts culminating in several efficient and elegant total syntheses. The botanical distribution of these alkaloids seems limited to the Securinega, Flueggea, Margaritaria, and Breynia genera (Phyllanthaceae). However, only a limited number of plant species have been considered for their alkaloid contents, and additional phytochemical as well as genetic studies are needed. Concerning the biosynthesis, experiments carried out with radiolabelled aminoacids allowed to identify lysine and tyrosine as the precursors of the piperidine ring A and the CD rings of securinine (1), respectively. Besides, plausible biosynthetic pathways were proposed for virosaine A (38) and B (39), flueggine A (46), and also the different oligomers flueggenine A-D (48-51), fluevirosinine A (56), and flueggedine (20). The case of nirurine (45) and secu'amamine (37) remains elusive and additional studies seem necessary to understand their mode of production. The scope of biological of activities of the Securinega alkaloids was mainly centered on the CNS

  12. Alkaloids in Bulgarian Pancratium maritimum L.

    Science.gov (United States)

    Berkov, Strahil; Evstatieva, Luba; Popov, Simeon

    2004-01-01

    A GC/MS analysis of alkaloids from leaves, bulbs and roots of Pancratium maritimum was performed. From the identified 16 alkaloids, 5 alkaloids were reported for the first time for this plant. Several compounds with pharmacological activity were found. Haemanthamine was main alkaloid in the leaves and bulbs whereas galanthane was found to be main alkaloid in roots.

  13. Testing the Generalist-Specialist Dilemma: The Role of Pyrrolizidine Alkaloids in Resistance to Invertebrate Herbivores in Jacobaea Species

    NARCIS (Netherlands)

    Wei, X.; Vrieling, K.; Mulder, P.P.J.; Klinkhamer, P.G.L.

    2015-01-01

    Plants produce a diversity of secondary metabolites (SMs) to protect them from generalist herbivores. On the other hand, specialist herbivores use SMs for host plant recognition, feeding and oviposition cues, and even sequester SMs for their own defense. Therefore, plants are assumed to face an evol

  14. EFFECTS OF ANTIBACTERIAL AGENTS ON IN VITRO OVINE RUMINAL BIODEGRADATION OF THE HEPATOTOXIC PYRROLIZIDINE ALKALOID, JACOBINE. (R825689C006)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. Quinolizidine alkaloids from Lupinus lanatus

    Science.gov (United States)

    Neto, Alexandre T.; Oliveira, Carolina Q.; Ilha, Vinicius; Pedroso, Marcelo; Burrow, Robert A.; Dalcol, Ionara I.; Morel, Ademir F.

    2011-10-01

    In this study, one new quinolizidine alkaloid, lanatine A ( 1), together with three other known alkaloids, 13-α- trans-cinnamoyloxylupanine ( 2), 13-α-hydroxylupanine ( 3), and (-)-multiflorine ( 4) were isolated from the aerial parts of Lupinus lanatus (Fabaceae). The structures of alkaloids 1- 4 were elucidated by spectroscopic data analysis. The stereochemistry of 1 was determined by single crystal X-ray analysis. Bayesian statistical analysis of the Bijvoet differences suggests the absolute stereochemistry of 1. In addition, the antimicrobial potential of alkaloids 1- 4 is also reported.

  16. Integration of Transcriptome and Proteome Reveals the Alkaloids Biosynthesis in Macleaya cordata and Macleaya microcarpa

    Institute of Scientific and Technical Information of China (English)

    Yisong Liu; Wei Liu; Xiubing Liu; Peng Huang; Pengcheng Zhu; Pi Cheng; Jing Zeng

    2012-01-01

    The Macleaya spp.,including Macleaya cordata and Macleaya microcarpa,are traditional anti-virus,inflammation eliminating,and insecticide herb medicines for their isoquinoline alkaloids.The studies of their alkaloids biosyntheses are urgent for better application.To further characterize their alkaloids biosyntheses,we elaborately designed the transcriptome,proteome and metabolism profiling for 10 samples of both species to explore their alkaloids biosyntheses.From the transcriptome data,we obtained 69367 and 78255 unigenes for M.cordata and M.microcarpa,which two thirds of them were similar to sequences in public databases.By metabolism profiling,we observed reverse patterns in different organs of two species for alkaloids sanguinarine,chelerythrine,protopine,and allocryptopine.Thus,the expression of enzymes in alkaloid biosynthesis pathways and the differential gene expression for multiple interesting comparisons were analyzed.We identified more than 1000 proteins and hundreds of differentially expressed proteins from iTRAQ proteome data.Furthermore,the ultrastructure of laticifers by SEM proved the alkaloids accumulation in the mature roots.This study suggests strongly that root maybe the organ for major alkaloids biosynthesis.Except for biosynthesis,the alkaloids storage and transport were also important for their accumulation.This work provided the first genome scale analysis for Macleaya spp.and shed light on researches for non-model plants by integrating different high-throughput technologies.

  17. Profiling of alkaloids and eremophilanes in miracle tea (Packera candidissima and P. bellidifolia) products.

    Science.gov (United States)

    Fragoso-Serrano, Mabel; Figueroa-González, Gabriela; Castro-Carranza, Erick; Hernández-Solis, Francisco; Linares, Edelmira; Bye, Robert; Pereda-Miranda, Rogelio

    2012-05-25

    Commercial preparations of the Mexican herbal drug known as "miracle tea" (Packera candidissima and P. bellidifolia) have been profiled qualitatively by HPLC and GC-MS. Eremophilanes (3-7) were the major components found in the hexane-soluble fraction, while pyrrolizidine alkaloids (PAs) were identified in the alkaloid extracts. The content of free PAs and their N-oxides was determined for a total of 22 samples, and the results showed that the amount of these hepatotoxic compounds (0.0005-0.94% free PAs; 0.0004-0.55% N-oxides), through the presence of retrorsine (1) and senesionine (2) as the main constituents, may reach toxic levels. Hexane-soluble extracts from commercial presentations (dried whole plants) of both species afforded neoadenostylone (3), 6-(2-methylbutanoyloxy)-9-oxo-1-(10)-furanoeremophilene (4), and epineoadenostylone (5), in addition to methyl-4-hydroxyphenylacetate (8) and methyl-2-(1-hydroxy-4-oxocyclohexyl)acetate (9). Also, epicacalone (6) and the new compound 2β-hydroxyneoadenostylone (7) were isolated from P. bellidifolia.

  18. Occurrence of theobromine synthase genes in purine alkaloid-free species of Camellia plants.

    Science.gov (United States)

    Ishida, Mariko; Kitao, Naoko; Mizuno, Kouichi; Tanikawa, Natsu; Kato, Misako

    2009-02-01

    Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are purine alkaloids that are present in high concentrations in plants of some species of Camellia. However, most members of the genus Camellia contain no purine alkaloids. Tracer experiments using [8-(14)C]adenine and [8-(14)C]theobromine showed that the purine alkaloid pathway is not fully functional in leaves of purine alkaloid-free species. In five species of purine alkaloid-free Camellia plants, sufficient evidence was obtained to show the occurrence of genes that are homologous to caffeine synthase. Recombinant enzymes derived from purine alkaloid-free species showed only theobromine synthase activity. Unlike the caffeine synthase gene, these genes were expressed more strongly in mature tissue than in young tissue.

  19. Alkaloids from Galanthus nivalis.

    Science.gov (United States)

    Berkov, Strahil; Codina, Carles; Viladomat, Francesc; Bastida, Jaume

    2007-07-01

    Phytochemical studies on Galanthus nivalis of Bulgarian origin resulted in the isolation of five compounds: 11-O-(3'-hydroxybutanoyl)hamayne, 3,11-O-(3',3''-dihydroxybutanoyl)hamayne, 3-O-(2''-butenoyl)-11-O-(3'-hydroxybutanoyl)hamayne, 3,11,3''-O-(3',3'',3'''-trihydroxybutanoyl)hamayne, and 2-O-(3'-acetoxybutanoyl)lycorine, together with five known alkaloids: ungeremine, lycorine, tazettine, hamayne, and ismine. Their structures were determined by (1)H and (13)C NMR spectroscopy and two-dimensional (1)H-(1)H and (1)H-(13)C chemical shift correlation experiments.

  20. Ergot Alkaloids (Regenerate New Leads as Antiparasitics.

    Directory of Open Access Journals (Sweden)

    John D Chan

    Full Text Available Praziquantel (PZQ is a key therapy for treatment of parasitic flatworm infections of humans and livestock, but the mechanism of action of this drug is unresolved. Resolving PZQ-engaged targets and effectors is important for identifying new druggable pathways that may yield novel antiparasitic agents. Here we use functional, genetic and pharmacological approaches to reveal that serotonergic signals antagonize PZQ action in vivo. Exogenous 5-hydroxytryptamine (5-HT rescued PZQ-evoked polarity and mobility defects in free-living planarian flatworms. In contrast, knockdown of a prevalently expressed planarian 5-HT receptor potentiated or phenocopied PZQ action in different functional assays. Subsequent screening of serotonergic ligands revealed that several ergot alkaloids possessed broad efficacy at modulating regenerative outcomes and the mobility of both free living and parasitic flatworms. Ergot alkaloids that phenocopied PZQ in regenerative assays to cause bipolar regeneration exhibited structural modifications consistent with serotonergic blockade. These data suggest that serotonergic activation blocks PZQ action in vivo, while serotonergic antagonists phenocopy PZQ action. Importantly these studies identify the ergot alkaloid scaffold as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors.

  1. Transcription factors in alkaloid biosynthesis.

    Science.gov (United States)

    Yamada, Yasuyuki; Sato, Fumihiko

    2013-01-01

    Higher plants produce a large variety of low-molecular weight secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used pharmaceutically. Whereas alkaloid chemistry has been intensively investigated, alkaloid biosynthesis, including the relevant biosynthetic enzymes, genes and their regulation, and especially transcription factors, is largely unknown, as only a limited number of plant species produce certain types of alkaloids and they are difficult to study. Recently, however, several groups have succeeded in isolating the transcription factors that are involved in the biosynthesis of several types of alkaloids, including bHLH, ERF, and WRKY. Most of them show Jasmonate (JA) responsiveness, which suggests that the JA signaling cascade plays an important role in alkaloid biosynthesis. Here, we summarize the types and functions of transcription factors that have been isolated in alkaloid biosynthesis, and characterize their similarities and differences compared to those in other secondary metabolite pathways, such as phenylpropanoid and terpenoid biosyntheses. The evolution of this biosynthetic pathway and regulatory network, as well as the application of these transcription factors to metabolic engineering, is discussed.

  2. Actions of piperidine alkaloid teratogens at fetal nicotinic acetylcholine receptors.

    Science.gov (United States)

    Green, Benedict T; Lee, Stephen T; Panter, Kip E; Welch, Kevin D; Cook, Daniel; Pfister, James A; Kem, William R

    2010-01-01

    Teratogenic alkaloids are found in many species of plants including Conium maculatum L., Nicotiana glauca, Nicotiana tabaccum, and multiple Lupinus spp. Fetal musculoskeletal defects produced by alkaloids from these plants include arthrogyropisis, scoliosis, torticollis, kyposis, lordosis, and cleft palate. A pharmacodynamic comparison of the alkaloids ammodendrine, anabasine, anabaseine, anagyrine, and coniine in SH-SY5Y cells and TE-671 cells was made. These alkaloids and their enantiomers were more effective in depolarizing TE-671 cells which express the human fetal-muscle type nicotinic acetylcholine receptor (nAChR) relative to SH-SY5Y cells which predominately express autonomic nAChRs. The rank order of potency in TE-671 cells was: anabaseine>(+)-anabasine>(-)-anabasine > (+/-)-anabasine>anagyrine>(-)-coniine > (+/-)-coniine>(+)-coniine>(+/-)-ammodendrine>(+)-ammodendrine. The rank order potency in SH-SY5Y cells was: anabaseine>(+)-anabasine>(-)-coniine>(+)-coniine>(+)-ammodendrine>anagyrine>(-)-anabasine>(+/-)-coniine>(+/-)-anabasine>(-)-ammodendrine. The actions of these alkaloids at nAChRs in both cell lines could be distinguished by their maximum effects in depolarizing cell membrane potential. The teratogenic action of these compounds may be related to their ability to activate and subsequently desensitize nAChRs.

  3. Total Synthesis of Securinega Alkaloids

    Institute of Scientific and Technical Information of China (English)

    T. Honda

    2005-01-01

    @@ 1Introduction Naturally occurring Securinega alkaloids (1-4) (Fig. 1)[1], with their wide range of structural and stereochemical features, continue to provide challenging synthetic targets, since these alkaloids exhibit attractive biological activities. Securinine (1), isolated from Securinega suffruticosa [2], was structurally determined to contain an indolizidine skeleton with an azabicyclo[3.2.1 ]octane system together with an α, β-unsaturated γ-lactone ring. This alkaloid has been clinically used in Russia as a CNS stimulating drug[3], and has been shown to act as a stereospecific antagonist at the GABA binding site of the GABAA-receptor complex[4].Viroallosecurinine (2), a diastereoisomeric alkaloid of securinine, was also isolated from the leaves of Securinega virosa[5] as a cytotoxic alkaloid exhibiting a MIC of 0.48 μg/mL for Ps. aeruginosa and Staph.aureus[6]. This alkaloid is recognized to be bactericidal since the yields of MIC/MBC were less than 1[7].

  4. Identification of bovine prolactin in seminal fluid, and expression and localization of the prolactin receptor and prolactin-inducible protein in the testis and epididymis of bulls exposed to ergot alkaloids.

    Science.gov (United States)

    Pratt, S L; Calcatera, S M; Stowe, H M; Dimmick, M A; Schrick, F N; Duckett, S K; Andrae, J G

    2015-03-01

    The objectives of this study were to determine (1) the presence and expression levels of bovine prolactin receptor (PRLR) and prolactin-inducible protein (PIP) in bovine testis and epididymis, and (2) the presence and concentrations of prolactin (PRL) present in seminiferous fluid in bulls consuming diets with (E+) or without (E-) ergot alkaloids. Bulls (n = 8) were sacrificed after 126 days (group A) of E+ or E- treatment or 60 days after all bulls (n = 6) were switched to the E- ration (group B). End point and real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry were conducted on testis and epididymis samples to establish the presence and relative expression of PRLR and PIP. Seminal fluid samples obtained from bulls consuming E- and E+ diets were subjected to RIA for PRL. Both PIP and PRLR were present in testis and epididymis as determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Prolactin-inducible protein mRNA abundance was affected by time of slaughter in testis and epididymis head, respectively (P Prolactin receptor mRNA expression was affected by time of slaughter in the epididymis (P < 0.05) and differed in testis samples because of treatment (P < 0.05). Radioimmunoassay establishes the presence of PRL in seminal fluid; however, differences in the concentration of PRL over two separate studies were inconsistent, possibly because of differences in diet. The presence and localization of the PRLR are consistent with expression data reported for other species, and the presence of PIP and PRL in seminal fluid is consistent with data generated in humans.

  5. Ergovaline, an endophytic alkaloid. 1. Animal physiology and metabolism

    Science.gov (United States)

    Ergovaline is an ergot alkaloid found in some endophyte-infected ryegrasses and has been implicated in the expression of ergotism-like symptoms of grazing livestock, as well as in the protection of the plant against invertebrate predation and abiotic stresses. These selection pressures have resulted...

  6. Investigation of Symphytum cordatum alkaloids by liquid-liquid partitioning, thin-layer chromatography and liquid chromatography-ion-trap mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Mroczek, Tomasz [Department of Pharmacognosy with Medicinal Plants Laboratory, Medical University, 1 Chodzki St., 20-093 Lublin (Poland)]. E-mail: tmroczek@pharmacognosy.org; Ndjoko-Ioset, Karine [Laboratoire de Pharmacognosie et Phytochimie, Ecole de Pharmacie Geneve-Lausanne, Universite de Geneve, Quai Ernest-Ansermet 30, CH-1211 Geneva 4 (Switzerland); Glowniak, Kazimierz [Department of Pharmacognosy with Medicinal Plants Laboratory, Medical University, 1 Chodzki St., 20-093 Lublin (Poland); Mietkiewicz-Capala, Agnieszka [Department of Pharmacognosy with Medicinal Plants Laboratory, Medical University, 1 Chodzki St., 20-093 Lublin (Poland); Hostettmann, Kurt [Laboratoire de Pharmacognosie et Phytochimie, Ecole de Pharmacie Geneve-Lausanne, Universite de Geneve, Quai Ernest-Ansermet 30, CH-1211 Geneva 4 (Switzerland)

    2006-05-04

    From the alkalised crude extract of Symphytum cordatum (L.) W.K. roots, pyrrolizidine alkaloids (PAs) were extracted as free tertiary bases and polar N-oxides in a merely one-step liquid-liquid partitioning (LLP) in separation funnel and subsequently pre-fractionated by preparative multiple-development (MD) thin-layer chromatography (TLC) on silica gel plates. In this way three alkaloid fractions of different polarities and retention on silica gel plates were obtained as: the most polar N-oxides of the highest retention, the tertiary bases of medium retention, and diesterified N-oxides of the lowest retention. The former fraction was reduced into free bases by sodium hydrosulfite and purified by LLP on Extrelut-NT3 cartridge. It was further analysed together with the two other fractions by high-performance liquid chromatography (HPLC)-ion-trap mass spectrometry with atmospheric pressure chemical ionization (APCI) interface on XTerra C{sub 18} column using a gradient elution. Based on MS {sup n} spectra, 18 various alkaloids have been tentatively determined for the first time in this plant as the following types of structure: echimidine-N-oxide (three diasteroisomers), 7-sarracinyl-9-viridiflorylretronecine (two diasteroisomers), echimidine (two diasteroisomers), lycopsamine (two diasteroisomers), dihydroechinatine-N-oxide, dihydroheliospathuline-N-oxide, lycopsamine-N-oxide (three diasteroisomers), 7-acetyllycopsamine-N-oxide, symphytine-N-oxide (two diasteroisomers) and 2'',3''-epoxyechiumine-N-oxide.

  7. Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters.

    Science.gov (United States)

    He, Kai; Kou, Shuming; Zou, Zongyao; Hu, Yinran; Feng, Min; Han, Bing; Li, Xuegang; Ye, Xiaoli

    2016-05-01

    This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.

  8. Copper catalysed synthesis of indolylquinazolinone alkaloid bouchardatine

    Indian Academy of Sciences (India)

    Mayavan Viji; Rajagopal Nagarajan

    2014-07-01

    We describe the total synthesis of indolylquinazolinone alkaloid bouchardatine and some of the quinazolinone derivatives. The aerobic oxidation induced by copper(I) bromide, followed by Vilsmeier-Haack formylation gives the natural product bouchardatine alkaloid in good yield.

  9. The Chemistry of the Akuammiline Alkaloids.

    Science.gov (United States)

    Adams, Gregory L; Smith, Amos B

    2016-01-01

    An update on the literature covering the akuammiline family of alkaloids is presented. This chapter begins with a summary of new akuammiline alkaloids reported since 2000 and is followed by an overview of new reported bioactivities of akuammiline alkaloids since 2000. The remainder of the chapter comprises a comprehensive review of the synthetic chemistry that has been reported in the last 50 years concerning akuammiline alkaloids and their structural motifs.

  10. FIVE NEW NORDITERPENOID ALKALOIDS FROM ACONITUM SINOMONTANUM

    Institute of Scientific and Technical Information of China (English)

    FENG-PENG WANG; CHONG-SHENG PENG; XI-XIAN JIAN; DONG-LIN CHEN

    2001-01-01

    From the roots of A conitum sinomontanum, five new norditerpenoid alkaloids, sinomontanitines A (1) and B (2), sinomontanines A (3), B (4) and C (5), were isolated together with the known alkaloids lappaconitine (6) and ranaconitine (7), The structures of the new alkaloids were determined by spectral analysis.

  11. Alkaloids from Stems of Ervatamia yunnanensis (Ⅱ)

    Institute of Scientific and Technical Information of China (English)

    Shuang LIANG; Xin Gen LUO; Hai Sheng CHEN; Xiao Dong ZHANG; Mao HUANG; Wen Yong LIU

    2006-01-01

    Six indole alkaloids were isolated from the stems of Ervatamia yunnanensis. Among them, 10-hydroxy-19, 20-dihydroisositsirikine (Ⅰ) is new. The other five are known alkaloids,namely: matrine (Ⅱ), 19, 20-dihydroisositsuikine (Ⅲ), 19-s-voacangarine (Ⅳ), 11'-methoxyl- 19s-heyneanine (Ⅴ), conodurine (Ⅵ). The structural elucidation of the alkaloids was based on spectral means.

  12. Alkaloids from stems of Ervatamia yunnanensis

    Institute of Scientific and Technical Information of China (English)

    Xin Gen Luo; Hai Sheng Chen; Shuang Liang; Mao Huang; Wei Dong Xuan; Li Jin

    2007-01-01

    Six indole alkaloids were isolated from the stems of Ervatamia yunnanensis.Among them, yunnanensine (Ⅰ) is new.The other five are known alkaloids, namely: 19,20-E-vallesamine (Ⅱ), 19s-heyneanine (Ⅲ), ibogaine (Ⅳ), ibogamine (Ⅴ), coronaridine (Ⅵ).The structural elucidation of the alkaloids was based on spectral means.

  13. [Effects of alkaloids from Coptidis Rhizoma on mouse peritoneal macrophages in vitro].

    Science.gov (United States)

    Zhou, Xia; Peng, Yao-zong; Huang, Tao; Li, Ling; Mou, Shao-xia; Kou, Shu-ming; Li, Xue-gang

    2015-12-01

    This work was mainly studied the effects of the four alkaloids from Coptidis Rhizoma on the mouse peritoneal macrophages in vitro and preliminarily discussed the regulating mechanisms. The effect of alkaloids from Coptidis Rhizoma on the vitality of macrophages was measured by the MTT assay. The effect of alkaloids on the phagocytosis of macrophages was determined by neutral red trial and respiratory burst activity was tested by NBT. The expressions of respiratory-burst-associated genes influenced by alkaloids were detected by qRT-PCR. The conformation change of membrane protein in macrophages by the impact of alkaloids was studied by fluorospectro-photometer. Results showed that the four alkaloids from Coptidis Rhizoma could increase the phagocytosis of macrophages in different level and berberine had the best effect. Berberine, coptisine and palmatine had up-regulation effects on respiratory burst activity of mouse peritoneal macrophages stimulated by PMA and regulatory activity on the mRNA expression of PKC, p40phox or p47phox, whereas the epiberberine had no significant influence on respiratory burst. Moreover, alkaloids from Coptidis Rhizoma could change the conformation of membrane protein and the berberine showed the strongest activity. The results suggested that the four alkaloids from Coptidis Rhizoma might activate macrophages through changing the conformation of membrane protein of macrophages and then enhanced the phagocytosis and respiratory burst activity of macrophages. Furthermore, the regulatory mechanism of alkaloids on the respiratory burst activity of macrophages may be also related to the expression level of PKC, p40phox and p47phox.

  14. New extraction technique for alkaloids

    Directory of Open Access Journals (Sweden)

    Djilani Abdelouaheb

    2006-01-01

    Full Text Available A method of extraction of natural products has been developed. Compared with existing methods, the new technique is rapid, more efficient and consumes less solvent. Extraction of alkaloids from natural products such as Hyoscyamus muticus, Datura stramonium and Ruta graveolens consists of the use of a sonicated solution containing a surfactant as extracting agent. The alkaloids are precipitated by Mayer reagent, dissolved in an alkaline solution, and then extracted with chloroform. This article compares the results obtained with other methods showing clearly the advantages of the new method.

  15. The alkaloid profiles of Lupinus sulphureus.

    Science.gov (United States)

    Cook, Daniel; Lee, Stephen T; Gardner, Dale R; Pfister, James A; Welch, Kevin D; Green, Benedict T; Davis, T Zane; Panter, Kip E

    2009-02-25

    Lupines are common plants on the rangelands in the western United States. Lupines contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British Columbia. Specimens of L. sulphureus from field collections and herbaria were evaluated taxonomically and by chemical means. A total of seven distinct alkaloid profiles and the individual alkaloids associated with each profile were identified. Each alkaloid profile was unique in its geographical distribution and its potential risk to livestock. In conclusion, taxonomic classification is not sufficient to determine risk, as chemical characterization of the alkaloids must also be performed.

  16. Alkaloids with antioxidant activities from Aconitum handelianum.

    Science.gov (United States)

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

    2016-06-01

    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.

  17. Structural and quantitative analysis of Equisetum alkaloids.

    Science.gov (United States)

    Cramer, Luise; Ernst, Ludger; Lubienski, Marcus; Papke, Uli; Schiebel, Hans-Martin; Jerz, Gerold; Beuerle, Till

    2015-08-01

    Equisetum palustre L. is known for its toxicity for livestock. Several studies in the past addressed the isolation and identification of the responsible alkaloids. So far, palustrine (1) and N(5)-formylpalustrine (2) are known alkaloids of E. palustre. A HPLC-ESI-MS/MS method in combination with simple sample work-up was developed to identify and quantitate Equisetum alkaloids. Besides the two known alkaloids six related alkaloids were detected in different Equisetum samples. The structure of the alkaloid palustridiene (3) was derived by comprehensive 1D and 2D NMR experiments. N(5)-Acetylpalustrine (4) was also thoroughly characterized by NMR for the first time. The structure of N(5)-formylpalustridiene (5) is proposed based on mass spectrometry results. Twenty-two E. palustre samples were screened by a HPLC-ESI-MS/MS method after development of a simple sample work-up and in most cases the set of all eight alkaloids were detected in all parts of the plant. A high variability of the alkaloid content and distribution was found depending on plant organ, plant origin and season ranging from 88 to 597mg/kg dried weight. However, palustrine (1) and the alkaloid palustridiene (3) always represented the main alkaloids. For the first time, a comprehensive identification, quantitation and distribution of Equisetum alkaloids was achieved.

  18. Historical view on ergot alkaloids.

    Science.gov (United States)

    Hofmann, A

    1978-01-01

    A short survey of the history of ergot, of the original and, for a long time, only source of ergot alkaloids, is given. Once a dreaded poison, ergot has changed its role over the centuries to become a rich treasure house of valuable pharmaceuticals. In the Middle Ages it was the cause of epidemics of ergotism, which cost tens of thousands of people their lives. Ergot was first mentioned by the German physician Lonitzer in 1582 as a remedy used by midwives for quickening childbirth. The isolation of pharmacologically useful alkaloids started in 1906 with the discovery of ergotoxine and its adrenolytic activity by Barger, Carr and Dale. In 1918, Stoll isolated ergotamine, the first chemically pure ergot alkaloid, which found widespread therapeutic use in obstetrics and internal medicine. In 1935 the specific oxytocic principle of ergot, ergonovine, was discovered simultaneously in four separate laboratories. Since then, worldwide investigations on ergot alkaloids resulted in the elucidation of their structures and total syntheses and preparation of valuable therapeutics such as Methergine, Hydergine, Dihydergot, and others.

  19. Lycopodium alkaloids from Palhinhaea cernua

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fu-Wei [Graduate University of Chinese Academy of Sciences, Beijing (China); Luo, Ji-Feng; Wang, Yue-Hu, E-mail: wangyuehu@mail.kib.ac.cn [Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences (China); Sun, Qian-Yun; Yang, Fu-Mei [Key Laboratory of Chemistry for Natural Products, Guizhou Province and Chinese Academy of Sciences (China); Liu, Fang [College of Landscape and Horticulture, Yunnan Agricultural University (China); Long, Chun-Lin, E-mail: long@mail.kib.ac.cn [College of Life and Environmental Sciences, Minzu University of China, Beijing, (China)

    2012-07-01

    Two new Lycopodium alkaloids, acetyllycoposerramine M and palcernine A were isolated from whole plant extracts of Palhinhaea cernua L. together with ten previously identified compounds. The structures of the new compounds were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses using the Flack parameter. (author)

  20. Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities.

    Science.gov (United States)

    Cushnie, T P Tim; Cushnie, Benjamart; Lamb, Andrew J

    2014-11-01

    With reports of pandrug-resistant bacteria causing untreatable infections, the need for new antibacterial therapies is more pressing than ever. Alkaloids are a large and structurally diverse group of compounds that have served as scaffolds for important antibacterial drugs such as metronidazole and the quinolones. In this review, we highlight other alkaloids with development potential. Natural, semisynthetic and synthetic alkaloids of all classes are considered, looking first at those with direct antibacterial activity and those with antibiotic-enhancing activity. Potent examples include CJ-13,136, a novel actinomycete-derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL against Helicobacter pylori, and squalamine, a polyamine alkaloid from the dogfish shark that renders Gram-negative pathogens 16- to >32-fold more susceptible to ciprofloxacin. Where available, information on toxicity, structure-activity relationships, mechanisms of action and in vivo activity is presented. The effects of alkaloids on virulence gene regulatory systems such as quorum sensing and virulence factors such as sortases, adhesins and secretion systems are also described. The synthetic isoquinoline alkaloid virstatin, for example, inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing expression of cholera toxin and fimbriae and conferring in vivo protection against intestinal colonisation. The review concludes with implications and limitations of the described research and directions for future research.

