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Sample records for clerodane diterpenes casearins

  1. Clerodane diterpenes from bark of Croton urucurana baillon

    Energy Technology Data Exchange (ETDEWEB)

    Pizzolatti, Moacir G.; Bortoluzzi, Adailton J.; Brighente, Ines M.C.; Zuchinalli, Analice; Carvalho, Francieli K., E-mail: moacir.pizzolatti@ufsc.br [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Departamento de Qumica; Candido, Ana C. S.; Peres, Marize T.L.P. [Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Departamento de Hidraulica e Transportes

    2013-04-15

    The new clerodane diterpene methyl 3-oxo-12-epibarbascoate was isolated from the stem barks of Croton urucurana together with the known diterpene methyl 12-epibarbascoate. The structures of these compounds were elucidated by spectroscopic techniques and comparison with the literature data. The obtainment of crystals allowed the crystallographic analysis of X-ray diffraction of diterpenes, thus confirming the proposed structures. (author)

  2. Diterpene lactones with labdane, halimane and clerodane frameworks.

    Science.gov (United States)

    Silva, Lúcia; Gomes, Arlindo C; Rodilla, Jesus M L

    2011-04-01

    The labdane, halimane and clerodane type diterpenoids are compounds that have been isolated in plants of several families. These molecules and their derivatives with a lactone group on the side chain or on the decaline system, have a great interest because of their biological properties as insect antifeedant, antiviral, cytotoxic and trypanocidal. The scope of this review is lactones diterpenoids with labdane, halimane and clerodane frameworks.

  3. Isolation and structural elucidation of secondary metabolites from plants of the family Flacourtiaceae and Asclepiadaceae, and evaluation of biological activity of the sesquiterpene lactones and the diterpenes of Casearia sp

    International Nuclear Information System (INIS)

    Binns Quiros, Franklin

    2012-01-01

    A phytochemical study was realized of the plants Casearia aculeata, Casearia nitida and Asclepias verticillata, using experiments of nuclear magnetic resonance (NMR) of one and two dimensions. Ten secondary metabolites are isolated from C. aculeata and C. nitida. Three of the secondary metabolites have presented a structure known: a diterpene type kaurane: ent-kaurenic acid, a diterpene type pimarane: oxide of 3β-hydroximanoil and a steroid: 4-stigmastene-3-ona. Seven remaining compounds have corresponded to diterpene type clerodane of novel structure. Eight glycosides of poly oxidized pregnanes of novel structure are isolated from A. verticillata. In vitro tests of cytotoxicity and induction of caspase-3 are performed on leukemia cells type Jurkat T. These tests were performed at fifteen sesquiterpene lactones and at four diterpenes. The tests developed have had the purpose to describe structure-activity relationships that can be linked with the capacity to inhibit the factor NF-κB (sesquiterpene lactones) described in the literature and with the known mechanism of action induction of apoptosis in diterpenes type clerodane. A clear relationship between the capacity (high, intermediate or low) to inhibit the factor NF-κB and the capacity to induce to the caspase-3 has remained without observation in the sesquiterpene lactones. Some structural comparisons related with the cytotoxic capacity and the induction of the caspase-3 have been described for the series of LSs with carbon structure of pseudoguianolides. Diterpenes with carbon structure of diterpenes type clerodane have had greater cytotoxic activity with respect to without carbon structure. Diterpenes type clerodane isolated from the family Flacourtiaceae have been cytotoxics, their capacity to induce to the caspase-3 has remained without be nearby to induction realized by the actinomycin D (pure inducer of the caspase-3). (author) [es

  4. Natural and semi-synthetic clerodanes of Croton cajucara and their cytotoxic effects against ehrlich carcinoma and human K562 leukemia cells

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    Maciel, Maria Aparecida M. [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil). Dept. de Quimica; Martins, Jenilce R.; Pinto, Angelo C.; Kaiser, Carlos R. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Quimica; Esteves-Souza, Andressa; Echevarria, Aurea [Universidade Federal Rural do Rio de Janeiro, Seropedica, RJ (Brazil). Dept. de Quimica]. E-mail: echevarr@ufrrj.br

    2007-03-15

    The clerodane-type diterpene, trans-dehydrocrotonin (1) the major component of Croton cajucara has shown striking correlation with its therapeutic use in traditional folk medicine. Phytochemical investigations led to the isolation of the metabolites 1, cajucarinolide (6), isocajucarinolide (7), trans-crotonin (2), trans-cajucarin B (3), cis-cajucarin B (4), trans-cajucarin A (5), N-methyltyrosine, vanillic acid and 4-hydroxy-benzoic acid. 6 and 7 were synthesized in good yield by regiospecific oxidation of 1 using singlet-oxygen. All clerodanes were studied for their cytotoxic effects against human K562 leukemia and Ehrlich carcinoma cells. Ehrlich carcinoma assays with IC{sub 50} = 166 {mu}M (1), 164 {mu}M (2), 65 {mu}M (6) and 10 {mu}M (7) related to cell growth inhibitory effects were dose dependent. Furthermore, moderate cytotoxic activity against K562 leukemia cells was observed with IC{sub 50} = 38 {mu}M (3), 33 {mu}M (5), 36 {mu}M (6) and 43 {mu}M (7). The semi-synthetic 2, 6 and 7 showed similar results when compared to the corresponding natural clerodanes. (author)

  5. Natural and semi-synthetic clerodanes of Croton cajucara and their cytotoxic effects against ehrlich carcinoma and human K562 leukemia cells

    International Nuclear Information System (INIS)

    Maciel, Maria Aparecida M.; Martins, Jenilce R.; Pinto, Angelo C.; Kaiser, Carlos R.; Esteves-Souza, Andressa; Echevarria, Aurea

    2007-01-01

    The clerodane-type diterpene, trans-dehydrocrotonin (1) the major component of Croton cajucara has shown striking correlation with its therapeutic use in traditional folk medicine. Phytochemical investigations led to the isolation of the metabolites 1, cajucarinolide (6), isocajucarinolide (7), trans-crotonin (2), trans-cajucarin B (3), cis-cajucarin B (4), trans-cajucarin A (5), N-methyltyrosine, vanillic acid and 4-hydroxy-benzoic acid. 6 and 7 were synthesized in good yield by regiospecific oxidation of 1 using singlet-oxygen. All clerodanes were studied for their cytotoxic effects against human K562 leukemia and Ehrlich carcinoma cells. Ehrlich carcinoma assays with IC 50 = 166 μM (1), 164 μM (2), 65 μM (6) and 10 μM (7) related to cell growth inhibitory effects were dose dependent. Furthermore, moderate cytotoxic activity against K562 leukemia cells was observed with IC 50 = 38 μM (3), 33 μM (5), 36 μM (6) and 43 μM (7). The semi-synthetic 2, 6 and 7 showed similar results when compared to the corresponding natural clerodanes. (author)

  6. Methods for producing diterpenes

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention discloses that by combining different di TPS enzymes of class I and class II different diterpenes may be produced including diterpenes not identified in nature. Surprisingly it is revealed that a di TPS enzyme of class I of one species may be combined with a di TPS enzyme...... of class II from a different species, resulting in a high diversity of diterpenes, which can be produced....

  7. Clerodane Diterpenoids with Anti-hyperglycemic Activity from Tinospora crispa

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    Yuan Gao

    2016-10-01

    Full Text Available Abstract Four new clerodane diterpenoids, tinosporols A–C (2–4 and tinosporoside A (5, together with six known analogues were isolated from the vines of Tinospora crispa. Their structures were established by extensive spectroscopic analysis. The relative configuration at C-12 in the known diterpenoid borapetoside E (1, the major component of the plant, was firstly established with the aid of molecular model. Compound 1 significantly reduced serum glucose levels at dose-dependent manners in alloxan-induced hyperglycemic mice and db/db type 2 diabetic mice. Graphical Abstract

  8. Cytotoxic diterpenes from Scoparia dulcis.

    Science.gov (United States)

    Ahsan, Monira; Islam, S K N; Gray, Alexander I; Stimson, William H

    2003-07-01

    Four new labdane-derived diterpenes, iso-dulcinol (1), 4-epi-scopadulcic acid B (2), dulcidiol (4), and scopanolal (5), together with two known diterpenes, dulcinol/scopadulciol (3) and scopadiol (6), were isolated from the aerial parts of Scoparia dulcis. The structures were determined by extensive NMR studies. The crude extracts as well as the pure diterpenes showed cytotoxicity against a panel of six human stomach cancer cell lines.

  9. New neo-Clerodanes from Tinnea antiscorbutica Welv

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    Borges, Cristina M.P. [Agostinho Neto University, Luanda (Angola). Chemistry Department; Mendonca, Dina I.M.D. de; Pinheiro, Sandra C.S.; Vieira, Liliana, E-mail: disabel@ubi.pt [University of Beira Interior (UBI), Covilha (Portugal). Textile and Paper Materials Center and Chemistry Department; Mendonca, Antonio J.G. [University of Beira Interior (CICS/UBI), Covilha (Portugal). Health Sciences Research Centre; Gaspar, Jorge F.; Martins, Celia; Rueff, Jose [New University of Lisbon, Lisboa (Portugal). Faculty of Medical Sciences. Department of Genetics; Diakanawma, Carlos [Agostinho Neto University, Luanda (Angola). Biology Department

    2013-12-01

    Three new neo-clerodanes, antiscorbuticane A, antiscorbuticane B and antiscorbuticane C, and known compounds glutinol, friedelin, 5,7-dihydroxyflavanone (pinocembrin), 5-hydroxy-3,6,7,4'- tetramethoxyflavone, 5-hydroxy-3,6,7,3'4'-pentamethoxyflavone (artemetin), 5,4'-dihydroxy-3,6,7,3'-tetramethoxyflavone (penduletin) and 5,3',4'-trihydroxy-3,6,7-trimethoxyflavone (chrysosplenol D), were isolated from the methanol extract of Tinnea antiscorbutica. Antiscorbuticane B exhibited no mutagenic activity at doses of up to 250 Greek-Small-Letter-Mu g per plate (Ames test) and did not induce micronucleus formation in the V79 cell line at doses of up to 100 Greek-Small-Letter-Mu g mL{sup -1}. (author)

  10. New neo-Clerodanes from Tinnea antiscorbutica Welv

    International Nuclear Information System (INIS)

    Borges, Cristina M.P.; Mendonca, Dina I.M.D. de; Pinheiro, Sandra C.S.; Vieira, Liliana; Mendonca, Antonio J.G.; Gaspar, Jorge F.; Martins, Celia; Rueff, Jose; Diakanawma, Carlos

    2013-01-01

    Three new neo-clerodanes, antiscorbuticane A, antiscorbuticane B and antiscorbuticane C, and known compounds glutinol, friedelin, 5,7-dihydroxyflavanone (pinocembrin), 5-hydroxy-3,6,7,4'- tetramethoxyflavone, 5-hydroxy-3,6,7,3'4'-pentamethoxyflavone (artemetin), 5,4’-dihydroxy-3,6,7,3'-tetramethoxyflavone (penduletin) and 5,3',4'-trihydroxy-3,6,7-trimethoxyflavone (chrysosplenol D), were isolated from the methanol extract of Tinnea antiscorbutica. Antiscorbuticane B exhibited no mutagenic activity at doses of up to 250 μg per plate (Ames test) and did not induce micronucleus formation in the V79 cell line at doses of up to 100 μg mL -1 . (author)

  11. Furanolabdane diterpenes from Hypoestes purpurea.

    Science.gov (United States)

    Shen, Chien-Chang; Ni, Ching-Li; Huang, Yu-Ling; Huang, Ray-Ling; Chen, Chien-Chih

    2004-11-01

    Four new furanolabdane diterpenes, hypopurin A (1), hypopurin B (2), hypopurin C (3), and hypopurin D (4), together with eight lignans, alpha-O-methylcubebin, beta-O-methylcubebin, hinoquinin, helioxanthin, 7-hydroxyhinokinin, dehydroxycubebin, justicidine E, and (-)-hibalactone, as well as two triterpenes, lupeol and betulin, were isolated from the dried aerial part of Hypoestes purpurea. The structures of 1-4 were elucidated mainly on the basis of NMR and MS. Compound 1 was found to be moderately cytotoxic toward the KB cell line with an IC(50) value of 9.4 microM.

  12. Seasonal Variation of Cistus ladanifer L. Diterpenes

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    Juan Carlos Alías

    2012-07-01

    Full Text Available The exudate of Cistus ladanifer L. consists mainly of two families of secondary metabolites: flavonoids and diterpenes. The amount of flavonoids present in the leaves has a marked seasonal variation, being maximum in summer and minimum in winter. In the present study, we demonstrate that the amount of diterpenes varies seasonally, but with a different pattern: maximum concentration in winter and minimum in spring-summer. The experiments under controlled conditions have shown that temperature influences diterpene production, and in particular, low temperatures. Given this pattern, the functions that these compounds perform in C. ladanifer are probably different.

  13. Insect antifeedant ryanodane diterpenes from Persea indica

    OpenAIRE

    González-Coloma, Azucena; Terrero, David; Perales, Áurea; Escoubas, Pierre; Fraga, Braulio M.

    1996-01-01

    The new ryanodane diterpenes cinnzeylanone, ryanodol 14-monoacetate, and epi-cinnzeylanol have been isolated from Persea indica(Lauraceae). The structure of cinnzeylanone has been determined by X-ray analysis. These compounds proveds to be antifeedants against Spodoptera litura. Cinnzeylanol and ryanodol were the most active antifeedants of this plant, with a range of activity close to that of ryanodine. THis is the first report on the antifeedant effects of this class of diterpenes. Their st...

  14. Diterpenes: Advances in Neurobiological Drug Research.

    Science.gov (United States)

    Islam, Md Torequl; da Silva, Claucenira Bandeira; de Alencar, Marcus Vinícius Oliveira Barros; Paz, Márcia Fernanda Correia Jardim; Almeida, Fernanda Regina de Castro; Melo-Cavalcante, Ana Amélia de Carvalho

    2016-06-01

    A significant number of studies have been performed with diterpene effect on the brain. Our study aims to make a systematic revision on them. The initial purpose of this review was to screen diterpenes with neurological activity, in particular those that have already been studied and published in different journals (databases until August 2015). The second purpose was to make an action-wise discussion as results viewed on them by taking into drug discovery and development account. Diterpenes considered in this review were selected on the basis of updated information on them and having sufficient information on their screenings. We identified several examples of diterpenes having an interest in further study. We have included the possible sources of them as observed in evidence, their known molecular neurobiological mechanisms, and the active constituents responsible for such activities with the doses and test systems. Results suggest diterpenes to have neurobiological activities like neuro-protection, anti-epileptic, anxiolytic, anti-Alzheimer's disease, anti-Parkinson's disease, anti-cerebral ischemia, anti-neuropathic pain, anti-neuro-inflammatory, and many more. In conclusion, diterpenes may be the prominent candidates in neurobiological drug research. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Experimental and NMR theoretical methodology applied to geometric analysis of the bioactive clerodane trans-dehydrocrotonin

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    Soares, Breno Almeida; Firme, Caio Lima, E-mail: firme.caio@gmail.com, E-mail: caiofirme@quimica.ufrn.br [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Instituto de Quimica; Maciel, Maria Aparecida Medeiros [Universidade Potiguar, Natal, RN (Brazil). Programa de Pos-graduacao em Biotecnologia; Kaiser, Carlos R. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Quimica; Schilling, Eduardo; Bortoluzzi, Adailton J. [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Departamento de Quimica

    2014-04-15

    trans-Dehydrocrotonin (t-DCTN) a bioactive 19-nor-diterpenoid clerodane type isolated from Croton cajucara Benth, is one of the most investigated clerodane in the current literature. In this work, a new approach joining X-ray diffraction data, nuclear magnetic resonance (NMR) data and theoretical calculations was applied to the thorough characterization of t-DCTN. For that, the geometry of t-DCTN was reevaluated by X-ray diffraction as well as {sup 1}H and {sup 13}C NMR data, whose geometrical parameters where compared to those obtained from B3LYP/6-311G++(d,p) level of theory. From the evaluation of both calculated and experimental values of {sup 1}H and {sup 13}C NMR chemical shifts and spin-spin coupling constants, it was found very good correlations between theoretical and experimental magnetic properties of t-DCTN. Additionally, the delocalization indexes between hydrogen atoms correlated accurately with theoretical and experimental spin-spin coupling constants. An additional topological analysis from quantum theory of atoms in molecules (QTAIM) showed intramolecular interactions for t-DCTN. (author)

  16. Experimental and NMR theoretical methodology applied to geometric analysis of the bioactive clerodane trans-dehydrocrotonin

    International Nuclear Information System (INIS)

    Soares, Breno Almeida; Firme, Caio Lima; Maciel, Maria Aparecida Medeiros; Kaiser, Carlos R.; Schilling, Eduardo; Bortoluzzi, Adailton J.

    2014-01-01

    trans-Dehydrocrotonin (t-DCTN) a bioactive 19-nor-diterpenoid clerodane type isolated from Croton cajucara Benth, is one of the most investigated clerodane in the current literature. In this work, a new approach joining X-ray diffraction data, nuclear magnetic resonance (NMR) data and theoretical calculations was applied to the thorough characterization of t-DCTN. For that, the geometry of t-DCTN was reevaluated by X-ray diffraction as well as 1 H and 13 C NMR data, whose geometrical parameters where compared to those obtained from B3LYP/6-311G++(d,p) level of theory. From the evaluation of both calculated and experimental values of 1 H and 13 C NMR chemical shifts and spin-spin coupling constants, it was found very good correlations between theoretical and experimental magnetic properties of t-DCTN. Additionally, the delocalization indexes between hydrogen atoms correlated accurately with theoretical and experimental spin-spin coupling constants. An additional topological analysis from quantum theory of atoms in molecules (QTAIM) showed intramolecular interactions for t-DCTN. (author)

  17. Genus Cistus: a model for exploring labdane-type diterpenes' biosynthesis and a natural source of high value products with biological, aromatic and pharmacological properties

    Science.gov (United States)

    Papaefthimiou, Dimitra; Papanikolaou, Antigoni; Falara, Vasiliki; Givanoudi, Stella; Kostas, Stefanos; Kanellis, Angelos

    2014-06-01

    The family Cistaceae (Angiosperm, Malvales) consists of 8 genera and 180 species, with 5 genera native of the Mediterranean area (Cistus, Fumara, Halimium, Helianthemum and Tuberaria). Traditionally, a number of Cistus specie have been used in Mediterranean folk medicine as herbal tea infusions for healing, digestive problems and colds, as extracts for the treatment of diseases, and as fragrances. The resin, ladano, secreted by the glandular trichomes of certain Cistus species contains a number of phytochemicals with antioxidant, antibacterial, antifungal and anticancer properties. Furthermore, total leaf aqueous extracts possess anti-influenza virus activity. All these properties have been attributed to phytochemicals such as terpenoids, including diterpenes, labdane-type diterpenes and clerodanes, phenylpropanoids, including flavonoids and ellagitannins, several groups of alkaloids and other types of secondary metabolites. In the past 20 years, research on Cistus involved chemical, biological and phylogenetic analysis but recent investigations have involved genomic and molecular approaches. Our lab is exploring the biosynthetic machinery that generates terpenoids and phenylpropanoids, with a goal to harness their numerous properties that have applications in the pharmaceutical, chemical and aromatic industries. This review focuses on the systematics, botanical characteristics, geographic distribution, chemical analyses, biological function and biosynthesis of major compounds, as well as genomic analyses and biotechnological approaches of the main Cistus species found in the Mediterranean basin, namely C. albidus, C. creticus, C. crispus, C. parviflorus, C. monspeliensis, C. populifolius, C. salviifolius, C. ladanifer, C. laurifolius and C. clusii.

  18. Chemopreventive activity of compounds extracted from Casearia sylvestris (Salicaceae) Sw against DNA damage induced by particulate matter emitted by sugarcane burning near Araraquara, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Prieto, A.M. [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil, 1621, Araraquara (Brazil); Santos, A.G. [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Natural Principles and Toxicology, Rodovia Araraquara-Jau, km 01, Araraquara (Brazil); Csipak, A.R.; Caliri, C.M.; Silva, I.C. [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil, 1621, Araraquara (Brazil); Arbex, M.A. [UNIFESP — Federal University of São Paulo, Paulista College of Medicine, Department of Internal Medicine, Rua Pedro de Toledo, 720, São Paulo (Brazil); Silva, F.S.; Marchi, M.R.R. [UNESP — Univ. Estadual Paulista, Chemistry Institute, Department of Analytical Chemistry, Rua Francisco Degni, S/N, Araraquara (Brazil); Cavalheiro, A.J.; Silva, D.H.S.; Bolzani, V.S. [UNESP — Univ. Estadual Paulista, Chemistry Institute, Department of Organic Chemistry, Rua Francisco Degni, S/N, Araraquara (Brazil); Soares, C.P., E-mail: soarescp@hotmail.com [UNESP — Univ. Estadual Paulista, College of Pharmaceutical Sciences, Department of Clinical Analysis, Rua Expedicionários do Brasil, 1621, Araraquara (Brazil)

    2012-12-15

    Ethanolic extract of Casearia sylvestris is thought to be antimutagenic. In this study, we attempted to determine whether this extract and casearin X (a clerodane diterpene from C. sylvestris) are protective against the harmful effects of airborne pollutants from sugarcane burning. To that end, we used the Tradescantia micronucleus test in meiotic pollen cells of Tradescantia pallida, the micronucleus test in mouse bone marrow cells, and the comet assay in mouse blood cells. The mutagenic compound was total suspended particulate (TSP) from air. For the Tradescantia micronucleus test, T. pallida cuttings were treated with the extract at 0.13, 0.25, or 0.50 mg/ml. Subsequently, TSP was added at 0.3 mg/ml, and tetrads from the inflorescences were examined for micronuclei. For the micronucleus test in mouse bone marrow cells and the comet assay in mouse blood cells, Balb/c mice were treated for 15 days with the extract—3.9, 7.5, or 15.0 mg/kg body weight (BW)—or with casearin X—0.3, 0.25, or 1.2 mg/kg BW—after which they received TSP (3.75 mg/kg BW). In T. pallida and mouse bone marrow cells, the extract was antimutagenic at all concentrations tested. In mouse blood cells, the extract was antigenotoxic at all concentrations, whereas casearin X was not antimutagenic but was antigenotoxic at all concentrations. We conclude that C. sylvestris ethanolic extract and casearin X protect DNA from damage induced by airborne pollutants from sugarcane burning. -- Highlights: ► We assessed DNA protection of C. sylvestris ethanolic extract. ► We assessed DNA protection of casearin X. ► We used Tradescantia pallida micronucleus test as screening. ► We used comet assay and micronucleus test in mice. ► The compounds protected DNA against sugar cane burning pollutants.

  19. A new ent-clerodane diterpenoid from Crassocephalum bauchiense Huch. (Asteraceae).

    Science.gov (United States)

    Tchinda, Alembert T; Mouokeu, Simplice R; Ngono, Rosalie A N; Ebelle, Madeleine R E; Mokale, Aristide L K; Nono, Diane K; Frédérich, Michel

    2015-01-01

    A phytochemical investigation of the whole plant of Crassocephalum bauchiense Huch. resulted in the isolation of a new clerodane diterpenoid, ent-2β,18,19-trihydroxycleroda-3,13-dien-16,15-olide (1), together with two known flavonoids 3',5-dihydroxy-4',5',6,7,8-pentamethoxyflavone (2) and 4',5-dihydroxy-3',5',6,7,8-pentamethoxyflavone (3). The compounds were tested against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compound 2 showed weak activity (IC50 = 10.1 g/mL) whilst compounds 1 and 3 were inactive. The structures of the compounds were elucidated by using detailed spectral analyses, especially (1)H and (13)C NMR, (1)H-(1)H COSY, NOESY, HMBC and HR-ESI-MS.

  20. Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L. Jaeq.

    Directory of Open Access Journals (Sweden)

    Muhammad Khurram

    2015-08-01

    Full Text Available Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16, 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC = 64–128 µg/mL against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa.