  1. Contribution of fungal loline alkaloids to protection from aphids in a grass-endophyte mutualism.

    Science.gov (United States)

    Wilkinson, H H; Siegel, M R; Blankenship, J D; Mallory, A C; Bush, L P; Schardl, C L

    2000-10-01

    Fungal endophytes provide grasses with enhanced protection from herbivory, drought, and pathogens. The loline alkaloids (saturated 1-aminopyrrolizidines with an oxygen bridge) are fungal metabolites often present in grasses with fungal endophytes of the genera Epichloë or Neotyphodium. We conducted a Mendelian genetic analysis to test for activity of lolines produced in plants against aphids feeding on those plants. Though most loline-producing endophytes are asexual, we found that a recently described sexual endophyte, Epichloë festucae, had heritable variation for loline alkaloid expression (Lol+) or nonexpression (Lol-). By analyzing segregation of these phenotypes and of linked DNA polymorphisms in crosses, we identified a single genetic locus controlling loline alkaloid expression in those E. festucae parents. We then tested segregating Lol+ and Lol- full-sibling fungal progeny for their ability to protect host plants from two aphid species, and observed that alkaloid expression cosegregated with activity against these insects. The in planta loline alkaloid levels correlated with levels of anti-aphid activity. These results suggested a key role of the loline alkaloids in protection of host plants from certain aphids, and represent, to our knowledge, the first Mendelian analysis demonstrating how a fungal factor contributes protection to plant-fungus mutualism.

  2. Angustilobine and andranginine type indole alkaloids and an uleine-secovallesamine bisindole alkaloid from Alstonia angustiloba.

    Science.gov (United States)

    Ku, Wai-Foong; Tan, Shin-Jowl; Low, Yun-Yee; Komiyama, Kanki; Kam, Toh-Seok

    2011-12-01

    A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.

  3. Erythroidine alkaloids: a novel class of phytoestrogens.

    Science.gov (United States)

    Djiogue, Sefirin; Halabalaki, Maria; Njamen, Dieudonné; Kretzschmar, Georg; Lambrinidis, George; Hoepping, Josephine; Raffaelli, Francesca M; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Vollmer, Günter

    2014-07-01

    Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely α-erythroidine, β-erythroidine, and their oxo-derivatives 8-oxo-α-erythroidine and 8-oxo-β-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. α-Erythroidine and β-erythroidine showed binding affinity values for ERα of 0.015 ± 0.010% and 0.005 ± 0.010%, respectively, whereas only β-erythroidine bound to ERβ (0.006 ± 0.010%). In reporter gene assays, both erythroidines exhibited a significant dose-dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, α-erythroidine and β-erythroidine both induced the enhanced expression of the specific ERα-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ERα, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of

  4. New aporphine alkaloids of Ocotea minarum.

    Science.gov (United States)

    Vecchietti, V; Casagrande, C; Ferrari, G; Severini Ricca, G

    1979-10-01

    Fourteen aporphine alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea minarum Nees (Mez). The known alkaloids were identified through their physico-chemical properties as: leucoxylonine (VII), dicentrine (IV), ocoteine (V), leucoxine (VI), ocopodine (VIII), predicentrine (IX), dicentrinone (XIV) and thalicminine (XV). Six new aporphine alkaloids were also isolated: ocotominarine (I), ocominarine (III), nor-leucoxylonine (XI), iso-oconovine (xii), 4-hydroxydicentrine (XIII) and ocominarone (XVI). Their structures were determined using spectroscopic methods and chemical correlations.

  5. Four new fluorenone alkaloids and one new dihydroazafluoranthene alkaloid from Caulophyllum robustum Maxim.

    Science.gov (United States)

    Wang, Xiao-Ling; Liu, Bing-Rui; Chen, Chien-Kuang; Wang, Jun-Ru; Lee, Shoei-Sheng

    2011-09-01

    Four new fluorenone alkaloids, caulophylline A-D (1-4), and one new dihydroazafluoranthene alkaloid, caulophylline E (5) were isolated from the roots of Caulophyllum robustum Maxim. Their structures were elucidated by spectroscopic analysis. Among the isolated alkaloids, Caulophylline E showed good scavenging effects against DPPH radical with IC(50) of 39 μM.

  6. New alkaloids from Pancratium maritimum.

    Science.gov (United States)

    Ibrahim, Sabrin R M; Mohamed, Gamal A; Shaala, Lamiaa A; Youssef, Diaa T A; El Sayed, Khalid A

    2013-10-01

    As a part of ongoing search efforts for the discovery of anticancer lead entities from natural sources, bulbs and flowers of the amaryllidaceous plant Pancratium maritimum have been investigated. Fractionation of the extracts of the fresh flowers and bulbs of P. maritimum led to the isolation of four new alkaloids, namely pancrimatines A (1) and B (2), norismine (3), and pancrimatine C (4), together with the previously reported N-methyl-8,9-methylenedioxy-6-phenanthridone (5), trispheridine (6), and N-methyl-8,9-methylenedioxyphenanthridine (7). The structures of these alkaloids were established on the basis of extensive 1D and 2D NMR and high-resolution mass spectral analyses as well as comparison with the literature. Compounds 2 and 7 showed antiproliferative and antimigratory activity against the highly metastatic human prostate cancer cell line PC-3 cells without cytotoxicity. The phenanthridine alkaloid class was identified as having potential for use to control prostate cancer proliferation and migration. Georg Thieme Verlag KG Stuttgart · New York.

  7. Six new alkaloids from Melodinus henryi.

    Science.gov (United States)

    Ma, Ke; Wang, Jun-Song; Luo, Jun; Kong, Ling-Yi

    2015-01-01

    A total of six new alkaloids, melodinhenines A-F (1-6), were isolated from Melodinus henryi. Melodinhenines A and B are new eburnan-vindolinine-type bisindole alkaloids and melodinhenines C-F are new quinolinic melodinus alkaloids. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRESIMS analyses. The absolute configuration of 1 and 2 was determined using ECD exciton chirality method. To the best of our knowledge, this is the first report on the determination of the absolute configuration of eburnan-vindolinine-type bisindole alkaloid using this method.

  8. Alkaloids produced by endophytic fungi: a review.

    Science.gov (United States)

    Zhang, Yanyan; Han, Ting; Ming, Qianliang; Wu, Lingshang; Rahman, Khalid; Qin, Luping

    2012-07-01

    In recent years, a number of alkaloids have been discovered from endophytic fungi in plants, which exhibited excellent biological properties such as antimicrobial, insecticidal, cytotoxic, and anticancer activities. This review mainly deals with the research progress on endophytic fungi for producing bioactive alkaloids such as quinoline and isoquinoline, amines and amides, indole derivatives, pyridines, and quinazolines. The biological activities and action mechanisms of these alkaloids from endophytic fungi are also introduced. Furthermore, the relationships between alkaloid-producing endophytes and their host plants, as well as their potential applications in the future are discussed.

  9. Gene expression profiling provides insights into pathways of oxaliplatin-related sinusoidal obstruction syndrome in humans.

    Science.gov (United States)

    Rubbia-Brandt, Laura; Tauzin, Sébastien; Brezault, Catherine; Delucinge-Vivier, Céline; Descombes, Patrick; Dousset, Bertand; Majno, Pietro E; Mentha, Gilles; Terris, Benoit

    2011-04-01

    Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS.

  10. Widespread Chemical Detoxification of Alkaloid Venom by Formicine Ants.

    Science.gov (United States)

    LeBrun, Edward G; Diebold, Peter J; Orr, Matthew R; Gilbert, Lawrence E

    2015-10-01

    The ability to detoxify defensive compounds of competitors provides key ecological advantages that can influence community-level processes. Although common in plants and bacteria, this type of detoxification interaction is extremely rare in animals. Here, using laboratory behavioral assays and analyses of videotaped interactions in South America, we report widespread venom detoxification among ants in the subfamily Formicinae. Across both data sets, nine formicine species, representing all major clades, used a stereotyped grooming behavior to self-apply formic acid (acidopore grooming) in response to fire ant (Solenopsis invicta and S. saevissima) venom exposure. In laboratory assays, this behavior increased the survivorship of species following exposure to S. invicta venom. Species expressed the behavior when exposed to additional alkaloid venoms, including both compositionally similar piperidine venom of an additional fire ant species and the pyrrolidine/pyrroline alkaloid venom of a Monomorium species. In addition, species expressed the behavior following exposure to the uncharacterized venom of a Crematogaster species. However, species did not express acidopore grooming when confronted with protein-based ant venoms or when exposed to monoterpenoid-based venom. This pattern, combined with the specific chemistry of the reaction of formic acid with venom alkaloids, indicates that alkaloid venoms are targets of detoxification grooming. Solenopsis thief ants, and Monomorium species stand out as brood-predators of formicine ants that produce piperidine, pyrrolidine, and pyrroline venom, providing an important ecological context for the use of detoxification behavior. Detoxification behavior also represents a mechanism that can influence the order of assemblage dominance hierarchies surrounding food competition. Thus, this behavior likely influences ant-assemblages through a variety of ecological pathways.

  11. Staphylococcal enterotoxin A gene-carrying Staphylococcus aureus isolated from foods and its control by crude alkaloid from papaya leaves.

    Science.gov (United States)

    Handayani, Lita; Faridah, Didah Nur; Kusumaningrum, Harsi D

    2014-11-01

    Staphylococcus aureus is a known pathogen causing intoxication by producing enterotoxins in food. Staphylococcal enterotoxin A is one of the enterotoxins commonly implicated in staphylococcal food poisoning. The ability of crude alkaloid extract from papaya leaves to inhibit the growth of S. aureus and staphylococcal enterotoxin A synthesis was investigated. Staphylococcal enterotoxin A gene-carrying S. aureus was isolated from raw milk and ready-to-eat foods. Crude alkaloid was extracted from ground, dried papaya leaves using ultrasonic-assisted extraction, and a MIC of the alkaloid was determined by the broth macrodilution method. Furthermore, S. aureus isolate was exposed to the crude alkaloid extract at one- and twofold MIC, and the expression of sea was subsequently analyzed using a quantitative reverse transcription real-time PCR. Ten isolates of S. aureus were obtained, and nine of those isolates were sea carriers. The yield of crude alkaloid extract was 0.48 to 1.82% per dry weight of papaya leaves. A MIC of crude alkaloid to S. aureus was 0.25 mg/ml. After exposure to the alkaloid at 0.25 and 0.5 mg/ml for 2 h, a significant increase in cycle threshold values of sea was observed. The sea was expressed 29 and 41 times less when S. aureus was exposed to crude alkaloid at one- and twofold MIC, respectively. This study revealed that crude alkaloid of papaya leaves could control staphylococcal enterotoxin A gene-carrying S. aureus by suppressing the expression of sea, in addition to the ability to inhibit the growth of S. aureus. The expression of sea was successfully quantified.

  12. Intraspecific variability in the alkaloid metabolism of Galanthus elwesii.

    Science.gov (United States)

    Berkov, Strahil; Sidjimova, Borjana; Evstatieva, Luba; Popov, Simeon

    2004-03-01

    Alkaloid pattern of individuals from 16 Bulgarian Galanthus elwesii populations was investigated by GC/MS and TLC. Twenty-one Amaryllidaceae alkaloids were detected and 14 of them were identified. Crinane type alkaloids, haemanthamine or crinine, dominated alkaloid metabolism in most of the populations. With exception of one population, where the separate individuals showed variable alkaloid profiles (dominated by crinine or haemanthamine) the individuals of the rest of populations have identical and characteristic alkaloid profiles. Some populations showed remarkable differences in respect to their alkaloid pattern-type of biosynthesis, main alkaloids and number of alkaloids. Populations dominated by galanthamine type alkaloids were found as well. These data demonstrate that like the morphological features, the alkaloid metabolism of G. elwesii is also variable.

  13. Cytotoxic oxoisoaporphine alkaloids from Menispermum dauricum.

    Science.gov (United States)

    Yu, B W; Meng, L H; Chen, J Y; Zhou, T X; Cheng, K F; Ding, J; Qin, G W

    2001-07-01

    Four new oxoisoaporphine alkaloids, daurioxoisoporphines A-D (1-4), were isolated from the rhizomes of Menispermum dauricum. The structures of these alkaloids were established by spectroscopic methods. The cytotoxic evaluation of 1 and 2 is reported against four cancer cell lines.

  14. Alkaloids of some Asian Sedum species

    NARCIS (Netherlands)

    Kim, JH; THart, H; Stevens, JF

    1996-01-01

    The leafy parts of 16 Asian species belonging to the three sections of Sedum were investigated for the presence of alkaloids. Only in seven species of Sedum sect. Sedum were alkaloids found. Sedum bulbiferum, S. japonicum, S. lepidopodium, S. morrisomensis, S. oryzifolium, S. polytrichoides and S. s

  15. Alkaloids of the flowers of Pancratium maritimum.

    Science.gov (United States)

    Youssef, D T; Frahm, A W

    1998-10-01

    The defatted ethanolic extract of the fresh flowers of Pancratium maritimum L. yielded the four known alkaloids lycorine, maritidine, lycoramine, and galanthamine. The structures of the isolated alkaloids were determined mainly through spectroscopic studies including one- and two-dimensional NMR (COSY, NOESY, DEPT, HETCOR, and HMBC) and CD techniques. Some spectral data are newly reported or revised.

  16. New bisbenzylisoquinoline alkaloid from Laureliopsis philippiana

    DEFF Research Database (Denmark)

    Stærk, Dan; Thi, Loi Pham; Rasmussen, Hasse Bonde

    2009-01-01

    Phytochemical investigation of Laureliopsis philippiana resulted in isolation of a new bisbenzylisoquinoline alkaloid (1) named laureliopsine A. The structure was established by spectroscopic methods, including 2D homo- and heteronuclear NMR experiments. This finding of a bisbenzylisoquinoline...... alkaloid in Laureliopsis supports its close relationship to Atherosperma and its taxonomic segregation from Laurelia....

  17. Alkaloids from the Roots of Saccopetalum prolificum

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new alkaloid, named prolifine (1), was isolated along with four known alkaloids, liriodenine (2), 6-hydroxyonychine (3), isooncodine (4) and discretamine (5) from the roots of Saccopetalum prolificum. The structure of 1 was elucidated on the basis of spectroscopic and chemical methods.

  18. Alkaloids of Nelumbo lutea (Wild.) pers. (Nymphaeaceae)

    Science.gov (United States)

    Zelenski, S G

    1977-11-01

    A phytochemical investigation of an alcoholic extract of the petioles of Nelumbo lutea resulted in the identification of the alkaloids N-methylasimilobine, anonaine, and roemerine. The alkaloids nuciferine, armepavine, N-nornuciferine, and N-norarmepavine, previously previously reported in the whole plant, were also identified.

  19. Plant alkaloids of the polymethyleneamine series

    Energy Technology Data Exchange (ETDEWEB)

    Rogoza, Ludmila N; Salakhutdinov, Nariman F; Tolstikov, Genrikh A [N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk (Russian Federation)

    2005-04-30

    The published data on the structures and biological activities of the plant alkaloids of the biogenic polymethyleneamine series, viz., putrescine (1,4-diaminobutane), spermidine (1,8-diamino-4 -azaoctane), and spermine (1,12-diamino-4,9-diazadodecane), are considered and systematised. The structures and biological activities of some synthetic analogues of these alkaloids are also presented.

  20. Comparative analysis of Papaver somniferum genotypes having contrasting latex and alkaloid profiles.

    Science.gov (United States)

    Chaturvedi, Nidarshana; Singh, Mridula; Shukla, Ashutosh K; Shasany, Ajit K; Shanker, Karuna; Lal, Raj K; Khanuja, Suman P S

    2014-07-01

    Papaver somniferum produces therapeutically useful benzylisoquinoline alkaloids (BIAs) like papaverine, thebaine, codeine, and morphine that accumulate in its capsular latex. Morphine is a potent analgesic but is also abused as a narcotic, which has increased the demand for non-narcotic thebaine that can be converted into various analgesics. To curtail the narcotic menace, many distinct genotypes of the plant have been developed that are deficient in morphine and/or latex. Sujata is one such latex-less low alkaloid-producing variety developed from the alkaloid-rich gum harvest variety Sampada. Its utility for gene prospecting and studying differential gene regulation responsible for its low alkaloid, nutritive seed oil, and latex-less phenotype has been exploited in this study. BIA profiling of Sujata and Sampada capsules at the early and late stages indicated that except for thebaine, Sujata had a depressed alkaloid phenotype as compared to Sampada. Comparative transcript-based analysis of the two genotypes was carried out in the early stage capsule (higher thebaine) using subtractive hybridization and microarray. Interrogation of a P. somniferum array yielded many differentially expressing transcripts. Their homology-based annotation classified them into categories--latex related, oil/lipid related, alkaloid related, cell wall related, and others. These leads will be useful to characterize the highly sought after Sujata phenotype.

  1. Binary Stress Induces an Increase in Indole Alkaloid Biosynthesis in Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Wei eZhu

    2015-07-01

    Full Text Available Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to that in control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress.

  2. Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Elena Fossati

    Full Text Available Morphinan alkaloids are the most powerful narcotic analgesics currently used to treat moderate to severe and chronic pain. The feasibility of morphinan synthesis in recombinant Saccharomyces cerevisiae starting from the precursor (R,S-norlaudanosoline was investigated. Chiral analysis of the reticuline produced by the expression of opium poppy methyltransferases showed strict enantioselectivity for (S-reticuline starting from (R,S-norlaudanosoline. In addition, the P. somniferum enzymes salutaridine synthase (PsSAS, salutaridine reductase (PsSAR and salutaridinol acetyltransferase (PsSAT were functionally co-expressed in S. cerevisiae and optimization of the pH conditions allowed for productive spontaneous rearrangement of salutaridinol-7-O-acetate and synthesis of thebaine from (R-reticuline. Finally, we reconstituted a 7-gene pathway for the production of codeine and morphine from (R-reticuline. Yeast cell feeding assays using (R-reticuline, salutaridine or codeine as substrates showed that all enzymes were functionally co-expressed in yeast and that activity of salutaridine reductase and codeine-O-demethylase likely limit flux to morphine synthesis. The results of this study describe a significant advance for the synthesis of morphinans in S. cerevisiae and pave the way for their complete synthesis in recombinant microbes.

  3. Piperidine alkaloids: human and food animal teratogens.

    Science.gov (United States)

    Green, Benedict T; Lee, Stephen T; Panter, Kip E; Brown, David R

    2012-06-01

    Piperidine alkaloids are acutely toxic to adult livestock species and produce musculoskeletal deformities in neonatal animals. These teratogenic effects include multiple congenital contracture (MCC) deformities and cleft palate in cattle, pigs, sheep, and goats. Poisonous plants containing teratogenic piperidine alkaloids include poison hemlock (Conium maculatum), lupine (Lupinus spp.), and tobacco (Nicotiana tabacum) [including wild tree tobacco (Nicotiana glauca)]. There is abundant epidemiological evidence in humans that link maternal tobacco use with a high incidence of oral clefting in newborns; this association may be partly attributable to the presence of piperidine alkaloids in tobacco products. In this review, we summarize the evidence for piperidine alkaloids that act as teratogens in livestock, piperidine alkaloid structure-activity relationships and their potential implications for human health.

  4. Chromatographic behaviour of alkaloids on thin layers of anion and cation exhangers. I. AG 1-X4 and cellex D.

    Science.gov (United States)

    Lepri, L; Desideri, P G; Lepori, M

    1976-01-07

    The chromatographic behaviour of 48 alkaloids has been studied on Bio-Rad AG 1-X4, Cellex D and microcrystalline cellulose, eluting with solutions of different pH but constant ionic strength (0.5). Many interesting separations were effected on both AG 1-X4 and Cellex D layers. The influence of pH on the chromatographic behaviour of alkaloids has been quantitatively studied and an equation was used that expresses the behaviour of the alkaloids on both AG 1-X4 (AcO-) and microcrystalling cellulose layers. The nonapplicability of this equation to Cellex D layers is discussed.

  5. Genetic variation in alkaloid accumulation in leaves of Nicotiana

    Institute of Scientific and Technical Information of China (English)

    Bo SUN; Fen ZHANG; Guo-jun ZHOU; Guo-hai CHU; Fang-fang HUANG; Qiao-mei WANG; Li-feng JIN; Fu-cheng LIN; Jun YANG

    2013-01-01

    Alkaloids are plant secondary metabolites that are widely distributed in Nicotiana species and contribute greatly to the quality of tobacco leaves. Some alkaloids, such as nornicotine and myosmine, have adverse effects on human health. To reduce the content of harmful alkaloids in tobacco leaves through conventional breeding, a genetic study of the alkaloid variation among different genotypes is required. In this study, alkaloid profiles in leaves of five Nicotiana tabacum cultivars and Nicotiana tomentosiformis were investigated. Six alkaloids were identified from al six genotypes via gas chromatograph-mass spectrometry (GC-MS). Significant differences in alkaloid content were ob-served both among different leaf positions and among cultivars. The contents of nornicotine and myosmine were positively and significantly correlated (R2=0.881), and were also separated from those of other alkaloids by clustering. Thus, the genotype plays a major role in alkaloid accumulation, indicating a high potential for manipulation of alkaloid content through traditional breeding.

  6. Genetic variation in alkaloid accumulation in leaves of Nicotiana.

    Science.gov (United States)

    Sun, Bo; Zhang, Fen; Zhou, Guo-jun; Chu, Guo-hai; Huang, Fang-fang; Wang, Qiao-mei; Jin, Li-feng; Lin, Fu-cheng; Yang, Jun

    2013-12-01

    Alkaloids are plant secondary metabolites that are widely distributed in Nicotiana species and contribute greatly to the quality of tobacco leaves. Some alkaloids, such as nornicotine and myosmine, have adverse effects on human health. To reduce the content of harmful alkaloids in tobacco leaves through conventional breeding, a genetic study of the alkaloid variation among different genotypes is required. In this study, alkaloid profiles in leaves of five Nicotiana tabacum cultivars and Nicotiana tomentosiformis were investigated. Six alkaloids were identified from all six genotypes via gas chromatograph-mass spectrometry (GC-MS). Significant differences in alkaloid content were observed both among different leaf positions and among cultivars. The contents of nornicotine and myosmine were positively and significantly correlated (R(2)=0.881), and were also separated from those of other alkaloids by clustering. Thus, the genotype plays a major role in alkaloid accumulation, indicating a high potential for manipulation of alkaloid content through traditional breeding.

  7. Comparative Study of Alkaloid Pattern of Four Bulgarian Fumaria species.

    Science.gov (United States)

    Doncheva, Tsvetelina; Yordanova, Gabriela; Vutov, Vassil; Kostova, Nadezhda; Philipov, Stefan

    2016-02-01

    The alkaloid pattern of four Fumaria species (Fumaria kralikii, Fumaria rostellata, Fumaria schleicherii, Fumaria thureii) growing in Bulgaria was investigated by GC-MS and twenty isoquinoline alkaloids were determined. Phytochemical investigation of the alkaloid composition on Fumaria thuretii Boiss was made for the first time. The alkaloid profile of the species was compared at two levels, between different species and within two species from different habitats. Two chemotypical groups, based on the types of isoquinoline alkaloids were suggested. To group A belong species F. kralikii, F. rostellata (F. r. 1) and F. thuretii containing more than 50% spirobenzylisoquinoline alkaloids of the crude alkaloid mixtures. To group B belong species F. rostellata (F. r. 2) and F. schleicherii containing more than 40% protopine alkaloids and relatively high percentage phthaldeisoquinoline alkaloids (11-19%). In group A phthaldeisoquinoline alkaloids were not detected.

  8. Modulation of multidrug resistance in cancer cells by chelidonine and Chelidonium majus alkaloids.

    Science.gov (United States)

    El-Readi, Mahmoud Zaki; Eid, SafaaYehia; Ashour, Mohamed Lotfy; Tahrani, Ahmad; Wink, Michael

    2013-02-15

    Cancer cells often develop multidrug resistance (MDR) which is a multidimensional problem involving several mechanisms and targets. This study demonstrates that chelidonine and an alkaloid extract from Chelidonium majus, which contains protoberberine and benzo[c]phenanthridine alkaloids, has the ability to overcome MDR of different cancer cell lines through interaction with ABC-transporters, CYP3A4 and GST, by induction of apoptosis, and cytotoxic effects. Chelidonine and the alkaloid extract inhibited P-gp/MDR1 activity in a concentration-dependent manner in Caco-2 and CEM/ADR5000 and reversed their doxorubicin resistance. In addition, chelidonine and the alkaloid extract inhibited the activity of the drug modifying enzymes CYP3A4 and GST in a dose-dependent manner. The alkaloids induced apoptosis in MDR cells which was accompanied by an activation of caspase-3, -8,-6/9, and phosphatidyl serine (PS) exposure. cDNA arrays were applied to identify differentially expressed genes after treatment with chelidonine and the alkaloid extract. The expression analysis identified a common set of regulated genes related to apoptosis, cell cycle, and drug metabolism. Treatment of Caco-2 cells with 50 μg/ml alkaloid extract and 50 μM chelidonine for up to 48 h resulted in a significant decrease in mRNA levels of P-gp/MDR1, MRP1, BCRP, CYP3A4, GST, and hPXR and in a significant increase in caspase-3 and caspase-8 mRNA. Thus, chelidonine is a promising model compound for overcoming MDR and for enhancing cytotoxicity of chemotherapeutics, especially against leukaemia cells. Its efficacy needs to be confirmed in animal models. Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.

  9. Alkaloids and acetogenins in Annonaceae development: biological considerations

    Directory of Open Access Journals (Sweden)

    Alma Rosa González-Esquinca

    2014-01-01

    Full Text Available Chemical studies of the plant family Annonaceae have intensified in the last several decades due to the discovery of annonaceous molecules with medicinal potential (e.g., benzylisoquinoline alkaloids and acetogenins. Approximately 500 alkaloids have been identified in 138 Annonaceae species in 43 genera. In addition, until 2004, 593 annonaceous acetogenins (ACGs had been identified, from 51 species in 13 genera.This suggests that plants from this family allocate important resources to the biosynthesis of these compounds. Despite the diversity of these molecules, their biological roles, including their physiological and/or ecological functions, are not well understood. In this study, it was provided new data describing the variety and distribution of certain alkaloids and ACGs in annonaceous plants in distinct stages of development. The potential relationships among some of these compounds and the seasonally climatic changes occurring in the plant habitat are also discussed. These data will improve our understanding of the secondary metabolism of these pharmacologically important molecules and their expression patterns during development, which will help to determine the optimal growth conditions and harvest times for their production.

  10. Bromopyrrole Alkaloids from Okinawan Marine Sponges Agelas spp.

    Science.gov (United States)

    Tanaka, Naonobu; Kusama, Taishi; Kashiwada, Yoshiki; Kobayashi, Jun'ichi

    2016-01-01

    In our continuing study for structurally and biogenetically interesting natural products from marine organisms, Okinawan marine sponges Agelas spp. were investigated, resulting in the isolation of 18 unique alkaloids including five dimeric bromopyrrole alkaloids (1-5), ten monomeric bromopyrrole alkaloids (6-15), and three conjugates of monomeric bromopyrrole alkaloid and hydroxykynurenine (16-18). In this mini-review, the isolation, structure elucidation, and antimicrobial activities of these alkaloids are summarized.

  11. METABOLISM OF TOXIC PYRROLIZIDINE ALKALOIDS FROM TANSY RAGWORT, SENECIO JACOBAEA, IN BOVINE RUMINAL FLUID UNDER ANAEROBIC CONDITIONS. (R825689C006)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  12. 几种吡咯里西啶类生物碱对肝细胞毒性的探讨%Toxicity of Several Pyrrolizidine Alkaloids on Hepatocytes

    Institute of Scientific and Technical Information of China (English)

    季莉莉; 檀爱民; 汤俊; 张勉; 王峥涛

    2004-01-01

    目的:考察几种吡咯里西啶类生物碱体外实验中对肝细胞的毒性.方法:用MTT法检测了6种吡咯里西啶类生物碱clivorine,monocrotaline,isoline,LP-01(yamataimine),LP-02(12-acetyl yamataimine),LJ-09(platyphylline)对人正常肝细胞株L-02细胞活性的影响,对于其中有毒性的clivorine又用结晶紫染色的方法进一步确证其毒性.结果:Clivorine对肝细胞具有强烈的毒性作用,未发现其它几种吡咯里西啶生物碱对肝细胞的毒性.结论:Clivorine体外对肝细胞具毒性作用.

  13. 植物中吡咯里西啶生物碱的检测与分析%Analysis of Pyrrolizidine Alkaloids in Plants

    Institute of Scientific and Technical Information of China (English)

    张芳; 王长虹; 王峥涛

    2006-01-01

    吡咯里西啶生物碱广泛分布于植物界.很多吡咯里西啶生物碱对动物和人类有严重的毒性作用,包括肝脏毒性,肺脏毒性,致癌作用,致突变作用和神经毒性等.本文综述了植物中吡咯里西啶生物碱的分离,纯化,检测与分析.

  14. Isoquinoline and isoindole alkaloids from Menispermum dauricum.

    Science.gov (United States)

    Zhang, Xiaoqi; Ye, Wencai; Zhao, Shouxun; Che, Chun-Tao

    2004-04-01

    Three isoquinoline alkaloids and an isoindole alkaloid, along with eight known compounds, were isolated from the roots of Menispermum dauricum (Menispermacese). The alkaloids were characterized as 7-hydroxy-6-methoxy-1(2H)-isoquinolinone, 6,7-dimethoxy-N-methyl-3,4-dioxo-1(2H)-isoquinolinone, 1-(4-hydroxybenzoyl)-7-hydroxy-6-methoxy-isoquinoline and 6-hydroxy-5-methoxy-N-methylphthalimide, on the basis of spectral evidence including 1D- and 2D-NMR and MS analyses.

  15. Polycyclic Guanidine Alkaloids from Poecilosclerida Marine Sponges.

    Science.gov (United States)

    Sfecci, Estelle; Lacour, Thierry; Amade, Philippe; Mehiri, Mohamed

    2016-04-09

    Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological applications. A large number of cyclic guanidine alkaloids, including crambines, crambescins, crambescidins, batzelladines or netamins have been isolated from Poecilosclerida marine sponges. In this review, we will explore the chemodiversity of tri- and pentacyclic guanidine alkaloids. NMR and MS data tools will also be provided, and an overview of the wide range of bioactivities of crambescidins and batzelladines derivatives will be given.

  16. Marine Pyridoacridine Alkaloids: Biosynthesis and Biological Activities.

    Science.gov (United States)

    Ibrahim, Sabrin R M; Mohamed, Gamal A

    2016-01-01

    Pyridoacridines are a class of strictly marine-derived alkaloids that constitute one of the largest chemical families of marine alkaloids. During the last few years, both natural pyridoacridines and their analogues have constituted excellent targets for synthetic works. They have been the subject of intense study due to their significant biological activities; cytotoxic, antibacterial, antifungal, antiviral, insecticidal, anti-HIV, and anti-parasitic activities. In the present review, 95 pyridoacridine alkaloids isolated from marine organisms are discussed in term of their occurrence, biosynthesis, biological activities, and structural assignment.

  17. Norditerpenoid Alkaloids from Aconitum spicatum Stapf

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To search for pharmacologically and structurally interesting substances from traditional Chinese medicines,we investigated the chemical compounds of Aconitum spicatum Stapf. Two new norditerpenoid alkaloids,namely spicatine A (compound 1) and spicatine B (compound 2), as well as 11 known norditerpenoid alkaloids were isolated from the CHCl3 portion of the 90% ethanol extract of the roots of A. spicatum. The structures of the alkaloids were characterized on the basis of their spectral data, One of the isolated compounds showed significant cytotoxic activities (IC50 values < 200 μmol/L) against the HL-60 cell line.

  18. Racemic alkaloids from the fungus Ganoderma cochlear.

    Science.gov (United States)

    Wang, Xin-Long; Dou, Man; Luo, Qi; Cheng, Li-Zhi; Yan, Yong-Ming; Li, Rong-Tao; Cheng, Yong-Xian

    2017-01-01

    Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed.

  19. OVIPOSITION AND OVICIDAL ACTIVITIES OF ALKALOIDAL ...

    African Journals Online (AJOL)

    ... moderate ovicidal activity but inflict delayed effects such as high larval and low pupal and adult mortality. ... Key Words: Murraya koenigii; Rutaceae; alkaloidal extract; oviposition; ovicidal; Culex quinquefasciatus; Culex tritaeniorhynchus.

  20. Antiprotozoal and antioxidant alkaloids from Alternanthera littoralis.

    Science.gov (United States)

    Koolen, Hector H F; Pral, Elizabeth M F; Alfieri, Silvia C; Marinho, Jane V N; Serain, Alessandra F; Hernández-Tasco, Alvaro J; Andreazza, Nathalia L; Salvador, Marcos J

    2017-02-01

    Five alkaloids, in addition to hydroxytyrosol and uridine, were isolated from aerial parts of Alternanthera littoralis P. Beauv. Among the isolated compounds, alternamide A was an unusual tricyclic alkaloid with a bridged benzoazepine core. All isolated alkaloids have a catechol moiety, indicating a possible common biosynthetic route. Their structures were established by 1D and 2D NMR spectroscopy in combination with extensive tandem MS experiments by collisional induced dissociation (CID). The antiprotozoal activity of the isolated compounds was assayed against trypomastigote forms of Trypanosoma cruzi and amastigotes of Leishmania amazonensis. Alternamine A was the most active compound, reducing markedly the viability of both parasites. Antioxidant capacities evaluated by ORACFL assay showed that the isolated alkaloids (mainly alternamide B) contributed to the high activity recorded for the ethanolic crude extract; possibly, the catechol moiety present in all structures plays a central role in this result.

  1. Anxiolytic Activity of Diterpene Alkaloid Songorine.

    Science.gov (United States)

    Nesterova, Yu V; Povet'eva, T N; Suslov, N I; Shults, E E; Ziuz'kov, G N; Aksinenko, S G; Afanas'eva, O G; Krapivin, A V; Kharina, T G

    2015-09-01

    Antianxiety action of diterpene alkaloid songorine was studied using Vogel conflict test. Songorine in a dose of 0.25 mg/kg demonstrated high anxiolytic activity comparable to that of phenazepam and produced no sedative effect.

  2. Steroidal alkaloid toxicity to fish embryos.

    Science.gov (United States)

    Crawford, L; Kocan, R M

    1993-02-01

    Embryos of two species of fish were evaluated for their suitability as model systems for steroidal alkaloid toxicity, the Japanese rice fish, medaka (Oryzius latipes) and the rainbow trout (Oncorhynchus mykiss). Additionally, the equine neurotoxic sesquiterpene lactone repin, was also tested. A PROBIT program was used to evaluate the EC1, EC50 and EC99 as well as the associated confidence limits. The steroidal alkaloids tested were the Solanum potato glycoalkaloids alpha-chaconine, alpha-solanine, the aglyclones solanidine and solasodine and the Veratrum alkaloid, jervine. Embryo mortality, likely due to structural or functional abnormalities in the early development stages of the embryo, were the only response observed in both species. The rainbow trout exhibited a toxic response to chaconine, solasidine, repin and solanine but the medaka embryos were only affected by the compounds, chaconine and solanine. Rainbow trout may indeed serve as a good lower vertebrate model for studying the toxicity of steroidal alkaloids.

  3. Integration of transcriptome, proteome and metabolism data reveals the alkaloids biosynthesis in Macleaya cordata and Macleaya microcarpa.

    Directory of Open Access Journals (Sweden)

    Jianguo Zeng

    Full Text Available BACKGROUND: The Macleaya spp., including Macleaya cordata and Macleaya microcarpa, are traditional anti-virus, inflammation eliminating, and insecticide herb medicines for their isoquinoline alkaloids. They are also known as the basis of the popular natural animal food addictive in Europe. However, few studies especially at genomics level were conducted on them. Hence, we performed the Macleaya spp. transcriptome and integrated it with iTRAQ proteome analysis in order to identify potential genes involved in alkaloids biosynthesis. METHODOLOGY AND PRINCIPAL FINDINGS: We elaborately designed the transcriptome, proteome and metabolism profiling for 10 samples of both species to explore their alkaloids biosynthesis. From the transcriptome data, we obtained 69367 and 78255 unigenes for M. cordata and M. microcarpa, in which about two thirds of them were similar to sequences in public databases. By metabolism profiling, reverse patterns for alkaloids sanguinarine, chelerythrine, protopine, and allocryptopine were observed in different organs of two species. We characterized the expressions of enzymes in alkaloid biosynthesis pathways. We also identified more than 1000 proteins from iTRAQ proteome data. Our results strongly suggest that the root maybe the organ for major alkaloids biosynthesis of Macleaya spp. Except for biosynthesis, the alkaloids storage and transport were also important for their accumulation. The ultrastructure of laticifers by SEM helps us to prove the alkaloids maybe accumulated in the mature roots. CONCLUSIONS/SIGNIFICANCE: To our knowledge this is the first study to elucidate the genetic makeup of Macleaya spp. This work provides clues to the identification of the potential modulate genes involved in alkaloids biosynthesis in Macleaya spp., and sheds light on researches for non-model medicinal plants by integrating different high-throughput technologies.

  4. Alkaloids from Fissistigma latifolium (Dunal Merr.

    Directory of Open Access Journals (Sweden)

    Asmah Alias

    2010-06-01

    Full Text Available A phytochemical study of the bark of Fissistigma latifolium (Annonaceae yielded a new aporphine alkaloid, (--N-methylguattescidine (1, and eight known alkaloids: liriodenine (2, oxoxylopine (3, (--asimilobine (4, dimethyltryptamine (5, (--remerine (6, (--anonaine (7, columbamine (8 and lysicamine (9. The compounds were isolated using various chromatographic methods and structural elucidation was accomplished by means of spectroscopic methods, notably 1D-NMR (1H, 13C, DEPT, 2D-NMR (COSY, HMQC, HMBC, UV, IR and MS.

  5. Polycyclic alkaloids via transannular Mannich reactions

    DEFF Research Database (Denmark)

    Vital, Paulo; Hosseini, Masood; Shanmugham, M. S.

    2009-01-01

    The tricyclic compound 13, representing the framework of the cylindricine 4 and lepadiformine 5 alkaloids, was prepared in a single operation via the first example of a transannular Mannich reaction involving a macrocyclic diketoamine 12.......The tricyclic compound 13, representing the framework of the cylindricine 4 and lepadiformine 5 alkaloids, was prepared in a single operation via the first example of a transannular Mannich reaction involving a macrocyclic diketoamine 12....

  6. Two new diterpene alkaloids from Delphinium chrysotrichum

    Institute of Scientific and Technical Information of China (English)

    Yang Qing He; Xiao Mei Wei; Yi Li Han; Li Ming Gao

    2007-01-01

    Chemical investigation on the ethanol extract from the whole plants of Delphinium chrysotrichum resulted in the isolation of two new diterpene alkaloids named delphatisine A (1) and delphatisine B (2), respectively. The structures of the new compounds were deduced on the basis of their spectral data (IR, HREIMS, EIMS, 1D, 2D-NMR). This is the first report on the isolation of diterpenoid alkaloids from the D. Chrysotrichum.

  7. Curare Alkaloids: Constituents of a Matis Dart Poison.

    Science.gov (United States)

    Malca Garcia, Gonzalo R; Hennig, Lothar; Shelukhina, Irina V; Kudryavtsev, Denis S; Bussmann, Rainer W; Tsetlin, Victor I; Giannis, Athanassios

    2015-11-25

    A phytochemical study of dart and arrow poison from the Matis tribe led to the identification of D-(-)-quinic acid, L-malic acid, ethyldimethylamine, magnoflorine, and five new bisbenzyltetrahydroisoquinoline alkaloids (BBIQAs), 1-5. D-Tubocurarine could not be identified among these products. BBIQA (3) contains a unique linkage at C-8 and C-11'. All structures were characterized by a combination of NMR and HRESIMS data. The effects of Matis poison and individual BBIQAs (1-3) on rat muscle nAChR expressed in Xenopus oocytes have been investigated using the two-electrode voltage clamp technique.

  8. Visual identification of alkaloids in some medicinal plants: common alkaloid reagents versus bromocresol green

    Directory of Open Access Journals (Sweden)

    Shamsa F, Esfahani HR, Gamooshi RA

    2008-07-01

    Full Text Available "n Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Background: Alkaloids are a group of nitrogenous compounds with potential effects on the physiological behavior of human and animals. Some of these compounds are considered important drugs in modern medicine, such as atropine and morphine. Plants are considered the most important source of alkaloids. Therefore, investigating the presence of alkaloids in different plants is very important. Usually, alkaloids in plants are identified by methods such as those of Dragendorf, Wagner and Meyer, among others, which require milligrams of alkaloids for identification. In the present study, a fast and sensitive procedure for detecting of alkaloids in plants is presented.   "n"nMethods: Twelve dried plants samples were investigated for the presence alkaloids. After extracting the total alkaloid into methanol using a Soxhlet extractor, a few milligrams of the extract was transferred to a separatory funnel, buffered to pH 4.7, the bromocresol green (BCG solution (10-4 M was added, mixed and extracted with CHCl3 until a yellow color was observed in the CHCl3 layer, indicating the presence of the alkaloid. The crude extracts were also investigated by the standard methods of Dragendorf, Wagner and Meyer for the presence of alkaloids.   "n"nResults: Investigation of the 12 plant samples for the presence of alkaloids by the standard reagents of Dragendorf, Wagner, and Meyer showed that only Camelia sinensis (flowers, Echium amoenum Fisch & Mey (flowers, and Stachys (aerial parts are devoid

  9. Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.

    Science.gov (United States)

    Satake, Kazuhiro; Tsukamoto, Megumi; Mitani, Yuji; Regasini, Luis Octavio; da Silva Bolzani, Vanderlan; Efferth, Thomas; Nakagawa, Hiroshi

    2015-01-01

    Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and vinblastine compared to Flp-In-293/Mock cells although the four guanidine alkaloids exhibited cytotoxicity against the two Flp-In-293 cells. Furthermore, the four guanidine alkaloids were also found to stimulate the ATPase activity of ABCB1 in ATPase assays. These results suggest that ABCB1 can confer the resistance to the cytotoxic guanidine alkaloids by transporting them.

  10. Elucidating steroid alkaloid biosynthesis in Veratrum californicum: production of verazine in Sf9 cells.

    Science.gov (United States)

    Augustin, Megan M; Ruzicka, Dan R; Shukla, Ashutosh K; Augustin, Jörg M; Starks, Courtney M; O'Neil-Johnson, Mark; McKain, Michael R; Evans, Bradley S; Barrett, Matt D; Smithson, Ann; Wong, Gane Ka-Shu; Deyholos, Michael K; Edger, Patrick P; Pires, J Chris; Leebens-Mack, James H; Mann, David A; Kutchan, Toni M

    2015-06-01

    Steroid alkaloids have been shown to elicit a wide range of pharmacological effects that include anticancer and antifungal activities. Understanding the biosynthesis of these molecules is essential to bioengineering for sustainable production. Herein, we investigate the biosynthetic pathway to cyclopamine, a steroid alkaloid that shows promising antineoplastic activities. Supply of cyclopamine is limited, as the current source is solely derived from wild collection of the plant Veratrum californicum. To elucidate the early stages of the pathway to cyclopamine, we interrogated a V. californicum RNA-seq dataset using the cyclopamine accumulation profile as a predefined model for gene expression with the pattern-matching algorithm Haystack. Refactoring candidate genes in Sf9 insect cells led to discovery of four enzymes that catalyze the first six steps in steroid alkaloid biosynthesis to produce verazine, a predicted precursor to cyclopamine. Three of the enzymes are cytochromes P450 while the fourth is a γ-aminobutyrate transaminase; together they produce verazine from cholesterol.

  11. Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor currents in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Pedro Setti-Perdigão

    Full Text Available Crude extracts and three isolated alkaloids from Erythrina mulungu plants have shown anxiolytic effects in different animal models. We investigated whether these alkaloids could affect nicotinic acetylcholine receptors and if they are selective for different central nervous system (CNS subtypes. Screening experiments were performed using a single concentration of the alkaloid co-applied with acetylcholine in whole cell patch-clamp recordings in three different cell models: (i PC12 cells natively expressing α3* nicotinic acetylcholine receptors; (ii cultured hippocampal neurons natively expressing α7* nicotinic acetylcholine receptors; and (iii HEK 293 cells heterologoulsy expressing α4β2 nicotinic acetylcholine receptors. For all three receptors, the percent inhibition of acetylcholine-activated currents by (+-11á-hydroxyerysotrine was the lowest, whereas (+-erythravine and (+-11á-hydroxyerythravine inhibited the currents to a greater extent. For the latter two substances, we obtained concentration-response curves with a pre-application protocol for the α7* and α4β2 nicotinic acetylcholine receptors. The IC50 obtained with (+-erythravine and (+-11á-hydroxyerythravine were 6 µM and 5 µM for the α7* receptors, and 13 nM and 4 nM for the α4β2 receptors, respectively. Our data suggest that these Erythrina alkaloids may exert their behavioral effects through inhibition of CNS nicotinic acetylcholine receptors, particularly the α4β2 subtype.

  12. Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor currents in mammalian cells.

    Science.gov (United States)

    Setti-Perdigão, Pedro; Serrano, Maria A R; Flausino, Otávio A; Bolzani, Vanderlan S; Guimarães, Marília Z P; Castro, Newton G

    2013-01-01

    Crude extracts and three isolated alkaloids from Erythrina mulungu plants have shown anxiolytic effects in different animal models. We investigated whether these alkaloids could affect nicotinic acetylcholine receptors and if they are selective for different central nervous system (CNS) subtypes. Screening experiments were performed using a single concentration of the alkaloid co-applied with acetylcholine in whole cell patch-clamp recordings in three different cell models: (i) PC12 cells natively expressing α3* nicotinic acetylcholine receptors; (ii) cultured hippocampal neurons natively expressing α7* nicotinic acetylcholine receptors; and (iii) HEK 293 cells heterologoulsy expressing α4β2 nicotinic acetylcholine receptors. For all three receptors, the percent inhibition of acetylcholine-activated currents by (+)-11á-hydroxyerysotrine was the lowest, whereas (+)-erythravine and (+)-11á-hydroxyerythravine inhibited the currents to a greater extent. For the latter two substances, we obtained concentration-response curves with a pre-application protocol for the α7* and α4β2 nicotinic acetylcholine receptors. The IC50 obtained with (+)-erythravine and (+)-11á-hydroxyerythravine were 6 µM and 5 µM for the α7* receptors, and 13 nM and 4 nM for the α4β2 receptors, respectively. Our data suggest that these Erythrina alkaloids may exert their behavioral effects through inhibition of CNS nicotinic acetylcholine receptors, particularly the α4β2 subtype.

  13. Two New C19-Diterpenoid Alkaloids from Delphinium davidii Franch.

    Institute of Scientific and Technical Information of China (English)

    Xiao Xia LIANG; Dong Lin CHEN; Feng Peng WANG

    2006-01-01

    Two new C19-diterpenoid alkaloids, davidisines A (1) and B (2) along with thirteen known alkaloids were isolated from the whole herb of Delphinium davidii Franch. Their structures were established by spectral methods, especially 2D NMR techniques.

  14. Biosynthesis of Monoterpenoid Indole Alkaloid Ajmaline Catalyzed by Novel Reductases

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Introduction One of the major root alkaloids of the Indian medicinal plant Rauvolfia serpenlina Benth. Ex Kurz is named ajmaline. The enzymatic biosynthesisof this alkaloid has been studied for a long time by our group[1].

  15. Biological activity of alkaloids from Solanum dulcamara L.

    Science.gov (United States)

    Kumar, Padma; Sharma, Bindu; Bakshi, Nidhi

    2009-01-01

    Alkaloids are well known for their antimicrobial activity. Though all natural alkaloids come from plants, not all plants produce alkaloids. Plants of the Solanaceae family are known for their high alkaloid content. Alkaloids are found in all plant parts like roots, stems, leaves, flowers, fruits and seeds. In the present study, those plant parts of Solanum dulcamara were selected which have been reported to produce a high content of a specific alkaloid: solanine (from unripe fruits), solasodine (from flowers) and beta-solamarine (from roots). These alkaloids were extracted from various parts of S. dulcamara by well-established methods and were screened for their antibacterial activity. Human pathogenic bacteria, viz., Enterobacter aerogenes, Escherichia coli, Staphylococcus aureus, were selected for the study. All three alkaloids inhibited the growth of E. coli and S. aureus. However, no significant activity was observed against E. aerogenes. Minimum inhibitory concentration and minimum bactericidal concentration were also evaluated.

  16. An Acetylenic Alkaloid from the Calcareous Sponge Leucetta sp.

    OpenAIRE

    Nicole J de Voogd; Idam Hermawan; Junichi Tanaka

    2011-01-01

    A new acetylenic alkaloid was isolated from the sponge Leucetta sp. The structure was established by analyzing spectroscopic data. The alkaloid showed cytotoxicity IC50 2.5 mg/mL against NBT-T2 cells.

  17. The alkaloids of the madangamine group.

    Science.gov (United States)

    Amat, Mercedes; Pérez, Maria; Ballette, Roberto; Proto, Stefano; Bosch, Joan

    2015-01-01

    This chapter is focused on madangamines, a small group of complex diamine alkaloids isolated from marine sponges of the order Haplosclerida, and covers their isolation, characterization, biogenesis, biological activity, and synthesis. Structurally, madangamines are pentacyclic alkaloids with an unprecedented skeletal type, characterized by a common diazatricyclic core and two peripheral macrocyclic rings. The isolation of these alkaloids from Xestospongia ingens (madangamines A-E) and Pachychalina alcaloidifera (madangamine F) is described in detail. Physical and complete spectroscopic 1H and 13C NMR data are included. The proposed biogenesis of madangamines from ammonia, a functionalized three-carbon unit, and saturated or unsaturated linear long-chain dialdehydes, via partially reduced bis-alkylpyridine macrocycles, is discussed. The synthesis of alkaloids of the madangamine group has been little explored, with only one total synthesis reported so far, that of (+)-madangamine D. This review also describes several model synthetic approaches to the diazatricyclic ABC core of these alkaloids, as well as model studies on the construction of the (Z,Z)-unsaturated 11-membered E macrocycle common to madangamines A-E, the 13- and 14-membered D rings of madangamines C-E, and the all-cis-triunsaturated 15-membered D ring of madangamine A. Some members of this group have shown significant in vitro cytotoxicity against a number of cancer cell lines.

  18. Hemlock alkaloids from Socrates to poison aloes.

    Science.gov (United States)

    Reynolds, Tom

    2005-06-01

    Hemlock (Conium maculatum L. Umbelliferae) has long been known as a poisonous plant. Toxicity is due to a group of piperidine alkaloids of which the representative members are coniine and gamma-coniceine. The latter is the more toxic and is the first formed biosynthetically. Its levels in relation to coniine vary widely according to environmental conditions and to provenance of the plants. Surprisingly, these piperidine alkaloids have turned up in quite unrelated species in the monocotyledons as well as the dicotyledons. Aloes, for instance, important medicinal plants, are not regarded as poisonous although some species are very bitter. Nevertheless a small number of mostly local species contain the alkaloids, especially gamma-coniceine and there have been records of human poisoning. The compounds are recognized by their characteristic mousy smell. Both acute and chronic symptoms have been described. The compounds are neurotoxins and death results from respiratory failure, recalling the effects of curare. Chronic non-lethal ingestion by pregnant livestock leads to foetal malformation. Both acute and chronic toxicity are seen with stock in damp meadows and have been recorded as problems especially in North America. The alkaloids derive biosynthetically from acetate units via the polyketide pathway in contrast to other piperidine alkaloids which derive from lysine.

  19. Simulation of the type of coralin alkaloid-DNA binding

    Science.gov (United States)

    Kulikov, K. G.; Koshlan, T. V.

    2015-05-01

    Interaction between a synthesized coralin protoberberine alkaloid and the DNA double helix of the calf's thymus in a salt solution is studied by optical absorption spectroscopy and spectropolarimetry. The dependence of the spectral characteristics of the alkaloid on a ratio between the DNA base pair concentration and the alkaloid molecule concentration is considered. The parameters of bonds between the coralin alkaloid and the DNA double helix are determined using modified McGhee-von Hippel equations.

  20. [Study on optimum extraction conditions of alkaloids from Pinellia ternate].

    Science.gov (United States)

    Zeng, Jianhong; Peng, Zhengsong; Mao, Zicheng; Wei, Shuhong

    2003-05-01

    The optimum extraction conditions of alkaloids from Pinellia ternate (Thunb.) Breit were studied by orthogonal test. The results showed that the highest extraction rate of the alkaloids could be obtained by smashing the material in 60 (sieve number) of fragmentation and socking the material in 2.575 mol/L ammonia water, extracting alkaloids with 18 times as much chlorolform at room temperature for 25 hours. The highest extraction rate of alkaloids was 0.0817%.

  1. The Double-Bond Configuration of Corynanthean Alkaloids and Its Impact on Monoterpenoid Indole Alkaloid Biosynthesis.

    Science.gov (United States)

    Eckermann, Ruben; Gaich, Tanja

    2016-04-11

    Experimental evidence is provided for the coherence of the double-bond geometry and the occurrence of "secondary cyclizations" in the biosynthesis of monoterpenoid indole alkaloids. Biosynthetically, akuammiline, C-mavacurine, and Strychnos alkaloids are proposed to be derived from the corynanthean alkaloid geissoschizine, a key intermediate in the biosynthetic pathway of these monoterpenoid indole alkaloids. This process occurs by so-called "secondary cyclizations" from geissoschizine or its derivatives. Although corynanthean alkaloids like geissoschizine incorporate E or Z double bonds located at C19-C20, the alkaloids downstream in the biosynthesis exclusively exhibit the E double bond. This study shows that secondary cyclizations preferentially occur with the E isomer of geissoschizine or its derivatives. This is attributed to the flexibility of the quinolizidine system of the corynanthean alkaloids, which can adopt a cis or trans conformation. For the secondary cyclization to take place, the cis-quinolizidine conformation is required. Experimental evidence supports the hypothesis that the E double bond of geissoschizine induces the cis conformation, whereas the Z double bond induces the trans conformation, which prohibits secondary cyclization of the Z compounds.

  2. Two new alkaloids of the crinane series from Pancratium sickenbergeri.

    Science.gov (United States)

    Abou-Donia, Amina H; Amer, Masouda E; Darwish, Fikria A; Kassem, Fahima F; Hammoda, Hala M; Abdel-Kader, Maged S; Zhou, Bing-Nan; Kingston, David G I

    2002-04-01

    Two new alkaloids; ent-6alpha/6beta-hydroxybuphanisine, (-)-8-demethylmaritidine and seven known alkaloids were isolated from Pancratium sickenbergeri grown in Egypt. Three of the known alkaloids were tested in the NCI cytotoxicity screen, but were found to be inactive.

  3. Pancratium canariense as an important source of amaryllidaceae alkaloids.

    Science.gov (United States)

    Cedrón, Juan C; Oberti, Juan C; Estévez-Braun, Ana; Ravelo, Angel G; Del Arco-Aguilar, Marcelino; López, Matías

    2009-01-01

    Four new alkaloids (1-4) have been isolated from a methanolic extract of bulbs of Pancratium canariense, together with 12 known alkaloids (5-16). The structures of the new alkaloids were determined by extensive 1D and 2D NMR spectroscopic studies and X-ray diffraction.

  4. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  5. An Unusual Pentacyclic Dinitrogenous Alkaloid from Galanthus gracilis

    OpenAIRE

    ÜNVER, Nehir; KAYA, G. İrem

    2005-01-01

    A minor alkaloid, namely gracilamine, was isolated from Galanthus gracilis. This was the first example of a pentacyclic dinitrogenous alkaloid isolated from a member of Amaryllidaceae. The structure of this alkaloid was elucidated by means of comprehensive spectroscopic methods (1D and 2D NMR, MS, UV, IR).

  6. Two New Alkaloids from Narcissus serotinus L.

    Directory of Open Access Journals (Sweden)

    Francesc Viladomat

    2010-10-01

    Full Text Available The Amaryllidaceae family is well known for the presence of an exclusive group of alkaloids with a wide range of biological activities. Narcissus serotinus L. is a plant belonging to this family and its geographical distribution is mainly located along the Mediterranean coast. In the present work, specimens collected near Casablanca (Morocco were used to study the alkaloid content of this species. Starting with 350 g of the whole plant we used standard extraction and purification procedures to obtain fractions and compounds for GC-MS and NMR analysis. As well as five known alkaloids, we isolated two new compounds: 1-O-(3´-acetoxybutanoyllycorine and narseronine. The latter has been previously published, but with an erroneous structure.