  1. Natural membranes of Hevea brasiliensis latex as delivery system for Casearia sylvestris leaf components

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    Flávio A. Carvalho

    Full Text Available ABSTRACT Natural latex from Hevea brasiliensis (Wild. ex A.Juss Müll.Arg., Euphorbiaceae, showed angiogenic action and Casearia sylvestris Sw., Salicaceae, leaf derivatives presented anti-inflammatory and wound healing activities. Therefore, an association of these effects was interesting for wound healing applications. The aims of this study were the development of membranes of natural latex incorporated with C. sylvestris leaf derivatives (ethanolic extract, diterpene concentrated fraction and casearin J, their chemical and physical characterization, and the evaluation of in vitro skin permeation and retention of C. sylvestris bioactive secondary metabolites (diterpenes and phenolic compounds. The membranes were developed mixing hydroethanolic solutions of C. sylvestris derivatives with latex and drying them in a desiccator. They were characterized by infrared spectroscopy, scanning electron microscopy, water vapor permeability and mechanical resistance assays, demonstrating that all membranes were permeable, resistant and homogeneous in surfaces. The permeation and retention assays demonstrated dermal penetration of phenolic compounds for ethanolic extract membrane and of casearin-like clerodane diterpenes for all membranes, indicating that these membranes have great potential for therapeutical application as a topical system for C. sylvestris components releasing.

  2. Antifungal diterpenes from Hypoestes serpens (Acanthaceae).

    Science.gov (United States)

    Rasoamiaranjanahary, Lalao; Marston, Andrew; Guilet, David; Schenk, Kurt; Randimbivololona, Fanantenanirainy; Hostettmann, Kurt

    2003-02-01

    Two new diterpenes, fusicoserpenol A and dolabeserpenoic acid A, with antifungal activity, were isolated from leaves of Hypoestes serpens (Acanthaceae). Their structures were elucidated by means of spectrometric methods including 1D and 2D NMR experiments and MS analysis. X-ray crystallographic analysis confirmed the structure of fusicoserpenol A and established the relative configuration.

  3. Diterpenes from the Marine Algae of the Genus Dictyota.

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    Chen, Jiayun; Li, Hong; Zhao, Zishuo; Xia, Xue; Li, Bo; Zhang, Jinrong; Yan, Xiaojun

    2018-05-11

    Species of the brown algae of the genus Dictyota are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the discovery of diterpenes possessing broad chemical defensive activities from this genus. Most of these diterpenes exhibit significant biological activities, such as antiviral, cytotoxic and chemical defensive activities. In the present review, we summarized diterpenes isolated from the brown algae of the genus.

  4. New labdane diterpenes from Solidago canadensis.

    Science.gov (United States)

    Wangensteen, Helle; Phan, Thi T; Rise, Frode; Halvorsen, Trine G; Malterud, Karl E

    2012-01-01

    The ethanol extract of roots of Solidago canadensis yielded eight labdane-type diterpenes. Five of those were new natural compounds (9,13,15,16-bisepoxy-labdane-7-ene-6,15-dione (3a), 13-epi-9,13,15,16-bisepoxy-labdane-7-ene-6,15-dione (3b), 15,16-epoxy-labdane-7,13-diene-6,16-dione (5), 15-ethoxy-9,13,15,16-bisepoxy-labdane-7-ene-6-one (6a) and 13-epi-15-ethoxy-9,13,15,16-bisepoxy-labdane-7-ene-6-one (6b). The known labdane diterpenes deoxysolidagenone (1), solidagenone (2) and 15,16-epoxy-labdane-7,13-diene-6,15-dione (4) were also isolated. Chemical structures were determined using 1D and 2D NMR techniques and MS analysis.

  5. Pyrrolizidine alkaloids and diterpenes from Villasenoria orcuttii

    Energy Technology Data Exchange (ETDEWEB)

    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)

  6. Pyrrolizidine alkaloids and diterpenes from Villasenoria orcuttii

    International Nuclear Information System (INIS)

    Arciniegas, Amira; Pérez-Castorena, Ana L.; González, Karina; Vivar, Alfonso Romo de; Reyes-Lezama, Marisol; Villaseñor, José Luis

    2013-01-01

    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 α radiation, and its 1 H and 13 C nuclear magnetic resonance (NMR) data were corrected. (author)

  7. 13C-NMR of diterpenes with pimarane skeleton

    International Nuclear Information System (INIS)

    Garcez, W.S.; Pereira, A.L.; Silva Queiroz, P.P. da; Silva, R.S. da; Valente, L.M.M.; Peixoto, E.M.; Cunha Pinto, A. da

    1981-01-01

    The effect of substituent groups on the chemical shift of carbons using nuclear magnetic resonance spectra of carbon 13 ( 13 C-NMR) is discussed. Diterpenes having pimarane skeleton, isolated from plants of Velloziaceae family are analysed. (ARHC) [pt

  8. Neo-clerodane and abietane diterpenoids with neurotrophic activities from the aerial parts of Salvia leucantha Cav.

    Science.gov (United States)

    Li, Lai-Wei; Qi, Yan-Yan; Liu, Shi-Xi; Wu, Xing-De; Zhao, Qin-Shi

    2018-04-04

    Four new neoclerodane diterpenoids, leucansalvialins FI (1-4), and one rare 18(4 → 3)-abeo-abietane diterpenoid, leucansalvialin J (5), were isolated from the aerial part of Salvia leucantha Cav., along with 14 known analogues. Leucansalvialin F (1) represents the first rearranged salvigenane type clerodane-17,12:18,6-diolide. Their structures were elucidated by 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of 1, 2, 3, and 5 were determinded by X-ray diffraction crystal analysis and the ECD technique. All of the isolated components were evaluated for their neurotrophic activities on PC12 cells and all new compounds were evaluated for their cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480). Compounds 2 and 5 showed moderate neuroprotective effects in an in vitro assay. Copyright © 2018. Published by Elsevier B.V.

  9. Identificação de diterpenos clerodânicos em diferentes órgãos de Casearia sylvestris Swartz

    Directory of Open Access Journals (Sweden)

    Elisângela Simões de Carvalho

    2010-06-01

    Full Text Available

    Casearia sylvestris Swartz (Salicaceae é uma espécie vegetal arbórea ou arbustiva, disseminada pelo território brasileiro e bastante utilizada em nossa medicina popular. Diversos diterpenos clerodânicos bioativos típicos do gênero Casearia foram isolados desta espécie (ex. casearinas e casearvestrinas. O objetivo principal deste trabalho foi avaliar a presença de diterpenos clerodânicos em diferentes órgãos de C. sylvestris, utilizando técnicas analíticas cromatográficas e espectroscópicas. Os extratos dos diferentes órgãos foram analisados por cromatografia em camada delgada, cromatografia líquida de alta eficiência com detector de arranjo de diodos e ressonância magnética nuclear de 1H. Nas análises cromatográficas foram utilizados diterpenos clerodânicos isolados de C. sylvestris como padrões, incluindo rel-19S-acetóxi- 18R- butanoilóxi-18,19- epóxi -6S -hidróxi -2R- (2 metilbutanoilóxi -5S,8R, 9R, 10S -cleroda-3,13(16,14-trieno, isolado do caule pela primeira vez. Foram obtidos perfis fitoquímicos dos órgãos avaliados. Os resultados indicaram a presença de diterpenos clerodânicos em toda planta, prevalecendo em maior número nas folhas. Além disso, os resultados também indicam que em caules, flores e raízes há predomínio de diterpenos clerodânicos com padrão diênico diferente daqueles obtidos de folhas de C. sylvestris. Palavras-chave: Casearia sylvestris. Diterpenos clerodânicos. Salicaceae. Flacourtiaceae. Cromatografia. ABSTRACT Identification of clerodane diterpenes in different organs of Casearia sylvestris Swartz Casearia sylvestris Swartz (Salicaceae is a tree or shrub distributed widely in Brazil, where it is used in popular medicine. Several bioactive clerodane diterpenes typical of Casearia have been isolated from this species (e.g. casearins and casearvestrins. The main objective of this study was to identify clerodane diterpenes in various organs of C. sylvestris

  10. Evolution of Conifer Diterpene Synthases: Diterpene Resin Acid Biosynthesis in Lodgepole Pine and Jack Pine Involves Monofunctional and Bifunctional Diterpene Synthases1[W][OA

    Science.gov (United States)

    Hall, Dawn E.; Zerbe, Philipp; Jancsik, Sharon; Quesada, Alfonso Lara; Dullat, Harpreet; Madilao, Lina L.; Yuen, Macaire; Bohlmann, Jörg

    2013-01-01

    Diterpene resin acids (DRAs) are major components of pine (Pinus spp.) oleoresin. They play critical roles in conifer defense against insects and pathogens and as a renewable resource for industrial bioproducts. The core structures of DRAs are formed in secondary (i.e. specialized) metabolism via cycloisomerization of geranylgeranyl diphosphate (GGPP) by diterpene synthases (diTPSs). Previously described gymnosperm diTPSs of DRA biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of GGPP followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. In contrast, similar diterpenes of gibberellin primary (i.e. general) metabolism are produced by the consecutive activity of two monofunctional class II and class I diTPSs. Using high-throughput transcriptome sequencing, we discovered 11 diTPS from jack pine (Pinus banksiana) and lodgepole pine (Pinus contorta). Three of these were orthologous to known conifer bifunctional levopimaradiene/abietadiene synthases. Surprisingly, two sets of orthologous PbdiTPSs and PcdiTPSs were monofunctional class I enzymes that lacked functional class II active sites and converted (+)-copalyl diphosphate, but not GGPP, into isopimaradiene and pimaradiene as major products. Diterpene profiles and transcriptome sequences of lodgepole pine and jack pine are consistent with roles for these diTPSs in DRA biosynthesis. The monofunctional class I diTPSs of DRA biosynthesis form a new clade within the gymnosperm-specific TPS-d3 subfamily that evolved from bifunctional diTPS rather than monofunctional enzymes (TPS-c and TPS-e) of gibberellin metabolism. Homology modeling suggested alterations in the class I active site that may have contributed to their functional specialization relative to other conifer diTPSs. PMID:23370714

  11. Evolution of conifer diterpene synthases: diterpene resin acid biosynthesis in lodgepole pine and jack pine involves monofunctional and bifunctional diterpene synthases.

    Science.gov (United States)

    Hall, Dawn E; Zerbe, Philipp; Jancsik, Sharon; Quesada, Alfonso Lara; Dullat, Harpreet; Madilao, Lina L; Yuen, Macaire; Bohlmann, Jörg

    2013-02-01

    Diterpene resin acids (DRAs) are major components of pine (Pinus spp.) oleoresin. They play critical roles in conifer defense against insects and pathogens and as a renewable resource for industrial bioproducts. The core structures of DRAs are formed in secondary (i.e. specialized) metabolism via cycloisomerization of geranylgeranyl diphosphate (GGPP) by diterpene synthases (diTPSs). Previously described gymnosperm diTPSs of DRA biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of GGPP followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. In contrast, similar diterpenes of gibberellin primary (i.e. general) metabolism are produced by the consecutive activity of two monofunctional class II and class I diTPSs. Using high-throughput transcriptome sequencing, we discovered 11 diTPS from jack pine (Pinus banksiana) and lodgepole pine (Pinus contorta). Three of these were orthologous to known conifer bifunctional levopimaradiene/abietadiene synthases. Surprisingly, two sets of orthologous PbdiTPSs and PcdiTPSs were monofunctional class I enzymes that lacked functional class II active sites and converted (+)-copalyl diphosphate, but not GGPP, into isopimaradiene and pimaradiene as major products. Diterpene profiles and transcriptome sequences of lodgepole pine and jack pine are consistent with roles for these diTPSs in DRA biosynthesis. The monofunctional class I diTPSs of DRA biosynthesis form a new clade within the gymnosperm-specific TPS-d3 subfamily that evolved from bifunctional diTPS rather than monofunctional enzymes (TPS-c and TPS-e) of gibberellin metabolism. Homology modeling suggested alterations in the class I active site that may have contributed to their functional specialization relative to other conifer diTPSs.

  12. Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

    Science.gov (United States)

    Lovell, Kimberly M.; Prevatt-Smith, Katherine M.; Lozama, Anthony; Prisinzano, Thomas E.

    Salvinorin A is a neoclerodane diterpene that has been shown to be an agonist at kappa opioid receptors. Its unique structure makes it an attractive target for synthetic organic chemists due to its seven chiral centers and diterpene scaffold. This molecule is also interesting to pharmacologists because it is a non-serotonergic hallucinogen, and the first opioid ligand discovered that lacks a basic nitrogen. There have been several total synthesis approaches to salvinorin A, and these will be detailed within this chapter. Additionally, research efforts have concentrated on structure modification of the salvinorin A scaffold through semi-synthetic methods. Most modifications have focused on the manipulation of the acetate at C-2 and the furan ring. However, chemistry has also been developed to generate analogs at the C-1 ketone, the C-4 methyl ester, and the C-17 lactone. The synthetic methodologies developed for the salvinorin A scaffold will be described, as well as specific analogs with interesting biological activities.

  13. Antimicrobial Activity of Diterpenes from Viguiera arenaria against Endodontic Bacteria

    Directory of Open Access Journals (Sweden)

    Carlos H. G. Martins

    2011-01-01

    Full Text Available Six pimarane-type diterpenes isolated from Viguiera arenaria Baker and two semi-synthetic derivatives were evaluated in vitro against a panel of representative microorganisms responsible for dental root canal infections. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC against Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia, Prevotella buccae, Fusobacterium nucleatum, Bacteroides fragilis, Actinomyces naeslundii, Actinomyces viscosus, Peptostreptococcus micros, Enterococcus faecalis and Aggregatibacter actinomycetemcomitans. The compounds ent-pimara-8(14,15-dien-19-oic acid, its sodium salt and ent-8(14,15-pimaradien-3β-ol were the most active, displaying MIC values ranging from 1 to 10 μg mL-1. The results also allow us to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to the discovery of new chemicals for use as a complement to instrumental endodontic procedures.

  14. Antileishmanial activity of diterpene acids in copaiba oil

    Directory of Open Access Journals (Sweden)

    Adriana Oliveira dos Santos

    2013-02-01

    Full Text Available Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50 values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.

  15. Trachylobane and kaurane diterpenes from Croton floribundus spreng

    Energy Technology Data Exchange (ETDEWEB)

    Uchoa, Paula Karina S.; Silva Junior, Jose Nunes da; Silveira, Edilberto Rocha; Lima, Mary Anne S., E-mail: mary@dqoi.ufc.br [Departamento de Quimica Organica e Inorganica, Centro de Ciencias, Universidade Federal do Ceara, Fortaleza, CE (Brazil); Braz-Filho, Raimundo [Laboratorio de Ciencias Quimicas, Centro de Ciencias Tecnologicas, Universidade Estadual do Norte Fluminense, Campo dos Goytacazes, RJ (Brazil); Costa-Lotufo, Leticia Veras; Araujo, Ana Jersia; Moraes, Manoel Odorico de; Pessoa, Claudia do O [Departamento de Farmacologia e Fisiologia, Centro de Ciencias da Saude, Universidade Federal do Ceara, Fortaleza, CE (Brazil)

    2013-09-01

    A new trachylobane diterpene ent-trachyloban-18,19-diol (1) was isolated from root bark of Croton floribundus, along with known diterpenes ent-trachyloban-19-oic acid (2), 15{beta}-hydroxy-ent-trachyloban-19-oic acid (3), ent-trachyloban-19-ol (4), ent-kaur-16-en-19-oic acid (5), ent-kaur-16-ene-6{alpha},19-diol (6) and ent-16{alpha}-hydroxykaur-11-en-19-oic acid (7). ent-trachyloban-18,19-diol (1) was submitted to derivatization reactions affording four new compounds (8-11). Cytotoxic activity of diterpenes 1, 3, 4, 7-11 against three human cancer cell lines was evaluated. No compounds showed cytotoxic potential with IC{sub 50} values greater than 25 {mu}g/mL. Compound 6 was evaluated against five human cancer cell lines, showing moderate effect against three cancer cell lines, MDA-MB-435, HCT-8 and HCT-116, with IC{sub 50} values of 14.32, 13.47 and 12.1 {mu}g/mL, respectively. (author)

  16. Trachylobane and kaurane diterpenes from Croton floribundus spreng

    International Nuclear Information System (INIS)

    Uchôa, Paula Karina S.; Silva Junior, José Nunes da; Silveira, Edilberto Rocha; Lima, Mary Anne S.; Braz-Filho, Raimundo; Costa-Lotufo, Letícia Veras; Araújo, Ana Jérsia; Moraes, Manoel Odorico de; Pessoa, Claudia do Ó

    2013-01-01

    A new trachylobane diterpene ent-trachyloban-18,19-diol (1) was isolated from root bark of Croton floribundus, along with known diterpenes ent-trachyloban-19-oic acid (2), 15β-hydroxy-ent-trachyloban-19-oic acid (3), ent-trachyloban-19-ol (4), ent-kaur-16-en-19-oic acid (5), ent-kaur-16-ene-6α,19-diol (6) and ent-16α-hydroxykaur-11-en-19-oic acid (7). ent-trachyloban-18,19-diol (1) was submitted to derivatization reactions affording four new compounds (8-11). Cytotoxic activity of diterpenes 1, 3, 4, 7-11 against three human cancer cell lines was evaluated. No compounds showed cytotoxic potential with IC 50 values greater than 25 μg/mL. Compound 6 was evaluated against five human cancer cell lines, showing moderate effect against three cancer cell lines, MDA-MB-435, HCT-8 and HCT-116, with IC 50 values of 14.32, 13.47 and 12.1 μg/mL, respectively. (author)

  17. The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats

    Science.gov (United States)

    Campos, Debora Ribeiro; Celotto, Andrea Carla; Albuquerque, Agnes Afrodite S.; Ferreira, Luciana Garros; Monteiro, Ariadne Santana e Neves; Coelho, Eduardo Barbosa; Evora, Paulo Roberto Barbosa

    2017-01-01

    Background The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. Objective This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. Methods The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. Results The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. Conclusion The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects;The chemiluminescence plasmatic NO analysis showed no significant difference between groups andThe Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy. PMID:28678928

  18. A new labdane diterpene from the flowers of Solidago canadensis.

    Science.gov (United States)

    Bradette-Hébert, Marie-Eve; Legault, Jean; Lavoie, Serge; Pichette, André

    2008-01-01

    A new labdane diterpene, 9alpha,16xi-dihydroxy-6-oxo-7,13-labdadien-15,16-olide (solicanolide, 1) and six known compounds identified as quercetin (2), 3-O-caffeoylquinic acid (3, neochlorogenic acid), 5-O-caffeoylquinic acid (4, chlorogenic acid), 4,5-di-O-caffeoylquinic acid (5), 3,5-di-O-caffeoylquinic acid (6) and 3,4-di-O-caffeoylquinic acid (7) were isolated from the flowers of Solidago canadensis. To our knowledge, compound 7 was isolated for the first time in S. canadensis. This work describes the isolation of compounds 1-7 and the structure elucidation of a new compound identified as compound 1. Solicanolide (1) showed cytotoxic activity against A549 (IC(50): 13+/-2 microM), DLD-1 (IC(50): 26+/-2 microM) and WS1 (IC(50): 17+/-1 microM) cell lines.

  19. Diterpene and other constituents from Stemodia maritima (Scrophulariaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Francisco E.A.; Oliveira, Maria da Conceicao F. de; Vasconcelos, Jackson N.; Mafezoli, Jair; Arriaga, Angela M.C., E-mail: angelamcarriaga@yahoo.com.b [Universidade Federal do Ceara (DQOI/UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica. Curso de Pos-Graducao em Quimica; Lima, Jefferson Q. [Instituto Federal do Ceara, Juazeiro do Norte, CE (Brazil). Curso de Engenharia Ambiental; Santiago, Gilvandete M.P. [Universidade Federal do Ceara (DQOI/UFC), Fortaleza, CE (Brazil). Dept. de Farmacia; Braz-Filho, Raimundo [Universidade Estadual do Norte Fluminense Darcy Ribeiro (CCT/UENF), Campos dos Goytacazes, RJ (Brazil). Centro de Ciencias e Tecnologias

    2010-07-01

    A new diterpene, (5S{sup *},8S{sup *},9R{sup *},10S{sup *})-11{beta},12{beta}-epoxy-9{alpha}-hydroxy-19(4 -> 3)abeo-abieta-3,13-diene-19,18-olide, together with the known compounds stemodin, D-mannitol, betulinic acid, a mixture of 3{beta}-O-{beta}-D-glucopyranosyl-{beta}-sitosterol and 3{beta}-O-{beta}-D-glucopyranosylstigmasterol and 5,7,4'-trihydroxy-3,8,3'-trimethoxyflavone were isolated from the leaves and stems of Stemodia maritima. Structural elucidation of all compounds was based on interpretation of spectral data, mainly NMR (1D and 2D) and MS, including comparison with values described in the literature. (author)

  20. Diterpene and other constituents from Stemodia maritima (Scrophulariaceae)

    International Nuclear Information System (INIS)

    Rodrigues, Francisco E.A.; Oliveira, Maria da Conceicao F. de; Vasconcelos, Jackson N.; Mafezoli, Jair; Arriaga, Angela M.C.; Lima, Jefferson Q.; Santiago, Gilvandete M.P.; Braz-Filho, Raimundo

    2010-01-01

    A new diterpene, (5S * ,8S * ,9R * ,10S * )-11β,12β-epoxy-9α-hydroxy-19(4 -> 3)abeo-abieta-3,13-diene-19,18-olide, together with the known compounds stemodin, D-mannitol, betulinic acid, a mixture of 3β-O-β-D-glucopyranosyl-β-sitosterol and 3β-O-β-D-glucopyranosylstigmasterol and 5,7,4'-trihydroxy-3,8,3'-trimethoxyflavone were isolated from the leaves and stems of Stemodia maritima. Structural elucidation of all compounds was based on interpretation of spectral data, mainly NMR (1D and 2D) and MS, including comparison with values described in the literature. (author)

  1. Antiviral agents of plant origin. III. Scopadulin, a novel tetracyclic diterpene from Scoparia dulcis L.

    Science.gov (United States)

    Hayashi, T; Kawasaki, M; Miwa, Y; Taga, T; Morita, N

    1990-04-01

    The structure and stereochemistry of scopadulin, a novel aphidicolane-type diterpene isolated from Scoparia dulcis L. have been established from spectral data and single-crystal X-ray analysis of its acetone solvate.

  2. Volatile diterpene emission by two Mediterranean Cistaceae shrubs.

    Science.gov (United States)

    Yáñez-Serrano, A M; Fasbender, L; Kreuzwieser, J; Dubbert, D; Haberstroh, S; Lobo-do-Vale, R; Caldeira, M C; Werner, C

    2018-05-01

    Mediterranean vegetation emits a wide range of biogenic volatile organic compounds (BVOCs) among which isoprenoids present quantitatively the most important compound class. Here, we investigated the isoprenoid emission from two Mediterranean Cistaceae shrubs, Halimium halimifolium and Cistus ladanifer, under controlled and natural conditions, respectively. For the first time, diurnal emission patterns of the diterpene kaurene were detected in real-time by Proton-Transfer-Reaction-Time-of-Flight-Mass-Spectrometer. Kaurene emissions were strongly variable among H. halimifolium plants, ranging from 0.01 ± 0.003 to 0.06 ± 0.01 nmol m -2 s -1 in low and high emitting individuals, respectively. They were in the same order of magnitude as monoterpene (0.01 ± 0.01 to 0.11 ± 0.04 nmol m -2 s -1 ) and sesquiterpene (0.01 ± 0.01 to 0.52 nmol m -2 s -1 ) emission rates. Comparable range and variability was found for C. ladanifer under natural conditions. Labelling with 13 C-pyruvate suggested that emitted kaurene was not derived from de novo biosynthesis. The high kaurene content in leaves, the weak relationship with ecophysiological parameters and the tendency of higher emissions with increasing temperatures in the field indicate an emission from storage pools. This study highlights significant emissions of kaurene from two Mediterranean shrub species, indicating that the release of diterpenes into the atmosphere should probably deserve more attention in the future.