  7. Aporphine alkaloids from Ocotea macrophylla (Lauraceae

    Directory of Open Access Journals (Sweden)

    Ludy Cristina Pabon

    2010-01-01

    Full Text Available Four aporphine alkaloids from the wood of Ocotea macrophylla (Lauraceae were isolated and characterized as (S-3-methoxy-nordomesticine (1, (S-N-ethoxycarbonyl-3-methoxy-nordomesticine (2, (S-N-formyl-3-methoxy-nordomesticine (3 and (S-N-methoxycarbonyl-3-methoxy-nordomesticine (4; alkaloids 2-4 are being report for the first time. The structure the isolated compounds were determined based on their spectral data and by comparison of their spectral data with values described in literature. The alkaloid fraction and compound 1 showed antifungal activity against Fusarium oxysporum f. sp. lycopersici and also compound 1 showed antimicrobial activity towards Staphylococcus aureus, Enterococcus faecalis as well.

  8. Aporphine alkaloids from Ocotea macrophylla (Lauraceae)

    Energy Technology Data Exchange (ETDEWEB)

    Pabon, Ludy Cristina; Cuca, Luis Enrique, E-mail: lcpabonb@unal.edu.c [Universidad Nacional de Bogota (Colombia). Facultad de Ciencias. Dept. de Quimica

    2010-07-01

    Four aporphine alkaloids from the wood of Ocotea macrophylla (Lauraceae) were isolated and characterized as (S)-3-methoxy-nordomesticine (1), (S)-N-ethoxycarbonyl-3-methoxy-nordomesticine (2), (S)-N-formyl-3-methoxy-nordomesticine (3) and (S)-N-methoxycarbonyl-3-methoxy-nordomesticine (4); alkaloids 2-4 are being report for the first time. The structure the isolated compounds were determined based on their spectral data and by comparison of their spectral data with values described in literature. The alkaloid fraction and compound 1 showed antifungal activity against Fusarium oxysporum f. sp. lycopersici and also compound 1 showed antimicrobial activity towards Staphylococcus aureus, Enterococcus faecalis as well. (author)

  9. An efficient synthesis of loline alkaloids

    Science.gov (United States)

    Cakmak, Mesut; Mayer, Peter; Trauner, Dirk

    2011-07-01

    Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharpless epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.

  10. Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationships.

    Science.gov (United States)

    Umsumarng, Sonthaya; Pitchakarn, Pornsiri; Yodkeeree, Supachai; Punfa, Wanisa; Mapoung, Sariya; Ramli, Rosdayati Alino; Pyne, Stephen G; Limtrakul, Pornngarm

    2017-10-15

    Multidrug resistance (MDR) is a major reason for the failure of chemotherapy in the treatment of cancer patients. P-gp over-expression in MDR cancer cells is a multifactorial phenomenon with biochemical resistance mechanisms. Stemofoline (STF), isolated from Stemona bukillii, has been reported to be an MDR reversing compound. This study investigated whether other Stemona alkaloids that had been purified from Stemonaceae plants exerted MDR modulation activity. MTT assay was performed to determine the MDR reversing property of the alkaloids. Modulation of P-gp function by these compounds was investigated using cell cycle analysis and P-gp fluorescent substrate accumulation assays. P-gp expression was determined by Western blot analysis. We preliminarily examined the safety of these compounds in normal human fibroblasts and human peripheral blood mononuclear cells (PBMCs) using the MTT assay, and in red blood cells (human and rat) through in vitro hemolysis assays. Three of the eight alkaloids tested, isostemofoline (ISTF), 11Z -didehydrostemofoline (11Z-DSTF) and 11E-didehydrostemofoline (11E-DSTF), enhanced the chemotherapeutic sensitivity of MDR leukemic K562/Adr cells, which overexpressed P-gp. The P-gp functional studies showed that these three alkaloids increased the accumulation of P-gp substrates, calcein-AM (C-AM) and rhodamine123 (Rho 123) in K562/Adr cells, while this effect was not seen in drug sensitive parental K562 cells. Whereas, the alkaloids did not alter P-gp expression as was determined by Western blotting analysis. The alkaloids reversed MDR via the inhibition of P-gp function. For pharmaceutical safety testing, the alkaloids were found to be not toxic to normal human fibroblasts and PBMCs. Moreover, the effective compounds did not induce hemolysis in either human or rat erythrocytes. These compounds may be introduced as potential candidate molecules for treating cancers exhibiting P-gp-mediated MDR. Copyright © 2017 Elsevier GmbH. All rights

  11. Antiprotozoal alkaloids from Psychotria prunifolia (Kunth) Steyerm

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Lucilia; Oliveira, Cecilia M.A. de; Faria, Emiret O.; Ribeiro, Laryssa C.; Carvalho, Brenda G., E-mail: lucilia@quimica.ufg.br [Instituto de Quimica, Universidade Federal de Goias, Campus II, Samambaia, Goiania, GO (Brazil); Silva, Cleuza C. da; Santin, Silvana M.O. [Departamento de Quimica, Universidade Estadual de Maringa, Maringa, PR (Brazil); Schuque, Ivania T.A.; Nakamura, Celso V.; Britta, Elisandra A.; Miranda, Nathielle [Departamento de Farmacia e Farmacologia, Universidade Estadual de Maringa, PR (Brazil); Iglesias, Amadeu H. [Waters Technologies do Brasil LTDA, Barueri, SP (Brazil); Delprete, Piero G. [VHerbier de Guyane, Institut de Recherche pour le Developpement (IRD), UMR AMAP, French Guiana (France)

    2012-07-01

    The continuity of the phyto chemical study of crude extracts of P. prunifolia's roots and branches led to the isolation of five indole-{beta}-carboline alkaloids. Among them, the 10-hydroxy-iso-deppeaninol and N-oxide-10-hydroxy-antirhine derivatives are described here for the first time. The structures were achieved through 1D and 2D NMR, IR and HRMS analyses. The branches and roots crude extracts and the alkaloids 14-oxoprunifoleine and strictosamide showed selective activity against L. amazonensis, with IC{sub 50} values of 16.0 and 40.7 {mu}g per mL, respectively. (author)

  12. Total Synthesis of the Zoanthamine Alkaloid

    Institute of Scientific and Technical Information of China (English)

    M. Miyashita

    2005-01-01

    @@ 1Introduction The zoanthamine alkaloids, a type of heptacyclic marine alkaloid isolated from colonial zoanthids of the genus Zoanthus sp., have attracted much attention from a wide area of science, because of their distinctive biological and pharmacological properties as well as their chemical structures with stereochemical complexity.Namely, norzoanthamine (1)[1] can suppress the loss of bone weight and strength in ovariectomized mice and has been considered a promising candidate for an antiosteoporotic drug[1], whereas zoanthamine (2)[2] has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects[2]. See Fig. 1.

  13. Chemotaxonomy and geographical distribution of tropane alkaloids.

    Science.gov (United States)

    Griffin, W J; Lin, G D

    2000-03-01

    This review illustrates the distribution of tropane alkaloids within the families Solanaceae, Erythroxylaceae, Proteaceae, Euphorbiaceae, Rhizophoraceae, Convolvulaceae and Cruciferae. Whereas tropane alkaloids are characteristic of the genera Datura, Brugmansia (tree datura) and Duboisia of the Solanaceae, the distribution is more widespread with novel tropane derivatives in families not traditionally associated with these bases. The chemical nature of more recently discovered water-soluble calystegines and the di- and trimeric forms from the Convolvulaceae (e.g. schizanthines from Schizanthus spp.), truxillines from Bolivian coca leaves and moonines of Erythroxylum moonii are highlighted. Where possible and appropriate, links between the phytochemistry and taxonomy are discussed.

  14. Honatisine, a novel diterpenoid alkaloid, and six known alkaloids from Delphinium honanense and their cytotoxic activity.

    Science.gov (United States)

    He, Yang Qing; Ma, Zhan Ying; Wei, Xiao Mei; Liu, Dong Jie; Du, Bao Zhong; Yao, Bing Hua; Gao, Li Ming

    2011-11-01

    A novel diterpene alkaloid named honatisine (1) has been isolated from the whole plants of Delphinium honanense, along with six known alkaloids, siwanine E (2), isoatisine (3), atisine (4), delcorinine (5), uraphine (6), and nordhagenine A (7). Their structures were deduced on the basis of their spectral data. All of them were evaluated by a SRB assay for their cytotoxicity, and compound 1 showed a significant cytotoxic activity (IC(50) =3.16 μM) against the MCF-7 cell line.

  15. Alkaloid diversity in Galanthus elwesii and Galanthus nivalis.

    Science.gov (United States)

    Berkov, Strahil; Bastida, Jaume; Sidjimova, Borjana; Viladomat, Francesc; Codina, Carles

    2011-01-01

    Seventy alkaloids of galanthamine, lycorine, homolycorine, tazettine, haemanthamine, narciclasine, and tyramine types were detected by GC/MS in 25 Galanthus elwesii and seven Galanthus nivalis populations, collected from different locations in Bulgaria. Intraspecies diversity in the alkaloid profiles regarding the main alkaloid types (chemotypes) was observed. Tyramine-type protoalkaloids (namely, hordenine and its derivatives) were dominant in 19 populations of G. elwesii. In other populations of G. elwesii, the plants accumulated mainly homolycorine-, lycorine-, and galanthamine-type alkaloids. The alkaloid profiles of G. nivalis were dominated by narciclasine-, galanthamine-, lycorine-, haemanthamine-, or tazettine-type compounds. Geographical distribution of chemotypes indicated a relationship between populations, since adjacent populations often displayed similar alkaloid profiles. The results from year-to-year sampling and transplantation experiments imply genetic determination of alkaloid synthesis in the two studied species of Galanthus.

  16. Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases.

    Science.gov (United States)

    Jiang, Qi-Wei; Chen, Mei-Wan; Cheng, Ke-Jun; Yu, Pei-Zhong; Wei, Xing; Shi, Zhi

    2016-01-01

    Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases.

  17. Alkaloid production by callous tissue cultures of Cereus peruvianus (Cactaceae).

    Science.gov (United States)

    de Oliveira, Arildo José Braz; Machado, Maria Fátima Pires da Silva

    2003-02-01

    The morphologically undifferentiated cells of nonregenerant callous tissue of Cereus peruvianus cultured in the original medium and in medium supplemented with tyrosine were used as an alkaloid source. Comparison of alkaloid production by C. peruvianus plants and by callous tissues indicated that alkaloid levels were almost twice as high in callous tissues as in shoots of C. peruvianus plants. The ratio of alkaloid concentration between mature plant and morphologically undifferentiated cells of callous tissue was 1:1.7. A relationship between culture medium containing tyrosine and alkaloid production was also observed in the callous tissues of C. peruvianus. Since increased alkaloid production may be induced by additional factors such as tyrosine, increasing levels of tyrosine or other conditions of the culture medium may be considered factors for inducing higher alkaloid production by C. peruvianus callous tissues.

  18. Carbazole alkaloids from Murraya koenigii trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells.

    Science.gov (United States)

    Utaipan, Tanyarath; Athipornchai, Anan; Suksamrarn, Apichart; Jirachotikoon, Canussanun; Yuan, Xiaohong; Lertcanawanichakul, Monthon; Chunglok, Warangkana

    2017-01-01

    Carbazole alkaloids, a major constituent of Murraya koenigii (L.) Sprengel (Rutaceae), exhibit biological effects such as anticancer activity via the induction of apoptosis, and they represent candidate chemotherapeutic agents. Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the oral cavity and a growing and serious health problem worldwide. In this study, we investigated the anticancer properties and mechanisms of action of two carbazole alkaloids derived from M. koenigii leaves, mahanine and isomahanine, in the OSCC cell line CLS-354. At 15 μM, mahanine and isomahanine were cytotoxic to CLS-354 cells, triggering apoptosis via caspase-dependent and -independent mechanisms. Autophagosomes, visualised using monodansylcadaverine (MDC) labelling, were numerous in carbazole alkaloid-treated cells. Mahanine and isomahanine markedly induced the expression of the autophagosome marker microtubule-associated protein 1 light chain 3, type II (LC3B-II). Genetic and chemical inhibition of autophagy via silencing of the Autophagy protein 5 gene and exposure to bafilomycin A1 (BafA1), respectively, did not arrest carbazole alkaloid-induced apoptosis, indicating that it occurs independently of autophagic activation. Surprisingly, both carbazole alkaloids caused increased accumulation of p62/sequestosome1 (p62/SQSTM1), with coordinated expression of LC3B-II and cleaved caspase-3, suggesting inhibition of autophagic flux. Our results suggest that inhibition of autophagic flux is associated with carbazole alkaloid-induced apoptosis. Our findings provide evidence of a novel cytotoxic action of natural carbazole alkaloids and support their use as candidate chemotherapeutic agents for the treatment of OSCC.

  19. Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors

    Directory of Open Access Journals (Sweden)

    Milan Fedurco

    2015-01-01

    Full Text Available The California poppy (Eschscholzia californica Cham. contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understanding of these biological effects at the molecular level is still lacking. Alkaloids detected in E. californica could be hypothesized to act at GABAA receptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinant α1β2γ2 GABAA receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S-reticuline behaved as positive allosteric modulator at the α3, α5, and α6 isoforms of GABAA receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S-reticuline at the α3β2γ2 and α5β2γ2 GABAA receptors. Interestingly, α1, α3, and α5 were not significantly affected by (R-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S-reticuline metabolites in the rodent brain.

  20. The Alkaloid Profiles of Lupinus sulphureus

    Science.gov (United States)

    Lupines are common plants found on the rangelands in the western United States. Lupines are known to contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British ...

  1. Two New Oxoaporphine Alkaloids from Thalictrum elegans

    Institute of Scientific and Technical Information of China (English)

    梁志远; 杨小生; 汪冶; 郝小江

    2005-01-01

    Two new oxoaporphine alkaloids, 1,2,3,10-tetramethoxy-9-(2-hydroxy-4,5-dimethoxybenzyloxy)oxoaporphine (1) and 1,2,3,10-tetramethoxy-9-(4,5-dimethoxy-2-formylphenoxy)oxoaporphine (2), were isolated from Thalictrum elegans. Their structures were elucidated based on spectroscopic analysis including 1D, 2D NMR, IR and MS.

  2. Alkaloids from Oriciopsis glaberrima Engl. (Rutaceae).

    Science.gov (United States)

    Wansi, Jean Duplex; Wandji, Jean; Kamdem Waffo, Alain François; Ngeufa, Happi Emmanuel; Ndom, Jean Claude; Fotso, Serge; Maskey, Rajendra Prasad; Njamen, Dieudonné; Fomum, Tanee Zacharias; Laatsch, Harmut

    2006-03-01

    Two alkaloid derivatives, oriciacridone A and B, were isolated from the stem bark of Oriciopsis glaberrima (Rutaceae). The structures were elucidated by a detailed spectroscopic analysis. The extract exhibited in vitro significant antimicrobial activity against a range of micro-organisms.

  3. Ergot alkaloids decrease rumen epithelial blood flow

    Science.gov (United States)

    Two experiments were conducted to determine if ergot alkaloids affect blood flow to the absorptive surface of the rumen of steers. Steers (n=8 total) were pair-fed alfalfa cubes at 1.5× NEM and received ground endophyte-infected tall fescue seed (E+) or endophyte-free tall fescue seed (E-) via rumen...

  4. Histrionicotoxin alkaloids finally detected in an ant

    DEFF Research Database (Denmark)

    Jones, Tappey H.; Adams, Rachelle Martha Marie; Spande, Thomas F.

    2012-01-01

    Workers of the ant Carebarella bicolor collected in Panama were found to have two major poison-frog alkaloids, cis- and trans-fused decahydroquinolines (DHQs) of the 269AB type, four minor 269AB isomers, two minor 269B isomers, and three isomers of DHQ 271D. For the first time in an ant, however......, the DHQs were accompanied by six histrionicotoxins (HTXs), viz., 283A, 285A, 285B, 285C, 287A, and 287D. This co-occurrence of the HTX and DHQ alkaloids is the usual pattern seen in dendrobatid frogs. This finding contrasts with our earlier study, where workers of a Brazilian ant, Solenopsis (Diplorhoptrum......) sp., were found to have a very similar DHQ complex but failed to show HTXs. Several new DHQ alkaloids of MW 271 (named in the frog as 271G) are reported from the above ants that have both m/z 202 and 204 as major fragment ions, unlike the spectrum seen for the poison-frog alkaloid 271D, which has...

  5. A New Quinolizidine Alkaloid from Boehmeria siamensis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new quinolizidine alkaloid, 3-(4-hydroxyphenyl)-4-(3-methoxy-4-hydroxyphenyl)-3, 4-dehydroquinolizidine (1), was isolated from the ethanol extract of the whole plants of Boehmeria siamensis Craib. Its structure was elucidated on the analysis of 1D NMR and 2D NMR spectrum.

  6. A New Alkaloid from Sinomenium acutum

    Institute of Scientific and Technical Information of China (English)

    Wei Ming CHENG; Feng QIU; Li Jun WU; Xin Sheng YAO

    2005-01-01

    Sinomenium acutum is widely used in East and South Asia for the treatment of many diseases, especially rheumatoid arthritis (RA). The chemical research on Sinomenium acutum led to the isolation of a new alkaloid compound (1). On the basis of chemical evidences and spectral analysis, 1 was identified as N-(1, 7-dimethoxylphenanthren-2-yl)acetamide.

  7. A New Alkaloid from Isatis costata

    OpenAIRE

    Fatima, Itrat; Anis, Itrat; Ahmad, Ijaz; Malik, Abdul; Afza, Nighat

    2014-01-01

    A new alkaloid has been isolated from Isatis costata C.A.Mey. and assigned structure 1 on the basis of spectroscopic data including 1D and 2D NMR techniques. Methyl 2-acetoamidobenzoate (2), b-sitosterol (3), and ursolic acid (4) were also isolated for the first time from this species.

  8. A Novel Alkaloid from Stapelia hirsuta

    OpenAIRE

    SHABANA, Marwan; GONAID, Mariam; SALAMA, Maha Mahmoud; ABDEL-SATTAR, Essam

    2006-01-01

    A novel alkaloid (1,8,8-trimethyl-5,8-dihydro-1H-pyrano[3,4-b]pyridine-4,6-dione) was isolated from the chloroformic traction obtained from the total alcoholic extract of the aerial parts of Stapelia hirsuta L. In addition, apigenin, luteolin and b-sitosterol-3-O-b-D- glucopyranoside were also isolated.

  9. 27 CFR 21.99 - Brucine alkaloid.

    Science.gov (United States)

    2010-04-01

    ... dissolved by hydrochloric acid when several drops of a 1 N barium chloride solution are added to 10 ml of a... OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.99 Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of...

  10. Alkaloids in the pharmaceutical industry: Structure, isolation and application

    Directory of Open Access Journals (Sweden)

    Nikolić Milan

    2003-01-01

    Full Text Available By the end of the 18th and the beginning of the 19th century a new era began in medicine, pharmaceutics and chemistry that was strongly connected with alkaloids and alkaloid drugs. Even before that it was known that certain drugs administered in limited doses were medicines, and toxic if taken in larger doses (opium, coke leaves, belladonna roots, monkshood tubers crocus or hemlock seeds. However, the identification, isolation and structural characterization of the active ingredients of the alkaloid drugs was only possible in the mid 20th century by the use of modern extraction equipment and instrumental methods (NMR, X-ray diffraction and others.In spite of continuing use over a long time, there is still great interest in investigating new drugs, potential raw materials for the pharmaceutical industry, as well as the more detailed investigation and definition of bio-active components and the indication of their activity range, and the partial synthesis of new alkaloid molecules based on natural alkaloids. The scope of these investigations, especially in the field of semi-synthesis is to make better use of the bio-active ingredients of alkaloid drugs, i.e. to improve the pharmacological effect (stronger and prolonged effect of the medicine, decreased toxicity and side effects, or to extend or change the applications. A combined classification of alkaloids was used, based on the chemical structure and origin, i.e. the source of their isolation to study alkaloid structure. For practical reasons, the following classification of alkaloids was used: ergot alkaloids, poppy alkaloids, tropanic alkaloids purine derivative alkaloids, carbon-cyclic alkaloids, and other alkaloids. The second part of this report presents a table of general procedures for alkaloid isolation from plant drugs (extraction by water non-miscible solvents, extraction by water-miscible solvents and extraction by diluted acid solutions. Also, methods for obtaining chelidonine and

  11. Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California Poppy) and Its Alkaloids.

    Science.gov (United States)

    Manda, Vamshi K; Ibrahim, Mohamed A; Dale, Olivia R; Kumarihamy, Mallika; Cutler, Stephen J; Khan, Ikhlas A; Walker, Larry A; Muhammad, Ilias; Khan, Shabana I

    2016-04-01

    Eschscholzia californica, a native US plant, is traditionally used as a sedative, analgesic, and anxiolytic herb. With the rapid rise in the use of herbal supplements together with over-the-counter and prescription drugs, the risk for potential herb-drug interactions is also increasing. Most of the clinically relevant pharmacokinetic drug interactions occur due to modulation of cytochrome P450 enzymes (CYPs), P-glycoprotein, and the pregnane X receptor by concomitantly used herbs. This study aimed to determine the effects of an EtOH extract, aqueous extract (tea), basic CHCl3 fractions, and isolated major alkaloids, namely protopine (1), escholtzine (2), allocryptopine (3), and californidine (4), of E. californica on the activity of cytochrome P450s, P-glycoprotein and the pregnane X receptor. The EtOH extract and fractions showed strong time-dependent inhibition of CYP 3A4, CYP 2C9, and CYP 2C19, and reversible inhibition of CYP 2D6. Among the alkaloids, escholtzine (2) and allocryptopine (3) exhibited time-dependent inhibition of CYP 3A4, CYP 2C9, and CYP 2C19 (IC50 shift ratio > 2), while protopine (1) and allocryptopine (3) showed reversible inhibition of CYP 2D6 enzyme. A significant activation of the pregnane X receptor (> 2-fold) was observed with the EtOH extract, basic CHCl3 fraction, and alkaloids (except protopine), which resulted into an increased expression of mRNA and the activity of CYP 3A4 and CYP 1A2. The expression of P-glycoprotein was unaffected. However, aqueous extract (tea) and its main alkaloid californidine (4) did not affect cytochrome P450s, P-glycoprotein, or the pregnane X receptor. This data suggests that EtOH extract of E. californica and its major alkaloids have a potential of causing interactions with drugs that are metabolized by cytochrome P450s, while the tea seems to be safer.

  12. Insecticidal Constituents and Activity of Alkaloids from Cynanchum mongolicum.

    Science.gov (United States)

    Ge, Yang; Liu, Pingping; Yang, Rui; Zhang, Liu; Chen, Hongxing; Camara, Ibrahima; Liu, Yiqing; Shi, Wangpeng

    2015-09-21

    Based on MS and NMR data and bioassay-guided tracing, three insecticidal alkaloids I, II and III from Cynanchum mongolicum were identified to be antofine N-oxide, antofine and tylophorine. Alkaloid I was more toxic than alkaloids II and III, but they were less active against Spodoptera litura than total alkaloids. The contact toxicity from these alkaloids against the aphid Lipaphis erysimi was significant, as the 24 h-LC50 values of alkaloids I, II, III and total alkaloids were 292.48, 367.21, 487.791 and 163.52 mg/L, respectively. The development disruption of S. litura larvae was tested, the pupation and emergence rates of S. litura decreased and the acute mortality of S. litura increased significantly by day 3 after being injected in their body cavity with 10-40 mg/L of total alkaloid. The ecdysone titer of treated S. litura larvae and prepupae declined with increasing alkaloid concentration. The alkaloids of Cynanchum mongolicum are potential insect growth inhibitors.

  13. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

    Science.gov (United States)

    Li, Yanran; Smolke, Christina D.

    2016-01-01

    Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4′-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery. PMID:27378283

  14. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast.

    Science.gov (United States)

    Li, Yanran; Smolke, Christina D

    2016-07-05

    Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4'-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery.

  15. Cytochrome P450 as dimerization catalyst in diketopiperazine alkaloid biosynthesis.

    Science.gov (United States)

    Saruwatari, Takayoshi; Yagishita, Fumitoshi; Mino, Takashi; Noguchi, Hiroshi; Hotta, Kinya; Watanabe, Kenji

    2014-03-21

    As dimeric natural products frequently exhibit useful biological activities, identifying and understanding their mechanisms of dimerization is of great interest. One such compound is (−)-ditryptophenaline, isolated from Aspergillus flavus, which inhibits substance P receptor for potential analgesic and anti-inflammatory activity. Through targeted gene knockout in A. flavus and heterologous yeast gene expression, we determined for the first time the gene cluster and pathway for the biosynthesis of a dimeric diketopiperazine alkaloid. We also determined that a single cytochrome P450, DtpC, is responsible not only for pyrroloindole ring formation but also for concurrent dimerization of N-methylphenylalanyltryptophanyl diketopiperazine monomers into a homodimeric product. Furthermore, DtpC exhibits relaxed substrate specificity, allowing the formation of two new dimeric compounds from a non-native monomeric precursor, brevianamide F. A radical-mediated mechanism of dimerization is proposed.

  16. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Jin-Jian Lu

    2012-01-01

    Full Text Available Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

  17. Chlorinated alkaloids in Menispermum dauricum DC: root culture.

    Science.gov (United States)

    Sugimoto, Y; Babiker, H A; Saisho, T; Furumoto, T; Inanaga, S; Kato, M

    2001-05-18

    Feeding experiments using (36)Cl showed that Menispermum dauricum root culture produces four alkaloids containing chlorine. They included the novel alkaloids dauricumine and dauricumidine as well as the known alkaloids acutumine and acutumidine. The structures of novel alkaloids were established by spectroscopic, crystallographic, and chemical methods. These four alkaloids were labeled with (36)Cl, isolated, and fed independently to root cultures. Mutual conversion between acutumine and acutumidine, and between dauricumine and dauricumidine by N-methylation and N-demethylation, was demonstrated. Moreover, dauricumine was converted to acutumine and acutumidine. Epimerization of acutumidine to dauricumidine or vice versa was not observed. These results suggest that dauricumine is the first chlorinated alkaloid formed in cultured M. dauricum roots. Skewed distribution of radioactivity derived from labeled dauricumine is proof that epimerization at C-1 proceeds at a lower rate than N-demethylation.

  18. Recent developments in the chemistry of quinazolinone alkaloids.

    Science.gov (United States)

    Kshirsagar, U A

    2015-09-28

    Quinazolinones, an important class of fused heterocyclic alkaloids has attracted high attention in organic and medicinal chemistry due to their significant and wide range of biological activities. There are approximately 150 naturally occurring quinazolinone alkaloids known till 2005. Several new quinazolinone alkaloids (∼55) have been isolated in the last decade. Natural quinazolinones with exotic structural features and remarkable biological activities have incited a lot of activities in the synthetic community towards the development of new synthetic strategies and approaches for the total synthesis of quinazolinone alkaloids. This review is focused on these advances in the chemistry of quinazolinone alkaloids in the last decade. This article covers the newly isolated quinazolinone natural products with their biological activities and the recently reported total syntheses of quinazolinone alkaloids from 2006 to 2015.

  19. Synthesis of the Marine Pyrroloiminoquinone Alkaloids, Discorhabdins

    Directory of Open Access Journals (Sweden)

    Yasufumi Wada

    2010-04-01

    Full Text Available Manynatural products with biologically interesting structures have been isolated from marine animals and plants such as sponges, corals, worms, etc. Some of them are discorhabdin alkaloids. The discorhabdin alkaloids (discorhabdin A-X, isolated from marine sponges, have a unique structure with azacarbocyclic spirocyclohexanone and pyrroloiminoquinone units. Due to their prominent potent antitumor activity, discorhabdins have attracted considerable attention. Many studies have been reported toward the synthesis of discorhabdins. We have accomplished the first total synthesis of discorhabdin A (1, having the strongest activity in vitro among discorhabdins in 2003. In 2009, we have also accomplished the first total synthesis of prianosin B (2, having the 16,17-dehydropyrroloiminoquinone moiety, by a novel dehydrogenation reaction with a catalytic amount of NaN3. These synthetic studies, as well as syntheses of the discorhabdins by various chemists to-date, are reviewed here.

  20. Total synthesis of the Daphniphyllum alkaloid daphenylline

    Science.gov (United States)

    Lu, Zhaoyong; Li, Yong; Deng, Jun; Li, Ang

    2013-08-01

    The Daphniphyllum alkaloids are a large class of natural products isolated from a genus of evergreen plants widely used in Chinese herbal medicine. They display a remarkable range of biological activities, including anticancer, antioxidant, and vasorelaxation properties as well as elevation of nerve growth factor. Daphenylline is a structurally unique member among the predominately aliphatic Daphniphyllum alkaloids, and contains a tetrasubstituted arene moiety mounted on a sterically compact hexacyclic scaffold. Herein, we describe the first total synthesis of daphenylline. A gold-catalysed 6-exo-dig cyclization reaction and a subsequent intramolecular Michael addition reaction, inspired by Dixon's seminal work, were exploited to construct the bridged 6,6,5-tricyclic motif of the natural product at an early stage, and the aromatic moiety was forged through a photoinduced olefin isomerization/6π-electrocyclization cascade followed by an oxidative aromatization process.

  1. Evaluation of Aconitum diterpenoid alkaloids as antiproliferative agents

    OpenAIRE

    Wada, Koji; Ohkoshi, Emika; Zhao, Yu; Goto, Masuo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2015-01-01

    Little information has been reported on the antitumor effects of the diterpenoid alkaloid constituents of Aconitum plants, used in the herbal drug “bushi”. This study was aimed at determining the antitumor activities of Aconitum C19-and C20-diterpenoid alkaloids and synthetic derivatives against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines. Newly synthesized C20-diterpenoid alkaloid derivatives showed substantial suppr...

  2. A new monoterpenoid oxindole alkaloid from Hamelia patens micropropagated plantlets.

    Science.gov (United States)

    Paniagua-Vega, David; Cerda-García-Rojas, Carlos M; Ponce-Noyola, Teresa; Ramos-Valdivia, Ana C

    2012-11-01

    Chemical studies on Hamelia patens (Rubiaceae) micropropagated plantlets allowed production of a new monoterpenoid oxindole alkaloid, named (-)-hameline (7), together with eight known alkaloids, tetrahydroalstonine (1), aricine (2), pteropodine (3), isopteropodine (4), uncarine F (5), speciophylline (6), palmirine (8), and rumberine (9). The structure of the new alkaloid was assigned on the basis of 1D and 2D NMR spectroscopy, mass spectrometry, and molecular modeling.

  3. Initial Studies on Alkaloids from Lombok Medicinal Plants

    Directory of Open Access Journals (Sweden)

    John B. Bremner

    2001-01-01

    Full Text Available Initial investigation of medicinal plants from Lombok has resulted in the collection of 100 plant species predicted to have antimicrobial, including antimalarial, properties according to local medicinal uses. These plants represent 49 families and 80 genera; 23% of the plants tested positively for alkaloids. Among the plants testing positive, five have been selected for further investigation involving structure elucidation and antimicrobial testing on the extracted alkaloids. Initial work on structural elucidation of some of the alkaloids is reported briefly.

  4. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    OpenAIRE

    Mihali, Troco K; Moffitt, Michelle C.; Neilan, Brett A.; Maria Wiese; D’Agostino, Paul M.

    2010-01-01

    Saxitoxin (STX) and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). PSTs are the causative agents of paralytic shellfish poisoning (PSP) and are mostly associated with marine dinoflagellates (eukaryotes) and freshwater cyanobacteria (prokaryotes), which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified...

  5. New indole alkaloids from Sarcocephalus latifolius.

    Science.gov (United States)

    Abreu, P; Pereira, A

    2001-01-01

    Phytochemical investigation of the root extract of Sarcocephalus latifolius has led to the isolation of the new indole alkaloids 21-O-methylstrictosamide aglycone and 21-O-ethylstrictosamide aglycone, together with strictosamide, angustine, nauclefine, angustidine, angustoline, 19-O-ethylangustoline, naucleidinal, 19-epi-naucleidinal, quinovic acid-3 beta-O-beta-D-fucopyranoside, quinovic acid-3 beta-O-alpha-L-rhamnopyranoside, scopoletin, and beta-sitosterol. Strictosamide displayed moderate antiplasmodial activity against Plasmodium falciparum.

  6. A new diketopiperazine alkaloid from Aspergillus oryzae.

    Science.gov (United States)

    Shaaban, Mohamed; El-Metwally, Mohammad Magdy; Nasr, Hamdi

    2014-01-01

    Investigation of bioactive secondary metabolites from terrestrial Aspergillus oryzae sp. MMAO1 using M2 medium afforded a new diketopiperazine alkaloid, 7,9-dihydroxy-3-(1H-indol-3-ylmethyl)-8-methoxy-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione (1a), containing the unusual amino acid L-6,8-dihydroxy-7-methoxyphenylalanine. This was co-isolated with ditryptophenaline (2), cyclo-(Tryp,Tyr) (4), cyclo-(Pro,Val), α-cyclopiazonic acid (3), kojic acid and uridine. Re-cultivation of the fungal strain on Dox medium led to the production of bisdethio(bismethylthio)gliotoxin (5), pseurotin A (6) along with linoleic acid, α-cyclopiazonic acid (3) and kojic acid. The chemical structure of the new diketopiperazine alkaloid including the relative configuration was determined by 1D and 2D NMR spectroscopy and HR-ESI-MS spectrometry, and by comparison with the related literature. The new alkaloid (1a) showed no antimicrobial activity or cytotoxicity against brine shrimps.

  7. Drug development against tuberculosis: Impact of alkaloids.

    Science.gov (United States)

    Mishra, Shardendu K; Tripathi, Garima; Kishore, Navneet; Singh, Rakesh K; Singh, Archana; Tiwari, Vinod K

    2017-09-08

    Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Plant alkaloids as drug leads for Alzheimer's disease.

    Science.gov (United States)

    Ng, Yu Pong; Or, Terry Cho Tsun; Ip, Nancy Y

    2015-10-01

    Alzheimer's disease (AD) is a neurodegenerative illness associated with dementia and is most prevalent among the elderly population. Current medications can only treat symptoms. Alkaloids are structurally diverse and have been an important source of therapeutics for various brain disorders. Two US Food and Drug Administration (FDA)-approved acetylcholinesterase inhibitors for AD, galantamine and rivastigmine, are in fact alkaloids. In addition, clinical trials of four other extensively studied alkaloids-huperzine A, caffeine, nicotine, and indomethacin-have been conducted but do not convincingly demonstrate their clinical efficacy for AD. Interestingly, rhynchophylline, a known neuroprotective alkaloid, was recently discovered by in silico screening as an inhibitor of EphA4, a novel target for AD. Here, we review the pathophysiological mechanisms underlying AD, current treatment strategies, and therapeutic potential of several selected plant alkaloids in AD, highlighting their various drug targets and the key supportive preclinical and clinical studies. Future research should include more rigorous clinical studies of the most promising alkaloids, the further development of recently discovered candidate alkaloids, and the continual search for new alkaloids for relevant drug targets. It remains promising that an alkaloid drug candidate could significantly affect the progression of AD in addition to providing symptomatic relief.

  9. New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids.

    Science.gov (United States)

    Plodek, Alois; Bracher, Franz

    2016-01-26

    Secondary metabolites from marine organisms are a rich source of novel leads for drug development. Among these natural products, polycyclic aromatic alkaloids of the pyridoacridine type have attracted the highest attention as lead compounds for the development of novel anti-cancer and anti-infective drugs. Numerous sophisticated total syntheses of pyridoacridine alkaloids have been worked out, and many of them have also been extended to the synthesis of libraries of analogues of the alkaloids. This review summarizes the progress in the chemistry of pyridoacridine alkaloids that was made in the last one-and-a-half decades.

  10. Binding Parameters of Alkaloids Berberine and Sanguinarine with DNA

    CERN Document Server

    Gumenyuk, V G; Kutovyy, S Yu; Yashchuk, V M; Zaika, L A

    2012-01-01

    We study the interaction of berberine and sanguinarine (plant alkaloids) with DNA in aqueous solutions, by using optical spectroscopy methods (absorption and fluorescence). The dependencies of alkaloid spectral characteristics on the concentration ratio N/c between the DNA base pairs and alkaloid molecules in the solutions are considered, and the manifestations of the alkaloid-DNA binding are revealed. The character of binding is found to depend on N/c. The parameters of the binding of berberine and sanguinarine with DNA are determined, by using the modified Scatchard and McGhee-von Hippel equations

  11. Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids

    Directory of Open Access Journals (Sweden)

    Shinji Kishimoto

    2016-08-01

    Full Text Available Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants and at a trace level of production. In this review, we focus on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes. The alkaloids discussed in this review are ditryptophenaline (dimeric diketopiperazine alkaloid, saframycin (tetrahydroisoquinoline alkaloid, strictosidine (monoterpene indole alkaloid, ergotamine (ergot alkaloid and opiates (benzylisoquinoline and morphinan alkaloid. This review also discusses the engineered biosynthesis of these compounds, primarily through heterologous reconstitution of target biosynthetic pathways in suitable hosts, such as Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. Those heterologous biosynthetic systems can be used to confirm the functions of the isolated genes, economically scale up the production of the alkaloids for commercial distributions and engineer the biosynthetic pathways to produce valuable analogs of the alkaloids. In particular, extensive involvement of oxidation reactions catalyzed by oxidoreductases, such as cytochrome P450s, during the secondary metabolite biosynthesis is discussed in details.

  12. Dietary alkaloid sequestration in a poison frog: an experimental test of alkaloid uptake in Melanophryniscus stelzneri (Bufonidae).

    Science.gov (United States)

    Hantak, Maggie M; Grant, Taran; Reinsch, Sherri; McGinnity, Dale; Loring, Marjorie; Toyooka, Naoki; Saporito, Ralph A

    2013-12-01

    Several lineages of brightly colored anurans independently evolved the ability to secrete alkaloid-containing defensive chemicals from granular glands in the skin. These species, collectively referred to as 'poison frogs,' form a polyphyletic assemblage that includes some species of Dendrobatidae, Mantellidae, Myobatrachidae, Bufonidae, and Eleutherodactylidae. The ability to sequester alkaloids from dietary arthropods has been demonstrated experimentally in most poison frog lineages but not in bufonid or eleutherodactylid poison frogs. As with other poison frogs, species of the genus Melanophryniscus (Bufonidae) consume large numbers of mites and ants, suggesting they might also sequester defensive alkaloids from dietary sources. To test this hypothesis, fruit flies dusted with alkaloid/nutritional supplement powder were fed to individual Melanophryniscus stelzneri in two experiments. In the first experiment, the alkaloids 5,8-disubstituted indolizidine 235B' and decahydroquinoline were administered to three individuals for 104 days. In the second experiment, the alkaloids 3,5-disubstituted indolizidine 239Q and decahydroquinoline were given to three frogs for 153 days. Control frogs were fed fruit flies dusted only with nutritional supplement. Gas chromatography/mass spectrometry analyses revealed that skin secretions of all experimental frogs contained alkaloids, whereas those of all control frogs lacked alkaloids. Uptake of decahydroquinoline was greater than uptake of 5,8-disubstituted indolizidine, and uptake of 3,5-disubstituted indolizidine was greater than uptake of decahydroquinoline, suggesting greater uptake efficiency of certain alkaloids. Frogs in the second experiment accumulated a greater amount of alkaloid, which corresponds to the longer duration and greater number of alkaloid-dusted fruit flies that were consumed. These findings provide the first experimental evidence that bufonid poison frogs sequester alkaloid-based defenses from dietary

  13. Monoterpene Indole Alkaloids from the Fruit of Tabernaemontana litoralis and Differential Alkaloid Composition in Various Fruit Components.

    Science.gov (United States)

    Qu, Yang; Simonescu, Razvan; De Luca, Vincenzo

    2016-12-23

    Two new monoterpene indole alkaloids, isoakuammiline (1) and 18-hydroxypseudovincadifformine (2), and five known alkaloids, coronaridine (3), heyneanine (4), 3,19-oxidocoronaridine (5), tabersonine, and strictosidine, were identified from the fruit of Tabernaemontana litoralis. The structures of the alkaloids were determined using NMR and MS data analyses. While 18-hydroxypseudovincadifformine (2) showed a new hydroxylation pattern, isoakuammiline (1) revealed a novel skeleton for monoterpene indole alkaloids. In spite of the isolation of stemmadenine from the fruit tissues in other Tabernaemontana species, this vital biosynthetic precursor of iboga, aspidosperma, and pseudoaspidosperma skeletons was not found in T. litoralis.

  14. Alkaloids modulate motility, biofilm formation and antibiotic susceptibility of uropathogenic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Devendra H Dusane

    Full Text Available Alkaloid-containing natural compounds have shown promise in the treatment of microbial infections. However, practical application of many of these compounds is pending a mechanistic understanding of their mode of action. We investigated the effect of two alkaloids, piperine (found in black pepper and reserpine (found in Indian snakeroot, on the ability of the uropathogenic bacterium Escherichia coli CFT073 to colonize abiotic surfaces. Sub-inhibitory concentrations of both compounds (0.5 to 10 µg/mL decreased bacterial swarming and swimming motilities and increased biofilm formation. qRT-PCR revealed a decrease in the expression of the flagellar gene (fliC and motility genes (motA and motB along with an increased expression of adhesin genes (fimA, papA, uvrY. Interestingly, piperine increased penetration of the antibiotics ciprofloxacin and azithromycin into E. coli CFT073 biofilms and consequently enhanced the ability of these antibiotics to disperse pre-established biofilms. The findings suggest that these alkaloids can potentially affect bacterial colonization by hampering bacterial motility and may aid in the treatment of infection by increasing antibiotic penetration in biofilms.

  15. A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine.

    Science.gov (United States)

    Winzer, Thilo; Gazda, Valeria; He, Zhesi; Kaminski, Filip; Kern, Marcelo; Larson, Tony R; Li, Yi; Meade, Fergus; Teodor, Roxana; Vaistij, Fabián E; Walker, Carol; Bowser, Tim A; Graham, Ian A

    2012-06-29

    Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in the commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F(2) mapping population indicated that these genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed that they exist as a complex gene cluster for plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway intermediates, allowing gene function to be linked to noscapine synthesis and a novel biosynthetic pathway to be proposed.

  16. Galanthindole: a new indole alkaloid from Galanthus plicatus ssp. byzantinus.

    Science.gov (United States)

    Unver, Nehir; Kaya, G Irem; Werner, Christa; Verpoorte, Robert; Gözler, Belkis

    2003-09-01

    A new indole alkaloid, galanthindole, was isolated from Galanthus plicatus ssp. byzantinus (Amaryllidaceae), a plant native to northwestern Turkey. Incorporating a non-fused indole ring, galanthindole may represent the prototype of a new subgroup of the Amaryllidaceae alkaloids. Two other bases, (+)-11-hydroxyvittatine and hordenine, are also reported from the same plant.

  17. Gindarudine, a novel morphine alkaloid from Stephania glabra

    Institute of Scientific and Technical Information of China (English)

    Deepak Kumar Semwal; Usha Rawat

    2009-01-01

    A novel morphine alkaloid, named gindarudine 1 has been isolated from ethanol extract of Stephania glabra tubers, together with four known alkaloids, palmatine, dehydrocorydalmine, stepharanine, and 8-(4'-methoxybenzyl)-xylopinine. Compound 1 was elucidated as 3,6-O,N-detrimethyl-10-hydroxy-1-methoxy-thebaine by means of spectroscopic data including 2D NMR studies.

  18. [A new alkaloid of Menispermum dauricum DC--dauriciline].

    Science.gov (United States)

    Pang, X P; Chen, Y W; Li, X J; Long, J G

    1991-01-01

    A new phenolic dauricine-type alkaloid, named "dauriciline", was isolated from the rhizome of Menispermum dauricum DC. It is a pale yellow powder. Based on spectrometric analysis (UV.FAB-MS and 1HNMR) and chemical reaction the structure of the new alkaloid was elucidated as RR,7,7'-demethyldauricine (VI).

  19. Binding of quinolizidine alkaloids to nicotinic and muscarinic acetylcholine receptors.

    Science.gov (United States)

    Schmeller, T; Sauerwein, M; Sporer, F; Wink, M; Müller, W E

    1994-09-01

    Fourteen quinolizidine alkaloids, isolated from Lupinus albus, L. mutabilis, and Anagyris foetida, were analyzed for their affinity for nicotinic and/or muscarinic acetylcholine receptors. Of the compounds tested, the alpha-pyridones, N-methylcytisine and cytisine, showed the highest affinities at the nicotinic receptor, while several quinolizidine alkaloid types were especially active at the muscarinic receptor.

  20. Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids.

    Science.gov (United States)

    Cedrón, Juan C; Ravelo, Ángel G; León, Leticia G; Padrón, José M; Estévez-Braun, Ana

    2015-07-30

    The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined.

  1. Studies of interaction between two alkaloids and double helix DNA

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yantao [Key Laboratory of Preparation and Applications of Environmentally Friendly Materials (Jilin Normal University), Ministry of Education China, Siping 136000 (China); College of Chemistry, Jilin Normal University, Siping 136000 (China); Peng, Tingting [College of Chemistry, Jilin Normal University, Siping 136000 (China); College of Chemistry, Baicheng Normal University, Baicheng, 130032 (China); Zhao, Lei [Siping Institute for Food and Drug Control, Siping 136000 (China); Jiang, Dayu [Key Laboratory of Preparation and Applications of Environmentally Friendly Materials (Jilin Normal University), Ministry of Education China, Siping 136000 (China); College of Chemistry, Jilin Normal University, Siping 136000 (China); Cui, Yuncheng, E-mail: 1979yanzi@163.com [Key Laboratory of Preparation and Applications of Environmentally Friendly Materials (Jilin Normal University), Ministry of Education China, Siping 136000 (China); College of Chemistry, Jilin Normal University, Siping 136000 (China)

    2014-12-15

    This article presents the study on the interaction of two alkaloids (matrine and evodiamine) and hs-DNA by absorption, fluorescence, circular dichroism (CD), DNA melting and viscosity experiments. The spectroscopic studies suggested that two alkaloids can bind to DNA through an intercalative mode. The viscosity measurement and thermal denaturation also indicated that two alkaloids can intercalate to DNA. The binding constants (K{sub A}) and the number of binding sites (n) were determined. At the same time, some significant thermodynamic parameters of the binding of the alkaloids to DNA were obtained. Competitive binding studies revealed that alkaloids had an effect on ethidium bromide (EB) bound DNA. In addition, it was also proved that the fluorescence quenching was influenced by ionic strength. - Highlights: • Interaction between two alkaloids and DNA is studied by spectral methods. • The binding constant and the binding sites between two alkaloids and DNA are obtained. • There are a classical intercalative mode between alkaloids and DNA. • The binding of matrine with DNA is weaker than that of evodiamine. • It is important for us to understand the alkaloids–DNA interactions at a molecular level.

  2. ALKALOIDS OF SOME EUROPEAN AND MACARONESIAN SEDOIDEAE AND SEMPERVIVOIDEAE (CRASSULACEAE)

    NARCIS (Netherlands)

    STEVENS, JF; THART, H; HENDRIKS, H; MALINGRE, TM

    1992-01-01

    Some 22 pyrrolidine and piperdine alkaloids were detected in the leafy parts of Sedum acre, S. aetnense, S. anglicum, S. brissemoreti, S. farinosum, S. fusiforme, S. lancerottense, S. melanantherum, and S. nudum. In addition to the alkaloids known from S. acre, 1-(2-pyrrolidyl)-propan-2-one and 2-mo

  3. Two New Norditerpenoid Alkaloids from Aconitum spicatum Stapf

    Institute of Scientific and Technical Information of China (English)

    Li Ming GAO; Xiao Mei WEI; Li YANG

    2005-01-01

    Two new norditerpenoid alkaloids, spicatine A (1) and spicatine B (2) were isolated from the root of Aconitum spicatum. The new compounds were deduced on the basis of their spectral data (IR, HREIMS, EIMS, 1D, 2D-NMR). This is the first whole report on the isolation of diterpenoid alkaloids from the A. spicatum Stapf.

  4. Evolution of alkaloid biosynthesis in the genus Narcissus.

    Science.gov (United States)

    Berkov, Strahil; Martínez-Francés, Vanessa; Bastida, Jaume; Codina, Carles; Ríos, Segundo

    2014-03-01

    In an attempt to reveal the relationships between alkaloid biosynthesis and phylogeny, we investigated by GC-MS the alkaloid patterns of 22 species and 3 hybrids (from 45 locations) from seven main sections of the genus Narcissus (Amaryllidaceae). The results indicate that the first alkaloids to evolve in the genus Narcissus were of the lycorine- and homolycorine-type. The alkaloid pattern of the Nevadensis section supports its recent separation from the Pseudonarcissus section. The plants of Narcissus pallidulus (Ganymedes section) show a predominance of Sceletium-type compounds, which are quite rare in the Amaryllidaceae family. Two successful evolutionary strategies involving alkaloid biosynthesis and leading to an expansion in taxa and occupied area were determined. Firstly, a diversification of alkaloid patterns and a high alkaloid concentration in the organs of the large Narcissus species (in the Pseudonarcissus section) resulted in an improved chemical defence in diverse habitats. Secondly, both plant size and alkaloid biosynthesis were reduced (in the Bulbocodium and Apodanthi sections) relegated to dry pastures and rocky places.

  5. Leptopyrine, new alkaloid from Leptopyrum fumarioides L. (Ranunculaceae).

    Science.gov (United States)

    Doncheva, Tsvetelina; Solongo, Amgalan; Kostova, Nadezhda; Gerelt-Od, Yadamsuren; Selenge, Dangaa; Philipov, Stefan

    2015-01-01

    A new type of isoquinoline alkaloid leptopyrine was isolated from the aerial parts of Leptopyrum fumarioides L. (Ranunculaceae) of Mongolian origin. The known alkaloids protopine and thalifoline were isolated for the first time from this the species. All structures were established by physical and spectral analyses.

  6. Alkaloids and Coumarins from the Leaves of Amyris diatripa.

    Science.gov (United States)

    Laguna, A

    1984-02-01

    The alkaloids edulinine and (+/-) isoplatydesmine were isolated from the leaves of Amyris diatripa, being the first report of the presence of alkaloids in species of this genus. The presence of coumarins in the plant was also shown by isolation of psoralen, bergapten, marmesin, ulopterol and suberenol.

  7. Alkaloids from the root barks of Goniothalamus cheliensis

    Institute of Scientific and Technical Information of China (English)

    Miao Miao Jiang; Xue Zhang; Yi Dai; Hao Gao; Hong Wei Liu; Nai Li Wang; Wen Cai Ye; Xin Sheng Yao

    2008-01-01

    (3S)-2-Oxo-5,12-dimethoxy-3-hydroxy-3-methylbenz[f]indoline (1), a new benzoxindole alkaloid, along with two known alkaloids, was isolated from the root barks of Goniothalamus cheliensis Hu. The structure was elucidated by spectroscopic evidences, and the absolute configuration was determined by CD spectrum.

  8. A new indole alkaloid isolated from Tabernaemontana hystrix steud (Apocynaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Monnerat, Cecilia Silva; Souza, Jucimar Jorgeane de; Mathias, Leda; Braz-Filho, Raimundo; Vieira, Ivo Jose C. [Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacases, RJ (Brazil). Setor de Quimica de Produtos Naturais]. E-mail: curcino@uenf.br

    2005-11-15

    A new alkaloid, named hystrixnine (1), and five known indole alkaloids, ibogamine (2), olivacine (3), affinine (4), affinisine (5) and Nb-methylaffinisine (6), were isolated from the root bark of Tabernaemontana hystrix. The known triterpenes a-amyrin acetate, b-amyrin acetate and lupeol acetate were also identified. The structures of the compounds were elucidated based on spectopic studies. (author)

  9. An Acetylenic Alkaloid from the Calcareous Sponge Leucetta sp.

    Directory of Open Access Journals (Sweden)

    Nicole J. de Voogd

    2011-03-01

    Full Text Available A new acetylenic alkaloid was isolated from the sponge Leucetta sp. The structure was established by analyzing spectroscopic data. The alkaloid showed cytotoxicity IC50 2.5 mg/mL against NBT-T2 cells.

  10. [Alkaloids of Vinca rosea L. introduced to Western Georgia].

    Science.gov (United States)

    Vachnadze, N S; Kintsurashvili, L G; Suladze, T Sh; Bakuridze, A D; Vachnadze, V Iu

    2013-11-01

    Vinca roseae L. (Саtharanthus rosea (L.) G. Don) was introduced at Kobuleti experimental station of medical plants. The object of investigation was the plant material of Vinca roseae L. collected in May, 2005., September, 2006 and October, 2009. Total alkaloids were obtained in accordance with Atta- ur-Rachman method. The variability of the quantitative and qualitative composition of total alkaloids and vincaleikoblastin (VLB) fraction during vegetation was studied. It was established that the maximal content of total alkaloids and VLB fraction of Vinca roseae L. is accumulated in the phase of secondary flowering, hence the collecting of a plant material is recommended to be made during the aforesaid vegetation phase as for this period it is a rather high output of a raw material, alkaloid complex and VLB faction. Alkaloids vinkaleikoblastin, ajmalicine and new epimer tetrahydroalstonine with С3Н-α- orientation were yielded, separated and identified using modern physical-chemical and spectral methods (13С NMR).

  11. hERG Blockade by Iboga Alkaloids.

    Science.gov (United States)

    Alper, Kenneth; Bai, Rong; Liu, Nian; Fowler, Steven J; Huang, Xi-Ping; Priori, Silvia G; Ruan, Yanfei

    2016-01-01

    The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC50 values: ibogaine manufactured by semisynthesis via voacangine (4.09 ± 0.69 µM) or by extraction from T. iboga (3.53 ± 0.16 µM); ibogaine's principal metabolite noribogaine (2.86 ± 0.68 µM); and voacangine (2.25 ± 0.34 µM). In contrast, the IC50 of 18-methoxycoronaridine, a product of rational synthesis and current focus of drug development was >50 µM. hERG blockade was voltage dependent for all of the compounds, consistent with low-affinity blockade. hERG channel binding affinities (K i) for the entire set of compounds, including 18-MC, ranged from 0.71 to 3.89 µM, suggesting that 18-MC binds to the hERG channel with affinity similar to the other compounds, but the interaction produces substantially less hERG blockade. In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion. The apparent structure-activity relationships regarding positions of substitutions on the ibogamine skeleton suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel.

  12. [Non-alkaloid constituents of Gelsemium elegans].

    Science.gov (United States)

    Zhang, Binfeng; Chou, Guixin; Wang, Zhengtao

    2009-09-01

    To study the non-alkaloid chemical constituents of Gelsemium elegans. Compounds were isolated and purified by repeated column chromatography, and their structures were elucidated by spectroscopic methods. Ten compounds were isolated and their structures were identified as tamarixin (1), tamarixetin 3-O-beta-D-galactopyranoside (2), scopolin (3), scopoletin (4), uradine (5), caffeic acid (6), caffeic acid ethyl ester (7), ferulic acid ethyl ester (8), ethyl-alpha-D-fructofuranoside (9), and ethyl-beta-D-fructopyranoside (10). Compounds 1-3,5-10 are firstly isolated from this plant and compounds 1, 2, and 5-10 are isolated from the genus Gelsemium for the first time.

  13. New ester alkaloids from lupins (genus lupinus).

    Science.gov (United States)

    Mühlbauer, P; Witte, L; Wink, M

    1988-06-01

    Esters of 13-hydroxylupanine and 4-hydroxylupanine with acetic, propionic, butyric, isobutyric, valeric, isovaleric, tiglic, benzoic, and TRANS-cinnamic acid have been synthesized and characterized by capillary gas-liquid chromatography and mass spectrometry (EI-MS, CI-MS). In LUPINUS POLYPHYLLUS, L. ALBUS, L. ANGUSTIFOLIUS, and L. MUTABILIS we could identify new ester alkaloids (e.g. 13-propyloxylupanine, 13-butyryloxylupanine, 13-isobutyryloxylupanine, and 4-tigloyloxylupanine) besides the known esters, i.e. 13-acetoxylupanine, 13-isovaleroyloxylupanine, 13-angeloyloxylupanine, 13-tigloyloxylupanine, 13-benzoyloxylupanine, 13- CIS-cinnamoyloxylupanine nine, and 13- TRANS-cinnamoyloxylupanine.