  3. Structure and mechanism of the diterpene cyclase ent-copalyl diphosphate synthase

    Energy Technology Data Exchange (ETDEWEB)

    Köksal, Mustafa; Hu, Huayou; Coates, Robert M.; Peters, Reuben J.; Christianson, David W. (UIUC); (Iowa State); (Penn)

    2011-09-20

    The structure of ent-copalyl diphosphate synthase reveals three {alpha}-helical domains ({alpha}, {beta} and {gamma}), as also observed in the related diterpene cyclase taxadiene synthase. However, active sites are located at the interface of the {beta}{gamma} domains in ent-copalyl diphosphate synthase but exclusively in the {alpha} domain of taxadiene synthase. Modular domain architecture in plant diterpene cyclases enables the evolution of alternative active sites and chemical strategies for catalyzing isoprenoid cyclization reactions.

  4. Variability of some diterpene esters in coffee beverages as influenced by brewing procedures.

    Science.gov (United States)

    Moeenfard, Marzieh; Erny, Guillaume L; Alves, Arminda

    2016-11-01

    Several coffee brews, including classical and commercial beverages, were analyzed for their diterpene esters content (cafestol and kahweol linoleate, oleate, palmitate and stearate) by high performance liquid chromatography with diode array detector (HPLC-DAD) combined with spectral deconvolution. Due to the coelution of cafestol and kahweol esters at 225 nm, HPLC-DAD did not give accurate quantification of cafestol esters. Accordingly, spectral deconvolution was used to deconvolve the co-migrating profiles. Total cafestol and kahweol esters content of classical coffee brews ranged from 5-232 to 2-1016 mg/L, respectively. Commercial blends contained 1-54 mg/L of total cafestol esters and 2-403 mg/L of total kahweol esters. Boiled coffee had the highest diterpene esters content, while filtered and instant brews showed the lowest concentrations. However, individual diterpene esters content was not affected by brewing procedure as in terms of kahweol esters, kahweol palmitate was the main compound in all samples, followed by kahweol linoleate, oleate and stearate. Higher amounts of cafestol palmitate and stearate were also observed compared to cafestol linoleate and cafestol oleate. The ratio of diterpene esters esterified with unsaturated fatty acids to total diterpene esters was considered as measure of their unsaturation in analyzed samples which varied from 47 to 52%. Providing new information regarding the diterpene esters content and their distribution in coffee brews will allow a better use of coffee as a functional beverage.

  5. Molecular Signaling Pathways Behind the Biological Effects of Salvia Species Diterpenes in Neuropharmacology and Cardiology.

    Science.gov (United States)

    Akaberi, M; Iranshahi, M; Mehri, S

    2016-06-01

    The genus Salvia, from the Lamiaceae family, has diverse biological properties that are primarily attributable to their diterpene contents. There is no comprehensive review on the molecular signaling pathways of these active components. In this review, we investigated the molecular targets of bioactive Salvia diterpenes responsible for the treatment of nervous and cardiovascular diseases. The effects on different pathways, including apoptosis signaling, oxidative stress phenomena, the accumulation of amyloid beta plaques, and tau phosphorylation, have all been considered to be mechanisms of the anti-Alzheimer properties of Salvia diterpenes. Additionally, effects on the benzodiazepine and kappa opioid receptors and neuroprotective effects are noted as neuropharmacological properties of Salvia diterpenes, including tanshinone IIA, salvinorin A, cryptotanshinone, and miltirone. Tanshinone IIA, as the primary diterpene of Salvia miltiorrhiza, has beneficial activities in heart diseases because of its ability to scavenge free radicals and its effects on transcription factors, such as nuclear transcription factor-kappa B (NF-κB) and the mitogen-activated protein kinases (MAPKs). Additionally, tanshinone IIA has also been proposed to have cardioprotective properties including antiarrhythmic activities and effects on myocardial infarction. With respect to the potential therapeutic effects of Salvia diterpenes, comprehensive clinical trials are warranted to evaluate these valuable molecules as lead compounds. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases.

    Directory of Open Access Journals (Sweden)

    Kyle A Pelot

    Full Text Available Plants produce an immense diversity of natural products (i.e. secondary or specialized metabolites that offer a rich source of known and potentially new pharmaceuticals and other desirable bioproducts. The Traditional Chinese Medicinal plant Isodon rubescens (Lamiaceae contains an array of bioactive labdane-related diterpenoid natural products. Of these, the ent-kauranoid oridonin is the most prominent specialized metabolite that has been extensively studied for its potent antimicrobial and anticancer efficacy. Mining of a previously established transcriptome of I. rubescens leaf tissue identified seven diterpene synthase (diTPSs candidates. Here we report the functional characterization of four I. rubescens diTPSs. IrTPS5 and IrTPS3 were identified as an ent-copalyl diphosphate (CPP synthase and a (+-CPP synthase, respectively. Distinct transcript abundance of IrTPS5 and the predicted ent-CPP synthase IrTPS1 suggested a role of IrTPS5 in specialized ent-kaurene metabolism possibly en route to oridonin. Nicotiana benthamiana co-expression assays demonstrated that IrTPS4 functions sequentially with IrTPS3 to form miltiradiene. In addition, IrTPS2 converted the IrTPS3 product (+-CPP into the hydroxylated tricyclic diterpene nezukol not previously identified in I. rubescens. Metabolite profiling verified the presence of nezukol in I. rubescens leaf tissue. The proposed IrTPS2-catalyzed reaction mechanism proceeds via the common ionization of the diphosphate group of (+-CPP, followed by formation of an intermediary pimar-15-en-8-yl+ carbocation and neutralization of the carbocation by water capture at C-8 to yield nezukol, as confirmed by nuclear magnetic resonance (NMR analysis. Oxygenation activity is rare for the family of class I diTPSs and offers new catalysts for developing metabolic engineering platforms to produce a broader spectrum of bioactive diterpenoid natural products.

  7. The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats.

    Science.gov (United States)

    Campos, Debora Ribeiro; Celotto, Andrea Carla; Albuquerque, Agnes Afrodite S; Ferreira, Luciana Garros; Monteiro, Ariadne Santana E Neves; Coelho, Eduardo Barbosa; Evora, Paulo Roberto Barbosa

    2017-06-29

    The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects; The chemiluminescence plasmatic NO analysis showed no significant difference between groups and The Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy. O diterpeno Esclareol tem ação antimicrobiana, efeitos citotóxicos e citostáticos e atividades antitumorais. No entanto, pesquisas sobre o sistema cardiovascular são escassas. Este estudo foi desenvolvido para investigar os mecanismos envolvidos no efeito cardiovascular de Esclareol em ratos normotensos e hipertensos. A hipertensão arterial foi promovida utilizando modelo de

  8. Additional Minor Diterpene Glycosides from Stevia rebaudiana Bertoni

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2013-10-01

    Full Text Available Two additional novel minor diterpene glycosides were isolated from the commercial extract of the leaves of Stevia rebaudiana Bertoni. The structures of the new compounds were identified as 13-{β-D-glucopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-xylopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3]-O-β-D-glucupyranosyl-ester} (1, and 13-{β-D-6-deoxy-glucopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-glucopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3-β-D-gluco-pyranosyl-ester} (2, on the basis of extensive 1D (1H- and 13C- 2D NMR (COSY, HSQC and HMBC and MS spectroscopic data as well as chemical studies.

  9. Three New Cytotoxic ent-Kaurane Diterpenes from Isodon excisoides

    Directory of Open Access Journals (Sweden)

    Li-Ping Dai

    2015-09-01

    Full Text Available Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1; 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2; and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3; together with six known diterpenes henryin (4; kamebanin (5; reniformin C (6; kamebacetal A (7; kamebacetal B (8; and oridonin (9. The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC50 values ranging from 1.09–8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC50 values ranging from 1.31–2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity.

  10. Diterpenes from buds of Wikstroemia chamaedaphne showing anti-hepatitis B virus activities.

    Science.gov (United States)

    Li, Shi-Fei; Jiao, Ying-Ying; Zhang, Zhi-Qiang; Chao, Jian-Bin; Jia, Jie; Shi, Xun-Long; Zhang, Li-Wei

    2018-07-01

    Phytochemical study of the buds of Wikstroemia chamaedaphne Meisn. led to the isolation of seven previously undescribed diterpenes, including one tigliane diterpene (wikstchalide A), two daphnane diterpenes (wikstroelides W-X), and four lathyrane diterpenes (laurifoliosides A-B and 2-epi-laurifoliosides A-B), along with four known diterpenes. The structures of these compounds were established by extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. Wikstchalide A possesses a 5,6-epoxy ring in the tigliane skeleton. Two compounds exhibited potential anti-hepatitis B virus activities, with IC 50 values of 46.5 and 88.3 μg/mL against hepatitis B virus (HBV) surface antigen (HBsAg), and six compounds showed certain inhibitory effects on HBV-DNA replication with the inhibition ratios ranging from 2.0% to 33.0% at the concentrations ranging from 0.39 to 6.25 μg/mL. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. The Remarkable Structural Diversity Achieved in ent-Kaurane Diterpenes by Fungal Biotransformations

    Directory of Open Access Journals (Sweden)

    Jacqueline A. Takahashi

    2014-02-01

    Full Text Available The use of biotransformations in organic chemistry is widespread, with highlights of interesting applications in the functionalization of natural products containing unactivated carbons, like the kaurane diterpenes. A number of compounds with kaurane skeletons can be isolated in large amounts from several plant species and a myriad of biological activities has been related to these compounds. Studies on structure versus activity have showed that, in most cases, in kaurane diterpenes, activity increases with the increase of functionalization. Since naturally occurring kaurane diterpenes usually have limited functional groups to be used as targets for semi-synthetic modifications, production of more polar derivatives from kaurane diterpenes have been achieved mostly through the use of fungal biotransformations. In this review, selected examples the wonderful chemical diversity produced by fungi in kaurane diterpenes is presented. This diversity includes mainly hydroxylation of nearly all carbon atoms of the kaurane molecule, many of them carried out stereoselectively, as well as ring rearrangements, among other chemical modifications. Sources of starting materials, general biotransformation protocols employed, fungi with most consistent regioselectivity towards kaurane skeleton, as well as biological activities associated with starting materials and products are also described.

  12. Effects of diterpene acids on components of a conifer bark beetle-fungal interaction : tolerance by Ips pini and sensitivity by its associate Ophiostoma ips

    Science.gov (United States)

    Brian J. Kopper; Barbara L. Illman; Philip J. Kersten; Kier D. Klepzig; Kenneth F. Raffa

    2005-01-01

    Conifer resin and phloem tissue contain several phytochemical groups, composed primarily of monoterpenes, diterpene acids, and stilbene phenolics. The effects of monoterpenes and phenolics on stem-colonizing bark beetles and their associated microorganisms have been studied to some extent, but the roles of diterpene acids are largely unknown. Diterpene acids are known...

  13. Effects of diterpene acids on components of a conifer bark beetle–fungal interaction: tolerance by Ips pini and sensitivity by its associate Ophiostoma ips

    Science.gov (United States)

    Brian J. Kopper; Barbara L. Illman; Philip J. Kersten; Kier D. Klepzig; Kenneth F. Raffa

    2005-01-01

    Conifer resin and phloem tissue contain several phytochemical groups,composed primarily of monoterpenes,diterpene acids, and stilbene phenolics. The effects of monoterpenes and phenolics on stem-colonizing bark beetles and their associated microorganisms have been studied to some extent, but the roles of diterpene acids are largely unknown. Diterpene acids are known to...

  14. Spectroscopic data of Labdane Diterpenes: a theoretical analysis via NMR and DFT

    International Nuclear Information System (INIS)

    Souza, Fabrine S. de; Silva, Silvana de O.; Alves, Cláudio N.; Guilhon, Giselle M.S.P.

    2015-01-01

    Labdane diterpenes exhibit important bioactivities such as cardiovascular effects in rats as well as effects in the treatment of autoimmune diseases and Alzheimer syndrome. Recently, the labdane diterpenes ent-13-epi-manoil oxide, ribenone and ribenol were isolated from Croton palanostigma. The computational method DFT/B3LYP/cc-pVDZ was used to optimize the structures of these diterpenes and to calculate infrared data. Chemical shifts (δ H and δ C ) of the minimum energy structures (local minimum) were calculated and compared with the experimental data. Comparison of the NMR data by simple linear regression (SLR) showed satisfactory statistical results with a correlation coefficient (R 2 ) and predictive ability (Q 2 ) of over 98%. The predicted NMR data were used to confirm the δ H values that have not been published. (author)

  15. Three new cyathane diterpenes with neurotrophic activity from the liquid cultures of Hericium erinaceus.

    Science.gov (United States)

    Zhang, Yuting; Liu, Li; Bao, Li; Yang, Yanlong; Ma, Ke; Liu, Hongwei

    2018-05-21

    Three new cyathane diterpenes erinacines T-V (1-3), and two known cyathane diterpenes erinacine A (4) and erinacine P (5) were isolated from the liquid cultures of Hericium erinaceus. The structures of 1-3 were determined by extensive spectroscopic analysis. All isolated compounds were evaluated for the cytotoxicity, and neurite-promoting activities using PC12 cell line. Compounds 1-3, and 5 exhibited pronounced neurite outgrowth-promoting effects on PC12 cells in the range of 2.5-10 μM. Compound 4 showed weak cytotoxicity against PC12 cells with IC 50 of 73.7 μM.

  16. The effect of the diterpene 5-epi-icetexone on the cell cycle of Trypanosoma cruzi.

    NARCIS (Netherlands)

    Lozano, E.; Barrera, P.; Tonn, C.; Nieto, M.; Sartor, T.; Sosa, M.A.

    2012-01-01

    Numerous natural compounds have been used against Trypanosoma cruzi, the causative agent of Chagas' disease. Here, we studied the effect of the diterpene 5-epi-icetexone on growth and morphology of parasites synchronized with hydroxyurea, at different periods of time after removal of the nucleotide.

  17. Investigation on traditional medicines of Guarany Indio and studies on diterpenes from Scoparia dulcis.

    Science.gov (United States)

    Hayashi, Toshimitsu

    2011-01-01

    In interviews on the traditional herbal medicines of Tupi-Guarany Indians at the herbal market of Asuncion and questionnaire from their users, it was clarified that various useful medicinal plants are available in Paraguay and most of them are generally used without drying. In the search for bioactive substances from those plants, a β-glucuronidase-inhibitory diterpene called scoparic acid A (SA) was isolated from Scoparia dulcis L. together with scoparic acid B, scoparic acid C, and the aphidicolin-like tetracyclic diterpenes scopadulcic acid A (SDA) and scopadulcic acid B (SDB). HPLC analysis of diterpenes in the individual plants of Paraguayan and Asian S. dulcis revealed the presence of three chemotypes based on major component, i.e., SA type, SDB type, and SDX type containing mainly scopadiol and scopadulciol (SDC). SA and SDB were elucidated to be mainly biosynthesized in the leaves via 2-C-methyl-D-erythritol- 4-phosphate pathway, and a leaf organ culture system containing methyl jasmonate 10 µM was found to enhance the production of diterpenes by activation of Ca-signal transduction systems such as calmodulin and protein kinase C. On the other hand, SDB and SDC were found to show multifaceted pharmacological effects such as inhibitory effects on gastric acid excretion, bone resorption, replication of herpes simplex virus type 1 (HSV-1), etc. In addition, SDC was suggested to be applicable to cancer gene therapy using ganciclovir or acyclovir and the HSV-1 thymidine kinase gene called the suicide gene.

  18. Overcoming the plasticity of plant specialized metabolism for selective diterpene production in yeast

    DEFF Research Database (Denmark)

    Ignea, Codruta; Athanasakoglou, Anastasia; Andreadelli, Aggeliki

    2017-01-01

    of the enzymes involved. The pathway of carnosic acid-related diterpenes in rosemary and sage involves promiscuous cytochrome P450s whose combined activity results in a multitude of structurally related compounds. Some of these minor products, such as pisiferic acid and salviol, have established bioactivity...

  19. Artificial intelligence applied to natural products; computer study of pimarane diterpene

    International Nuclear Information System (INIS)

    Lopes, M.N.; Borges, J.H.G.; Furlan, M.; Gastmans, J.P.; Emerenciano, V. de

    1989-01-01

    This paper describes the study of the sup(13)C NMR characteristic signals of naturally occurring pimarane. The analysis is performed by computer, starting from a data base which encloses about 400 diterpenes and using the PICKUPS programm. BNy this way it is possible to analyse substructure from one to five atoms as well as the effects of substituents on them. (author)

  20. Expanding the landscape of diterpene structural diversity by stereochemically controlled combinatorial biosynthesis

    DEFF Research Database (Denmark)

    Andersen-Ranberg, Johan; Kongstad, Kenneth Thermann; Nielsen, Morten Thrane

    2016-01-01

    Plant derived diterpenoids are relevant as pharmaceuticals, food additives and fragrances, yet a broader industrial utilization of these bioproducts is limited due to their low natural abundance and high structural complexity. Mimicking the modularity of diterpene biosynthesis in plants, we const...

  1. Chemotaxonomy of three genera of the Annonaceae family using self-organizing maps and 13C NMR data of diterpenes

    International Nuclear Information System (INIS)

    Scotti, Luciana; Tavares, Josean Fechine; Silva, Marcelo Sobral da; Falcao, Emanuela Viana; Silva, Luana de Morais e; Soares, Gabriela Cristina da Silva; Scotti, Marcus Tullius

    2012-01-01

    The Annonaceae family is distributed throughout Neotropical regions of the world. In Brazil, it covers nearly all natural formations particularly Annona, Xylopia and Polyalthia and is characterized chemically by the production of sources of terpenoids (mainly diterpenes), alkaloids, steroids, polyphenols and, flavonoids. Studies from 13 C NMR data of diterpenes related with their botanical occurrence were used to generate self-organizing maps. Results corroborate those in the literature obtained from morphological and molecular data for three genera and the model can be used to project other diterpenes. Therefore, the model produced can predict which genera are likely to contain a compound. (author)

  2. Comparison of Stevia plants grown from seeds, cuttings and stem-tip cultures for growth and sweet diterpene glucosides.

    Science.gov (United States)

    Tamura, Y; Nakamura, S; Fukui, H; Tabata, M

    1984-10-01

    The growth and sweet diterpene glucosides of Stevia plants propagated by stem-tip cultures were compared with those of the control plants propagated by seeds. There was no significant difference between the two groups both in growth and in chemical composition. As for the contents of sweet diterpene glucosides, however, the clonal plants showed significantly smaller variations than the sexually propagated plants; they were almost as homogeneous as the plants propagated by cuttings. These results suggest that the clonal propagation by stem-tip culture is an effective method of obtaining a population of uniform plants for the production of sweet diterpene glucosides.

  3. Characterization of two genes for the biosynthesis of abietane-type diterpenes in rosemary (Rosmarinus officinalis) glandular trichomes

    NARCIS (Netherlands)

    Brückner, K.; Bozic, D.; Manzano, D.; Papaefthimiou, D.; Pateraki, I.; Scheler, U.; Ferrer, A.; Vos, de R.C.H.; Kanellis, A.K.; Tissier, A.

    2014-01-01

    Rosemary (Rosmarinus officinalis) produces the phenolic diterpenes carnosic acid and carnosol, which, in addition to their general antioxidant activities, have recently been suggested as potential ingredients for the prevention and treatment of neurodegenerative diseases. Little is known about the

  4. Cardiovascular Activity of Labdane Diterpenes from Andrographis paniculata in Isolated Rat Hearts

    Directory of Open Access Journals (Sweden)

    Khalijah Awang

    2012-01-01

    Full Text Available The dichloromethane (DCM extract of Andrographis paniculata Nees was tested for cardiovascular activity. The extract significantly reduced coronary perfusion pressure by up to 24.5±3.0 mm Hg at a 3 mg dose and also reduced heart rate by up to 49.5±11.4 beats/minute at this dose. Five labdane diterpenes, 14-deoxy-12-hydroxyandrographolide (1, 14-deoxy-11,12-didehydroandrographolide (2, 14-deoxyandrographolide (3, andrographolide (4, and neoandrographolide (5, were isolated from the aerial parts of this medicinal plant. Bioassay-guided studies using animal model showed that compounds, (2 and (3 were responsible for the coronary vasodilatation. This study also showed that andrographolide (4, the major labdane diterpene in this plant, has minimal effects on the heart.

  5. Cardiovascular Activity of Labdane Diterpenes from Andrographis paniculata in Isolated Rat Hearts

    Science.gov (United States)

    Awang, Khalijah; Abdullah, Nor Hayati; Hadi, A. Hamid A.; Su Fong, Yew

    2012-01-01

    The dichloromethane (DCM) extract of Andrographis paniculata Nees was tested for cardiovascular activity. The extract significantly reduced coronary perfusion pressure by up to 24.5 ± 3.0 mm Hg at a 3 mg dose and also reduced heart rate by up to 49.5 ± 11.4 beats/minute at this dose. Five labdane diterpenes, 14-deoxy-12-hydroxyandrographolide (1), 14-deoxy-11,12-didehydroandrographolide (2), 14-deoxyandrographolide (3), andrographolide (4), and neoandrographolide (5), were isolated from the aerial parts of this medicinal plant. Bioassay-guided studies using animal model showed that compounds, (2) and (3) were responsible for the coronary vasodilatation. This study also showed that andrographolide (4), the major labdane diterpene in this plant, has minimal effects on the heart. PMID:22536026

  6. A new Labdane Diterpene and Other Constituents from Marrubium deserti Noe ex coss.

    Directory of Open Access Journals (Sweden)

    Hocine Dendougui

    2011-01-01

    Full Text Available The phytochemical study of the chloroform soluble part of the hydroalcoholic extract of Marrubium deserti allowed us to describe a new labdane diterpene, 6-dehydroxy-19-acetyl-marrubenol (3 beside three other diterpenes : 19-acetyl-marrubenol (6 , 6-acetyl-marrubenol (7 and 16-epoxy-9-hydroxy-labda-13(16, 14- diene (1. This latter derivative is described for the first time as natural compound. Phytol (2, and three sterols: b -sitosterol (4, stigmasterol (5 and b -sitosterol 3-O-glucoside (8 were also isolated from this species. Structure elucidation of the isolated compounds was accomplished by means of spectroscopic techniques, especially NMR spectroscopy and mass spectrometry.

  7. Microwave-assisted extraction of green coffee oil and quantification of diterpenes by HPLC.

    Science.gov (United States)

    Tsukui, A; Santos Júnior, H M; Oigman, S S; de Souza, R O M A; Bizzo, H R; Rezende, C M

    2014-12-01

    The microwave-assisted extraction (MAE) of 13 different green coffee beans (Coffea arabica L.) was compared to Soxhlet extraction for oil obtention. The full factorial design applied to the microwave-assisted extraction (MAE), related to time and temperature parameters, allowed to develop a powerful fast and smooth methodology (10 min at 45°C) compared to a 4h Soxhlet extraction. The quantification of cafestol and kahweol diterpenes present in the coffee oil was monitored by HPLC/UV and showed satisfactory linearity (R(2)=0.9979), precision (CV 3.7%), recovery (yield calculated on the diterpenes content for sample AT1 (Arabica green coffee) showed a six times higher value compared to the traditional Soxhlet method. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF DITERPENES FOR TREATMENT OF ALZHEIMER'S DISEASE

    Directory of Open Access Journals (Sweden)

    Gabriel F. dos Santos

    Full Text Available Alzheimer's disease is an irreversible, degenerative and age-related disease which is growing more and more with the increase in life expectancy. Kaurane diterpenes are a class of natural products available in large amounts in nature and isolated from plants grown worldwide. In the present work¸ twenty-seven kaurane diterpenes of natural origin and some readily available derivatives were assayed for acetylcholinesterase inhibition and the structure-activity relationship was analyzed. The kaurenoic acid derivatives screened showed to be promising inhibitors of AChE, which could provide new leads for drugs to fight Alzheimer's disease symptoms. Among them, eleven compounds showed activities comparable or higher than the positive control galantamine. Existence of an allylic hydroxyl group showed to be an important structural feature for AChE inhibition. In addition, presence of free hydroxyl groups at C-17 and C-19, furnished a diol especially active, able to completely inhibit AChE.

  9. A new rearranged dolabellane diterpene from the soft coral Clavularia inflata.

    Science.gov (United States)

    Alea, Glenn V; Bowden, Bruce F; Ragasa, Consolacion Y

    2008-06-15

    A new dolabellane type diterpene 1 has been isolated through its acetate 1a. The structure of 1a was elucidated by extensive 1D and 2D NMR spectroscopy and confirmed by mass spectrometry. The structure of 1 was deduced by comparison of its NMR spectral data with those of 1a, while its relative stereochemistry was deduced by NOESY. The absolute stereochemistry of C-7 was determined by analyses of 1 separately esterified with R and S O-mandelic acids.

  10. Simplexins P–S, Eunicellin-Based Diterpenes from the Soft Coral Klyxum simplex

    Science.gov (United States)

    Wu, Shwu-Li; Su, Jui-Hsin; Huang, Chiung-Yao; Tai, Chi-Jen; Sung, Ping-Jyun; Liaw, Chih-Chung; Sheu, Jyh-Horng

    2012-01-01

    Four new eunicellin-based diterpenes, simplexins P–S (1–4), and the known compound simplexin A (5), have been isolated from the soft coral Klyxum simplex. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly 1D and 2D NMR experiments. Compounds 1 and 3–5 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines, 3 being the most cytotoxic. PMID:22822367

  11. Diterpenes Synthesized from the Natural Serrulatane Leubethanol and Their in Vitro Activities against Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Ricardo Escarcena

    2015-04-01

    Full Text Available Seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity against the H37Rv strain of Mycobacterium tuberculosis. Some compounds showed antimycobacterial selectivity indices higher than leubethanol.

  12. A Novel Diterpene Glycoside with Nine Glucose Units from Stevia rebaudiana Bertoni

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2017-01-01

    Full Text Available Following our interest in new diterpene glycosides with better taste profiles than that of Rebaudioside M, we have recently isolated and characterized Rebaudioside IX—a novel steviol glycoside—from a commercially‐supplied extract of Stevia rebaudiana Bertoni. This molecule contains a hexasaccharide group attached at C‐13 of the central diterpene core, and contains three additional glucose units when compared with Rebaudioside M. Here we report the complete structure elucidation—based on extensive Nuclear Magnetic Resonance (NMR analysis (1H, 13C, Correlation Spectroscopy (COSY, Heteronuclear Single Quantum Coherence‐Distortionless Enhancement Polarization Transfer (HSQC‐DEPT, Heteronuclear Multiple Bond Correlation (HMBC, 1D Total Correlation Spectroscopy (TOCSY, Nuclear Overhauser Effect Spectroscopy (NOESY and mass spectral data—of this novel diterpene glycoside with nine sugar moieties and containing a relatively rare 16 α‐linked glycoside. A steviol glycoside bearing nine glucose units is unprecedented in the literature, and could have an impact on the natural sweetener catalog.

  13. Immunomodulatory Effects of Diterpene Quinone Derivatives from the Roots of Horminum pyrenaicum in Human PBMC

    Directory of Open Access Journals (Sweden)

    K. Becker

    2018-01-01

    Full Text Available Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN-γ- dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1 and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I represent prominent targets, as IFN-γ-related signaling is strongly sensitive to oxidative triggers. Herein, the analysis of these pathway activities in human peripheral mononuclear cells was successfully applied in a bioactivity-guided fractionation strategy to screen for anti-inflammatory substances contained in the root of Horminum (H. pyrenaicum L. (syn. Dragon’s mouth, the only representative of the monophyletic genus Horminum. Four abietane diterpene quinone derivatives (horminone, 7-O-acetylhorminone, inuroyleanol and its 15,16-dehydro-derivative, a novel natural product, two nor-abietane diterpene quinones (agastaquinone and 3-deoxyagastaquinone and two abeo 18 (4 → 3 abietane diterpene quinones (agastol and its 15,16-dehydro-derivative could be identified. These compounds were able to dose-dependently suppress the above mentioned pathways with different potency. Beside the description of new active compounds, this study demonstrates the feasibility of integrating IDO-1 and GTP-CH-I activity in the search for novel anti-inflammatory compounds, which can then be directed towards a more detailed mode of action analysis.

  14. A Novel Diterpene Glycoside with Nine Glucose Units from Stevia rebaudiana Bertoni.

    Science.gov (United States)

    Prakash, Indra; Ma, Gil; Bunders, Cynthia; Charan, Romila D; Ramirez, Catherine; Devkota, Krishna P; Snyder, Tara M

    2017-01-31

    Following our interest in new diterpene glycosides with better taste profiles than that of Rebaudioside M, we have recently isolated and characterized Rebaudioside IX-a novel steviol glycoside-from a commercially-supplied extract of Stevia rebaudiana Bertoni. This molecule contains a hexasaccharide group attached at C-13 of the central diterpene core, and contains three additional glucose units when compared with Rebaudioside M. Here we report the complete structure elucidation-based on extensive Nuclear Magnetic Resonance (NMR) analysis (1H, 13C, Correlation Spectroscopy (COSY), Heteronuclear Single Quantum Coherence-Distortionless Enhancement Polarization Transfer (HSQC-DEPT), Heteronuclear Multiple Bond Correlation (HMBC), 1D Total Correlation Spectroscopy (TOCSY), Nuclear Overhauser Effect Spectroscopy (NOESY)) and mass spectral data-of this novel diterpene glycoside with nine sugar moieties and containing a relatively rare 16 α-linked glycoside. A steviol glycoside bearing nine glucose units is unprecedented in the literature, and could have an impact on the natural sweetener catalog.

  15. Cytotoxic diterpenes from roots of Crossopetalum gaumeri, a Celastraceae species from Yucatan Peninsula.

    Science.gov (United States)

    Miron-Lopez, Gumersindo; Bazzocchi, Isabel L; Jimenez-Diaz, Ignacio A; Moujir, Laila M; Quijano-Quiñones, Ramiro; Quijano, Leovigildo; Mena-Rejon, Gonzalo J

    2014-05-01

    Four new diterpenes, crossogumerins A-D (1-4) along with six known ones (5-10) were isolated from the root bark of Crossopetalum gaumeri, an endemic medicinal plant from the Yucatan Peninsula. Their structures were elucidated on the basis of 1D and 2D NMR techniques, including HMQC, HMBC, and ROESY experiments. Compounds 1-5, 8-10 were evaluated for cytotoxicity against HeLa (carcinoma of the cervix) and Hep-2 (lung carcinoma) human tumor cells lines and against normal Vero cells (African green monkey kidney) in lag and log phase of growth. Podocarpane diterpenes, crossogumerin B (2) and nimbiol (10), exhibited the highest activity against HeLa cells (IC50 values of 3.1 and 8.1 μM, respectively), but also selectivity on Vero cells (SI 22.6 and 7.5, respectively). The preliminary SAR studies suggest that an epoxy moiety in ring B and a hydrogen bond-donor group strategically positioned in the diterpene core are important requirements for cytotoxicity and selectivity. Copyright © 2014. Published by Elsevier Ltd.

  16. ent-Pimarane and ent-Kaurane Diterpenes from Aldama discolor (Asteraceae and Their Antiprotozoal Activity

    Directory of Open Access Journals (Sweden)

    Mauro S. Nogueira

    2016-09-01

    Full Text Available Aldama discolor (syn.Viguiera discolor is an endemic Asteraceae from the Brazilian “Cerrado”, which has not previously been investigated for its chemical constituents and biological activity. Diterpenes are common secondary metabolites found in Aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. In this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1, as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2, ent-2S,4S-2-19-epoxy-pimara-8(3,15-diene-7β-ol (3 and ent-7-oxo-pimara-8,15-diene-3β-ol (4, were isolated from the dichloromethane extract of A. discolor leaves and identified by means of MS and NMR. The compounds were assayed in vitro against Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, Plasmodium falciparum and also tested for cytotoxicity against mammalian cells (L6 cell line. The ent-kaurane 1 showed significant in vitro activity against both P. falciparum (IC 50 = 3.5 μ M and L. donovani (IC 50 = 2.5 μ M and ent-pimarane 2 against P. falciparum (IC 50 = 3.8 μ M. Both compounds returned high selectivity indices (SI >10 in comparison with L6 cells, which makes them interesting candidates for in vivo tests. In addition to the diterpenes, the sesquiterpene lactone budlein A (5, which has been reported to possess a strong anti-T. b. rhodesiense activity, was identified as major compound in the A. discolor extract and explains its high activity against this parasite (100% growth inhibition at 2 μ g/mL.

  17. ent-Pimarane and ent-Kaurane Diterpenes from Aldama discolor (Asteraceae) and Their Antiprotozoal Activity.

    Science.gov (United States)

    Nogueira, Mauro S; Da Costa, Fernando B; Brun, Reto; Kaiser, Marcel; Schmidt, Thomas J

    2016-09-15

    Aldama discolor (syn.Viguiera discolor) is an endemic Asteraceae from the Brazilian "Cerrado", which has not previously been investigated for its chemical constituents and biological activity. Diterpenes are common secondary metabolites found in Aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. In this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2), ent-2S,4S-2-19-epoxy-pimara-8(3),15-diene-7β-ol (3) and ent-7-oxo-pimara-8,15-diene-3β-ol (4), were isolated from the dichloromethane extract of A. discolor leaves and identified by means of MS and NMR. The compounds were assayed in vitro against Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, Plasmodium falciparum and also tested for cytotoxicity against mammalian cells (L6 cell line). The ent-kaurane 1 showed significant in vitro activity against both P. falciparum (IC 50 = 3.5 μ M) and L. donovani (IC 50 = 2.5 μ M) and ent-pimarane 2 against P. falciparum (IC 50 = 3.8 μ M). Both compounds returned high selectivity indices (SI >10) in comparison with L6 cells, which makes them interesting candidates for in vivo tests. In addition to the diterpenes, the sesquiterpene lactone budlein A (5), which has been reported to possess a strong anti-T. b. rhodesiense activity, was identified as major compound in the A. discolor extract and explains its high activity against this parasite (100% growth inhibition at 2 μ g/mL).

  18. Andrographis paniculata transcriptome provides molecular insights into tissue-specific accumulation of medicinal diterpenes.

    Science.gov (United States)

    Garg, Anchal; Agrawal, Lalit; Misra, Rajesh Chandra; Sharma, Shubha; Ghosh, Sumit

    2015-09-02

    Kalmegh (Andrographis paniculata) has been widely exploited in traditional medicine for the treatment of infectious diseases and health disorders. Ent-labdane-related diterpene (ent-LRD) specialized (i.e., secondary) metabolites of kalmegh such as andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide, are known for variety of pharmacological activities. However, due to the lack of genomic and transcriptomic information, underlying molecular basis of ent-LRDs biosynthesis has remained largely unknown. To identify candidate genes of the ent-LRD biosynthetic pathway, we performed comparative transcriptome analysis using leaf and root tissues that differentially accumulate ent-LRDs. De novo assembly of Illumina HiSeq2000 platform-generated paired-end sequencing reads resulted into 69,011 leaf and 64,244 root transcripts which were assembled into a total of 84,628 unique transcripts. Annotation of these transcripts to the Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active Enzymes (CAZy) databases identified candidate transcripts of the ent-LRD biosynthetic pathway. These included transcripts that encode enzymes of the plastidial 2C-methyl-D-erythritol-4-phosphate pathway which provides C5 isoprenoid precursors for the ent-LRDs biosynthesis, geranylgeranyl diphosphate synthase, class II diterpene synthase (diTPS), cytochrome P450 monooxygenase and glycosyltransferase. Three class II diTPSs (ApCPS1, ApCPS2 and ApCPS3) that showed distinct tissue-specific expression profiles and are phylogenetically related to the dicotyledon ent-copalyl diphosphate synthases, are identified. ApCPS1, ApCPS2 and ApCPS3 encode for 832-, 817- and 797- amino acids proteins of 55-63 % identity, respectively. Spatio-temporal patterns of transcripts and ent-LRDs accumulation are consistent with the involvement of ApCPS1 in general (i.e., primary) metabolism for the biosynthesis of phytohormone gibberellin, ApCPS2 in leaf specialized ent

  19. Diterpenes and a new benzaldehyde from the mangrove plant Rhizophora mangle

    Directory of Open Access Journals (Sweden)

    Jhessica N. Martins

    Full Text Available ABSTRACT This work describes the isolation, by high-speed counter-current chromatography, of the diterpenes manool, jhanol and steviol and the benzaldehyde p-oxy-2-ethylhexyl benzaldehyde from the stilt roots hexane extract of the mangrove plant Rhizophora mangle L., Rhizophoraceae. For this, a non-aqueous biphasic solvent system composed of hexane–acetonitrile–methanol 1:1:0.5 (v/v/v was applied. As far as we know, only steviol was previously isolated in Rhizophoraceae and this is the first time that p-oxy-2-ethylhexyl benzaldehyde is reported.

  20. Synthesis and Sensory Evaluation of ent-Kaurane Diterpene Glycosides

    Directory of Open Access Journals (Sweden)

    Venkata Sai Prakash Chaturvedula

    2012-07-01

    Full Text Available Catalytic hydrogenation of the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana, namely rubusoside, stevioside, and rebaudioside-A has been carried out using Pd(OH2 and their corresponding dihydro derivatives have been isolated as the products. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data and chemical studies. Also, we report herewith the sensory evaluation of all the reduced compounds against their corresponding original steviol glycosides and sucrose for the sweetness property of these molecules.

  1. Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare

    DEFF Research Database (Denmark)

    Zerbe, Philipp; Chiang, Angela; Dullat, Harpreet

    2014-01-01

    Marrubium vulgare (Lamiaceae) is a medicinal plant whose major bioactive compounds, marrubiin and other labdane-related furanoid diterpenoids, have potential applications as anti-diabetics, analgesics or vasorelaxants. Metabolite and transcriptome profiling of M. vulgare leaves identified five...... different candidate diterpene synthases (diTPSs) of the TPS-c and TPS-e/f clades. We describe the in vitro and in vivo functional characterization of the M. vulgare diTPS family. In addition to MvEKS ent-kaurene synthase of general metabolism, we identified three diTPSs of specialized metabolism: MvCPS3...

  2. Antimicrobial Evaluation of Diterpenes from Copaifera langsdorffii Oleoresin Against Periodontal Anaerobic Bacteria

    Directory of Open Access Journals (Sweden)

    Rodrigo C. S. Veneziani

    2011-11-01

    Full Text Available The antimicrobial activity of four labdane-type diterpenes isolated from the oleoresin of Copaifera langsdorffii as well as of two commercially available diterpenes (sclareol and manool was investigated against a representative panel of microorganisms responsible for periodontitis. Among all the evaluated compounds, (−-copalic acid (CA was the most active, displaying a very promising MIC value (3.1 µg mL−1; 10.2 µM against the key pathogen (Porphyromonas gingivalis involved in this infectious disease. Moreover, CA did not exhibit cytotoxicity when tested in human fibroblasts. Time-kill curve assays performed with CA against P. gingivalis revealed that this compound only inhibited the growth of the inoculums in the first 12 h (bacteriostatic effect. However, its bactericidal effect was clearly noted thereafter (between 12 and 24 h. It was also possible to verify an additive effect when CA and chlorhexidine dihydrochloride (CHD, positive control were associated at their MBC values. The time curve profile resulting from this combination showed that this association needed only six hours for the bactericidal effect to be noted. In summary, CA has shown to be an important metabolite for the control of periodontal diseases. Moreover, the use of standardized extracts based on copaiba oleoresin with high CA contents can be an important strategy in the development of novel oral care products.

  3. Bifurcatriol, a New Antiprotozoal Acyclic Diterpene from the Brown Alga Bifurcaria bifurcata

    Directory of Open Access Journals (Sweden)

    Vangelis Smyrniotopoulos

    2017-08-01

    Full Text Available Linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. This study reports bifurcatriol (1, a new linear diterpene featuring two stereogenic centers isolated from the Irish brown alga Bifurcaria bifurcata. The gross structure of this new natural product was elucidated based on its spectroscopic data (IR, 1D and 2D-NMR, HRMS. Its absolute configuration was identified by experimental and computational vibrational circular dichroism (VCD spectroscopy, combined with the calculation of 13C-NMR chemical shielding constants. Bifurcatriol (1 was tested for in vitro antiprotozoal activity towards a small panel of parasites (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, and Leishmania donovani and cytotoxicity against mammalian primary cells. The highest activity was exerted against the malaria parasite P. falciparum (IC50 value 0.65 μg/mL with low cytotoxicity (IC50 value 56.6 μg/mL. To our knowledge, this is the first successful application of VCD and DP4 probability analysis of the calculated 13C-NMR chemical shifts for the simultaneous assignment of the absolute configuration of multiple stereogenic centers in a long-chain acyclic natural product.

  4. Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

    Directory of Open Access Journals (Sweden)

    Rebeca Cristina Costa Pereira

    2017-03-01

    Full Text Available Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60, which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents.

  5. Chemotaxonomy of three genera of the Annonaceae family using self-organizing maps and {sup 13}C NMR data of diterpenes

    Energy Technology Data Exchange (ETDEWEB)

    Scotti, Luciana; Tavares, Josean Fechine; Silva, Marcelo Sobral da [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Ciencias Farmaceuticas; Falcao, Emanuela Viana; Silva, Luana de Morais e; Soares, Gabriela Cristina da Silva; Scotti, Marcus Tullius, E-mail: mtscotti@ccae.ufpb.br [Universidade Federal da Paraiba (UFPB), Rio Tinto, PB (Brazil). Dept. de Engenharia e Meio Ambiente

    2012-07-01

    The Annonaceae family is distributed throughout Neotropical regions of the world. In Brazil, it covers nearly all natural formations particularly Annona, Xylopia and Polyalthia and is characterized chemically by the production of sources of terpenoids (mainly diterpenes), alkaloids, steroids, polyphenols and, flavonoids. Studies from {sup 13}C NMR data of diterpenes related with their botanical occurrence were used to generate self-organizing maps. Results corroborate those in the literature obtained from morphological and molecular data for three genera and the model can be used to project other diterpenes. Therefore, the model produced can predict which genera are likely to contain a compound. (author)

  6. Characterization of two genes for the biosynthesis of abietane-type diterpenes in rosemary (Rosmarinus officinalis) glandular trichomes

    DEFF Research Database (Denmark)

    Brückner, Kathleen; Božić, Dragana; Manzano, David

    2014-01-01

    normal CDP to produce an abietane diterpene. Comparison to the already characterized diterpene synthase from Salvia miltiorrhiza (SmKSL) demonstrates that the product of RoKSL1 and RoKSL2 is miltiradiene. Expression analysis supports a major contributing role for RoKSL2. Like SmKSL and the sclareol...... synthase from Salvia sclarea, RoKSL1/2 are diterpene synthases of the TPS-e group which have lost the internal gamma-domain. Furthermore, phylogenetic analysis indicates that RoKSL1 and RoKSL2 belong to a distinct group of KSL enzymes involved in specialized metabolism which most likely emerged before...

  7. Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes--current status and future opportunities.

    Science.gov (United States)

    Lange, B Markus; Ahkami, Amirhossein

    2013-02-01

    Terpenoids (a.k.a. isoprenoids) represent the most diverse class of natural products found in plants, with tens of thousands of reported structures. Plant-derived terpenoids have a multitude of pharmaceutical and industrial applications, but the natural resources for their extraction are often limited and, in many cases, synthetic routes are not commercially viable. Some of the most valuable terpenoids are not accumulated in model plants or crops, and genetic resources for breeding of terpenoid natural product traits are thus poorly developed. At present, metabolic engineering, either in the native producer or a heterologous host, is the only realistic alternative to improve yield and accessibility. In this review article, we will evaluate the state of the art of modulating the biosynthetic pathways for the production of mono-, sesqui- and diterpenes in plants. © 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  8. Two new ent-kaurane-type diterpene glycosides from zucchini (Cucurbita pepo L.) seeds.

    Science.gov (United States)

    Kikuchi, Takashi; Ando, Hiromi; Maekawa, Ken-Ichiro; Arie, Hiroki; Yamada, Takeshi; Tanaka, Reiko

    2015-12-01

    Two new ent-kaurane diterpene glycosides; 12α-(β-d-glucopyranosyloxy)-7β-hydroxykaurenolide (1) and 7β-(β-d-glucopyranosyloxy)-12α-hydroxykaurenolide (2), a new steroid; (24S)-stigmasta-7,22E,25-trien-3-one (12), and known compounds (3-11, 13-14) were isolated from zucchini (Cucurbita pepo L.) seeds. The absolute structures of 1 and 2 were determined by acid hydrolysis and application of a modified Moscher's method. Furthermore, isolated compounds (1-14), and a derivative, 1a, were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. A New Abietene Diterpene and Other Constituents from Kaempferia angustifolia Rosc.

    Directory of Open Access Journals (Sweden)

    Abdul Manaf Ali

    2011-04-01

    Full Text Available A new abietene diterpene, kaempfolienol (5S,6S,7S,9S,10S,11R,13S-abiet-8(14-enepenta-6,7,9,11,13-ol, 1, was isolated from a rhizome extract of Kaempferia angustifolia Rosc. along with the known compounds crotepoxide, boesenboxide, zeylenol, 2′-hydroxy-4,4′,6′-trimethoxychalcone, (24S-24-methyl-5α-lanosta-9(11,25-dien-3β-ol, β-sitosterol and β-sitosterol-3-O-β-D-glucopyranoside. The structures of all compounds were elucidated on the basis of mass spectroscopic and NMR data. Zeylenol (2, the major constituent of the plant, was derivatized into diacetate, triacetate and epoxide derivatives through standard organic reactions. The cytotoxic activity of compounds 1, 2 and the zeylenol derivatives was evaluated against the HL-60, MCF-7, HT-29 and HeLa cell lines.

  10. New Ent-Kaurane-Type Diterpene Glycosides and Benzophenone from Ranunculus muricatus Linn.

    Directory of Open Access Journals (Sweden)

    Bi-Ling Wu

    2015-12-01

    Full Text Available Two new ent-kaurane diterpene glycosides, ranunculosides A (1 and B (2, and a new benzophenone, ranunculone C (3, were isolated from the aerial part of Ranunculus muricatus Linn. The chemical structures of compounds 1–3 were established to be (2S-ent-kauran-2β-ol-15-en-14-O-β-d-glucopyranoside, (2S,4S-ent-kauran-2β,18-diol-15-en-14-O-β-d-glucopyranoside, and (R-3-[2-(3,4-dihydroxybenzoyl-4,5-dihydroxy-phenyl]-2-hydroxylpropanoic acid, respectively, by spectroscopic data and chemical methods. The absolute configuration of 1 was determined by the combinational application of RP-HPLC analysis and Mosher’s method.

  11. Antiangiogenic properties of cafestol, a coffee diterpene, in human umbilical vein endothelial cells

    International Nuclear Information System (INIS)

    Wang, Shuaiyu; Yoon, Yeo Cho; Sung, Mi-Jeong; Hur, Haeng-Jeon; Park, Jae-Ho

    2012-01-01

    Highlights: ► Cafestol inhibits tube formation and migration of VEGF-stimulated HUVEC. ► Cafestol inhibits phosphorylation of FAK and Akt. ► Cafestol decreases NO production. -- Abstract: As angiogenesis plays important roles in tumor growth and metastasis, searching for antiangiogenic compounds is a promising tactic for treating cancers. Cafestol, a diterpene found mainly in unfiltered coffee, provides benefit through varied biological activity, including antitumorigenic, antioxidative, and anti-inflammatory effects. This study aimed to investigate the effects of cafestol on angiogenesis and to uncover the associated mechanism. We show that cafestol inhibits angiogenesis of human umbilical vascular endothelial cells. This inhibition affects the following specific steps of the angiogenic process: proliferation, migration, and tube formation. The inhibitory effects of cafestol are accompanied by decreasing phosphorylation of FAK and Akt and by a decrease in nitric oxide production. Overall, cafestol inhibits angiogenesis by affecting the angiogenic signaling pathway.