  14. A new pyrroloquinazoline alkaloid from Linaria vulgaris.

    Science.gov (United States)

    Hua, Huiming; Cheng, Maosheng; Li, Xian; Pei, Yuehu

    2002-10-01

    A new alkaloid, 1,2,3,9-tetrahydropyrrolo(2,1-b)quinazolin-1-carboxylic acid (1), together with eight known compounds, 7-hydroxy vasicine (2), benzyl alcohol beta-D-(2'-O-beta-xylopyranosyl)glucopyranoside (3), benzyl alcohol O-beta-D-glucopyranoside (4), benzyl alcohol O-beta-D-primveroside (5), 3,5-dimethyl-4-hydroxy benzaldehyde (6), gluco-syringic acid (7), syringin (8), and liriodendrin (9), were isolated from the plants of Linaria vulgaris. Their structures were established by spectroscopic methods.

  15. Chromone and Flavonoid Alkaloids: Occurrence and Bioactivity

    Directory of Open Access Journals (Sweden)

    Robin J. Marles

    2011-12-01

    Full Text Available The chromone and flavonoid alkaloids represent an unusual group of structurally diverse secondary metabolites, derived from the convergence of multiple biosynthetic pathways that are widely distributed through the plant and animal kingdoms. Many of them have been discovered through bioassay-guided chemical investigations of traditional medicines, suggesting potential therapeutic significance. Their unique structures and varied pharmacological activities may provide important new leads for the discovery of drugs with novel mechanisms of action. Potential therapeutic indications are as diverse as cancer and viral infections, inflammation and immunomodulation, neurological and psychiatric conditions, and diabetes.

  16. Alkaloids from Piper sarmentosum and Piper nigrum.

    Science.gov (United States)

    Ee, G C L; Lim, C M; Lim, C K; Rahmani, M; Shaari, K; Bong, C F J

    2009-01-01

    Detailed chemical studies on the roots of Piper sarmentosum and Piper nigrum have resulted in several alkaloids. The roots of P. sarmentosum gave a new aromatic compound, 1-nitrosoimino-2,4,5-trimethoxybenzene (1). Piper nigrum roots gave pellitorine (2), (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (3), 2,4-tetradecadienoic acid isobutyl amide (4), piperine (5), sylvamide (6), cepharadione A (7), piperolactam D (8) and paprazine (9). Structural elucidation of these compounds was achieved through NMR and MS techniques. Cytotoxic activity screening of the plant extracts indicated some activity.

  17. 分散固相萃取-高效液相色谱-串联质谱法测定蜂蜜中生物碱%Determination of Alkaloids in Honey by Dispersive Solid Phase Extraction and High Performance Liquid Chromatography-Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    郭伟华; 周金慧; 黄京平; 王鹏; 李熠

    2014-01-01

    建立了分散固相萃取-高效液相色谱-串联质谱法( QuEChERS-HPLC-MS/MS)同时测定蜂蜜中吡咯里西啶生物碱(倒千里光、千里光菲林、千里光宁、克氏千里光宁)和异喹啉类生物碱(小檗碱、荷叶碱)的方法。蜂蜜样品经乙腈提取,乙二胺-N-丙基硅烷( PSA)吸附剂净化,HPLC-MS/MS测定。采用Agilent Poroshell 120 SB-C18色谱柱(100 mm ×2.1 mm,2.7μm)分离。以0.1%甲酸溶液和乙腈为流动相进行梯度洗脱,电喷雾正离子(ESI+)模式电离,多反应监测模式(MRM)下进行测定,外标法定量。结果表明,在0.1~100μg/L范围内,6种生物碱的相关系数均大于0.99;在1~100μg/kg的添加水平下,所有生物碱回收率均在70%~110%之间;6种生物碱日内精密度小于15%,日间精密度小于20%;方法检出限和定量限分别为0.3和1.0μg/kg。本方法可用于蜂蜜中吡咯里西啶生物碱和异喹啉类生物碱的同时定性和定量分析。%A method was developed for simultaneous determination of pyrrolizidine alkaloids and isoquinoline alkaloids in honey by dispersive solid phase extraction and high performance liquid chromatography-tandem mass spectrometry ( QuEChERS-HPLC-MS/MS) . The honey samples were extracted with acetonitrile solution and cleaned up with PSA absorbent. Agilent Poroshell 120 SB-C18 chromatographic column was used to separate alkaloids with high sensitivity and satisfactory resolution. The identification and quantification were achieved by using electrospray ionization in positive ion mode ( ESI+) with multiple reaction monitoring (MRM). Matrix-matched calibration curves with good correlation coefficients (R2>0. 99) were obtained in the concentration range of 0. 1-100 μg/L. The recoveries of the spiked samples at 1-100 μg/kg were in the range of 70% to 110% with the RSD of intra-day and inter-day lower than 15% and 20%, respectively. The limits of detection ( LOD) and limits of quantification ( LOQ) for all alkaloids were 0

  18. 特异茶树资源生物碱测定及相关基因表达分析%Determination of Alkaloid and Analysis of Gene Expression in Peculiar Tea Plant

    Institute of Scientific and Technical Information of China (English)

    夏丽飞; 陈林波; 梁名志; 邓威威; 田易萍; 刘本英; 刘军

    2013-01-01

    The component of caffeine and theobromine of five tea plants was determined by high performance liquid chromatography.The results showed that the theobromine content was low,but caffeine content was high in the same tea plant.The theobromine was accumulated in the tea resource of low caffeine content.The expression level of sAMS and TIDH were nearly affected by the change of caffeine content,according to the differences of expression level of S-adenosylmethionine Synthetase gene(sAMS),Inosine 5'-monophosphate Dehydroge-nase (TIDH) and Caffeine Synthase gene (TCSI) analyzed by RT-PCR in different tea species and the date of caffeine content.TCSI could be expressed whatever in the high caffeine content material or in the low one,but its expression level was higher in the high caffeine content material.The reason could be that the Caffeine Synthase of vitality was low in the low caffeine content tea plant,or other regulation mechanisms could lead to the blockage of biosynthesis of caffeine and the accumulation of theobromine.%利用高效液相色谱对5份茶树资源中的咖啡碱、可可碱组分进行测定,发现咖啡碱含量高的茶树资源可可碱含量低,而咖啡碱含量低茶树资源的可可碱被积累.利用RT-PCR分析了S-腺苷甲硫氨酸合成酶基因(sAMS)、次黄嘌呤苷-5-单酸脱氢酶基因(TIDH)、咖啡碱合成酶基因(TCSI)在咖啡碱含量不同的茶树品种间的表达水平差异,并结合咖啡碱含量数据发现,sAMS和TIDH的表达水平对咖啡碱含量变化影响不明显.TCSI在高咖啡碱和低咖啡碱材料中均有表达,且TCSI在高咖啡碱材料中的表达比在低咖啡碱材料中高.推测可能是低咖啡碱茶树资源中咖啡碱合成酶活性低或者存在其他的调控机制,导致咖啡碱的生物合成受阻,使得可可碱被积累.

  19. Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells.

    Science.gov (United States)

    Nakamura, Seikou; Nakashima, Souichi; Tanabe, Genzo; Oda, Yoshimi; Yokota, Nami; Fujimoto, Katsuyoshi; Matsumoto, Takahiro; Sakuma, Rika; Ohta, Tomoe; Ogawa, Keiko; Nishida, Shino; Miki, Hisako; Matsuda, Hisashi; Muraoka, Osamu; Yoshikawa, Masayuki

    2013-02-01

    Methanolic extracts from the flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) were found to show inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extracts, a new alkaloid, N-methylasimilobine N-oxide, was isolated together with eleven benzylisoquinoline alkaloids. The absolute stereostructure of the new alkaloid was determined from chemical and physicochemical evidence. Among the constituents isolated, nuciferine, N-methylasimilobine, (-)-lirinidine, and 2-hydroxy-1-methoxy-6a,7-dehydroaporphine showed potent inhibition of melanogenesis. Comparison of the inhibitory activities of synthetic related alkaloids facilitated characterization of the structure-activity relationships of aporphine- and benzylisoquinoline-type alkaloids. In addition, 3-30 μM nuciferine and N-methylasimilobine inhibited the expression of tyrosinase mRNA, 3-30 μM N-methylasimilobine inhibited the expression of TRP-1 mRNA, and 10-30 μM nuciferine inhibited the expression of TRP-2 mRNA.

  20. Effect of Iboga alkaloids on µ-opioid receptor-coupled G protein activation.

    Directory of Open Access Journals (Sweden)

    Tamara Antonio

    Full Text Available OBJECTIVE: The iboga alkaloids are a class of small molecules defined structurally on the basis of a common ibogamine skeleton, some of which modify opioid withdrawal and drug self-administration in humans and preclinical models. These compounds may represent an innovative approach to neurobiological investigation and development of addiction pharmacotherapy. In particular, the use of the prototypic iboga alkaloid ibogaine for opioid detoxification in humans raises the question of whether its effect is mediated by an opioid agonist action, or if it represents alternative and possibly novel mechanism of action. The aim of this study was to independently replicate and extend evidence regarding the activation of μ-opioid receptor (MOR-related G proteins by iboga alkaloids. METHODS: Ibogaine, its major metabolite noribogaine, and 18-methoxycoronaridine (18-MC, a synthetic congener, were evaluated by agonist-stimulated guanosine-5´-O-(γ-thio-triphosphate ([(35S]GTPγS binding in cells overexpressing the recombinant MOR, in rat thalamic membranes, and autoradiography in rat brain slices. RESULTS AND SIGNIFICANCE: In rat thalamic membranes ibogaine, noribogaine and 18-MC were MOR antagonists with functional Ke values ranging from 3 uM (ibogaine to 13 uM (noribogaine and 18MC. Noribogaine and 18-MC did not stimulate [(35S]GTPγS binding in Chinese hamster ovary cells expressing human or rat MORs, and had only limited partial agonist effects in human embryonic kidney cells expressing mouse MORs. Ibogaine did not did not stimulate [(35S]GTPγS binding in any MOR expressing cells. Noribogaine did not stimulate [(35S]GTPγS binding in brain slices using autoradiography. An MOR agonist action does not appear to account for the effect of these iboga alkaloids on opioid withdrawal. Taken together with existing evidence that their mechanism of action also differs from that of other non-opioids with clinical effects on opioid tolerance and withdrawal, these

  1. Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives.

    Science.gov (United States)

    Qian, Jia-Qing

    2002-12-01

    Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihypertensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experimental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacological mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na+,K+ and Ca2+ ion currents. Differing from quinidine and sotalol, which exhibited reverse use-dependent effect, dauricine prolonged APD in a normal use-dependent manner in experimental studies. The antiarrhythmic effect of daurisoline and neferine which is an alkaloid isolated from Nelumbo nucifera Gaertn, and their mechanisms of actions have also been studied. The antiarrhythmic effect of daurisoline is more potent than that of dauricine.

  2. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  3. Alkaloid toxins in endophyte-infected grasses.

    Science.gov (United States)

    Powell, R G; Petroski, R J

    1992-01-01

    Grasses infected with clavicipitaceous fungi have been associated with a variety of diseases including classical ergotism in humans and animals, fescue foot and summer syndrome in cattle, and rye-grass staggers in sheep. During the last decade it has been recognized that many of these fungal infections are endophytic; a fungal endophyte is a fungus that grows entirely within the host plant. Inspection of field collections and herbarium specimens has revealed that such infections are widespread in grasses. The chemistry associated with these grass-fungal interactions has proved to be interesting and complex, as each grass-fungal pair results in a unique "fingerprint" of various alkaloids, of which some are highly toxic to herbivores. In many cases the presence of an endophyte appears to benefit the plant by increasing drought resistance, or by increasing resistance to attack by insects, thus improving the overall survivability of the grass. This review will focus on alkaloids that have been reported in endophyte-infected grasses.

  4. Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite

    Directory of Open Access Journals (Sweden)

    VICTOR D.A. SILVA

    Full Text Available ABSTRACT Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD and autophagy on the mechanism of cell death induced by a total extract (TAE of alkaloids and fraction (F32 from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL and F32 (7.5 µg/mL induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

  5. Phytochemical genomics of the Madagascar periwinkle: Unravelling the last twists of the alkaloid engine.

    Science.gov (United States)

    Dugé de Bernonville, Thomas; Clastre, Marc; Besseau, Sébastien; Oudin, Audrey; Burlat, Vincent; Glévarec, Gaëlle; Lanoue, Arnaud; Papon, Nicolas; Giglioli-Guivarc'h, Nathalie; St-Pierre, Benoit; Courdavault, Vincent

    2015-05-01

    The Madagascar periwinkle produces a large palette of Monoterpenoid Indole Alkaloids (MIAs), a class of complex alkaloids including some of the most valuable plant natural products with precious therapeutical values. Evolutionary pressure on one of the hotspots of biodiversity has obviously turned this endemic Malagasy plant into an innovative alkaloid engine. Catharanthus is a unique taxon producing vinblastine and vincristine, heterodimeric MIAs with complex stereochemistry, and also manufactures more than 100 different MIAs, some shared with the Apocynaceae, Loganiaceae and Rubiaceae members. For over 60 years, the quest for these powerful anticancer drugs has inspired biologists, chemists, and pharmacists to unravel the chemistry, biochemistry, therapeutic activity, cell and molecular biology of Catharanthus roseus. Recently, the "omics" technologies have fuelled rapid progress in deciphering the last secret of strictosidine biosynthesis, the central precursor opening biosynthetic routes to several thousand MIA compounds. Dedicated C. roseus transcriptome, proteome and metabolome databases, comprising organ-, tissue- and cell-specific libraries, and other phytogenomic resources, were developed for instance by PhytoMetaSyn, Medicinal Plant Genomic Resources and SmartCell consortium. Tissue specific library screening, orthology comparison in species with or without MIA-biochemical engines, clustering of gene expression profiles together with various functional validation strategies, largely contributed to enrich the toolbox for plant synthetic biology and metabolic engineering of MIA biosynthesis.

  6. Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit.

    Science.gov (United States)

    Schimpl, Flávia Camila; Kiyota, Eduardo; Mayer, Juliana Lischka Sampaio; Gonçalves, José Francisco de Carvalho; da Silva, José Ferreira; Mazzafera, Paulo

    2014-09-01

    Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein.

  7. A new cytotoxic carbazole alkaloid and two new other alkaloids from Clausena excavata.

    Science.gov (United States)

    Peng, Wen-Wen; Zeng, Guang-Zhi; Song, Wei-Wu; Tan, Ning-Hua

    2013-07-01

    One new carbazole alkaloid, excavatine A (1), and two additional new alkaloids, excavatine B (2) and excavatine C (3), were isolated from the stems and leaves of Clausena excavata Burm.f. (Rutaceae). Their structures were determined on the basis of detailed spectroscopic analyses, especially 2D-NMR and HR-EI-MS data. Compounds 1-3 were tested for their cytotoxic activities against A549, HeLa, and BGC-823 cancer cell lines, and for their antimicrobial activities against Candida albicans and Staphylococcus aureus. Only 1 exhibited cytotoxicity against A549 and HeLa cell lines with the IC50 values of 5.25 and 1.91 μg/ml, respectively.

  8. Indolopyridoquinazoline alkaloids from Esenbeckia grandiflora mart. (Rutaceae); Alkaloides {beta}-indolopiridoquinazolinicos de Esenbeckia grandiflora mart. (Rutaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Januario, Ana Helena; Vieira, Paulo Cezar; Silva, Maria Fatima das Gracas Fernandes da; Fernandes, Joao Batista [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Quimica], e-mail: anahjanuario@unifran.br; Silva, Jorge Jose de Brito; Conserva, Lucia Maria [Universidade Federal de Alagoas (UFAL), Maceio, AL (Brazil). Inst. de Quimica e Biotecnologia

    2009-07-01

    The chemical composition of two specimens of Esenbeckia grandiflora, collected in the south and northeast regions of Brazil, was investigated. In this study, three b-indolopyridoquinazoline alkaloids from the leaves (rutaecarpine, 1-hydroxyrutaecarpine) and roots (euxylophoricine D) were isolated for the first time in this genus. In addition, the triterpenes {alpha}-amyrin, {beta}-amyrin, {alpha}-amyrenonol, {beta}-amyrenonol, 3{alpha}-hydroxy-ursan-12-one, and 3{alpha}-hydroxy-12,13-epoxy-oleanane, the coumarins auraptene, umbelliferone, pimpinelin, and xanthotoxin, the furoquinoline alkaloids delbine and kokusaginine, and the phytosteroids sitosterol, stigmasterol, campesterol and 3{beta}-O-{beta}-D-glucopyranosylsitosterol were also isolated from the leaves, twigs, roots and stems of this species. Structures of these compounds were established by spectral analysis. (author)

  9. [A new alkaloid from Menispermum dauricum DC--N-desmethyldauricine].

    Science.gov (United States)

    Pan, X P

    1992-01-01

    A new phenolic dauricine-type alkaloid together with the know dauricine were isolated from the rhizoma of Menispermum dauricum DC cultivated in Xianning district, Hubei province. Dauricine was obtained as the major alkaloid and was confirmed by comparison with authentic sample. The new alkaloid is an unstable white powder: Based on spectrometric analysis (UV, IR, FAB-MS and 1HNMR) and N-methylation which offered dauricine dimethiodide (V), the structure was elucidated as RR, N-desmethyldauricine (II), which was isolated for the first time from nature.

  10. Prenylindole alkaloids from Raputia praetermissa (Rutaceae) and their chemosystematic significance

    Energy Technology Data Exchange (ETDEWEB)

    Rosas, Lisandra V.; Veiga, Thiago Andre M.; Fernandes, Joao B.; Vieira, Paulo C.; Silva, M. Fatima das G.F. da, E-mail: dmfs@power.ufscar.b [Universidade Federal de Sao Carlos (DQ/UFSCar), SP (Brazil). Dept. de Quimica

    2011-07-01

    The dichloromethane extract from the stems of Raputia praetermissa afforded four new compounds, 4-deoxyraputindole C (1), raputimonoindole A-B (2, 3), and hexadecanyl 2-hydroxy- 4-methoxy-cinnamate (5), besides the alkaloids 5-(4-methoxymethylfuran-2-yl)-1H-indole (raputimonoindole C), furoquinolines maculosidine, robustine, evolitrine and dictamnine. The hexane extract yielded N-methyl-4-methoxyquinoline-2(1H)-one, skimmianine, cycloartenone, sitosterol, stigmasterol and sitostenone. The anthranilate alkaloid content indicates that the genus is strongly related to those included in Cusparieae tribe, but differs from Neoraputia by the absence of prenylindole alkaloids in the late, whose species have previously been placed in Raputia. (author)

  11. γ-Lactam alkaloids from the flower buds of daylily.

    Science.gov (United States)

    Matsumoto, Takahiro; Nakamura, Seikou; Nakashima, Souichi; Ohta, Tomoe; Yano, Mamiko; Tsujihata, Junichiro; Tsukioka, Junko; Ogawa, Keiko; Fukaya, Masashi; Yoshikawa, Masayuki; Matsuda, Hisashi

    2016-07-01

    Four new alkaloids, hemerocallisamines IV-VII, were isolated from the methanol extract of flower buds of daylily. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The absolute stereochemistry of the hemerocallisamines IV-VI was elucidated by the application of the modified Mosher's method, HPLC analysis, and optical rotation. In the present study, the isolated alkaloids significantly inhibited the aggregation of Aβ42 in vitro. This is the first report about bioactive alkaloids with a γ-lactam ring from daylily. In addition, isolated nucleosides showed accelerative effects on neurite outgrowth under the non-fasting condition.

  12. Qualitative determination of indole alkaloids of Tabernaemontana fuchsiaefolia (Apocynaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Zocoler, Marcos A. [Universidade do Oeste Paulista, Presidente Prudente, SP (Brazil). Dept. de Farmacos e Medicamentos; Oliveira, Arildo J.B. de [Universidade Estadual de Maringa, PR (Brazil). Dept. de Farmacia e Farmacologia; Sarragiotto, Maria H.; Grzesiuk, Viviane L.; Vidotti, Gentil J. [Universidade Estadual de Maringa, PR (Brazil). Dept. de Quimica]. E-mail: gjvidotti@uem.br

    2005-11-15

    This p describes a fast and efficient procedure to separate and identify indole alkaloids from the ethanolic extract of Tabernaemontana fuchsiaefolia (Apocynaceae). The alkaloidal fractions obtained from ethanolic extracts of leaves and stem barks and root barks were fractioned and analyzed by Thin-Layer Chromatography (TLC) and by Gas Chromatography coupled to Mass Spectrometry (GC-MS). The following indole alkaloids were identified: ibogamine, coronaridine, ibogaine pseudoindoxyl, voacangine hydroxyindolenine, voacangine pseudoindoxyl, tabernanthine, catharanthine, voacangine, 19-oxovoacangine, 10-hydroxycoronaridine, affinisine, 16-epi-affinine, voachalotine, ibogaline, and conopharyngine. (author)

  13. Alkaloid content of the seeds from Erythroxylum Coca var. Coca.

    Science.gov (United States)

    Casale, John F; Toske, Steven G; Colley, Valerie L

    2005-11-01

    Alkaloid extracts from the seeds of Erythroxylum Coca var. Coca grown in the Chapare Valley of Bolivia were subjected to gas and liquid chromatographic-mass spectrometric analyses. Several alkaloids from these seeds were detected and characterized, including methylecgonidine, tropine, 3alpha-acetoxytropane, ecgonine methyl ester, cuscohygrine, N-norbenzoyltropine, benzoyltropine, hexanoylecgonine methyl ester, cocaine, cis-cinnamoylcocaine, and trans-cinnamoylcocaine. Methylecgonidine was determined to be the primary constituent and not an analytical artifact. Additionally, two significant new uncharacterized alkaloids were established as present. Recent evidence suggests that some cocaine processors are adding this seed extraction material to cocaine extracted from coca leaf and may impact cocaine impurity signature profiles.

  14. Cytotoxic alkaloids from stems, leaves and twigs of Dasymaschalon blumei.

    Science.gov (United States)

    Chanakul, Waraporn; Tuchinda, Patoomratana; Anantachoke, Natthinee; Pohmakotr, Manat; Piyachaturawat, Pawinee; Jariyawat, Surawat; Suksen, Kanoknetr; Jaipetch, Tharworn; Nuntasaen, Narong; Reutrakul, Vichai

    2011-10-01

    Bioassay-guided fractionation of the cytotoxic ethyl acetate extract from the stems of Dasymaschalon blumei (Annonaceae) led to the isolation of four aristololactam alkaloids, including the hitherto unknown 3,5-dihydroxy-2,4-dimethoxyaristolactam (1), as well as the three known compounds, aristolactam BI, goniopedaline, and griffithinam. Additionally, the cytotoxic extract from the combined leaves and twigs of the same plant yielded three known oxoaporphine alkaloids, oxodiscoguattine, dicentrinone, and duguevalline. The structures of aristolactams and oxoaporphine alkaloids were elucidated on the basis of spectroscopic methods. All isolates were evaluated for cytotoxicity against a panel of mammalian cancer cell lines and a noncancerous human embryonic kidney cell Hek 293.

  15. Reversal of Vinca alkaloid resistance but not multiple drug resistance in human leukemic cells by verapamil.

    Science.gov (United States)

    Beck, W T; Cirtain, M C; Look, A T; Ashmun, R A

    1986-02-01

    We examined the ability of verapamil, a Ca2+ channel blocker, to overcome Vinca alkaloid and multiple drug resistance in our CEM/VLB100 and CEM/DOX human leukemic lymphoblasts. Compared with the parent CCRF-CEM cells, CEM/VLB100 cells are approximately equal to 200- to 800-fold resistant to vinblastine and express cross-resistance to vincristine, doxorubicin, and other "natural product" drugs, as determined by comparing 50% inhibitory concentrations in a 48-h growth inhibition assay. Verapamil (10 microM) decreased the 50% inhibitory concentrations for Vinca alkaloids in CEM/VLB100 cells by approximately equal to 75- to 85-fold but caused only slight (approximately equal to 2- to 5-fold) decreases in 50% inhibitory concentrations for anthracyclines, epipodophyllotoxins, and other tubulin-binding drugs (colchicine and podophyllotoxin). Qualitatively similar results were obtained with doxorubicin-resistant cells, termed CEM/DOX; verapamil caused a 19-fold increase in doxorubicin toxicity but 67- and 3500-fold increases in the toxicities of vinblastine and vincristine, respectively. These results indicate that the effect of verapamil is relatively greater for Vinca alkaloids, with less pronounced effects for the other natural product drugs against which these cells express multiple drug resistance. In flow cytometric studies, individually nontoxic or minimally toxic concentrations of vinblastine plus verapamil caused measurable accumulation in the G2 + M phase as early as 4 h after the drug combination was added to cultures of CEM/VLB100 cells; this finding correlated with a comparable increase in the number of cells in mitosis and measurable decreases in the total number of cells. Since similar effects on cell cycle distribution, percentage of cells in mitosis, and cell number were seen when CEM/VLB100 cells were treated with toxic concentrations of vinblastine alone, we conclude that the primary toxicity of the vinblastine-verapamil combination stems from the

  16. Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants.

    Science.gov (United States)

    Hagel, Jillian M; Morris, Jeremy S; Lee, Eun-Jeong; Desgagné-Penix, Isabel; Bross, Crystal D; Chang, Limei; Chen, Xue; Farrow, Scott C; Zhang, Ye; Soh, Jung; Sensen, Christoph W; Facchini, Peter J

    2015-09-18

    Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites sharing a common biosynthetic origin beginning with tyrosine. Many BIAs have potent pharmacological activities, and plants accumulating them boast long histories of use in traditional medicine and cultural practices. The decades-long focus on a select number of plant species as model systems has allowed near or full elucidation of major BIA pathways, including those of morphine, sanguinarine and berberine. However, this focus has created a dearth of knowledge surrounding non-model species, which also are known to accumulate a wide-range of BIAs but whose biosynthesis is thus far entirely unexplored. Further, these non-model species represent a rich source of catalyst diversity valuable to plant biochemists and emerging synthetic biology efforts. In order to access the genetic diversity of non-model plants accumulating BIAs, we selected 20 species representing 4 families within the Ranunculales. RNA extracted from each species was processed for analysis by both 1) Roche GS-FLX Titanium and 2) Illumina GA/HiSeq platforms, generating a total of 40 deep-sequencing transcriptome libraries. De novo assembly, annotation and subsequent full-length coding sequence (CDS) predictions indicated greater success for most species using the Illumina-based platform. Assembled data for each transcriptome were deposited into an established web-based BLAST portal ( www.phytometasyn.ca) to allow public access. Homology-based mining of libraries using BIA-biosynthetic enzymes as queries yielded ~850 gene candidates potentially involved in alkaloid biosynthesis. Expression analysis of these candidates was performed using inter-library FPKM normalization methods. These expression data provide a basis for the rational selection of gene candidates, and suggest possible metabolic bottlenecks within BIA metabolism. Phylogenetic analysis was performed for each of 15 different enzyme/protein groupings

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

    Institute of Scientific and Technical Information of China (English)

    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 ).

  18. Transcriptomic insight into terpenoid and carbazole alkaloid biosynthesis, and functional characterization of two terpene synthases in curry tree (Murraya koenigii)

    Science.gov (United States)

    Meena, Seema; Rajeev Kumar, Sarma; Dwivedi, Varun; Kumar Singh, Anup; Chanotiya, Chandan S.; Akhtar, Md. Qussen; Kumar, Krishna; Kumar Shasany, Ajit; Nagegowda, Dinesh A.

    2017-01-01

    Curry tree (Murraya koenigii L.) is a rich source of aromatic terpenes and pharmacologically important carbazole alkaloids. Here, M. koenigii leaf transcriptome was generated to gain insight into terpenoid and alkaloid biosynthesis. Analysis of de novo assembled contigs yielded genes for terpene backbone biosynthesis and terpene synthases. Also, gene families possibly involved in carbazole alkaloid formation were identified that included polyketide synthases, prenyltransferases, methyltransferases and cytochrome P450s. Further, two genes encoding terpene synthases (MkTPS1 and MkTPS2) with highest in silico transcript abundance were cloned and functionally characterized to determine their involvement in leaf volatile formation. Subcellular localization using GFP fusions revealed the plastidial and cytosolic localization of MkTPS1 and MkTPS2, respectively. Enzymatic characterization demonstrated the monoterpene synthase activity of recombinant MkTPS1, which produced primarily (−)-sabinene from geranyl diphosphate (GPP). Recombinant MkTPS2 exhibited sesquiterpene synthase activity and formed (E,E)-α-farnesene as the major product from farnesyl diphosphate (FPP). Moreover, mRNA expression and leaf volatile analyses indicated that MkTPS1 accounts for (−)-sabinene emitted by M. koenigii leaves. Overall, the transcriptome data generated in this study will be a great resource and the start point for characterizing genes involved in the biosynthetic pathway of medicinally important carbazole alkaloids. PMID:28272514

  19. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids

    Directory of Open Access Journals (Sweden)

    Benedict T. Green

    2016-07-01

    Full Text Available Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs. We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh, which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50 was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic.