  12. Antimicrobial monomeric and dimeric diterpenes from the leaves of Helichrysum tenax var tenax.

    Science.gov (United States)

    Drewes, Siegfried E; Mudau, K Esther; van Vuuren, Sandy F; Viljoen, Alvaro M

    2006-04-01

    The hexane extract of fresh air-dried leaves of Helichrysum tenax (Asteraceae) afforded ent-beyer-15-en-19-ol (1), its 4-epimer ent-beyer-15-en-18-ol (2), 15beta,16beta-epoxide-ent-beyeran-19-ol (3), as well as (4) consisting of two units of (1) linked as a diester of malonic acid, and (5), a compound. Its constituents are (1) and (3) also linked as a diester of malonic acid. The leaves of the plant are densely covered in fine glandular trichomes. These are extremely sticky and exude a mixture of the above diterpenes. Antimicrobial tests showed that (1), in particular, was highly active (3.1 and 3.6 microg/ml) against Bacillus cereus and Staphylococcus epidermidis, respectively.

  13. In Vitro Antimicrobial Activity of Plant-Derived Diterpenes against Bovine Mastitis Bacteria

    Directory of Open Access Journals (Sweden)

    Rodrigo C. S. Veneziani

    2013-07-01

    Full Text Available We evaluated the antibacterial activity of three diterpenes isolated from natural sources against a panel of microorganisms responsible for bovine mastitis. ent-Copalic acid (CA was the most active metabolite, with promising MIC values (from 1.56 to 6.25 µg mL−1 against Staphylococcus aureus (ATCC and clinical isolate, Staphylococcus epidermidis, Streptococcus agalactiae, and Streptococcus dysgalactiae. We conducted time-kill assays of CA against S. aureus, a commensal organism considered to be a ubiquitous etiological agent of bovine mastitis in dairy farms worldwide. In the first 12 h, CA only inhibited the growth of the inoculums (bacteriostatic effect, but its bactericidal effect was clearly noted thereafter (between 12 and 24 h. In conclusion, CA should be considered for the control of several Gram-positive bacteria related to bovine mastitis.

  14. Two residues determine the product profile of the class II diterpene synthases TPS14 and TPS21 of Tripterygium wilfordii

    DEFF Research Database (Denmark)

    Hansen, Nikolaj Lervad; Nissen, Jakob N.; Hamberger, Björn Robert

    2017-01-01

    residue gave mixed product profiles. Two mutants, TwTPS14:Y265H and TwTPS21:A325V, also produced ent-copalyl diphosphate, highlighting the evolutionary potential of enzymes of this family to drive rapid diversification of plant diterpene biosynthesis through neo-functionalization. Our study contributes......The medicinal plant Tripterygium wilfordii (Celastraceae) contains a pair of class II diterpene synthases (diTPS) of specialized labdane-type metabolism that, despite remarkably close homology, form strikingly different products. TwTPS21 catalyzes bicyclization of the linear C20 precursor......-directed mutagenesis, we generated a panel of six variants, where one, or both positions were exchanged between the enzymes. In coupled heterologous assays with a corresponding class I diTPS, TwTPS2, complete product interchange was observed in variants with both reciprocal mutations, while substitutions of either...

  15. Biologically active secondary metabolites from fungi. 12.(1) oidiolactones A-F, labdane diterpene derivatives isolated from oidiodendron truncata

    Science.gov (United States)

    John; Krohn; Florke; Aust; Draeger; Schulz

    1999-09-01

    Two known (1 and 2) and four new (3-6) diterpenes named oidiolactones A-F, respectively, and the antibiotic cladosporin were isolated from the fungus Oidiodendron truncata. The structure determination was mainly based on 1D and 2D NMR spectroscopy. The structures of compound 4, displaying an equilibrium between open-chain and cyclized form, and of cladosporin were confirmed by X-ray analysis.

  16. Rhizovarins A-F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189.

    Science.gov (United States)

    Gao, Shu-Shan; Li, Xiao-Ming; Williams, Katherine; Proksch, Peter; Ji, Nai-Yun; Wang, Bin-Gui

    2016-08-26

    Genome mining of the fungus Mucor irregularis (formerly known as Rhizomucor variabilis) revealed the presence of various gene clusters for secondary metabolite biosynthesis, including several terpene-based clusters. Investigation into the chemical diversity of M. irregularis QEN-189, an endophytic fungus isolated from the fresh inner tissue of the marine mangrove plant Rhizophora stylosa, resulted in the discovery of 20 structurally diverse indole-diterpenes including six new compounds, namely, rhizovarins A-F (1-6). Among them, compounds 1-3 represent the most complex members of the reported indole-diterpenes. The presence of an unusual acetal linked to a hemiketal (1) or a ketal (2 and 3) in an unprecedented 4,6,6,8,5,6,6,6,6-fused indole-diterpene ring system makes them chemically unique. Their structures and absolute configurations were elucidated by spectroscopic analysis, modified Mosher's method, and chemical calculations. Each of the isolated compounds was evaluated for antitumor activity against HL-60 and A-549 cell lines.

  17. Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer.

    Science.gov (United States)

    Islam, Muhammad Torequl; Ali, Eunüs S; Uddin, Shaikh Jamal; Islam, Md Amirul; Shaw, Subrata; Khan, Ishaq N; Saravi, Seyed Soheil Saeedi; Ahmad, Saheem; Rehman, Shahnawaz; Gupta, Vijai Kumar; Găman, Mihnea-Alexandru; Găman, Amelia Maria; Yele, Santosh; Das, Asish Kumar; de Castro E Sousa, João Marcelo; de Moura Dantas, Sandra Maria Mendes; Rolim, Hercília Maria Lins; de Carvalho Melo-Cavalcante, Ana Amélia; Mubarak, Mohammad S; Yarla, Nagendra Sastry; Shilpi, Jamil A; Mishra, Siddhartha Kumar; Atanasov, Atanas G; Kamal, Mohammad Amjad

    2018-04-28

    The diterpene lactone andrographolide, isolated from Andrographis paniculata, has been proven to possess several important protective biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiseptic, antimicrobial, cytotoxic, hypolipidemic, cardioprotective, hepatoprotective, and neuroprotective effects. In addition, it has been reported to play a therapeutic role in the treatment of major human diseases, such as Parkinson's disease, rheumatoid arthritis, and colitis. This systematic review aims to highlight andrographolide as a promising agent in cancer treatment. To this purpose, a number of databases were used to search for the cytotoxic/anticancer effects of andrographolide in pre-clinical and clinical studies. Among 1703 identified literature articles, 139 were included in this review; 109 were investigated as non-clinical, whereas 24, 3, and 3 were pre-clinical, clinical, and non-pre-clinical trials, respectively. Among the model systems, cultured cell lines appeared as the most frequently (79.14%) used, followed by in vivo models using rodents, among others. Furthermore, andrographolide was found to exert cytotoxic/anticancer effects on almost all types of cell lines with the underlying mechanisms involving oxidative stress, cell cycle arrest, anti-inflammatory and immune system mediated effects, apoptosis, necrosis, autophagy, inhibition of cell adhesion, proliferation, migration, invasion, anti-angiogenic activity, and other miscellaneous actions. After careful consideration of the relevant evidence, we suggest that andrographolide can be one of the potential agents in the treatment of cancer in the near future. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Furano diterpenes from Pterodon pubescens Benth with selective in vitro anticancer activity for prostate cell line

    International Nuclear Information System (INIS)

    Spindola, Humberto M.; Carvalho, Joao E. de; Ruiz, Ana Lucia T.G.; Rodrigues, Rodney A. F.; Denny, Carina; Sousa, Ilza M. de Oliveira; Foglio, Mary Ann; Tamashiro, Jorge Y.

    2009-01-01

    Activity guided fractionation of Pterodon pubescens Benth. methylene chloride-soluble fraction afforded novel 6α-acetoxi 7β-hydroxy-vouacapan 1 and four known diterpene furans 2, 3, 4, 5. The compounds were evaluated for in vitro cytotoxic activities against human normal cells and tumour cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-H460 (lung, non-small cells), OVCAR-03 (ovarian), PC-3 (prostate), HT-29 (colon), 786-0 (renal), K562 (leukemia) and NCI-ADR/RES (ovarian expressing phenotype multiple drugs resistance). Results were expressed by three concentration dependent parameters GI 50 (concentration that produces 50% growth inhibition), TGI (concentration that produces total growth inhibition or cytostatic effect) and LC 50 (concentration that produces .50% growth, a cytotoxicity parameter). Also, in vitro cytotoxicity was evaluated against 3T3 cell line (mouse embryonic fibroblasts). Antiproliferative properties of compounds 1, 4 and 5 are herein reported for the first time. These compounds showed selectivity in a concentration-dependent way against human PC-3. Compound 1 demonstrated selectivity 26 fold more potent than the positive control, doxorubicin, for PC-3 (prostrate) cell line based on GI 50 values, causing cytostatic effect (TGI value) at a concentration fifteen times less than positive control. Moreover comparison of 50% lethal concentration (LC 50 value) with positive control (doxorubicin) suggested that compound 1 was less toxic. (author)

  19. Effect of Diterpenes Isolated of the Marine Alga Canistrocarpus cervicornis against Some Toxic Effects of the Venom of the Bothrops jararaca Snake

    Directory of Open Access Journals (Sweden)

    Thaisa Francielle Souza Domingos

    2015-02-01

    Full Text Available Snake venoms are composed of a complex mixture of active proteins and peptides which induce a wide range of toxic effects. Envenomation by Bothrops jararaca venom results in hemorrhage, edema, pain, tissue necrosis and hemolysis. In this work, the effect of a mixture of two secodolastane diterpenes (linearol/isolinearol, previously isolated from the Brazilian marine brown alga, Canistrocarpus cervicornis, was evaluated against some of the toxic effects induced by B. jararaca venom. The mixture of diterpenes was dissolved in dimethylsulfoxide and incubated with venom for 30 min at room temperature, and then several in vivo (hemorrhage, edema and lethality and in vitro (hemolysis, plasma clotting and proteolysis assays were performed. The diterpenes inhibited hemolysis, proteolysis and hemorrhage, but failed to inhibit clotting and edema induced by B. jararaca venom. Moreover, diterpenes partially protected mice from lethality caused by B. jararaca venom. The search for natural inhibitors of B. jararaca venom in C. cervicornis algae is a relevant subject, since seaweeds are a rich and powerful source of active molecules which are as yet but poorly explored. Our results suggest that these diterpenes have the potential to be used against Bothropic envenomation accidents or to improve traditional treatments for snake bites.

  20. Anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenes from Daphne genkwa based on hierarchical cluster and principal component analysis.

    Science.gov (United States)

    Wang, Ling; Lan, Xin-Yi; Ji, Jun; Zhang, Chun-Feng; Li, Fei; Wang, Chong-Zhi; Yuan, Chun-Su

    2018-06-01

    Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory and angiogenic diseases. The aim of this study was to evaluate the anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenoids isolated from Daphne genkwa. LC-MS was used to identify diterpenes isolated from D. genkwa. The anti-inflammatory and anti-angiogenic activities of eight diterpenoids were evaluated on LPS-induced macrophage RAW264.7 cells and TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) using hierarchical cluster analysis (HCA) and principal component analysis (PCA). The eight diterpenes isolated from D. genkwa were identified as yuanhuaphnin, isoyuanhuacine, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuagine, isoyuanhuadine, yuanhuadine, yuanhuaoate C and yuanhuacine. All the eight diterpenes significantly down-regulated the excessive secretion of TNF-α, IL-6, IL-1β and NO in LPS-induced RAW264.7 macrophages. However, only 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl markedly reduced production of VEGF, MMP-3, ICAM and VCAM in TNF-α-stimulated HUVECs. HCA obtained 4 clusters, containing 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, isoyuanhuacine, isoyuanhuadine and five other compounds. PCA showed that the ranking of diterpenes sorted by efficacy from highest to lowest was 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuaphnin, isoyuanhuacine, yuanhuacine, yuanhuaoate C, yuanhuagine, isoyuanhuadine, yuanhuadine. In conclusion, eight diterpenes isolated from D. genkwa showed different levels of activity in LPS-induced RAW264.7 cells and TNF-α-stimulated HUVECs. The comprehensive evaluation of activity by HCA and PCA indicated that of the eight diterpenes, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl was the best, and can be developed as a new drug for RA therapy.

  1. Involvement of an ent-copalyl diphosphate synthase in tissue-specific accumulation of specialized diterpenes in Andrographis paniculata.

    Science.gov (United States)

    Misra, Rajesh Chandra; Garg, Anchal; Roy, Sudeep; Chanotiya, Chandan Singh; Vasudev, Prema G; Ghosh, Sumit

    2015-11-01

    Ent-labdane-related diterpene (ent-LRD) specialized (i.e. secondary) metabolites of the medicinal plant kalmegh (Andrographis paniculata) have long been known for several pharmacological activities. However, our understanding of the ent-LRD biosynthetic pathway has remained largely incomplete. Since ent-LRDs accumulate in leaves, we carried out a comparative transcriptional analysis using leaf and root tissues, and identified 389 differentially expressed transcripts, including 223 transcripts that were preferentially expressed in leaf tissue. Analysis of the transcripts revealed various specialized metabolic pathways, including transcripts of the ent-LRD biosynthetic pathway. Two class II diterpene synthases (ApCPS1 and ApCPS2) along with one (ApCPS1') and two (ApCPS2' and ApCPS2″) transcriptional variants that were the outcomes of alternative splicing of the precursor mRNA and alternative transcriptional termination, respectively, were identified. ApCPS1 and ApCPS2 encode for 832- and 817-amino acids proteins, respectively, and are phylogenetically related to the dicotyledons ent-copalyl diphosphate synthases (ent-CPSs). The spatio-temporal patterns of ent-LRD metabolites accumulation and gene expression suggested a likely role for ApCPS1 in general (i.e. primary) metabolism, perhaps by providing precursor for the biosynthesis of phytohormone gibberellin (GA). However, ApCPS2 is potentially involved in tissue-specific accumulation of ent-LRD specialized metabolites. Bacterially expressed recombinant ApCPS2 catalyzed the conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP), the general precursor of diterpenes to ent-copalyl diphosphate (ent-CPP), the precursor of ent-LRDs. Taken together, these results advance our understanding of the tissue-specific accumulation of specialized ent-LRDs of medicinal importance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Gaschromatographic and mass spectroscopic investigations of tall oil rosin acids and diterpenioc compounds and modified diterpene acids

    International Nuclear Information System (INIS)

    Mayr, M.

    1984-12-01

    Diterpene resin acids are important constituents of the coniferous wood. The composition of these nonvolatile extractives have been studied by a number of investigations; both naturally occurring resins (oleoresin) and distillation products of the alkaline sulfate pulping process (tall oil) were analyzed. These mixtures find important uses in chemical intermediates, paper sizes, ester gums, coatings and numerous other applications. Owing to the more ameliorate physical properties a major part of tall oil resin acids is chemically modified and is used in intermediate chemicals. Such modifications are the disproportionation in the presence of certain catalysts and the formation of Diels-Alder adducts. The present study was undertaken to obtain detailed information of the overall composition of diterpenoid compounds and to achieve a separation of the complex natural and tall oil mixtures using high resolution glass capillary columns. Furthermore, one objective was to characterize the identified diterpene compounds and Diels-Alder adducts by relative retention values. Additionally the presence of some major adduct components in the modified samples was checked by comparison with pure specimens, independently synthesized or purified by crystallization and the mechanism of the Diels-Alder reaction was investigated. A compilation of the mass spectra of the substances detected in the different samples closes this work. (Author)

  3. Artificial intelligence applied to natural products; computer study of pimarane diterpene. Aplicacao da inteligencia artificial em quimica de produtos naturais: estudo, por computador, dos diterpenos pimaranicos

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, M N; Borges, J H.G.; Furlan, M; Gastmans, J P [UNESP, Araraquara, SP (Brazil). Dept. de Quimica Organica; Emerenciano, V de [Sao Paulo Univ., SP (Brazil). Dept. de Quimica Organica

    1989-01-01

    This paper describes the study of the sup(13)C NMR characteristic signals of naturally occurring pimarane. The analysis is performed by computer, starting from a data base which encloses about 400 diterpenes and using the PICKUPS programm. By this way it is possible to analyse substructure from one to five atoms as well as the effects of substituents on them. (author).

  4. The coffee diterpene cafestol increases plasma triacylglycerol by increasing the production rate of large VLDL apolipoprotein B in healthy normolipidemic subjects

    NARCIS (Netherlands)

    Roos, de B.; Caslake, M.J.; Stalenhoef, A.F.H.; Bedford, D.; Demacker, P.N.; Katan, M.B.; Packard, C.J.

    2001-01-01

    Background: Cafestol is a diterpene in unfiltered coffee that raises plasma triacylglycerol in humans. Objective: We studied whether cafestol increases plasma triacylglycerol by increasing the production rate or by decreasing the fractional catabolic rate of VLDL1 [Svedberg flotation unit (Sf)

  5. Contrasting Patterns of Diterpene Acid Induction by Red Pine and White Spruce to Simulated Bark Beetle Attack, and Interspecific Differences in Sensitivity Among Fungal Associates

    Science.gov (United States)

    Charles J. Mason; Kier D. Klepzig; Brian J. Kopper; Philip J. Kersten; Barbara L. Illman; Kenneth F. Raffa

    2015-01-01

    Conifers possess a suite of physiochemical defenses that protect their subcortical tissues from bark beetle -fungal complexes. These defenses include rapid induction of terpenoids and phenolics at the site of attack. Studies of the distribution, induction, and bioactivity of conifer terpenoids have focused heavily on monoterpenes. We assessed induction of diterpene...

  6. Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L. and their relevance for perfume manufacture

    Directory of Open Access Journals (Sweden)

    Caniard Anne

    2012-07-01

    Full Text Available Abstract Background Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species. Results Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S-copalyl diphosphate. A class I diTPS (SsSS then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae. Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants. Conclusions SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid

  7. Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture.

    Science.gov (United States)

    Caniard, Anne; Zerbe, Philipp; Legrand, Sylvain; Cohade, Allison; Valot, Nadine; Magnard, Jean-Louis; Bohlmann, Jörg; Legendre, Laurent

    2012-07-26

    Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea) and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species. Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS) enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS) produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP) with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S)-copalyl diphosphate. A class I diTPS (SsSS) then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae). Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants. SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid specialized metabolite sclareol in a two-step process. They

  8. Andrographolide: A Novel Antimalarial Diterpene Lactone Compound from Andrographis paniculata and Its Interaction with Curcumin and Artesunate

    Directory of Open Access Journals (Sweden)

    Kirti Mishra

    2011-01-01

    Full Text Available Andrographolide (AND, the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plant Andrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of Plasmodium falciparum in vitro and Plasmodium berghei ANKA in vivo. IC50s for artesunate (AS, andrographolide (AND, and curcumin (CUR were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND was found synergistic with curcumin (CUR and addictively interactive with artesunate (AS. In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%, compared to the control (81%, but also by extending the life span by 2-3 folds. Being nontoxic to the in vivo system this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

  9. The coffee diterpene kahweol inhibits tumor necrosis factor-α-induced expression of cell adhesion molecules in human endothelial cells

    International Nuclear Information System (INIS)

    Kim, Hyung Gyun; Kim, Ji Young; Hwang, Yong Pil; Lee, Kyung Jin; Lee, Kwang Youl; Kim, Dong Hee; Kim, Dong Hyun; Jeong, Hye Gwang

    2006-01-01

    Endothelial cells produce adhesion molecules after being stimulated with various inflammatory cytokines. These adhesion molecules play an important role in the development of atherogenesis. Recent studies have highlighted the chemoprotective and anti-inflammatory effects of kahweol, a coffee-specific diterpene. This study examined the effects of kahweol on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. Kahweol inhibited the adhesion of TNFα-induced monocytes to endothelial cells and suppressed the TNFα-induced protein and mRNA expression of the cell adhesion molecules, VCAM-1 and ICAM-1. Furthermore, kahweol inhibited the TNFα-induced JAK2-PI3K/Akt-NF-κB activation pathway in these cells. Overall, kahweol has anti-inflammatory and anti-atherosclerotic activities, which occurs partly by down-regulating the pathway that affects the expression and interaction of the cell adhesion molecules on endothelial cells

  10. Improving the sensory and oxidative stability of cooked and chill-stored lamb using dietary rosemary diterpenes.

    Science.gov (United States)

    Serrano, Rafael; Ortuño, Jordi; Bañón, Sancho

    2014-09-01

    Two dietary rosemary extracts (DREs) containing diterpenes (carnosic acid and carnosol at 1:1 and 2:1 w:w) were tested in fattening lambs to stabilize the sensory quality of cooked and chill-stored patties. A total of 63 lambs were fed freely for 80 ± 5 d with a basal diet supplemented or not with DRE. Minced leg meat from each lamb was used to make patty batches. The patties were cooked at 72 ºC for 2 min, aerobically packed, kept at 2 ºC for up to 4 d and then reheated. Sensory traits (color, odor, flavor, and texture), CIELab color, and lipid oxidation (assessed as TBARS) were determined. In a first experiment, the lamb diet was supplemented with 600 mg of 1:1-DRE or 2:1-DRE kg(-1) feed. The 1:1-DRE diet delayed discoloration, flavor deterioration, and rancidity, while the 2:1-DRE diet was ineffective in this respect. In a second experiment, 4 supplementation levels of 1:1-DRE (0, 200, 400, and 600 mg kg(-1) feed) were compared. Flavor deterioration was delayed when the lamb diet was supplemented with at least 400 mg 1:1-DRE kg(-1) feed. The effects of the diet on the odor, flavor, and color were corroborated by differences in TBARS and CIELab. The results obtained suggest that rosemary diterpenes and/or their active secondary compounds deposited in muscle can act as endogenous antioxidants in cooked lamb. The carnosol intake seems crucial in the antioxidant actions achieved through DRE. The use of rosemary antioxidants in animal feeding would allow meat-based dishes to be preserved longer without adding preservatives. © 2014 Institute of Food Technologists®

  11. Ectopic expression of protein kinase C-β sensitizes head and neck squamous cell carcinoma to diterpene esters.

    Science.gov (United States)

    Adams, Ryan A; D'Souza, Marjorie M A; Pierce, Carly J; Korica, Natasa; Wallwork, Ben; Parsons, Peter G; Panizza, Benedict; Boyle, Glen M

    2015-03-01

    The objective of this study was to examine the effect of specific Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly head and neck squamous cell carcinoma cell lines, and the impact this may have on treatment with known activators of PKC. The constitutive expression of PKC isoforms were determined in six head and neck squamous cell carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was established. Viral transduction to re-express PKCβ isoforms in two of these cell lines was performed, and its effect on the sensitivity to the compounds was quantified. Tongue and hypopharyngeal SCC cell lines were resistant to both TPA and PEP005, with the concentration required to inhibit growth by 50% (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell lines re-expressing PKCβI and -βII isoforms demonstrated IC50 of 1-5 ng/ml with TPA or PEP005. Re-expression of PKCβ in head and neck SCC cell lines leads to cells one thousand-times more sensitive to the cytotoxic effects of phorbol or diterpene esters in culture. This highlights the importance of the isoform in tumor progression and presents the potential benefit of these compounds in malignancies expressing the protein, and in combination therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. A novel conversion of C(19)-diterpenoid alkaloids into aconane-type diterpenes with eight-membered ring system via skeletal rearrangement of corresponding diazonium derivatives.

    Science.gov (United States)

    Ji, Hong; Chen, Qiao-Hong; Wang, Feng-Peng

    2009-03-01

    A new and efficient approach toward the conversion of C(19)-diterpenoid alkaloids into diterpenes with [6+8+5+6] ring system is reported. Treatment of imines 5, 14, and 24 derived from the C(19)-diterpenoid alkaloids with NaNO(2)-NaOAc-HOAc afforded a series of novel rearrangement diterpenes 6-8, 15-19, and 25-27, respectively. The lactone 11 was obtained in 41% yield by treating 5 with NaNO(2)-HBr-Br(2). The formation of diazonium intermediate is postulated, which was subsequently subjected to skeletal rearrangement, leading to the enlargement of B ring. All the new compounds were isolated and fully characterized.

  13. Use of (S)-trans-gamma-monocyclofarnesol as a useful chiral building block for the stereoselective synthesis of diterpenic natural products.

    Science.gov (United States)

    Serra, Stefano; Cominetti, Alessandra A; Lissoni, Veronica

    2014-03-01

    A comprehensive study of the exploitation of (S)-trans-gamma-monocyclofarnesol as a useful chiral building block for the stereoselective synthesis of natural diterpene derivatives is here described. The farnesol derivative (+)-1 was used as starting material in the preparation of the diterpenes (S)-dehydroambliol-A and (S)-trixagol, as well as for the syntheses of the dinorditerpene (S)-dinortrixagone and of the guanidine-interrupted terpenoid (S)-dotofide. Key steps of the presented syntheses were the cross-coupling between an allyl acetate and a Grignard reagent, the Wittig reaction, the selective preparation ofa diacylguanidine derivative and the alkylation of a sulfone derivative, followed by the reductive removal of the same functional group. It is worth noting that the natural products (+)-8, (+)-12 and (+)-15 were prepared stereoselectively for the first time, thus allowing the unambiguous assignment of their absolute configuration.

  14. NaCl stress-induced changes in the essential oil quality and abietane diterpene yield and composition in common sage

    Directory of Open Access Journals (Sweden)

    Taieb Tounekti

    2015-09-01

    Full Text Available Aim: The purpose of this study was to evaluate how increasing NaCl salinity in the medium can affects the essential oils (EOs composition and phenolic diterpene content and yield in leaves of Salvia officinalis L. The protective role of such compounds against NaCl stress was also argued with regard to some physiological characteristics of the plant (water and ionic relations as well as the leaf gas exchanges. Materials and Methods: Potted plants were exposed to increasing NaCl concentrations (0, 50, 75 and 100 mM for 4 weeks during July 2012. Replicates from each treatment were harvested after 0, 2, 3 and 4 weeks of adding salt to perform physiological measurements and biochemical analysis. Results: Sage EOs were rich in manool, viridiflorol, camphor, and borneol. Irrigation with a solution containing 100 mM NaCl for 4 weeks increased considerably 1.8-cineole, camphor and beta-thujone concentrations, whereas lower concentrations (50 and 75 mM had no effects. On the contrary, borneol and viridiflorol concentrations decreased significantly under the former treatment, while manool and total fatty acid concentrations were not affected. Leaf extracts contained also several diterpenes such as carnosic acid (CA, carnosol (CAR and 12- and #1054;-methoxy carnosic acid (MCA. The concentrations and total contents of CA and MCA increased after 3 weeks of irrigation with 75 or 100 mM NaCl. The 50 mM NaCl had no effect on these diterpenes. Our results suggest a protective role for CA against salinity stress. Conclusion: This study may provide ways to manipulate the concentration and yield of some phenolic diterpenes and EOs in sage. In fact soil salinity may favour a directional production of particular components of interest. [J Intercult Ethnopharmacol 2015; 4(3.000: 208-216

  15. Indole-diterpenes and ergot alkaloids in Cynodon dactylon (Bermuda grass) infected with Claviceps cynodontis from an outbreak of tremors in cattle.

    Science.gov (United States)

    Uhlig, Silvio; Botha, Christo J; Vrålstad, Trude; Rolén, Elin; Miles, Christopher O

    2009-12-09

    Tremorgenic syndromes in mammals are commonly associated with indole-diterpenoid alkaloids of fungal origin. Cattle are sometimes affected by tremors (also called "staggers") when they graze on toxic grass pastures, and Bermuda grass ( Cynodon dactylon , kweek) has been known to be associated with tremors for several decades. This study reports the identification of paspalitrems and paspaline-like indole-diterpenes in the seedheads of Claviceps cynodontis -infected Bermuda grass collected from a pasture that had caused a staggers syndrome in cattle in South Africa and thereby links the condition to specific mycotoxins. The highest concentration (about 150 mg/kg) was found for paspalitrem B. Ergonovine and ergine (lysergic acid amide), together with their C-8 epimers, were found to co-occur with the indole-diterpenes at concentrations of about 10 microg/kg. The indole-diterpene profile of the extract from the ergotized Bermuda grass was similar to that of Claviceps paspali sclerotia. However, the C. paspali sclerotia contained in addition agroclavine and elymoclavine. This is the first study linking tremors associated with grazing of Bermuda grass to specific tremorgenic indole-diterpenoid mycotoxins.

  16. Conifer Diterpene Resin Acids Disrupt Juvenile Hormone-Mediated Endocrine Regulation in the Indian Meal Moth Plodia interpunctella.

    Science.gov (United States)

    Oh, Hyun-Woo; Yun, Chan-Seok; Jeon, Jun Hyoung; Kim, Ji-Ae; Park, Doo-Sang; Ryu, Hyung Won; Oh, Sei-Ryang; Song, Hyuk-Hwan; Shin, Yunhee; Jung, Chan Sik; Shin, Sang Woon

    2017-07-01

    Diterpene resin acids (DRAs) are important components of oleoresin and greatly contribute to the defense strategies of conifers against herbivorous insects. In the present study, we determined that DRAs function as insect juvenile hormone (JH) antagonists that interfere with the juvenile hormone-mediated binding of the JH receptor Methoprene-tolerant (Met) and steroid receptor coactivator (SRC). Using a yeast two-hybrid system transformed with Met and SRC from the Indian meal moth Plodia interpunctella, we tested the interfering activity of 3704 plant extracts against JH III-mediated Met-SRC binding. Plant extracts from conifers, especially members of the Pinaceae, exhibited strong interfering activity, and four active interfering DRAs (7α-dehydroabietic acid, 7-oxodehydroabietic acid, dehydroabietic acid, and sandaracopimaric acid) were isolated from roots of the Japanese pine Pinus densiflora. The four isolated DRAs, along with abietic acid, disrupted the juvenile hormone-mediated binding of P. interpunctella Met and SRC, although only 7-oxodehydroabietic acid disrupted larval development. These results demonstrate that DRAs may play a defensive role against herbivorous insects via insect endocrine-disrupting activity.

  17. Quantitative Variation of Flavonoids and Diterpenes in Leaves and Stems of Cistus ladanifer L. at Different Ages

    Directory of Open Access Journals (Sweden)

    Cristina Valares Masa

    2016-02-01

    Full Text Available The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of the plant and they may be modified as a response to biotic and/or abiotic stress. As a consequence, the resistance state of a plant may vary in space and time. The secondary metabolites of Cistus ladanifer have been quantified in leaves and stems throughout autumn, winter, spring and summer, and at different ages of the plant. This study shows that there are significant differences between young leaves, mature leaves and stems, and between individuals of different ages. Young leaves show significantly greater synthesis of flavonoids and diterpenes than mature leaves and stems, with a clear seasonal variation, and the differences between leaves at different growth stages and stems is maintained during the quantified seasons. With respect to age, specimens under one year of age secreted significantly lower amounts of compounds. The variation in the composition of secondary metabolites between different parts of the plant, the season and the variations in age may determine the interactions of Cistus ladanifer with the biotic and abiotic factors to which it is exposed.

  18. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    Science.gov (United States)

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

  19. Molecular Docking Studies of Marine Diterpenes as Inhibitors of Wild-Type and Mutants HIV-1 Reverse Transcriptase

    Directory of Open Access Journals (Sweden)

    Alessandra M. T. de Souza

    2013-10-01

    Full Text Available AIDS is a pandemic responsible for more than 35 million deaths. The emergence of resistant mutations due to drug use is the biggest cause of treatment failure. Marine organisms are sources of different molecules, some of which offer promising HIV-1 reverse transcriptase (RT inhibitory activity, such as the diterpenes dolabelladienotriol (THD, IC50 = 16.5 µM, (6R-6-hydroxydichotoma-3,14-diene-1,17-dial (HDD, IC50 = 10 µM and (6R-6-acetoxydichotoma-3,14-diene-1,17-dial (ADD, IC50 = 35 µM, isolated from a brown algae of the genus Dictyota, showing low toxicity. In this work, we evaluated the structure-activity relationship (SAR of THD, HDD and ADD as anti HIV-1 RT, using a molecular modeling approach. The analyses of stereoelectronic parameters revealed a direct relationship between activity and HOMO (Highest Occupied Molecular Orbital-LUMO (Lowest Unoccupied Molecular Orbital gap (ELUMO–EHOMO, where antiviral profile increases with larger HOMO-LUMO gap values. We also performed molecular docking studies of THD into HIV-1 RT wild-type and 12 different mutants, which showed a seahorse conformation, hydrophobic interactions and hydrogen bonds with important residues of the binding pocket. Based on in vitro experiments and docking studies, we demonstrated that mutations have little influence in positioning and interactions of THD. Following a rational drug design, we suggest a modification of THD to improve its biological activity.

  20. Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate.

    Science.gov (United States)

    Barnett, Catherine M E; Broit, Natasa; Yap, Pei-Yi; Cullen, Jason K; Parsons, Peter G; Panizza, Benedict J; Boyle, Glen M

    2018-04-18

    The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1 nu and NOD/SCID mice and treated with intratumoral injection of 30 μg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1 nu mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.

  1. Spectroscopic data of Labdane Diterpenes: a theoretical analysis via NMR and DFT; Dados espectroscópicos de diterpenos Labdânicos: uma análise teórica via RMN e DFT

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Fabrine S. de; Silva, Silvana de O.; Alves, Cláudio N.; Guilhon, Giselle M.S.P. [Universidade Federal do Pará (UFPA), Belém, PA (Brazil). Instituto de Ciências Exatas e Naturais; Faria, Lênio J.G. de; Brasil, Davi do S.B., E-mail: davibb@ufpa.br [Universidade Federal do Pará, Belém, PA (Brazil). Instituto de Tecnologia; Muller, Adolfo H. [Centro Universitário do Estado do Pará, Belém, PA (Brazil)

    2015-06-15

    Labdane diterpenes exhibit important bioactivities such as cardiovascular effects in rats as well as effects in the treatment of autoimmune diseases and Alzheimer syndrome. Recently, the labdane diterpenes ent-13-epi-manoil oxide, ribenone and ribenol were isolated from Croton palanostigma. The computational method DFT/B3LYP/cc-pVDZ was used to optimize the structures of these diterpenes and to calculate infrared data. Chemical shifts (δ{sub H} and δ{sub C}) of the minimum energy structures (local minimum) were calculated and compared with the experimental data. Comparison of the NMR data by simple linear regression (SLR) showed satisfactory statistical results with a correlation coefficient (R{sup 2} ) and predictive ability (Q{sup 2}) of over 98%. The predicted NMR data were used to confirm the δ{sub H} values that have not been published. (author)

  2. Efficient preparation of incensole and incensole acetate, and quantification of these bioactive diterpenes in Boswellia papyrifera by a RP-DAD-HPLC method.

    Science.gov (United States)

    Paul, Michael; Jauch, Johann

    2012-03-01

    Incensole and incensole acetate, found in incense, are encouraging potent bioactive diterpenic cembrenoids, inhibiting Nuclear Factor-kappaB activation. Furthermore, incensole acetate elicits psycho-activity in mice by activating the TRPV3 channels in the brain. Starting from crude extracts of the incense species Boswellia papyrifera Hochst., a convenient procedure for the efficient large-scale synthesis of incensole and its acetate is presented. Additionally, a reversed-phase, diode-array-detection, high-performance liquid chromatography (RP-DAD-HPLC) method for the quantification of incensole and incensole acetate is reported, indicating that these two compounds are typical biomarkers for B. papyrifera.

  3. Involvement of 2-C-methyl-D-erythritol-4-phosphate pathway in biosynthesis of aphidicolin-like tetracyclic diterpene of Scoparia dulcis.

    Science.gov (United States)

    Nkembo, Marguerite Kasidimoko; Lee, Jung-Bum; Nakagiri, Takeshi; Hayashi, Toshimitsu

    2006-05-01

    Specific inhibitors of the MVA pathway (pravastatin) and the MEP pathway (fosmidomycin) were used to interfere with the biosynthetic flux which leads to the production of aphidicolin-like diterpene in leaf organ cultures of Scoparia dulcis. Treatment of leaf organs with fosmidomycin resulted in dose dependent inhibition of chlorophylls, carotenoids, scopadulcic acid B (SDB) and phytol production, and no effect on sterol production was observed. In response to the pravastatin treatment, a significant decrease in sterol and perturbation of SDB production was observed.

  4. Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract

    Directory of Open Access Journals (Sweden)

    Liqian Wang

    2017-06-01

    Full Text Available Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.. Chromatographic separation was carried out on a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 mm × 100 mm with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water and solution B (acetonitrile at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM mode with electrospray ionization (ESI. The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well.

  5. Hydrogenation of the Exocyclic Olefinic Bond at C-16/C-17 Position of ent-Kaurane Diterpene Glycosides of Stevia rebaudiana Using Various Catalysts

    Science.gov (United States)

    Chaturvedula, Venkata Sai Prakash; Prakash, Indra

    2013-01-01

    Catalytic hydrogenation of the exocyclic double bond present between C16 and C17 carbons of the four ent-kaurane diterpene glycosides namely rebaudioside A, rebaudioside B, rebaudioside C, and rebaudioside D isolated from Stevia rebaudiana has been carried out using Pt/C, Pd(OH)2, Rh/C, Raney Ni, PtO2, and 5% Pd/BaCO3 to their corresponding dihydro derivatives with 17α and 17β methyl group isomers. Reactions were performed using the above-mentioned catalysts with the solvents methanol, water, and ethanol/water (8:2) under various conditions. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data, including a comparison with reported spectral data. PMID:23896597

  6. Hydrogenation of the Exocyclic Olefinic Bond at C-16/C-17 Position of ent-Kaurane Diterpene Glycosides of Stevia rebaudiana Using Various Catalysts

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2013-07-01

    Full Text Available Catalytic hydrogenation of the exocyclic double bond present between C16 and C17 carbons of the four ent-kaurane diterpene glycosides namely rebaudioside A, rebaudioside B, rebaudioside C, and rebaudioside D isolated from Stevia rebaudiana has been carried out using Pt/C, Pd(OH2, Rh/C, Raney Ni, PtO2, and 5% Pd/BaCO3 to their corresponding dihydro derivatives with 17α and 17β methyl group isomers. Reactions were performed using the above-mentioned catalysts with the solvents methanol, water, and ethanol/water (8:2 under various conditions. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data, including a comparison with reported spectral data.

  7. Cholesterol-raising diterpenes in types of coffee commonly consumed in Singapore, Indonesia and India and associations with blood lipids: a survey and cross sectional study.

    Science.gov (United States)

    Naidoo, Nasheen; Chen, Cynthia; Rebello, Salome A; Speer, Karl; Tai, E Shyong; Lee, Jeanette; Buchmann, Sandra; Koelling-Speer, Isabelle; van Dam, Rob M

    2011-05-15

    To measure the content of cholesterol-raising diterpenes in coffee sold at the retailer level in Singapore, Indonesia and India and to determine the relationship of coffee consumption with lipid levels in a population-based study in Singapore. Survey and cross-sectional study in local coffee shops in Singapore, Indonesia and India to measure the diterpene content in coffee, and a population-based study in Singapore to examine the relationship of coffee consumption and blood lipid levels. Interviews and coffee samples (n=27) were collected from coffee shops in Singapore, Indonesia and India. In addition, 3000 men and women who were Chinese, Malay, and Indian residents of Singapore participated in a cross-sectional study. The traditional 'sock' method of coffee preparation used in Singapore resulted in cafestol concentrations comparable to European paper drip filtered coffee (mean 0.09±SD 0.064 mg/cup). This amount would result in negligible predicted increases in serum cholesterol and triglyceride concentrations. Similarly low amounts of cafestol were found in Indian 'filter' coffee that used a metal mesh filter (0.05±0.05 mg/cup). Coffee samples from Indonesia using the 'sock' method (0.85±0.41 mg/cup) or a metal mesh filter (0.98 mg/cup) contained higher amounts of cafestol comparable to espresso coffee. Unfiltered coffee from Indonesia contained an amount of cafestol (4.43 mg/cup) similar to Scandinavian boiled, Turkish and French press coffee with substantial predicted increases in serum cholesterol (0.33 mmol/l) and triglycerides (0.20 mmol/l) concentrations for consumption of 5 cups per day. In the Singaporean population, higher coffee consumption was not substantially associated with serum lipid concentrations after adjustment for potential confounders [LDL-cholesterol: 3.07 (95% confidence interval 2.97-3.18) for Singapore and India, coffee consumption in these countries does not appear to be a risk factor for elevation of serum cholesterol, whereas

  8. Intermedin A, a New Labdane Diterpene Isolated from Alpinia intermedia, Prolonged the Survival Time of P-388D1 Tumor-Bearing CDF1 Mice.

    Science.gov (United States)

    Chen, Lih-Geeng; Su, Pei-Jung; Tsai, Po-Wei; Yang, Ling-Ling; Wang, Ching-Chiung

    2017-01-01

    Eight ethanolic extracts of indigenous Taiwanese plants of the genus Alpinia were tested for tumor cytotoxicity against AGS, Hep G2, HeLa, KB, and HL-60 cells. Among the 50 % and 95 % EtOH extracts of eight Alpinia species, the cytotoxic effects of Alpinia intermedia leaves were the strongest. When the leaf extract of A. intermedia was partitioned using n -hexane and aqueous solvents, the n -hexane layer showed a greater cytotoxic effect and could prolong the survival time of P-388D 1 tumor-bearing CDF1 mice. Two new labdane diterpene derivatives, intermedin A ( 1 ) and intermedin B ( 2 ), and coronarin E ( 3 ) were isolated from the n -hexane layer of A. intermedia . Intermedin A induced apoptosis in HL-60 cells at 30 µg/mL and significantly prolonged the survival time of P-388D 1 tumor-bearing CDF 1 mice by 48.7 % at 20 mg/kg of body weight. We suggest that intermedin A is a major compound of A. intermedia and has a cytotoxic effect on HL-60 and P-388D 1 cells. Georg Thieme Verlag KG Stuttgart · New York.

  9. Synthesis of model compounds derived from natural clerodane insect antifeedants

    NARCIS (Netherlands)

    Klein Gebbinck, E.A.

    1999-01-01

    Insect antifeedants are compounds with the ability to reduce or inhibit insect feeding without directly killing the insect. Such compounds offer a number of properties that are highly desirable in environmentally friendly crop protection agents. Although the principle of insect control

  10. Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

    Energy Technology Data Exchange (ETDEWEB)

    Lizarte, F.S. Neto; Tirapelli, D.P.C. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Ambrosio, S.R. [Universidade de Franca, Núcleo de Pesquisa em Ciências e Tecnologia, Franca, SP (Brazil); Tirapelli, C.R. [Universidade de São Paulo, Laboratório de Farmacologia, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Escola de Enfermagem de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Oliveira, F.M. [Universidade de São Paulo, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Novais, P.C. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Peria, F.M.; Oliveira, H.F. [Universidade de São Paulo, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Carlotti, C.G. Junior; Tirapelli, L.F. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil)

    2013-01-11

    Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

  11. Structure of the ent-Copalyl Diphosphate Synthase PtmT2 from Streptomyces platensis CB00739, a Bacterial Type II Diterpene Synthase.

    Science.gov (United States)

    Rudolf, Jeffrey D; Dong, Liao-Bin; Cao, Hongnan; Hatzos-Skintges, Catherine; Osipiuk, Jerzy; Endres, Michael; Chang, Chin-Yuan; Ma, Ming; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N; Shen, Ben

    2016-08-31

    Terpenoids are the largest and most structurally diverse family of natural products found in nature, yet their presence in bacteria is underappreciated. The carbon skeletons of terpenoids are generated through carbocation-dependent cyclization cascades catalyzed by terpene synthases (TSs). Type I and type II TSs initiate cyclization via diphosphate ionization and protonation, respectively, and protein structures of both types are known. Most plant diterpene synthases (DTSs) possess three α-helical domains (αβγ), which are thought to have arisen from the fusion of discrete, ancestral bacterial type I TSs (α) and type II TSs (βγ). Type II DTSs of bacterial origin, of which there are no structurally characterized members, are a missing piece in the structural evolution of TSs. Here, we report the first crystal structure of a type II DTS from bacteria. PtmT2 from Streptomyces platensis CB00739 was verified as an ent-copalyl diphosphate synthase involved in the biosynthesis of platensimycin and platencin. The crystal structure of PtmT2 was solved at a resolution of 1.80 Å, and docking studies suggest the catalytically active conformation of geranylgeranyl diphosphate (GGPP). Site-directed mutagenesis confirmed residues involved in binding the diphosphate moiety of GGPP and identified DxxxxE as a potential Mg(2+)-binding motif for type II DTSs of bacterial origin. Finally, both the shape and physicochemical properties of the active sites are responsible for determining specific catalytic outcomes of TSs. The structure of PtmT2 fundamentally advances the knowledge of bacterial TSs, their mechanisms, and their role in the evolution of TSs.

  12. Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein

    International Nuclear Information System (INIS)

    Higgins, Larry G.; Cavin, Christophe; Itoh, Ken; Yamamoto, Masayuki; Hayes, John D.

    2008-01-01

    Mice fed diets containing 3% or 6% coffee for 5 days had increased levels of mRNA for NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase class Alpha 1 (GSTA1) of between 4- and 20-fold in the liver and small intestine. Mice fed 6% coffee also had increased amounts of mRNA for UDP-glucuronosyl transferase 1A6 (UGT1A6) and the glutamate cysteine ligase catalytic (GCLC) subunit of between 3- and 10-fold in the small intestine. Up-regulation of these mRNAs was significantly greater in mice possessing Nrf2 (NF-E2 p45 subunit-related factor 2) than those lacking the transcription factor. Basal levels of mRNAs for NQO1, GSTA1, UGT1A6 and GCLC were lower in tissues from nrf2 -/- mice than from nrf2 +/+ mice, but modest induction occurred in the mutant animals. Treatment of mouse embryonic fibroblasts (MEFs) from nrf2 +/+ mice with either coffee or the coffee-specific diterpenes cafestol and kahweol (C + K) increased NQO1 mRNA up to 9-fold. MEFs from nrf2 -/- mice expressed less NQO1 mRNA than did wild-type MEFs, but NQO1 was induced modestly by coffee or C + K in the mutant fibroblasts. Transfection of MEFs with nqo1-luciferase reporter constructs showed that induction by C + K was mediated primarily by Nrf2 and required the presence of an antioxidant response element in the 5'-upstream region of the gene. Luciferase reporter activity did not increase following treatment of MEFs with 100 μmol/l furan, suggesting that this ring structure within C + K is insufficient for gene induction. Priming of nrf2 +/+ MEFs, but not nrf2 -/- MEFs, with C + K conferred 2-fold resistance towards acrolein

  13. FT-IR, FT-Raman, UV-visible, and NMR spectroscopy and vibrational properties of the labdane-type diterpene 13-epi-sclareol.

    Science.gov (United States)

    Chain, Fernando E; Leyton, Patricio; Paipa, Carolina; Fortuna, Mario; Brandán, Silvia A

    2015-03-05

    In this work, FT-IR, FT-Raman, UV-Visible and NMR spectroscopies and density functional theory (DFT) calculations were employed to study the structural and vibrational properties of the labdane-type diterpene 13-epi-sclareol using the hybrid B3LYP method together with the 6-31G(∗) basis set. Three stable structures with minimum energy found on the potential energy curves (PES) were optimized, and the corresponding molecular electrostatic potentials, atomic charges, bond orders, stabilization energies and topological properties were computed at the same approximation level. The complete assignment of the bands observed in the vibrational spectrum of 13-epi-sclareol was performed taking into account the internal symmetry coordinates for the three structures using the scaled quantum mechanical force field (SQMFF) methodology at the same level of theory. In addition, the force constants were calculated and compared with those reported in the literature for similar compounds. The predicted vibrational spectrum and the calculated (1)H NMR and (13)C NMR chemical shifts are in good agreement with the corresponding experimental results. The theoretical UV-Vis spectra for the most stable structure of 13-epi-sclareol demonstrate a better correlation with the corresponding experimental spectrum. The study of the three conformers by means of the theory of atoms in molecules (AIM) revealed different H bond interactions and a strong dependence of the interactions on the distance between the involved atoms. Furthermore, the natural bond orbital (NBO) calculations showed the characteristics of the electronic delocalization for the two six-membered rings with chair conformations. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

    International Nuclear Information System (INIS)

    Lizarte, F.S. Neto; Tirapelli, D.P.C.; Ambrosio, S.R.; Tirapelli, C.R.; Oliveira, F.M.; Novais, P.C.; Peria, F.M.; Oliveira, H.F.; Carlotti, C.G. Junior; Tirapelli, L.F.