  20. One new alkaloid from Chelidonium majus L.

    Science.gov (United States)

    Zhang, Wen-Juan; You, Chun-Xue; Wang, Cheng-Fang; Fan, Li; Wang, Ying; Su, Yang; Deng, Zhi-Wei; Du, Shu-Shan

    2014-01-01

    One new alkaloid, together with 10 known compounds were isolated from the aerial parts of Chelidonium majus L. by repeated silica gel column chromatography. Their chemical structures were elucidated on the basis of physicochemical and spectroscopic data. Among them, 6-acetonyldihydrochelerythrine (4), 6-acetonyldihydrosanguinarine (5), 6-ketenesanguinarine (6), demethylchelerythrine (7) and demethylsanguinarine (11) were isolated for the first time from this plant. Compound 6 was identified as a new compound. These compounds were screened for cytotoxicity against human non-small lung carcinoma (H1299), breast cancer (MCF-7) and liver cancer (SMMC-7721). In a series of cytotoxic tests, compounds 9 and 10 displayed potent cytotoxic activity against H1299, MCF-7 and SMMC-7721, with the IC50 values of 8.16-35.25 μg/mL.

  1. Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

    Directory of Open Access Journals (Sweden)

    Laurent Meijer

    2008-10-01

    Full Text Available Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dualspecificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.

  2. Tetrahydroberberine, a pharmacologically active naturally occurring alkaloid.

    Science.gov (United States)

    Pingali, Subramanya; Donahue, James P; Payton-Stewart, Florastina

    2015-04-01

    Tetrahydroberberine (systematic name: 9,10-dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the molecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core. The intermolecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole -CH2···OCH3 and -OCH3···OCH3 interactions between neighboring molecules.

  3. Antifouling Alkaloids from Crinum augustum (Amaryllidaceae

    Directory of Open Access Journals (Sweden)

    John Refaat

    2009-01-01

    Full Text Available Fractionation and purification of the ethanolic extract of the bulbs of Crinum augustum Rox. (Amaryllidaceae cultivated in Egypt yielded five alkaloids 6-methoxy-crinamine (1 , crinamine (2 , buphanisine (3 , ungeremine (4 , and hippadine (5 ; two fatty acid derivatives: myristic acid ethyl ester (6 and palmitic acid ethyl ester (7 ; four terpenoidal and steroidal compounds: ursolic acid (8 , β-sitosterol-O- β glucopyranoside (9 and mixture of β--sitosterol (10 and stigmasterol (11 . The structures of all compounds were determined by interpretation of their spectroscopic data; 1D ( 1 H and 13 C, 2D (HSQC, COSY, DQF, NOE and HMBC NMR; MS and UV analyses. The compounds (1 -4 and (6-8 were tested towards biofouling activity using larvae of barnacle Balance amphitrie. Significant activities of 1, 2 and 3 with EC 50 1.8, 1.2 and 0.75 μg/mL respectively, were observed.

  4. Pyrrolidonyl and pyridyl alkaloids in Lymantria dispar.

    Science.gov (United States)

    Deml, Reinhold

    2003-01-01

    The occurrence and metabolism of nicotine and related N-containing compounds in body fluids of the gipsy moth were addressed. Thin layer chromatographic studies clearly showed the simultaneous presence of GABA and 2-pyrrolidone but not of GABamide in the larval haemolymph and osmeterial secretion of Lymantria dispar as well as in the corresponding body fluids of the saturniids, Saturnia pavonia and Attacus atlas. Furthermore, feeding and injection experiments using alkylated precursors and combined gas chromatography/mass spectrometry gave evidence of the transformation of 2-pyrrolidone to nicotine and of nicotinic acid to nicotinamide in caterpillars of L. dispar. Based on these results, on the earlier described variation of the secondary-compound patterns of L. dispar during its development, and on literature data, metabolic pathways for the hitherto detected pyridyl and pyrrolidonyl alkaloids in Lymantriidae (and possibly Saturniidae) are proposed.

  5. The Use of Nitrone Cycloadditions in the Synthesis of Beta-Amino Aldehydes and Unsaturated Amines.

    Science.gov (United States)

    1986-01-01

    extensively exploited in the synthesis of natural products. For example, retronecine (14), a pyrrolizidine alkaloid , was synthesized by converting nitrone...mesylate gave amino alcohol 12 which was cyclized to the pyrrolizidine . Dehydration of the pyrrolizidine gave 13 which was subsequently converted to

  6. New bisbenzylisoquinoline alkaloid from Laureliopsis philippiana

    DEFF Research Database (Denmark)

    Stærk, Dan; Thi, Loi Pham; Rasmussen, Hasse Bonde;

    2009-01-01

    Phytochemical investigation of Laureliopsis philippiana resulted in isolation of a new bisbenzylisoquinoline alkaloid (1) named laureliopsine A. The structure was established by spectroscopic methods, including 2D homo- and heteronuclear NMR experiments. This finding of a bisbenzylisoquinoline al...

  7. New bromotyrosine alkaloids from the marine sponge Psammaplysilla purpurea

    Digital Repository Service at National Institute of Oceanography (India)

    Tilvi, S.; Rodrigues, C; Naik, C; Parameswaran, P.S.; Wahidullah, S.

    Seven new bromotyrosine alkaloids Purpurealidin A, B, C, D, F, G, H and the known compounds Purealidin Q, Purpurealidin E, 16-Debromoaplysamine-4 and Purpuramine I have been isolated from the marine sponge Psammaplysilla purpurea. Their structure...

  8. Arginine decarboxylase as the source of putrescine for tobacco alkaloids

    Science.gov (United States)

    Tiburcio, A. F.; Galston, A. W.

    1986-01-01

    The putrescine which forms a part of nicotine and other pyrrolidine alkaloids is generally assumed to arise through the action of ornithine decarboxylase (ODC). However, we have previously noted that changes in the activity of arginine decarboxylase (ADC), an alternate source of putrescine, parallel changes in tissue alkaloids, while changes in ODC activity do not. This led us to undertake experiments to permit discrimination between ADC and ODC as enzymatic sources of putrescine destined for alkaloids. Two kinds of evidence presented here support a major role for ADC in the generation of putrescine going into alkaloids: (a) A specific 'suicide inhibitor' of ADC effectively inhibits the biosynthesis of nicotine and nornicotine in tobacco callus, while the analogous inhibitor of ODC is less effective, and (b) the flow of 14C from uniformly labelled arginine into nicotine is much more efficient than that from ornithine.

  9. Alkaloids with Different Carbon Units from Myrioneuron faberi.

    Science.gov (United States)

    Cao, Ming-Ming; Zhang, Yu; Huang, Sheng-Dian; Di, Ying-Tong; Peng, Zong-Gen; Jiang, Jian-Dong; Yuan, Chun-Mao; Chen, Duo-Zhi; Li, Shun-Lin; He, Hong-Ping; Hao, Xiao-Jiang

    2015-11-25

    Three new Myrioneuron alkaloids, myrifamines A-C (1-3), with unique skeletons were isolated from Myrioneuron faberi. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis, and the stereochemistry of the other two alkaloids was determined using a combination of ROESY experiments and calculated and experimental electronic circular dichroism spectra. Myrifamine C (3) is the first example of a symmetric dimer among the Myrioneuron alkaloids. Known alkaloids myrionamide (4) and schoberine (5) were also isolated, and experimental NMR and X-ray diffraction data suggest their structural revision. Compound 2 showed significant inhibitory activity toward the hepatitis C virus in vitro, with a therapeutic index (CC50/EC50) greater than 108.7.

  10. Microcalorimetry studies of the antimicrobial actions of Aconitum alkaloids.

    Science.gov (United States)

    Shi, Yan-bin; Liu, Lian; Shao, Wei; Wei, Ting; Lin, Gui-mei

    2015-08-01

    The metabolic activity of organisms can be measured by recording the heat output using microcalorimetry. In this paper, the total alkaloids in the traditional Chinese medicine Radix Aconiti Lateralis were extracted and applied to Escherichia coli and Staphylococcus aureus. The effect of alkaloids on bacteria growth was studied by microcalorimetry. The power-time curves were plotted with a thermal activity monitor (TAM) air isothermal microcalorimeter and parameters such as growth rate constant (μ), peak-time (Tm), inhibitory ratio (I), and enhancement ratio (E) were calculated. The relationships between the concentration of Aconitum alkaloids and μ of E. coli or S. aureus were discussed. The results showed that Aconitum alkaloids had little effect on E. coli and had a potentially inhibitory effect on the growth of S. aureus.

  11. Gastric and Duodenal Antiulcer Activity of Alkaloids: A Review

    Directory of Open Access Journals (Sweden)

    José Maria Barbosa-Filho

    2008-12-01

    Full Text Available Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including this one. These products usually derive from plant and animal sources that contain active constituents such as alkaloids, flavonoids, terpenoids, tannins and others. The alkaloids are natural nitrogen-containing secondary metabolites mostly derived from amino acids and found in about 20% of plants. There has been considerable pharmacological research into the antiulcer activity of these compounds. In this work we review the literature on alkaloids with antiulcer activity, which covers about sixty-one alkaloids, fifty-five of which have activity against this disease when induced in animals.

  12. NEW NORDITERPENOID ALKALOIDS FROM THE ROOTS OF ACONITUM GENICULATUM

    Institute of Scientific and Technical Information of China (English)

    ZHENG-BANG LI; LIANG XU; XI-XIAN JIAN; FENG-PENG WANG

    2001-01-01

    Four new norditerpenoid alkaloids, geniculatines A (1), B (4), C (7) and D (8), were isolated from the roots of Aconitum geniculatum Fletcher, and their structures were elucidated by spectral methods.

  13. A new pyrrole alkaloid from seeds of Castanea sativa.

    Science.gov (United States)

    Hiermann, Alois; Kedwani, Samir; Schramm, Hans Wolfgang; Seger, Christoph

    2002-02-01

    A new pyrrole alkaloid, methyl-(5-formyl-1H-pyrrole-2-yl)-4-hydroxybutyrate (1), was isolated from sweet chestnut seeds and its structure elucidated on the basis of data from NMR spectroscopy and by comparison with synthetic analogues.

  14. Coptis chinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBP-α and PPAR-γ.

    Science.gov (United States)

    Choi, Jae Sue; Kim, Ji-Hye; Ali, Md Yousof; Min, Byung-Sun; Kim, Gun-Do; Jung, Hyun Ah

    2014-10-01

    Obesity is a complex, multifactorial, and chronic disease that increases the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem. Developing novel anti-obesity drugs from natural products is a promising solution to the global health problem of obesity. While screening anti-obesity potentials of natural products, the methanol extract of the rhizome of Coptis chinensis (Coptidis Rhizoma) was found to significantly inhibit adipocyte differentiation and lipid contents in 3T3-L1 cells, as assessed by Oil-Red O staining. Five known alkaloids, berberine, epiberberine, coptisine, palmatine, and magnoflorine, were isolated from the n-BuOH fraction of the methanol extract of Coptidis Rhizoma. We determined the chemical structure of these alkaloids through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these alkaloids for their ability to inhibit adipogenesis over a range of concentrations (12.5-50 μM). All five Coptidis Rhizoma alkaloids significantly inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability in a concentration dependent manner. In addition, the five alkaloids significantly reduced the expression levels of several adipocyte marker genes including proliferator activated receptor-γ (PPAR-γ) and CCAAT/enhancer-binding protein-α (C/EBP-α). In the present study, we found that the isolated alkaloids inhibited adipogenesis in a dose-dependent manner in 3T3-L1 cells; this inhibition was attributed to their abilities to downregulate the protein levels of the adipocyte marker proteins PPAR-γ and C/EBP-α. Thus, these results suggest that Coptidis Rhizoma extract and its isolated alkaloids may be of therapeutic interest with respect to the treatment of obesity.

  15. Computational Studies on Cinchona Alkaloid-Catalyzed Asymmetric Organic Reactions.

    Science.gov (United States)

    Tanriver, Gamze; Dedeoglu, Burcu; Catak, Saron; Aviyente, Viktorya

    2016-06-21

    Remarkable progress in the area of asymmetric organocatalysis has been achieved in the last decades. Cinchona alkaloids and their derivatives have emerged as powerful organocatalysts owing to their reactivities leading to high enantioselectivities. The widespread usage of cinchona alkaloids has been attributed to their nontoxicity, ease of use, stability, cost effectiveness, recyclability, and practical utilization in industry. The presence of tunable functional groups enables cinchona alkaloids to catalyze a broad range of reactions. Excellent experimental studies have extensively contributed to this field, and highly selective reactions were catalyzed by cinchona alkaloids and their derivatives. Computational modeling has helped elucidate the mechanistic aspects of cinchona alkaloid catalyzed reactions as well as the origins of the selectivity they induce. These studies have complemented experimental work for the design of more efficient catalysts. This Account presents recent computational studies on cinchona alkaloid catalyzed organic reactions and the theoretical rationalizations behind their effectiveness and ability to induce selectivity. Valuable efforts to investigate the mechanisms of reactions catalyzed by cinchona alkaloids and the key aspects of the catalytic activity of cinchona alkaloids in reactions ranging from pharmaceutical to industrial applications are summarized. Quantum mechanics, particularly density functional theory (DFT), and molecular mechanics, including ONIOM, were used to rationalize experimental findings by providing mechanistic insights into reaction mechanisms. B3LYP with modest basis sets has been used in most of the studies; nonetheless, the energetics have been corrected with higher basis sets as well as functionals parametrized to include dispersion M05-2X, M06-2X, and M06-L and functionals with dispersion corrections. Since cinchona alkaloids catalyze reactions by forming complexes with substrates via hydrogen bonds and long

  16. Effect of Phenolic Alkaloids from Menispermum dauricum on EAAC1 mRNA Expression in Hippocampal Neurons of Rats with Focal Cerebral Ischemia%蝙蝠葛酚性碱对局灶性脑缺血大鼠海马神经细胞谷氨酸转运体 EAAC1 mRNA 表达的影响

    Institute of Scientific and Technical Information of China (English)

    瞿小兰; 陈诚; 卢云; 罗攀; 郭莲军

    2016-01-01

    目的:探讨蝙蝠葛酚性碱(PAMd)对大鼠局灶性脑缺血后海马神经细胞谷氨酸转运体 EAAC1 mRNA 表达的影响,及其对脑缺血的保护机制。方法 SD 大鼠42只,随机分为假手术组(不给药)、模型对照组(不给药)、PAMd 组(灌胃给予 PAMd 10 mg·kg-1),每组14只。线栓法制备大鼠局灶性脑缺血模型。采用2,3,5-氯化三苯基四氮唑(TTC)染色检测脑梗死体积,逆转录-聚合酶链反应(RT-PCR)检测海马神经细胞谷氨酸转运体 EAAC1 mRNA 表达。结果缺血24 h 后,假手术组、模型对照组和 PAMd 组脑梗死比例分别为(0.0±0.0)%,(35.3±2.9)%,(21.3±3.8)%(P<0.05);缺血侧海马 EAAC1 mRNA 相对表达量分别为0.97±0.04,2.46±0.13,1.91±0.15(P<0.05)。结论 PAMd 可能通过下调缺血后 EAAC1的表达升高,从而减轻谷氨酸的兴奋毒性作用,发挥对脑缺血的保护作用。%Objective To investigate the effect of phenolic alkaloids from Menispermum dauricum( PAMd)on the mRNA expression of the glutamate transporter EAAC1 in hippocampal neurons of rats subjected to focal cerebral ischemia and to elucidate its neuroprotective mechanisms. Methods A total of 42 Sprague Dawley(SD)rats were randomly divided into three groups:sham group,model control group,and PAMd(10 mg·kg-1 ,i.g)group(n = 14 each).The focal cerebral ischemia model of rat was induced by the middle cerebral artery occlusion( MCAO). The 2,3,5-triphenyltetrazolium chloride( TTC) staining was applied to measure the cerebral infarct size and the reverse transcriptase-polymerase chain reaction(RT-PCR)assay to detect EAAC1 mRNA expression in hippocampal neurons. Results After 24 h ischemia,the cerebral infarct volumes were (0.0±0.0)%,(35.3±2.9)% and(21.3±3.8)% in sham group,model control group and PAMd group,respectively(P<0.05). The relative expression levels of EAAC1 mRNA were 0.97±0.04,2.46±0.13,and 1.91±0.15 in the three

  17. A comparison of the antimalarial activity of the cinchona alkaloids against Plasmodium falciparum in vitro.

    Science.gov (United States)

    Wesche, D L; Black, J

    1990-06-01

    The effects of four major cinchona alkaloids: (-) quinine, (+) quinidine, (-)cinchonidine, and (+)cinchonine against Plasmodium falciparum FCQ-27/PNG were studied. The alkaloids were tested in vitro as either single alkaloids, racemic mixtures of stereoisomers, or as an equimolar combination of all four alkaloids. Results indicate (+)quinidine to be most effective and both (+)stereoisomers were more potent than the (-)stereoisomers. Inhibitory concentrations 50% (Ki) of racemic mixtures of stereoisomers were similar to those of the (+)stereoisomers alone. The Ki of four alkaloids in equimolar combination were similar to that of the (-) cinchonidine/(+)cinchonine racemic mixture. A total alkaloidal extract of Cinchona sp. was tested and compared with the pure alkaloids. HPLC analysis indicated that (+)cinchonine, (-)cinchonidine and (-)quinine were present in a ratio of approximately 1:1:2, respectively. The total alkaloid extract, with (-)stereoisomers predominating, was less effective than the four alkaloids in combination. The nature of the interaction between stereoisomers was investigated and appears to be one of addition.

  18. Aporphine alkaloids from Guatteria spp. with leishmanicidal activity.

    Science.gov (United States)

    Montenegro, Hector; Gutiérrez, Marcelino; Romero, Luz I; Ortega-Barría, Eduardo; Capson, Todd L; Rios, Luis Cubilla

    2003-07-01

    Fractionation of Guatteria amplifolia yielded the alkaloids xylopine (1), nornuciferine (4), lysicamine (6), and laudanosine (5). Fractionation of Guatteria dumetorum yielded the alkaloids cryptodorine (2) and nornantenine (3). Compounds 1-4 demonstrated significant activity against Leishmania mexicana and L. panamensis. Xylopine (1) was among the most active compounds (LD 50 = 3 microM) and showed a 37-fold higher toxicity towards L. mexicana than macrophages, the regular host cells of Leishmania spp.

  19. Identification and determination of ergot alkaloids in Morning Glory cultivars

    OpenAIRE

    Nowak, Julia; Woźniakiewicz, Michał; Klepacki, Piotr; Sowa, Anna; Kościelniak, Paweł

    2016-01-01

    Seeds of plants from Ipomoea genera contain numerous ergot alkaloids, including psychoactive ergine and ergometrine, and are often abused as so-called “legal highs.” In this work, an analytical method for determination of ergine and ergometrine, and identification of other alkaloids was developed, optimized, and validated. Three extraction techniques, ultrasound-assisted extraction in bath, or with sonotrode, and microwave-assisted extraction were evaluated, and it was concluded that ultrason...

  20. Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum.

    Science.gov (United States)

    Dewey, Ralph E; Xie, Jiahua

    2013-10-01

    Alkaloids represent an extensive group of nitrogen-containing secondary metabolites that are widely distributed throughout the plant kingdom. The pyridine alkaloids of tobacco (Nicotiana tabacum L.) have been the subject of particularly intensive investigation, driven largely due to the widespread use of tobacco products by society and the role that nicotine (16) (see Fig. 1) plays as the primary compound responsible for making the consumption of these products both pleasurable and addictive. In a typical commercial tobacco plant, nicotine (16) comprises about 90% of the total alkaloid pool, with the alkaloids nornicotine (17) (a demethylated derivative of nicotine), anatabine (15) and anabasine (5) making up most of the remainder. Advances in molecular biology have led to the characterization of the majority of the genes encoding the enzymes directly responsible the biosynthesis of nicotine (16) and nornicotine (17), while notable gaps remain within the anatabine (15) and anabasine (5) biosynthetic pathways. Several of the genes involved in the transcriptional regulation and transport of nicotine (16) have also been elucidated. Investigations of the molecular genetics of tobacco alkaloids have not only provided plant biologists with insights into the mechanisms underlying the synthesis and accumulation of this important class of plant alkaloids, they have also yielded tools and strategies for modifying the tobacco alkaloid composition in a manner that can result in changing the levels of nicotine (16) within the leaf, or reducing the levels of a potent carcinogenic tobacco-specific nitrosamine (TSNA). This review summarizes recent advances in our understanding of the molecular genetics of alkaloid biosynthesis in tobacco, and discusses the potential for applying information accrued from these studies toward efforts designed to help mitigate some of the negative health consequences associated with the use of tobacco products.

  1. Total synthesis of the bridged indole alkaloid apparicine.

    Science.gov (United States)

    Bennasar, M-Lluïsa; Zulaica, Ester; Solé, Daniel; Roca, Tomàs; García-Díaz, Davinia; Alonso, Sandra

    2009-11-06

    An indole-templated ring-closing metathesis or a 2-indolylacyl radical cyclization constitute the central steps of two alternative approaches developed to assemble the tricyclic ABC substructure of the indole alkaloid apparicine. From this key intermediate, an intramolecular vinyl halide Heck reaction accomplished the closure of the strained 1-azabicyclo[4.2.2]decane framework of the alkaloid with concomitant incorporation of the exocyclic alkylidene substituents.

  2. ISOLASI SENYAWA ALKALOID DARI DAUN SIDAGURI (Sida rhombifolia L.

    Directory of Open Access Journals (Sweden)

    Sovia Lenny

    2016-02-01

    Full Text Available The secondary metabolite compound was isolated from sidaguri (Sida rhombifolia L. leaves. The diethylether extract was subjected to a column chromatography with a mixture of chloroform:methanol (7:3 was obtained as amorf  (59 mg. The FT-IR and 1H-NMR spectrum indicated the isolated compound was alkaloid compound. Keywords : Sidaguri (Sida rhombifolia L., column chromatography, alkaloid

  3. Identification and determination of ergot alkaloids in Morning Glory cultivars.

    Science.gov (United States)

    Nowak, Julia; Woźniakiewicz, Michał; Klepacki, Piotr; Sowa, Anna; Kościelniak, Paweł

    2016-05-01

    Seeds of plants from Ipomoea genera contain numerous ergot alkaloids, including psychoactive ergine and ergometrine, and are often abused as so-called "legal highs." In this work, an analytical method for determination of ergine and ergometrine, and identification of other alkaloids was developed, optimized, and validated. Three extraction techniques, ultrasound-assisted extraction in bath, or with sonotrode, and microwave-assisted extraction were evaluated, and it was concluded that ultrasonic bath is the most suitable technique for extraction of ergot alkaloids. The extraction method was later optimized using a Doehlert experimental design with response surface methodology and used together with the optimized LC-Q-TOF-MS method. The analytical procedure was validated in terms of recovery and matrix effect, repeatability, and intermediate precision. Limits of detection and quantification were 1.0 and 3.0 ng mL(-1), respectively, and were sufficient for determination of ergot alkaloids in Ipomoea seeds. The analysis revealed that from five kinds of seeds purchased from different vendors, only three contained ergot alkaloids. Concentration of alkaloids and their relative abundance was similar in samples representative for whole seeds packs; however, when single seeds were analyzed, significant discrepancies in ergine and ergometrine concentrations were detected.

  4. Evaluation of Aconitum diterpenoid alkaloids as antiproliferative agents.

    Science.gov (United States)

    Wada, Koji; Ohkoshi, Emika; Zhao, Yu; Goto, Masuo; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2015-04-01

    Little information has been reported on the antitumor effects of the diterpenoid alkaloid constituents of Aconitum plants, used in the herbal drug 'bushi'. This study was aimed at determining the antitumor activities of Aconitum C19-and C20-diterpenoid alkaloids and synthetic derivatives against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines. Newly synthesized C20-diterpenoid alkaloid derivatives showed substantial suppressive effects against all human tumor cell lines tested. In contrast, natural and derivatized C19-diterpenoid alkaloids showed only a slight or no effect. Most of the active compounds were hetisine-type C20-diterpenoid alkaloids, specifically kobusine and pseudokobusine analogs with two different substitution patterns, C-11 and C-11,15. Notably, several C20-diterpenoid alkaloids were more potent against multidrug-resistant KB subline KB-VIN cells. Pseudokobusine 11-3'-trifluoromethylbenzoate (94) is a possible promising new lead meriting additional evaluation against multidrug-resistant tumors.

  5. Analysis of Norditerpenoid Alkaloids Extracted from Aconitum sinomantanum Nakai by Electrospray Ionization Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Electrospray ionization mass spectrometry(ESI-MS) was applied simultaneously in determining norditerpenoid alkaloids from the roots of Aconitum sinomantanum Nakai (RAS) based on molecular mass information. The tandem mass spectra(ESI-MSn) provided the alkaloidal structural information, through which the existence of these alkaloids was further confirmed. Accordingly, six known norditerpenoid alkaloids were simultaneously determined on the basis of their ESI-MSn spectra. Furthermore, based on the diagnostic fragmentation pathways of alkaloidal MSn, a rapid method for direct detection and characterization of alkaloids from an ethanolic extract of RAS was described.

  6. Effect of Alkaloid-Free and Alkaloid-Rich preparations from Uncaria tomentosa bark on mitotic activity and chromosome morphology evaluated by Allium Test.

    Science.gov (United States)

    Kuraś, Mieczysław; Pilarski, Radosław; Nowakowska, Julita; Zobel, Alicja; Brzost, Krzysztof; Antosiewicz, Justyna; Gulewicz, Krzysztof

    2009-01-12

    Uncaria tomentosa (Willd.) DC. is the most popular Peruvian plant, used in folk medicine for different purposes. It contains thousands of active compounds with great content of alkaloids. Two different fractions of Alkaloid-Rich and Alkaloid-Free were researched on chromosome morphology, mitotic activity and phases indexes. Cells of Allium Test (meristematic cells of root tips) were incubated up to 24h in different concentrations of Alkaloid-Free and Alkaloid-Rich fraction obtained from Uncaria tomentosa bark followed by 48 h of postincubation in water. The chromosome morphology was analyzed and the content of mitotic and phase indexes were done. Individual compounds, oxindole alkaloids, phenolic compounds and sugars were determined. In Alkaloid-Rich and Alkaloid-Free fractions (different in chemical composition) we observed condensation and contraction of chromosomes (more in Alkaloid-Rich) with retardation and/or inhibition of mitoses and changed mitotic phases. Postincubation reversed results in the highest concentration which was lethal (in mostly Alkaloid-Rich fraction). Our studies indicate that different action can depend on different groups of active compounds in a preparation either containing alkaloids or not. Other fraction analysis may be useful in the future.

  7. Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners.

    Science.gov (United States)

    Senchina, David S; Hallam, Justus E; Kohut, Marian L; Nguyen, Norah A; Perera, M Ann d N

    2014-01-01

    Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation.

  8. Transgenic and mutation-based suppression of a berberine bridge enzyme-like (BBL) gene family reduces alkaloid content in field-grown tobacco.

    Science.gov (United States)

    Lewis, Ramsey S; Lopez, Harry O; Bowen, Steve W; Andres, Karen R; Steede, William T; Dewey, Ralph E

    2015-01-01

    Motivation exists to develop tobacco cultivars with reduced nicotine content for the purpose of facilitating compliance with expected tobacco product regulations that could mandate the lowering of nicotine levels per se, or the reduction of carcinogenic alkaloid-derived tobacco specific nitrosamines (TSNAs). A berberine bridge enzyme-like (BBL) gene family was recently characterized for N. tabacum and found to catalyze one of the final steps in pyridine alkaloid synthesis for this species. Because this gene family acts downstream in the nicotine biosynthetic pathway, it may represent an attractive target for genetic strategies with the objective of reducing alkaloid content in field-grown tobacco. In this research, we produced transgenic doubled haploid lines of tobacco cultivar K326 carrying an RNAi construct designed to reduce expression of the BBL gene family. Field-grown transgenic lines carrying functional RNAi constructs exhibited average cured leaf nicotine levels of 0.684%, in comparison to 2.454% for the untransformed control. Since numerous barriers would need to be overcome to commercialize transgenic tobacco cultivars, we subsequently pursued a mutation breeding approach to identify EMS-induced mutations in the three most highly expressed isoforms of the BBL gene family. Field evaluation of individuals possessing different homozygous combinations of truncation mutations in BBLa, BBLb, and BBLc indicated that a range of alkaloid phenotypes could be produced, with the triple homozygous knockout genotype exhibiting greater than a 13-fold reduction in percent total alkaloids. The novel source of genetic variability described here may be useful in future tobacco breeding for varied alkaloid levels.