    2013-01-01

    Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors

  15. Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review

    Directory of Open Access Journals (Sweden)

    Paulo Michel P. Ferreira

    2011-12-01

    Full Text Available Folk uses and scientific investigations have highlighted the importance of Casearia sylvestris extracts and their relevant bioactive potential. The aim of this work was to review the pharmacological properties of C. sylvestris, emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor potentialities. Ethanolic extracts and essential oil of their leaves have antiulcerogenic activity and reduce gastric volume without altering the stomach pH, which corroborates their consumption on gastrointestinal disorders. Leaf water extracts show phospholipase A2 inhibitory activity that prevents damage effects on the muscular tissue after toxin inoculation. This antiphospholipasic action is probably related to the use as an anti-inflammatory, proposing a pharmacological blockage similar to that obtained with non-steroidal anti-inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided-assay fractionations lead to the identification of secondary metabolites, especially the clerodane diterpenes casearins (A-X and casearvestrins (A-C, compounds with a remarkable cytotoxic and antitumor action. Therefore, the C. sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive folk utilization, exciting searches for new molecules and a better comprehension about biological properties.Usos populares e pesquisas científicas têm destacado a importância dos extratos da planta Casearia sylvestris e seu grande potencial bioativo. Neste trabalho, objetiva-se revisar as propriedades farmacológicas de C. sylvestris, enfatizando sua potencialidade antiulcerogênica, antiinflamatória, antiofídica e antitumoral. O extrato etanólico e o óleo essencial das folhas possuem atividade antiulcerogênica promissora, diminuindo o volume gástrico sem alterar o pH estomacal, corroborando sua aplicação contra dores gastrointestinais. Já os extratos aquosos das folhas têm atividade inibitória contra fosfolipase A2 presente

  16. Identification and Functional Characterization of Monofunctional ent-Copalyl Diphosphate and ent-Kaurene Synthases in White Spruce Reveal Different Patterns for Diterpene Synthase Evolution for Primary and Secondary Metabolism in Gymnosperms1[W][OA

    Science.gov (United States)

    Keeling, Christopher I.; Dullat, Harpreet K.; Yuen, Mack; Ralph, Steven G.; Jancsik, Sharon; Bohlmann, Jörg

    2010-01-01

    The biosynthesis of the tetracyclic diterpene ent-kaurene is a critical step in the general (primary) metabolism of gibberellin hormones. ent-Kaurene is formed by a two-step cyclization of geranylgeranyl diphosphate via the intermediate ent-copalyl diphosphate. In a lower land plant, the moss Physcomitrella patens, a single bifunctional diterpene synthase (diTPS) catalyzes both steps. In contrast, in angiosperms, the two consecutive cyclizations are catalyzed by two distinct monofunctional enzymes, ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS). The enzyme, or enzymes, responsible for ent-kaurene biosynthesis in gymnosperms has been elusive. However, several bifunctional diTPS of specialized (secondary) metabolism have previously been characterized in gymnosperms, and all known diTPSs for resin acid biosynthesis in conifers are bifunctional. To further understand the evolution of ent-kaurene biosynthesis as well as the evolution of general and specialized diterpenoid metabolisms in gymnosperms, we set out to determine whether conifers use a single bifunctional diTPS or two monofunctional diTPSs in the ent-kaurene pathway. Using a combination of expressed sequence tag, full-length cDNA, genomic DNA, and targeted bacterial artificial chromosome sequencing, we identified two candidate CPS and KS genes from white spruce (Picea glauca) and their orthologs in Sitka spruce (Picea sitchensis). Functional characterization of the recombinant enzymes established that ent-kaurene biosynthesis in white spruce is catalyzed by two monofunctional diTPSs, PgCPS and PgKS. Comparative analysis of gene structures and enzyme functions highlights the molecular evolution of these diTPSs as conserved between gymnosperms and angiosperms. In contrast, diTPSs for specialized metabolism have evolved differently in angiosperms and gymnosperms. PMID:20044448

  17. The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells.

    Science.gov (United States)

    Park, Gwang Hun; Song, Hun Min; Jeong, Jin Boo

    2016-09-01

    Kahweol as a coffee-specific diterpene has been reported to exert anti-cancer properties. However, the mechanism responsible for the anti-cancer effects of kahweol is not fully understood. The main aim of this investigation was to determine the effect of kahweol on cell proliferation and the possible mechanisms in human colorectal cancer cells. Kahweol inhibited markedly the proliferation of human colorectal cancer cell lines such as HCT116, SW480. Kahweol decreased cyclin D1 protein level in HCT116 and SW480 cells. Contrast to protein levels, cyclin D1 mRNA level and promoter activity did not be changed by kahweol treatment. MG132 treatment attenuated kahweol-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in kahweol-treated cells. Kahweol increased phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by kahweol. Inhibition of ERK1/2 by PD98059, JNK by SP600125 or GSK3β by LiCl suppressed cyclin D1 phosphorylation and downregulation by kahweol. Furthermore, the inhibition of nuclear export by LMB attenuated cyclin D1 degradation by kahweol. In conclusion, kahweol-mediated cyclin D1 degradation may contribute to the inhibition of the proliferation in human colorectal cancer cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Optimization of diterpenes bioconversion process by the fungus Cephalosporium aphidicola Otimização do processo de bioconversão de compostos diterpênicos pelo fungo Cephalosporium aphidicola

    Directory of Open Access Journals (Sweden)

    Jacqueline Aparecida Takahashi

    2000-06-01

    Full Text Available Parameters for a more efficient biotransformation of diterpene-like compounds by the fungus Cephalosporium aphidicola were established by carrying out microscale feedings at several conditions. Experiments were guided by thin layer chromatography and gas chromatography analysis. It was observed that the substrate should be added in ethanol at concentrations between 15 to 30 mg per 100 ml of medium. The extraction of the product showed to be more efficient when carried out from both mycelia and broth and using ethylacetate as the extracting solvent. The experiment should be stopped six days after feeding the substrate to the fungus for the best product yield.Condições otimizadas para a biotransformação de compostos diterpênicos pelo fungo Cephalosporium aphidicola foram determinadas, realizando-se incubações em microescala nas quais variaram-se parâmetros como o tempo de incubação e a quantidade de substrato adicionado. A velocidade (índice de bioconversão foi monitorada analisando-se os extratos de cultivo através de cromatografia em camada delgada e cromatografia gasosa. Os resultados obtidos mostraram que, para melhores rendimentos, o substrato deve ser adicionado em solução etanólica, na concentração de 15-30 mg por 100 mL de meio de cultura. A extração de produtos deve ser realizada com acetato de etila, a partir da fase aquosa e do micélio, no sexto dia após a adição do substrato. Estes resultados podem ser utilizados como um roteiro para incubações de compostos estruturalmente semelhantes com o fungo Cephalosporium aphidicola.

  19. Structure of the ent -Copalyl Diphosphate Synthase PtmT2 from Streptomyces platensis CB00739, a Bacterial Type II Diterpene Synthase

    Energy Technology Data Exchange (ETDEWEB)

    Rudolf, Jeffrey D.; Dong, Liao-Bin; Cao, Hongnan; Hatzos-Skintges, Catherine; Osipiuk, Jerzy; Endres, Michael; Chang, Chin-Yuan; Ma, Ming; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N.; Shen, Ben

    2016-08-31

    Terpenoids are the largest and most structurally diverse family of natural products found in nature, yet their presence in bacteria is underappreciated. The carbon skeletons of terpenoids are generated through carbocation-dependent cyclization cascades catalyzed by terpene synthases (TSs). Type I and type II TSs initiate cyclization via diphosphate ionization and protonation, respectively, and protein structures of both types are known. Most plant diterpene synthases (DTSs) possess three alpha-helical domains (alpha beta gamma), which are thought to have arisen from the fusion of discrete, ancestral bacterial type I TSs (alpha) and type II TSs (beta gamma). Type II DTSs of bacterial origin, of which there are no structurally characterized members, are a missing piece in the structural evolution of TSs. Here, we report the first crystal structure of a type II DTS from bacteria. PtnaT2 from Streptomyces platensis CB00739 was verified as an ent-copalyl diphosphate synthase involved in the biosynthesis of platensimycin and platencin. The crystal structure of PtmT2 was solved at a resolution of 1.80 angstrom, and docking studies suggest the catalytically active conformation of geranylgeranyl diphosphate (GGPP). Site-directed mutagenesis confirmed residues involved in binding the diphosphate moiety of GGPP and identified DxxxxE as a potential Mg2+-binding motif for type II DTSs of bacterial origin. Finally, both the shape and physicochemical properties of the active sites are responsible for determining specific catalytic outcomes of TSs. The structure of PtmT2 fundamentally advances the knowledge of bacterial TSs, their mechanisms, and their role in the evolution of TSs.

  20. Isolation and structural elucidation of secondary metabolites from plants of the Rutaceae family, Rubiaceae, Euphorbiaceae and Salicaceae

    International Nuclear Information System (INIS)

    Calderon Castro, Carlos

    2014-01-01

    A phytochemical study was conducted of the Zuelania guidonia plants (Salicaceae), croton ovalifolius (Euphorbiaceae) erythrochiton gymnanthus (Rutaceae) and Faramea occidentalis (Rubiaceae). Purification of the compounds was carried out using chromatographic techniques while structural elucidation was performed by experiments using nuclear magnetic resonance (NMR) and mass spectrometry (MS). Of Z. guidonia has been possible the purification and structural elucidation of 22 compounds (Z1-Z22), two labdane type diterpenes and 20 clerodane-type diterpenes. The clerodanes have presented 16 innovative structure, highlighting the presence of a group of 3,6-dihydro -1.2-dioxin and xylose group in some of them. In addition, 11 of the clerodanes were evaluated with cytotoxicity assays in three cancer cell lines CCRF-CEM (acute lymphoblastic leukemia), CEM-ADR5000 (acute lymphoblastic leukemia resistant to doxorubicin) MIA-Paca-2 (metastatic pancreas) and a line of healthy cells PBMC (peripheral blood mononuclear cells). The Z4, Z6 and Z15 compounds stood out as the most cytotoxic, particularly against CCRF-CEM cells with IC 50 values between 1.6 and 2.5 μM. Seven compounds identified as glutarimide alkaloids (C1-C7) were isolated and elucidated, five of which have presented a novel structure from C. ovalifolius. Three compounds (E1-E3) that are triterpenes derivatives of known structure sitosterol, were isolated and elucidated from E. gymnanthus plant. From F. occidentalis was obtained the structure of a pure compound (F1], which is a flavonoid of known structure. (author) [es

  1. Vibrational Dynamics of the Diterpene-Neoandrographolide

    Directory of Open Access Journals (Sweden)

    P. K. Singh

    2009-01-01

    Full Text Available A complete normal coordinate analysis was performed for neoandrographolide in terms of the calculation by using Wilson’s G-F matrix method and Urey Bradley force field. Andrographis paniculata has been reported for its potent hepatoprotective. Andrographis paniculata has been reported to have antisecretory (antidiarrhoeal, immunostimulant, antimalarial, antifilarial activity. It is also reported to have anticancer, anti HIV, anti-inflammatory, hypotensive action. In addition, it has found to be effective in myocardial infraction.

  2. Pachydictyols B and C: New Diterpenes from Dictyota dichotoma Hudson

    Directory of Open Access Journals (Sweden)

    Hartmut Laatsch

    2013-08-01

    Full Text Available Two new diterpenoids, pachydictyol B (1a/1b and C (2, were isolated from the dichloromethane extract of the marine brown alga, Dictyota dichotoma, collected from the Red Sea coast of Egypt, along with the known metabolites, pachydictyol A (3a, dictyol E (4, cis-africanan-1α-ol (5a, fucosterol (6, tetrahydrothiophen-1,1-dioxide and poly-β-hydroxybutyric acid. GC-MS analysis of the nonpolar fractions also indicated the presence of β-bourbonene and nonanal, along with three hydrocarbons and five fatty acids or their simple derivatives, respectively. GC-MS analysis of the unsaponifiable algal petroleum ether extract revealed the presence of a further eight compounds, among them 2,2,6,7-tetramethyl-10-oxatricyclo[4.3.0.1(1,7]decan-5-one (7, N-(4-bromo-n-butyl-pipe ridin-2-one (8 and tert-hexadecanethiol. Structures 1–6 were assigned by 1D and 2D NMR, mass spectra (EI, CI, HREI and HRESI and by comparison with data from related structures. The crude algal extract was potently active against the breast carcinoma tumor cell line, MCF7 (IC50 = 0.6 µg mL−1; pachydictyol B (1a and dictyol E (4 showed weak antimicrobial properties, and the other compounds were inactive. Pachydictyols B (1a and C (2 demonstrated a weak and unselective cytotoxicity against twelve human tumor cell lines with a mean IC50 of >30.0 µM.

  3. New Lobane and Cembrane Diterpenes from Two Comorian Soft Corals

    Directory of Open Access Journals (Sweden)

    Maurice Aknin

    2010-02-01

    Full Text Available Preliminary biological investigation of a collection of Comorian soft corals resulted in the selection of two specimens, one of Sarcophyton and the other of Lobophytum, on the basis of their toxicity on larvae of the brine shrimp (Artemia salina and inhibition of acetylcholinesterase, respectively. Bioassay-guided fractionations provided a known antitumor promoter cembrane diterpenoid, (+-sarcophytol-A (1, along with a new lobane diterpenoid, carbomethoxyfuscol (2, from Sarcophyton sp., and a new cembranoid, crassumolide E (3, from Lobophytum sp. The structures of compounds 1–3 were determined by spectroscopic analysis and by comparison of the spectral data with previously reported values. The cembranoid 3 was found to exhibit a moderate inhibitory effect on acetylcholinesterase.

  4. Pseudopterosin Biosynthesis: Aromatization of the Diterpene Cyclase Product, Elisabethatriene

    Directory of Open Access Journals (Sweden)

    Amber C. Kohl

    2003-11-01

    Full Text Available Abstract: Putative precursors in pseudopterosin biosynthesis, the hydrocarbons isoelisabethatriene (10 and erogorgiaene (11, have been identified from an extract of Pseudopterogorgia elisabethae collected in the Florida Keys. Biosynthetic experiments designed to test the utilization of these compounds in pseudopterosin production revealed that erogorgiaene is transformed to pseudopterosins A-D. Together with our previous data, it is now apparent that early steps in pseudopterosin biosynthesis involve the cyclization of geranylgeranyl diphosphate to elisabethatriene followed by the dehydrogenation and aromatization to erogorgiaene.

  5. Casbane diterpenes and acetophenones of Croton nepetaefolius (Euphorbiaceae)

    International Nuclear Information System (INIS)

    Santos, Helcio Silva; Mesquita, Francisca Maria Rodrigues; Lemos, Telma Leda G.; Monte, Francisco Jose Queiroz; Braz-Filho, Raimundo

    2008-01-01

    Croton nepetaefolius is an aromatic plant native to the northeast of Brazil where it is extensively used in folk medicine as a sedative, orexigen and antispasmodic agent. The present work deals with the chromatographic analysis of the ethanolic extract of Croton nepetaefolius stalk. It allowed the isolation and characterization of two diterpenoids named 1,4-dihydroxy-2E,6E,12E-trien-5-one-casbane and 4-hydroxy- 2E,6E,12E-5-one-casbane, two acetophenones named 2-hydroxy-4,6-dimethoxyacetophenone and 2-hydroxy-3,4,6- trimethoxyacetophenone and the steroids 3-O-beta-D-glucopiranosylsitosterol and a mixture of beta-sitosterol and stigmasterol. Structural elucidation was done on the basis of spectral data, mainly high field NMR and EIMS. (author)

  6. A novel acyclic diterpenic alcohol isolated from antioxidant active ...

    African Journals Online (AJOL)

    Background: Isolation and characterization of a new compound from the antioxidant active ethanol extract of leaves of an endemic plant Centaurothamnus maximus. Methods: The air dried powdered leaves of the plant was extracted successively with n-hexane, dichloromethane, ethyl acetate and ethanol. The obtained ...

  7. Bioactive Diterpenes and Sesquiterpenes from the Rhizomes of Wild ...

    African Journals Online (AJOL)

    Wild ginger (Siphonochilus aethiopicus (Schweinf) B.L Burtt) is used in traditional medicines in the West and South of Africa. In the present study, the crude hexane extract of wild ginger was evaluated for in vitro bioactivity. The components isolated from the plant for the first time are: epi-curzerenone, furanodienone ...

  8. Analytical aspects of diterpene alkaloid poisoning with monkshood.

    Science.gov (United States)

    Colombo, Maria Laura; Bugatti, Carlo; Davanzo, Franca; Persico, Andrea; Ballabio, Cinzia; Restani, Patrizia

    2009-11-01

    A sensitive and specific method for aconitine extraction from biological samples was developed. Aconitine, the main toxic alkaloid from plants belonging to Aconitum species (family Ranunculaceae), was determined in plant material by an external standard method, and by a standard addition calibration method in biological fluids. Described here is one fatal case and five intoxications of accidental aconitine poisoning following the ingestion of aconite mistaken for an edible grass, Aruncus dioicus (Walt.) Fernald, "mountain asparagus", and Cicerbita alpina (L.) Wallroth. The aconitine content in urine was in the range 2.94 microg/mL (dead patient)-0.20 microg/mL (surviving patients), which was almost two to four times higher than that in plasma.

  9. Isolation of novel indole diterpenes and dihydrodibenzofuran from ...

    African Journals Online (AJOL)

    Twelve secondary metabolites were earlier isolated from two marine-derived fungal strains, Aspergillus sp. AF-119 and Aspergillus sp. JQG a-6f. The objectives of this investigation were to isolate and purify natural products produced in these fungi, and identify possible drug candidates. The chemical structures of these ...

  10. In vitro evaluation of potential bitterness-masking terpenoids from the Canada goldenrod (Solidago canadensis).

    Science.gov (United States)

    Li, Jie; Pan, Li; Fletcher, Joshua N; Lv, Wei; Deng, Ye; Vincent, Michael A; Slack, Jay P; McCluskey, T Scott; Jia, Zhonghua; Cushman, Mark; Kinghorn, A Douglas

    2014-07-25

    In a screening of extracts of selected plants native to Ohio against the human bitterness receptor hTAS2R31, a chloroform-soluble extract of the aerial parts of Solidago canadensis (Canada goldenrod) was determined to have hTAS2R31 antagonistic activity and, thus, was fractionated for isolation of potential bitterness-masking agents. One new labdane diterpenoid, solidagol (1), and six known terpenoids, including two labdane diterpenoids (2 and 3), three clerodane diterpenoids (6β-angeloyloxykolavenic acid, 6β-tigloyloxykolavenic acid, and crotonic acid), and a triterpenoid (longispinogenin), were isolated. Among these compounds, 3β-acetoxycopalic acid (2) was found to be the first member of the labdane diterpene class shown to have inhibitory activity against hTAS2R31 activation (IC50 8 μM). A homology model of hTAS2R31 was constructed, and the molecular docking of 2 to this model indicated that this diterpenoid binds well to the active site of hTAS2R31, whereas this was not the case for the closely structurally related compound 3 (sempervirenic acid). The content of 2 in the chloroform-soluble portion of the methanolic extract of S. canadensis was up to 2.24 g/100 g dry weight, as determined by HPLC.

  11. High resolution UHPLC-MS characterization and isolation of main compounds from the antioxidant medicinal plant Parastrephia lucida (Meyen

    Directory of Open Access Journals (Sweden)

    Carlos Echiburu-Chau

    2017-11-01

    Full Text Available High-resolution mass spectrometry is currently used to determine the mass of biologically active compounds in medicinal plants and food and UHPLC-Orbitrap is a relatively new technology that allows fast fingerprinting and metabolomics analysis. Forty-two metabolites including several phenolic acids, flavonoids, coumarines, tremetones and ent-clerodane diterpenes were accurately identified for the first time in the resin of the medicinal plant Parastrephia lucida (Asteraceae a Chilean native species, commonly called umatola, collected in the pre-cordillera and altiplano regions of northern Chile, by means of UHPLC-PDA-HR-MS. This could be possible by the state of the art technology employed, which allowed well resolved total ion current peaks and the proposal of some biosynthetic relationships between the compounds detected. Some mayor compounds were also isolated using HSCCC. The ethanolic extract showed high total polyphenols content and significant antioxidant capacity. Furthermore, several biological assays were performed that determined the high antioxidant capacity found for the mayor compound isolated from the plant, 11- p-coumaroyloxyltremetone.

  12. Briarane Diterpenes from the South China Sea Gorgonian Coral, Junceella gemmacea

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2014-01-01

    Full Text Available Four new briarane diterpenoids, junceellolides M–P (1–4, were isolated together with seven known analogs (5–11 from the South China Sea gorgonian, Junceella gemmacea. The structures of these compounds were elucidated by detailed spectroscopic analysis and comparison with the reported data. The absolute configuration of compounds 1–3 were determined based on an ECD experiment, while the absolute configuration of compound 4 was genetically determined. All the compounds were isolated for the first time from J. gemmacea. These compounds showed no growth inhibitory activity against A549, MG63 and SMMC-7721 cell lines in an in vitro bioassay.

  13. Two new labdane diterpenes from fresh leaves of Leonurus japonicus and their degradation during drying.

    Science.gov (United States)

    Fuchino, Hiroyuki; Daikonya, Akihiro; Kumagai, Takeo; Goda, Yukihiro; Takahashi, Yutaka; Kawahara, Nobuo

    2013-01-01

    Degradation of the components of Leonurus Herb was examined during drying. Compounds 1 and 2 were detected on TLC at lower temperature, but not at higher temperature. Their chemical structures were determined by spectral methods. They immediately decomposed even at 40°C in chloroform solution. They are believed to be transformed through a retro-aldol reaction. Compounds 1 and 2 have not been previously reported.

  14. Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

    DEFF Research Database (Denmark)

    Liu, Chengwei; Tagami, Koichi; Minami, Atsushi

    2015-01-01

    KULNJ). Importantly, without conventional gene disruption, reconstitution of the biosynthetic machinery provided sufficient data to determine the pathway. It was thus demonstrated that the Aspergillus oryzae reconstitution system is a powerful method for studying the biosynthesis of complex natural products....

  15. Two new cassane diterpene lactams from the fruits of Caesalpinia mimosoides Lam.

    Science.gov (United States)

    Bi, Dewen; Xia, Guanghui; Li, Yuanping; Liang, Xuesong; Zhang, Lanjun; Wang, Liqin

    2018-04-01

    Two new cassane ditepenoid lactams, caesmimotam A (1) and B (2), along with eight known compounds (3-10) were isolated from the fruits of Caesalpinia mimosoides Lam. Their structures were identified by 1D and 2D NMR spectral data. Compounds 1 and 2 were evaluated for their cytotoxicity on HL-60, SMMC-7721, A-549, MCF-7 and SW-480 human cancer cell lines, but they were inactive.

  16. Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation

    Directory of Open Access Journals (Sweden)

    Tanzeel ur Rehman

    2018-03-01

    Full Text Available In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis. Nepetolide concentration-dependently (1.0–1000 µg/mL exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus. In brine shrimp’s lethality model, nepetolide potently showed cytotoxic effect, with LC50 value of 8.7 µg/mL. When evaluated for antitumor activity in potato disc tumor assay, nepetolide exerted tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 µg/mL. Nepetolide at 20 mg/kg reduced carrageenan-induced inflammation (P < .001 vs. saline group in rat paw. Nepetolide dose-dependently (100–500 mg/kg decreased acetic acid evoked writhes, as exhibited by diclofenac sodium. In-silico investigation of nepetolide was carried out against cyclooxygenase-2, epidermal growth factor receptor and lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between ligand nepetolide and receptors proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6–8 hydrogen bonds per target. These results indicate that nepetolide exhibits antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stress-induced disorders, microbial infections, cancers, inflammations and pain.