  9. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Directory of Open Access Journals (Sweden)

    Bryan L. Stegelmeier

    2016-11-01

    Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

  10. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Science.gov (United States)

    Stegelmeier, Bryan L.; Colegate, Steven M.; Brown, Ammon W.

    2016-01-01

    Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. PMID:27916846

  11. Total synthesis of the indolizidine alkaloid tashiromine

    Directory of Open Access Journals (Sweden)

    McElhinney Alison D

    2008-01-01

    Full Text Available Abstract Background Tashiromine 1 is a naturally occurring indolizidine alkaloid. It has been the subject of thirteen successful total syntheses to date. Our own approach centres on the stereoselective construction of the indolizidine core by capture of an electrophilic acyliminium species by a pendant allylsilane. The key cyclisation precursor is constructed using olefin cross-metathesis chemistry, which has the potential to facilitate both racemic and asymmetric approaches, depending upon the choice of the allylsilane metathesis partner. Results The use of the allyltrimethylsilane cross-metathesis approach enables the rapid construction of the key cyclisation precursor 3 (3 steps from commercial materials, which undergoes acid-induced cyclisation to give the desired bicyclic indolizidine skeleton as a 96:4 mixture of diastereomers. Simple functional group interconversions allowed the completion of the total synthesis of racemic tashiromine in six steps (19% overall yield. Three chiral α-alkoxyallylsilanes (12,14 and 15 were prepared in enantioenriched form and their cross-metathesis reactions studied as part of a putative asymmetric approach to tashiromine. In the event, α-hydroxysilane 12 underwent isomerisation under the reaction conditions to acylsilane 17, while silanes 14 and 15 were unreactive towards metathesis. Conclusion A concise, stereoselective total synthesis of racemic tashiromine has been developed. Attempts to translate this into an asymmetric synthesis have thus far been unsuccessful.

  12. Alkaloids of the Annonaceae: occurrence and a compilation of their biological activities.

    Science.gov (United States)

    Lúcio, Ana Silvia Suassuna Carneiro; Almeida, Jackson Roberto Guedes da Silva; Da-Cunha, Emídio Vasconcelos Leitão; Tavares, Josean Fechine; Barbosa Filho, Jos Maria

    2015-01-01

    This chapter presents an overview of the chemistry and pharmacology of the alkaloids found in species of the Annonaceae family. The occurrence of alkaloids from Annonaceae species, as well as their chemical structures and pharmacological activities are summarized in informative and easy-to-understand tables. Within the Annonaceae family, the genera Annona, Duguetia, and Guatteria have led to many important publications. Valuable and comprehensive information about the structure of these alkaloids is provided. The alkaloids of the aporphine type represent the predominant group in this family. Many of the isolated alkaloids exhibit unique structures. In addition to the chemical structures, the pharmacological activities of some alkaloids are also presented in this chapter. Thus, the leishmanicidal, antimicrobial, antitumor, cytotoxic, and antimalarial activities observed for these alkaloids are highlighted. The chapter is presented as a contribution for the scientific community, mainly to enable the search for alkaloids in species belonging to the Annonaceae family.

  13. Biosynthesis, asymmetric synthesis, and pharmacology, including cellular targets, of the pyrrole-2-aminoimidazole marine alkaloids

    Digital Repository Service at National Institute of Oceanography (India)

    Al-Mourabit, A.; Zancanella, M.A.; Tilvi, S.; Romo, D.

    The pyrrole-2-aminoimidazole (P-2-AI) alkaloids are a growing family of marine alkaloids, now numbering well over 150 members, with high topographical and biological information content. Their intriguing structural complexity, rich and compact...

  14. Micelle assisted structural conversion with fluorescence modulation of benzophenanthridine alkaloids

    Science.gov (United States)

    Pradhan, Ankur Bikash; Bhuiya, Sutanwi; Haque, Lucy; Tiwari, Richa; Das, Suman

    2017-01-01

    In this study we have reported the anionic surfactant (Sodium dodecyl sulfate, SDS) driven structural conversion of two benzophenanthridine plant alkaloids namely Chelerythrine (herein after CHL) and Sanguinarine (herein after SANG). Both the alkaloids exist in two forms: the charged iminium and the neutral alkanolamine form. The iminium form is stable at low pH ( 10.1). The fluorescence intensity of the alkanolamine form is much stronger than the iminium form. The iminium form of both the alkaloids remains stable whereas the alkanolamine form gets converted to the iminium form in the SDS micelle environment. The iminium form possesses positive charge and it seems that electrostatic interaction between the positively charged iminium and negatively charged surfactant leads to the stabilization of the iminium form in the Stern layer of the anionic micelle. Whereas the conversion of the alkanolamine form into the iminium form takes place and that can be monitored in naked eye since the iminium form is orange in colour and the alkanolamine form has blue violet emission. Such a detail insight about the photophysical properties of the benzophenanthridine alkaloids would be a valuable addition in the field of alkaloid-surfactant interaction.

  15. HPTLC and GC/MS Study of Amaryllidaceae Alkaloids of Two Narcissus Species.

    Science.gov (United States)

    Shawky, Eman; Abou-Donia, Amina H; Darwish, Fikria A; Toaima, Soad M; Takla, Sarah S; Pigni, Natalia B; Bastida, Jaume

    2015-08-01

    In this article, we report on the alkaloid profile and dynamic of alkaloid content and diversity in two Narcissus plants at different stages of development. The alkaloid profile of the two Narcissus species was investigated by GC/MS and HPTLC. Fifty eight Amaryllidaceae alkaloids were detected, and 25 of them were identified in the different organs of N. tazetta and N. papyraceus. The alkaloid 3-O-methyl-9-O-demethylmaritidine is tentatively identified here for the first time from the Amaryllidaceae family, and four alkaloids (tazettamide, sternbergine, 1-O-acetyllycorine, 2,11-didehydro-2-dehydroxylycorine) are tentatively identified for the first time in the genus Narcissus. The different organs of the two species analyzed showed remarkable differences in their alkaloid pattern, type of biosynthesis, main alkaloid and number of alkaloids. Lycorine-type alkaloids dominated the alkaloid, metabolism in N. papyraceus, while alkaloids of narciclasine-, galanthamine- and homolycorine-types were found only in the species N. tazetta L.

  16. Steroidal glyco alkaloids and molluscicidal activity of Solanum asperum Rich. fruits

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Tania M.S. [Instituto Multidisciplinar em Saude, Vitoria da Conquista, BA (Brazil). Campus Avancado Anisio Teixeira]. E-mail: sarmento@pesquisador.cnpq.br; Camara, Celso A. [Universidade Federal Rural de Pernambuco, Recife, PE (Brazil). Dept. de Quimica; Freire, Kristerson R.L.; Silva, Thiago G. da; Agra, Maria de F.; Bhattacharyya, Jnanabrata [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica

    2008-07-01

    Bioassay-guided fractionation of the alkaloidal extract of the green fruits of Solanum asperum afforded a new compound, solanandaine along with solasonine and solamargine. The total crude alkaloids as well as the isolated pure alkaloids exhibited significant molluscicidal activity. (author)

  17. Three new C20-diterpenoid alkaloids from Delphinium anthriscifolium var. savatieri

    Institute of Scientific and Technical Information of China (English)

    Xiao Yu Liu; Qiao Hong Chen; Feng Peng Wang

    2009-01-01

    Three new C20-diterpenoid alkaloids, designated as anthriscifolmines A-C (1-3), together with two known alkaloids denudatine and delgramine, were isolated from the whole herb of Delphinium anthriscifolium var. savatieri. The structures of these new alkaloids were elucidated on the basis of spectral data.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. A Bisindole Alkaloid with Hedgehog Signal Inhibitory Activity from the Myxomycete Perichaena chrysosperma.

    Science.gov (United States)

    Shintani, Akinori; Toume, Kazufumi; Rifai, Yusnita; Arai, Midori A; Ishibashi, Masami

    2010-10-22

    6-Hydroxy-9'-methoxystaurosporinone (1), a new bisindole alkaloid, was isolated from field-collected fruiting bodies of the myxomycete Perichaena chrysosperma, together with two known compounds. The structure of the new alkaloid was elucidated from spectral data, and compound 1 was shown to have hedgehog signal inhibitory activity. A related new alkaloid, 6,9'-dihydroxystaurosporinone (4), was also isolated from Arcyria cinerea.

  20. Identification and quantification of isoquinoline alkaloids in the genus Sarcocapnos by GC-MS.

    Science.gov (United States)

    Suau, R; Cabezudo, B; Valpuesta, M; Posadas, N; Diaz, A; Torres, G

    2005-01-01

    Six cularine alkaloids, cularicine, O-methylcularicine, celtisine, cularidine, cularine and celtine, three isocularine alkaloids, sarcophylline, sarcocapnine and sarcocapnidine, and five non-cularine alkaloids, glaucine, protopine, ribasine, dihydrosanguinarine and chelidonine, were identified and quantified by GC-MS in nine taxa of the genus Sarcocapnos (Fumariaceae). The chemotaxonomic significance of the results is discussed.

  1. The Detection of Hepatotoxic Pyrrolizidine Alkaloids in Flos Farfarae by LC/MSn%中药款冬中肝毒吡咯里西啶生物碱的LC/MSn检测

    Institute of Scientific and Technical Information of China (English)

    濮社班; 徐德然; 张勉; 周红华; 王峥涛; 余国奠

    2004-01-01

    目的:中药款冬中微量成分肝毒吡咯里西啶生物碱(HPA)的检测.方法:采用薄层色谱法(TLC)、液相色谱与多级质谱联用法(LC/MSn).结果:从不同来源的款冬药材中检测到款冬中已有报道的2种HPA,并发现款冬中还含有另外3种HPA,分子量分别为299、341和366.结论:从7份款冬药材中共检测到5种HPA,对检测到的其他种类的HPA应进一步进行提取、分离与鉴定,并研究其毒性与活性;不同来源的款冬药材含有的HPA不完全相同,应分别检测.

  2. Molecular Identification of Ligularia Herbs Containing Hepatotoxic Pyrrolizidine Alkaloids%含吡咯里西啶生物碱的山紫菀类药材的分子鉴别

    Institute of Scientific and Technical Information of China (English)

    张达治; 张勉; 许翔鸿; 余国奠; 王峥涛

    2003-01-01

    目的:采用分子生物学的方法对含吡咯里西啶生物碱(HPAs)与不含吡咯里西啶生物碱的山紫菀类药材(橐吾属植物)进行鉴别.方法:采用CTAB法提取9种不同基源的山紫菀类药材的总DNA,进行PCR扩增和测序,并对序列进行系统分析.结果:通过提取、扩增和测序,得到了9种橐吾属植物的nrDNA ITS区间序列,统计分析结果得到了9种植物的遗传距离和转换、颠换数,分支分类结果得到了系统树.结论:9种橐吾属植物nrDNA ITS区间序列的分析结果表明了两类山紫菀类药材有着明显的区别,是两类药材鉴别的有效方法之一.

  3. 吡咯里西啶生物碱的细胞毒性及致毒机制研究进展%Advancement of investigation on cytotoxicity and mechanism of pyrrolizidine alkaloids

    Institute of Scientific and Technical Information of China (English)

    王军; 王长虹; 王峥涛

    2007-01-01

    吡咯里西啶生物碱广泛分布于6000多种高等植物中,是一类肝毒性很强的天然产物.吡咯里西啶生物碱在肝脏代谢成活性代谢物吡咯后产生肝毒性.利用体外细胞毒性研究方法评价吡咯里西啶生物碱的毒性,对于阐明吡咯里西啶生物碱的致毒机制,研究开发拮抗其毒性的药物及保证临床用药安全具有重要意义.本文对吡咯里西啶生物碱的细胞毒性及致毒机制的研究进展进行综述.

  4. 橐吾属植物中肝毒吡咯里西啶生物碱的LC/MSn检测%Detection of hepatotoxic pyrrolizidine alkaloids in Ligularia Cass.with LC/MSn

    Institute of Scientific and Technical Information of China (English)

    濮社班; 徐德然; 张勉; 周红华; 王峥涛; 余国奠

    2004-01-01

    目的橐吾属植物中微量成分肝毒吡咯里西啶生物碱(HPA)的检测.方法采用薄层色谱法(TLC)、液相色谱与多级质谱联用法(LC/MSn).结果对橐吾属22种植物进行了HPA的LC/MSn法检测,其中18种橐吾属植物中检测到了HPA.结论利用LC/MSn法首次检测到东俄洛橐吾等15种橐吾属植物含有不同类型和种类的HPA,应进一步进行提取、分离与鉴定,并研究其毒性与活性;对不同种类、不同来源的橐吾属植物材料应分别检测其滗HPA.

  5. Simultaneous determination of sesquiterpenes and pyrrolizidine alkaloids from the rhizomes of petasites hybridus (L.) G.M. et Sch. and dietary supplements using UPLC-UV and LC-TOF methods

    Science.gov (United States)

    Common Butterbur (Petasites hybridus) is a herbaceous perennial plant in the family Asteraceae, native to Europe and northern Asia. Petasites hybridus exists in two chemo-varieties: those containing petasins and those with furano-petasins which have been reported to be effective in reducing the occ...

  6. 含吡咯烷生物碱的中草药与肝小静脉闭塞病%Traditional Chinese Medicine Containing Pyrrolizidine Alkaloids and Hepatic Veno-Occlusive Disease

    Institute of Scientific and Technical Information of China (English)

    王强; 鲁重美; 郭涛

    2008-01-01

    目的 总结分析含吡咯烷生物碱(PAs)的中草药导致肝小静脉闭塞病(HVOD)的临床特点,提高对HVOD的病因及诊治认识.方法 对1980年至2006年国内报道的中草药导致HVOD病例10例,以及北京协和医院诊断的中草药导致HVOD 3例进行综合分析,并进行国内外相关文献复习.结果 国内报道的中草药致HVOD病例以土三七为主,占84.6%(11/13).土三七用量150 g~1 800 g(平均约582 g),用药持续时间10余天至4个月(平均42.5天);千里光致病者1例,嗜食茶叶致病者1例.HVOD临床症状主要为腹部胀痛、腹水、肝大、黄疸,可有不同程度的肝功能受损,多有GGT及ALP升高;超声下可见门脉血流减慢以及CT下不均匀脂肪肝样表现为其影像学特点;通过组织学诊断(9/13)和临床诊断(4/13).保守治疗好转者2例,肝移植2例,死亡5例.结论 含有吡咯烷生物碱的中草药是导致HVOD的一个重要原因,临床上应慎用此类药物.影像学检查有一定的特点,早期临床诊断对改善预后非常重要.

  7. 九里明抗菌镇痛有效部位中PAs的研究%Studies on Pyrrolizidine Alkaloids in Antimicrobial and Analgesic Part Extracted from Senecio Scandens

    Institute of Scientific and Technical Information of China (English)

    陈进军; 聂芳红; 赵生才; 林红英; 李明伟; 马驿; 徐晓彬; 冯羽裳

    2006-01-01

    采用试管分项提取预试法、系统提取预试法和圆形纸层析预试法,进行了九里明植物化学成分预试;利用硅胶G薄板层析法,Ehrlich试剂喷雾显色,对九里明全草及其抗菌镇痛有效部位中双稠吡咯啶生物碱进行了检查.结果发现,九里明全草含有黄酮及其甙类、蒽醌及其甙类、酚类、强心甙、氨基酸、鞣质、皂甙、有机酸和生物碱,不含氰甙、多肽、蛋白质、内酯、油脂和挥发油;九里明全草含有双稠吡咯啶生物碱,但九里明抗菌镇痛有效部位中则未检出双稠吡咯啶生物碱.

  8. The hepatotoxicity and detection methods for Chinese herb containing pyrrolizidine alkaloids%含吡咯烷生物碱中草药的肝毒性及其实验检测方法

    Institute of Scientific and Technical Information of China (English)

    李杨; 甘慧中; 许建明

    2010-01-01

    中草药中所含的吡咯烷生物碱(PA),是导致肝小静脉闭塞病(HVOD)的重要的植物性肝毒性成分.在体内和体外途径中,通过各种实验检测方法检测出PA的存在,对该病的早期诊断治疗以及中草药的管理都有重要意义.

  9. Activity of Alkaloids on Peptic Ulcer: What’s New?

    Directory of Open Access Journals (Sweden)

    Raphaela Francelino do Nascimento

    2015-01-01

    Full Text Available Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery of new drugs, due to their wide structural diversity and present, mostly specific and selective biological activities. Among natural products the alkaloids, biologically active secondary metabolites, that can be found in plants, animals or microorganisms stand out. The alkaloids are compounds consisting of a basic nitrogen atom that may or may not be part of a heterocyclic ring. This review will describe 15 alkaloids with antiulcer activity in animal models and in vitro studies.

  10. [Concentration and determination of strychnine alkaloid in biological fluids].

    Science.gov (United States)

    Zhang, Jing; He, Lang-chong; Fu, Qiang

    2005-02-01

    To establish a new method for determination of strychnine alkaloid in biological fluids based on molecularly imprinted polymers. A strychnine molecularly imprinted monolithic column was prepared by in-situ molecularly imprinted technique. The polymer was filled to a 1cm column, and a method was developed to concentrate and determine strychnine alkaloids in biological fluids. the limit of detection of the method was 4.9 ng, and the recoveries were more than 92%. The relative standard deviations were smaller than 6.59%. The linear correlation coefficients of standard curves were 0.999 1 and 0.9966 respectively. This method was applied to concentrate and determine strychnine in plasma and urine of poisoned rabbit. The new method could concentrate and simultaneously determine strychnine alkaloids in biological fluids, and it was applied to forensic toxicological analysis.

  11. Synthesis of bicyclic alkaloids from the iridoid antirrhinoside

    DEFF Research Database (Denmark)

    Frederiksen, Signe Maria

    The present thesis describes the isolation of the iridoid glucoside antirrhinoside from Antirrhinum majus, and the approaches made towards its transformation into analogues of biologically active compounds, with special interest in syntheses of bicyclic alkaloids.A synthetic piperidine monoterpene...... alkaloid was prepared from antirrhinoside by means of an enzymatic cleavage to afford the aglucone, followed by a double reductive amination with benzylamine hydrochloride and sodium cyanoborohydride. The resulting piperidine was modified by opening of the epoxide on the cyclopropane ring by azide...... strategy was therefore abandoned.A one-pot reaction involving ozonolysis and subsequent reduction of the 5,6-O-isopropylidene-2',3',4',6'-tetra-O-acetyl antirrhinoside yielded a diol, which was considered a potential intermediate in the preparation of enantiopure 3-azabicyclo[3.3.0]octane alkaloids...

  12. Nonaqueous CE ESI-IT-MS analysis of Amaryllidaceae alkaloids.

    Science.gov (United States)

    Zhang, Yulin; Chen, Zilin

    2013-03-01

    The Amaryllidaceae are widely distributed medical plants. Lycorine, lycoramine, lycoremine, and lycobetaine are the major active alkaloids in Amaryllidaceae plants. A nonaqueous CE ESI-IT-MS method for separation, identification, and quantification of the Amaryllidaceae alkaloids has been developed. The MS(1-3) behavior has been studied and the fragmentation pathways of main fragment ions have been proposed. The effects of several factors such as composition and concentration of buffer, applied voltage, composition, and flow rate of the sheath liquid, nebulizing gas pressure, flow rate, and temperature of drying gas were investigated. Under the optimal conditions, the linear concentration range of these compounds was wide with the correlation coefficient (R(2) ) >0.99. RSDs of migration time and peak areas were alkaloids in the Lycoris radiata roots.

  13. Terpenoid Indole Alkaloids Biosynthesis and Metabolic Engineering in Catharanthus roseus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Catharanthus roseus L. (Madagascar periwinkle) biosynthesizes a diverse array of secondary metabolites including anticancer dimeric alkaloids (vinblastine and vincristine) and antihypertensive alkaloids (ajmalicine and serpentine). The multi-step terpenoid indole alkaloids (TIAs) biosynthetic pathway in C. roseus is complex and is under strict molecular regulation. Many enzymes and genes involved in the TIAs biosynthesis have been studied in recent decades. Moreover,some regulatory proteins were found recently to control the production of TIAs in C. roseus. Based on mastering the rough scheme of the pathway and cloning the related genes, metabolic engineering of TIAs biosynthesis has been studied in C.roseus aiming at increasing the desired secondary metabolites in the past few years. The present article summarizes recent advances in isolation and characterization of TIAs biosynthesis genes and transcriptional regulators involved in the second metabolic control in C. roseus. Metabolic engineering applications in TIAs pathway via overexpression of these genes and regulators in C. roseus are also discussed.

  14. In vitro production of alkaloids: Factors, approaches, challenges and prospects

    Directory of Open Access Journals (Sweden)

    Sayeed Ahmad

    2013-01-01

    Full Text Available The wide diversity of plant secondary metabolites is largely used for the production of various pharmaceutical compounds. In vitro cell tissue or organ culture has been employed as a possible alternative to produce such industrial compounds. Tissue culture techniques provide continuous, reliable, and renewable source of valuable plant pharmaceuticals and might be used for the large-scale culture of the plant cells from which these secondary metabolites can be extracted. Alkaloids are one of the most important secondary metabolites known to play a vital role in various pharmaceutical applications leading to an increased commercial importance in recent years. The tissue culture techniques may be utilized to improve their production of alkaloids via somaclonal variations and genetic transformations. The focus of this review is toward the application of different tissue culture methods/techniques employed for the in vitro production of alkaloids with a systematic approach to improve their production.

  15. THE ALKALOID CYTISINE IN THE CELL CULTURE

    Directory of Open Access Journals (Sweden)

    Gazaliev A.M.

    2012-08-01

    Full Text Available Alkaloids are vegetative establishments of complex and original structure with nitrous heterocycles in the basis. For a long time they drew researchers’ attention because of their unique and specific physiological effect on alive organisms. Not all the representatives of the globe’s flora contain these unique substances. Alkaloid cytisine is to be found mainly in the plants of the fabaceous family - Fabaceae. For the cytisine production the seeds of Thermopsis lanceolata R.Br (T. lanceolata R.Br and Cytisus laburnum (C. laburnum are used as a raw material. The object of the research is T. lanceolata cell culture. Sterile sprouts are used at the first stage of the experiment. Callus genesis is accompanied with dedifferentiation. It leads to the cellular organization simplification. Based on an important property of a plant cell, such as totipotency, there appears the formation of the “de novo” biosynthetic device. The cultivation algorithm consists of two basic stages: (i the cultivation conditions optimization of callus with a high level of the primary metabolites biosynthesis (Aspartat – lysine; (ii the research of cultivation chemical and physical factors influence on the secondary metabolite (cytisine biosynthesis and accumulation. During the cultivation the Murashige and Skoog classical recipe of nutrient medium will be used. Optimization of the cultivation conditions will concern the phytohormones, macro- and micronutrients content, as the purpose of optimization is the production of the determined high-level competence embriogenical callus. The main problem is genetic heterogeneity of a cellular population and instability of morpho-physiological processes. The correct management of higher plants cells population is possible at the synchronization of a cellular cycle phases. The references analysis has shown that it is almost impossible to synchronize cellular cycles in the culture of plant tissue. The application of chemical

  16. Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids

    Science.gov (United States)

    Gonda, Steve R.; Valluri, Jagan V.

    2011-01-01

    microgravitation of an HFB do not need to maintain the same surface forces as in normal Earth gravitation, they can divert more energy sources to growth and differentiation and, perhaps, to biosynthesis of greater quantities of desired medicinal compounds. Because one can adjust the HFB to vary effective gravitation, one can also test the effects of intermediate levels of gravitation on biosynthesis of various products. The potential utility of this methodology for producing drugs was demonstrated in experiments in which sandalwood and Madagascar periwinkle cells were grown in an HFB. The conditions in the HFB were chosen to induce the cells to form into aggregate cultures that produced anti-cancer indole alkaloids in amounts greater than do comparable numbers of cells of the same species cultured according to previously known methodologies. The observations made in these experiments were interpreted as suggesting that the aggregation of the cells might be responsible for the enhancement of production of alkaloids.

  17. An insight on the alkaloid content of Capparis spinosa L. root by HPLC-DAD-MS, MS/MS and (1)H qNMR.

    Science.gov (United States)

    Khatib, Mohamad; Pieraccini, Giuseppe; Innocenti, Marzia; Melani, Fabrizio; Mulinacci, Nadia

    2016-05-10

    The Capparis spinosa L. has a wide distribution in the Old World from South Europe, North and East Africa, Madagascar, Southwest and Central Asia to Australia and Oceania. The consolidated traditional use of C. spinosa root as remedy against different pains in human is well known since the antiquity. Various secondary metabolites have been found in caper plant, nevertheless, few studies have been focused to the analysis of root constituents. To date, several free and glycosilated spermidine alkaloids and a more polar alkaloid, the stachydrine, have been isolated from the root of C. spinosa. Aim of this work was to improve the knowledge on the alkaloid content of the root of a Syrian sample of C. spinosa by HPLC-DAD-MS(n) and to propose methods to quantify these molecules in different raw extracts. A decoction, an hydroalcoholic extraction and a fractionation process to selectively recover the spermidine alkaloids were applied. To our knowledge, this is the first HPLC-DAD-MS(n) profile that pointed out the co-presence of stachydrine, several isobaric forms of capparispine and/or capparisine in free and glycosylated forms and some isobars of isocodonocarpine or codonocarpine as monoglycosides in extracts of C. spinosa root. The determination by HPLC/DAD for the spermidine alkaloids expressed as p-OH-coumaric acid gave values up to 3.5mg/g dried root and the stachydrine evaluated by (1)H NMR was close to 12.5mg/g dried root. Overall, the total alkaloids were almost doubled in hydroalcoholic extract with respect to the decoction, and the stachydrine in the cortex was almost double than in the whole root.

  18. Minor alkaloids from Guatteria dumetorum with antileishmanial activity.

    Science.gov (United States)

    Correa, Jhonny Edmith; Ríos, Carlos Hernán; del Rosario Castillo, Amparo; Romero, Luz I; Ortega-Barría, Eduardo; Coley, Phyllis D; Kursar, Thomas A; Heller, Maria Verónica; Gerwick, William H; Rios, Luis Cubilla

    2006-02-01

    Nine known alkaloids [(+)-isodomesticine (1), (+)-norisodomesticine (2), (+)-nantenine ( 3), (+)-neolitsine (4), (+)-lirioferine (5), (+)-N-methyllaurotetanine (6), (+)-norlirioferine (7), (+)-isoboldine (8) and (+)-reticuline (9)] were isolated from young leaves of Guatteria dumetorum. Their structures were confirmed by NMR, mass and UV spectral analysis and by comparison to literature data. The growth inhibitory activity of each alkaloid was determined against the parasite Leishmania mexicana. Compounds 1-4 all showed significant activity whereby potency increased when a methylenedioxy functionality was present, especially at the 1,2-positions.

  19. Molluscicidal acridone alkaloids from Angostura paniculata: isolation, structures, and synthesis.

    Science.gov (United States)

    Vieira, P C; Kubo, I; Kujime, H; Yamagiwa, Y; Kamikawa, T

    1992-08-01

    Two novel acridone alkaloids, cuspanine [1] and cusculine [2], were isolated from the CH2Cl2 extract of the leaves of Angostura paniculata (Rutaceae). Their structures were established as 1-hydroxy-2,3,5,6-tetramethoxy-9-acridone for 1 and 1,2,3,5,6-pentamethoxy-9-acridone for 2 by means of spectroscopic studies, in particular nmr. These structural assignments were confirmed by synthesis, using a direct metallation method as a key reaction. Both alkaloids exhibited moderate molluscicidal activity against an aquatic snail, Biomphalaria glabrata, and cytotoxicity against several types of carcinoma cell lines.

  20. Cat's claw oxindole alkaloid isomerization induced by common extraction methods

    Directory of Open Access Journals (Sweden)

    Samuel Kaiser

    2013-01-01

    Full Text Available Cat's claw oxindole alkaloids are prone to isomerization in aqueous solution. However, studies on their behavior in extraction processes are scarce. This paper addressed the issue by considering five commonly used extraction processes. Unlike dynamic maceration (DM and ultrasound-assisted extraction, substantial isomerization was induced by static maceration, turbo-extraction and reflux extraction. After heating under reflux in DM, the kinetic order of isomerization was established and equations were fitted successfully using a four-parameter Weibull model (R² > 0.999. Different isomerization rates and equilibrium constants were verified, revealing a possible matrix effect on alkaloid isomerization.