  17. Isolation, NMR Spectral Analysis and Hydrolysis Studies of a Hepta Pyranosyl Diterpene Glycoside from Stevia rebaudiana Bertoni

    Directory of Open Access Journals (Sweden)

    Guohong Mao

    2013-09-01

    Full Text Available From the commercial extract of the leaves of Stevia rebaudiana Bertoni, a minor steviol glycoside, 13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyloxy] ent-kaur-16-en-19-oic acid-[(2-O-(3-O-β-D-glucopyranosyl-α-L-rhamnopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyl ester] (1; also known as rebaudioside O having seven sugar units has been isolated. Its structural characterization has been achieved by the extensive 1D (1H and 13C, and 2D NMR (COSY, HMQC, HMBC as well as mass spectral data. Further, hydrolysis studies were performed on rebaudioside O using acid and enzymatic methods to identify aglycone and sugar residues in its structure as well as their configurations.

  18. Structural Characterization of the Degradation Products of a Minor Natural Sweet Diterpene Glycoside Rebaudioside M under Acidic Conditions

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2014-01-01

    Full Text Available Degradation of rebaudioside M, a minor sweet component of Stevia rebaudiana Bertoni, under conditions that simulated extreme pH and temperature conditions has been studied. Thus, rebaudioside M was treated with 0.1 M phosphoric acid solution (pH 2.0 and 80 °C temperature for 24 h. Experimental results indicated that rebaudioside M under low pH and higher temperature yielded three minor degradation compounds, whose structural characterization was performed on the basis of 1D (1H-, 13C- & 2D (COSY, HSQC, HMBC NMR, HRMS, MS/MS spectral data as well as enzymatic and acid hydrolysis studies.

  19. Identification and characterization of biosynthetic components involved in Vitex agnus-castus diterpenes biosynthesis

    DEFF Research Database (Denmark)

    Sundram, Tamil Chelvan Meenakshi

    Many plant terpenoids are commercially important compound, largely used in pharmaceuticals, nutraceuticals, cosmetics and fragrance industry. However, their low production levels in planta still remain as the major challenge in meeting the industrial demand for continuous supply of these valuable...

  20. Library-based discovery and characterization of daphnane diterpenes as potent and selective HIV inhibitors in Daphne gnidium.

    Science.gov (United States)

    Vidal, Vincent; Potterat, Olivier; Louvel, Séverine; Hamy, François; Mojarrab, Mahdi; Sanglier, Jean-Jacques; Klimkait, Thomas; Hamburger, Matthias

    2012-03-23

    Despite the existence of an extended armamentarium of effective synthetic drugs to treat HIV, there is a continuing need for new potent and affordable drugs. Given the successful history of natural product based drug discovery, a library of close to one thousand plant and fungal extracts was screened for antiretroviral activity. A dichloromethane extract of the aerial parts of Daphne gnidium exhibited strong antiretroviral activity and absence of cytotoxicity. With the aid of HPLC-based activity profiling, the antiviral activity could be tracked to four daphnane derivatives, namely, daphnetoxin (1), gnidicin (2), gniditrin (3), and excoecariatoxin (4). Detailed anti-HIV profiling revealed that the pure compounds were active against multidrug-resistant viruses irrespective of their cellular tropism. Mode of action studies that narrowed the site of activity to viral entry events suggested a direct interference with the expression of the two main HIV co-receptors, CCR5 and CXCR4, at the cell surface by daphnetoxin (1).

  1. 1 H NMR and sono chemistry: monitoration of elimination and isomerization reactions of diterpenes, catalysed by TFAA

    International Nuclear Information System (INIS)

    Uchoa, Daniel Esdras de Andrade; Silveira, Edilberto Rocha

    1997-01-01

    There are in the literature several papers dealing with the influence of ultrasound over chemical reactions [1-4]. According to Moon, S., the general mechanism of sonochemistry (the chemistry of sound and ultrasound) is not known, but it is generally agreed that the phenomenon of cavitation (formation and collapse of micro-bubbles) is responsible for its chemical effects. Although ultrasound has been known for more than 60 years its application to chemical reactions has not been investigated throughly. (author)

  2. The terpene synthase gene family in Tripterygium wilfordii harbors a labdane-type diterpene synthase among the monoterpene synthase TPS-b subfamily

    DEFF Research Database (Denmark)

    Hansen, Nikolaj Lervad; Heskes, Allison Maree; Hamberger, Britta

    2017-01-01

    Tripterygium wilfordii (Celastraceae) is a medicinal plant with anti-inflammatory and immunosuppressive properties. Identification of a vast array of unusual sesquiterpenoids, diterpenoids and triterpenoids in T. wilfordii has spurred investigations of their pharmacological properties. The tri-ep...

  3. Ectopic Expression of Hrf1 Enhances Bacterial Resistance via Regulation of Diterpene Phytoalexins, Silicon and Reactive Oxygen Species Burst in Rice

    Science.gov (United States)

    Zhong, Weigong; Yang, Jie; Okada, Kazunori; Yamane, Hisakazu; Zhang, Lei; Wang, Guang; Wang, Dong; Xiao, Shanshan; Chang, Shanshan; Qian, Guoliang; Liu, Fengquan

    2012-01-01

    Harpin proteins as elicitor derived from plant gram negative bacteria such as Xanthomonas oryzae pv. oryzae (Xoo), Erwinia amylovora induce disease resistance in plants by activating multiple defense responses. However, it is unclear whether phytoalexin production and ROS burst are involved in the disease resistance conferred by the expression of the harpinXoo protein in rice. In this article, ectopic expression of hrf1 in rice enhanced resistance to bacterial blight. Accompanying with the activation of genes related to the phytoalexin biosynthesis pathway in hrf1-transformed rice, phytoalexins quickly and consistently accumulated concurrent with the limitation of bacterial growth rate. Moreover, the hrf1-transformed rice showed an increased ability for ROS scavenging and decreased hydrogen peroxide (H2O2) concentration. Furthermore, the localization and relative quantification of silicon deposition in rice leaves was detected by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer (EDS). Finally, the transcript levels of defense response genes increased in transformed rice. These results show a correlation between Xoo resistance and phytoalexin production, H2O2, silicon deposition and defense gene expression in hrf1-transformed rice. These data are significant because they provide evidence for a better understanding the role of defense responses in the incompatible interaction between bacterial disease and hrf1-transformed plants. These data also supply an opportunity for generating nonspecific resistance to pathogens. PMID:22970151

  4. Ectopic expression of Hrf1 enhances bacterial resistance via regulation of diterpene phytoalexins, silicon and reactive oxygen species burst in rice.

    Directory of Open Access Journals (Sweden)

    Wenqi Li

    Full Text Available Harpin proteins as elicitor derived from plant gram negative bacteria such as Xanthomonas oryzae pv. oryzae (Xoo, Erwinia amylovora induce disease resistance in plants by activating multiple defense responses. However, it is unclear whether phytoalexin production and ROS burst are involved in the disease resistance conferred by the expression of the harpin(Xoo protein in rice. In this article, ectopic expression of hrf1 in rice enhanced resistance to bacterial blight. Accompanying with the activation of genes related to the phytoalexin biosynthesis pathway in hrf1-transformed rice, phytoalexins quickly and consistently accumulated concurrent with the limitation of bacterial growth rate. Moreover, the hrf1-transformed rice showed an increased ability for ROS scavenging and decreased hydrogen peroxide (H(2O(2 concentration. Furthermore, the localization and relative quantification of silicon deposition in rice leaves was detected by scanning electron microscopy (SEM and energy-dispersive X-ray spectrometer (EDS. Finally, the transcript levels of defense response genes increased in transformed rice. These results show a correlation between Xoo resistance and phytoalexin production, H(2O(2, silicon deposition and defense gene expression in hrf1-transformed rice. These data are significant because they provide evidence for a better understanding the role of defense responses in the incompatible interaction between bacterial disease and hrf1-transformed plants. These data also supply an opportunity for generating nonspecific resistance to pathogens.

  5. Carnosic Acid, a Natural Diterpene, Attenuates Arsenic-Induced Hepatotoxicity via Reducing Oxidative Stress, MAPK Activation, and Apoptotic Cell Death Pathway

    Directory of Open Access Journals (Sweden)

    Sonjit Das

    2018-01-01

    Full Text Available The present studies have been executed to explore the protective mechanism of carnosic acid (CA against NaAsO2-induced hepatic injury. CA exhibited a concentration dependent (1–4 μM increase in cell viability against NaAsO2 (12 μM in murine hepatocytes. NaAsO2 treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in in vitro and in vivo systems. Significant activation of MAPK, NF-κB, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO2-exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO2-mediated hepatotoxicity. NaAsO2 (10 mg/kg treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice (n=6. The serum biochemical and haematological parameters were significantly altered in the NaAsO2-exposed mice (n=6. Simultaneous treatment with CA (10 and 20 mg/kg could significantly reinstate the NaAsO2-mediated toxicological effects in the liver. Molecular docking and dynamics predicted the possible interaction patterns and the stability of interactions between CA and signal proteins. ADME prediction anticipated the drug-likeness characteristics of CA. Hence, there would be an option to employ CA as a new therapeutic agent against As-mediated toxic manifestations in future.

  6. Effect of harvest timing on leaf production and yield of diterpene glycosides in Stevia rebaudiana Bert: a specialty perennial crop for Mississippi

    Science.gov (United States)

    Stevia rebaundiana (Bertoni), a perennial shrub of the Asteraceae, is one of the most important sources of non-caloric natural sweeteners. Stevia’s plant extracts and glycosides have been used for several years in Paraguay and Brazil. Several studies suggest that Stevia and its glycosides exert ben...

  7. Identification of New Diterpenes as Putative Marker Compounds Distinguishing Agnus Castus Fruit (Chaste Tree) from Shrub Chaste Tree Fruit (Viticis Fructus).

    Science.gov (United States)

    Oshima, Naohiro; Masada, Sayaka; Suzuki, Ryuta; Yagi, Kanae; Matsufuji, Hiroshi; Suenaga, Emi; Takahashi, Yutaka; Yahagi, Tadahiro; Watanabe, Masato; Yahara, Shoji; Iida, Osamu; Kawahara, Nobuo; Maruyama, Takuro; Goda, Yukihiro; Hakamatsuka, Takashi

    2016-01-01

    Agnus Castus Fruit is defined in the European Pharmacopoeia as the dried ripe fruit of Vitex agnus-castus. In Europe it is used as a medicine targeting premenstrual syndrome and climacteric disorder. In Japan, Agnus Castus Fruit is becoming popular as a raw material for over-the-counter drugs and health food products, though its congenic species, Vitex rotundifolia and Vitex trifolia, have been used as Shrub Chaste Tree Fruit in traditional medicines. Therefore, it is important to discriminate these Vitex plants from the viewpoint of regulatory science. Here we tried to identify putative marker compounds that distinguish between Agnus Castus Fruit and Shrub Chaste Tree Fruit. We analyzed extracts of each crude drug by liquid chromatography-mass spectrometry, and performed differential analysis by comparison of each chromatogram to find one or more peaks characteristic of Agnus Castus Fruit. A peak was isolated and identified as an equilibrium mixture of new compounds named chastol (1) and epichastol (1a). The planar structures of 1 and 1a were determined spectroscopically. Their relative configurations were revealed by nuclear Overhauser effect spectroscopy and differential nuclear Overhauser effect-NMR data. Since avoiding contamination from closely related species is needed for the quality control of natural pharmaceuticals, this information will be valuable to establish a method for the quality control of both, Agnus Castus Fruit and Shrub Chaste Tree Fruit products. Georg Thieme Verlag KG Stuttgart · New York.

  8. Expression of microRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of Rosemary diterpenes in colon and pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Margarita González-Vallinas

    Full Text Available Colorectal and pancreatic cancers remain important contributors to cancer mortality burden and, therefore, new therapeutic approaches are urgently needed. Rosemary (Rosmarinus officinalis L. extracts and its components have been reported as natural potent antiproliferative agents against cancer cells. However, to potentially apply rosemary as a complementary approach for cancer therapy, additional information regarding the most effective composition, its antitumor effect in vivo and its main molecular mediators is still needed. In this work, five carnosic acid-rich supercritical rosemary extracts with different chemical compositions have been assayed for their antitumor activity both in vivo (in nude mice and in vitro against colon and pancreatic cancer cells. We found that the antitumor effect of carnosic acid together with carnosol was higher than the sum of their effects separately, which supports the use of the rosemary extract as a whole. In addition, gene and microRNA expression analyses have been performed to ascertain its antitumor mechanism, revealing that up-regulation of the metabolic-related gene GCNT3 and down-regulation of its potential epigenetic modulator miR-15b correlate with the antitumor effect of rosemary. Moreover, plasmatic miR-15b down-regulation was detected after in vivo treatment with rosemary. Our results support the use of carnosic acid-rich rosemary extract as a complementary approach in colon and pancreatic cancer and indicate that GCNT3 expression may be involved in its antitumor mechanism and that miR-15b might be used as a non-invasive biomarker to monitor rosemary anticancer effect.

  9. Natural diterpenes from coffee, cafestol and kahweol induce apoptosis through regulation of specificity protein 1 expression in human malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Lee Kyung-Ae

    2012-06-01

    Full Text Available Abstract Background Malignant pleural mesothelioma (MPM is a highly aggressive cancer with a very poor prognosis. Several clinical studies such as immunotherapy, gene therapy and molecular targeting agents have been tried for treatment of malignant mesothelioma, however, there is no application for effective clinical treatment. Coffee has various biological functions such as anti-oxidant, anti-inflammatory, anti-mutagenic and anti-carcinogenic activities. The therapeutic activities of the bioactive compounds in coffee was sugested to influence intracellular signaling of MPM. Regarding to the cancer-related functions, In this study, suppression of Sp1 protein level followed by induction of MSTO-211H cell apoptosis by cafestol and kahweol were investigated in oreder to determine Sp1's potential as a significant target for human MPM therapy as well. Methods Cells were treated separately with final concentration of cafestol and kahweol and the results were analyzed by MTS assay, DAPI staining, PI staining, luciferase assay, RT-PCR, and immunoblotting. Results Viability of MSTO-211H and H28 cells were decreased, and apoptotic cell death was increased in MSTO-211H as a result of cafestol and kahweol treatment. Cafestol and kahweol increased Sub-G1 population and nuclear condensation in MSTO-211H cells. Roles of Sp1 in cell proliferation and apoptosis of the MSTO-211H cells by the Sp1 inhibitor of Mithramycin A were previously confirmed. Cafestol and kahweol significantly suppressed Sp1 protein levels. Kahweol slightly attenuated Sp1 mRNA, while Cafestol did not affect in MSTO-211H cells. Cafestol and kahweol modulated the promoter activity and protein expression level of the Sp1 regulatory genes including Cyclin D1, Mcl-1, and Survivin in mesothelioma cells. Apoptosis signaling cascade was activated by cleavages of Bid, Caspase-3, and PARP with cafestol and by upregulation of Bax, and downregulation of Bcl-xl by kahweol. Conclusions Sp1 can be a novel molecular target of cafestol and kahweol in human MPM.

  10. Chemistry of the Calceolaria Genus. Structural and Biological Aspects

    Directory of Open Access Journals (Sweden)

    Juan A. Garbarino

    2000-03-01

    Full Text Available Autochthonous species of the Calceolaria (Scrophulariaceae genus are studied. From their apolar extracts 55 new diterpenes of six skeleton types, naphtoquinones and flavonoids have been isolated. Among the different diterpenes malonic substitutions and bis-diterpenes in which both units are joined by a malonic acid unit stand out. Pimaranes present C-9 epimerisation and, consequently, H-9 has the same orientation as Me-20. From C.sessilis naphthoquinones with antichagasic activity have been isolated; and the biotransformation of 2α,19-dihydroxy-9-epi-entpimara-7,15-diene with Giberella fujikuroi produced 7 new diterpenes.

  11. Preliminary studies on the volatile constitution of Mikania species

    Directory of Open Access Journals (Sweden)

    Anair A. Reis

    Full Text Available Volatile oils obtained from the aerial parts of three Mikania species plants were analyzed by GC-MS and NMR. Forty-six terpenes among monoterpenes, sesquiterpenes and diterpenes were identified by this methodology. The analysis classified Mikania hookriana as diterpene producer as the majority Mikania species occurring in Brazil.

  12. Terpenoid constituents from leaves of Guarea kunthiana

    International Nuclear Information System (INIS)

    Garcez, Fernanda R.; Garcez, Walmir S.; Bazzo, Rita de Cassia; Silva, Ana Francisca G. da; Resende, Ubirazilda M.

    2004-01-01

    From leaves of Guarea kunthiana one new kaurene diterpene (ent-kaur-16-en-2-one) was isolated along with eight known diterpenes (ent-kaur-16-ene, ent-3α- and 3β-hydroxykaur-16-ene, kolavelool, kolavenol, kolavenal, ent-13-epi-manoyloxide and (-)-nephthenol), four sesquiterpenes (alismol, alismoxide, spathulenol and 4β,10α-aromadendranediol), polyprenol-12 and α- and δ-tocopherols. Kolavenal is reported for the first time as a natural product, as well as the occurrence of cembrane- and ent-kaurane-type diterpenes in the Meliaceae. (author)

  13. Molecular cloning and functional analysis of the gene encoding ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-06-07

    Jun 7, 2010 ... universal diterpenes biosynthesis, such as casbene. (Dudley et al., 1986), ... reported so far. Therefore, it is necessary to develop new ..... acid signaling pathways. Planta, 224: ... Taxus baccata cell cultures. An enzyme that ...

  14. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    School of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia ... ulcers. A wide range of secondary metabolites such as alkaloids, diterpenes, flavones, phenolics, and triterpenes .... potency than the synthetic antioxidant.

  15. Phytochemical and pharmacological investigation of Spiraea chamaedryfolia: a contribution to the chemotaxonomy of Spiraea genus.

    Science.gov (United States)

    Kiss, Tivadar; Cank, Kristóf Bence; Orbán-Gyapai, Orsolya; Liktor-Busa, Erika; Zomborszki, Zoltán Péter; Rutkovska, Santa; Pučka, Irēna; Németh, Anikó; Csupor, Dezső

    2017-12-21

    Diterpene alkaloids are secondary plant metabolites and chemotaxonomical markers with a strong biological activity. These compounds are characteristic for the Ranunculaceae family, while their occurrence in other taxa is rare. Several species of the Spiraea genus (Rosaceae) are examples of this rarity. Screening Spiraea species for alkaloid content is a chemotaxonomical approach to clarify the classification and phylogeny of the genus. Novel pharmacological findings make further investigations of Spiraea diterpene alkaloids promising. Seven Spiraea species were screened for diterpene alkaloids. Phytochemical and pharmacological investigations were performed on Spiraea chamaedryfolia, the species found to contain diterpene alkaloids. Its alkaloid-rich fractions were found to exert a remarkable xanthine-oxidase inhibitory activity and a moderate antibacterial activity. The alkaloid distribution within the root was clarified by microscopic techniques.

  16. Stereo-specific synthesis of (13r)-manoyl oxide

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a method for manufacturing enantiomerically pure (13R)-manoyl oxide, said method comprising the steps of contacting geranylgeranyl diphosphate (GGPP) with a class II diterpene synthase to obtain labd-13-en-8,15-diol diphosphate (LPP), and then contacting the LPP...... with a class I diterpene synthase to obtain (13R)-manoyl oxide. The invention further relates to (13R)-manoyl oxide obtained by the method of the invention....

  17. Elucidation of terpenoid metabolism in Scoparia dulcis by RNA-seq analysis.

    Science.gov (United States)

    Yamamura, Yoshimi; Kurosaki, Fumiya; Lee, Jung-Bum

    2017-03-07

    Scoparia dulcis biosynthesize bioactive diterpenes, such as scopadulcic acid B (SDB), which are known for their unique molecular skeleton. Although the biosynthesis of bioactive diterpenes is catalyzed by a sequence of class II and class I diterpene synthases (diTPSs), the mechanisms underlying this process are yet to be fully identified. To elucidate these biosynthetic machinery, we performed a high-throughput RNA-seq analysis, and de novo assembly of clean reads revealed 46,332 unique transcripts and 40,503 two unigenes. We found diTPSs genes including a putative syn-copalyl diphosphate synthase (SdCPS2) and two kaurene synthase-like (SdKSLs) genes. Besides them, total 79 full-length of cytochrome P450 (CYP450) genes were also discovered. The expression analyses showed selected CYP450s associated with their expression pattern of SdCPS2 and SdKSL1, suggesting that CYP450 candidates involved diterpene modification. SdCPS2 represents the first predicted gene to produce syn-copalyl diphosphate in dicots. In addition, SdKSL1 potentially contributes to the SDB biosynthetic pathway. Therefore, these identified genes associated with diterpene biosynthesis lead to the development of genetic engineering focus on diterpene metabolism in S. dulcis.

  18. DADOS ESPECTROSCÓPICOS DE DITERPENOS LABDÂNICOS: UMA ANÁLISE TEÓRICA VIA RMN E DFT

    Directory of Open Access Journals (Sweden)

    Fabrine S. de Souza

    2015-05-01

    Full Text Available Labdane diterpenes exhibit important bioactivities such as cardiovascular effects in rats as well as effects in the treatment of autoimmune diseases and Alzheimer syndrome. Recently, the labdane diterpenes ent-13-epi-manoil oxide, ribenone and ribenol were isolated from Croton palanostigma. The computational method DFT/B3LYP/cc-pVDZ was used to optimize the structures of these diterpenes and to calculate infrared data. Chemical shifts (δH and δC of the minimum energy structures (local minimum were calculated and compared with the experimental data. Comparison of the NMR data by simple linear regression (SLR showed satisfactory statistical results with a correlation coefficient (R2 and predictive ability (Q2 of over 98%. The predicted NMR data were used to confirm the δH values that have not been published.

  19. Further New Diterpenoids as PTP1B Inhibitors from the Xisha Soft Coral Sinularia polydactyla

    Directory of Open Access Journals (Sweden)

    Fei Ye

    2018-03-01

    Full Text Available A new prenyleudesmane type diterpene, sinupol (8, and a new capnosane type diterpenoid, sinulacetate (9, were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes (4–7 and 10. Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD calculations. Both new compounds (8 and 9 exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B, a potential drug target for the treatment of type II diabetes and obesity.

  20. Further New Diterpenoids as PTP1B Inhibitors from the Xisha Soft Coral Sinularia polydactyla.

    Science.gov (United States)

    Ye, Fei; Zhu, Zheng-Dan; Gu, Yu-Cheng; Li, Jia; Zhu, Wei-Liang; Guo, Yue-Wei

    2018-03-25

    A new prenyleudesmane type diterpene, sinupol ( 8 ), and a new capnosane type diterpenoid, sinulacetate ( 9 ), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes ( 4 - 7 and 10 ). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds ( 8 and 9 ) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity.

  1. Elucidating the mechanism behind the lipid-raising effect of cafestol

    NARCIS (Netherlands)

    Boekschoten, M.V.

    2004-01-01

    The objective of this thesis was to identify genes that control the response of serum lipid levels to diet. To this end we used cafestol as model substance for a food component that affects serum lipids and therefore health. Cafestol is a cholesterol‑raising diterpene present in coffee beans and

  2. Alkanes and terpenes in wood and leaves of Pinus jeffreyi and P. sabiniana

    Science.gov (United States)

    Robert P. Adams; Jessica W. Wright

    2012-01-01

    The wood oils of Pinus jeffreyi and P. sabiniana contain considerable amounts of heptane (76.6%, 92%), on a monoterpene basis. However, when entire wood extractables is considered, the amounts drop considerably (3.4%, 36.8%) with the major portion of the wood oils being diterpene acids. The leaf oil of P. jeffreyi...

  3. The decision to germinate is regulated by divergent molecular networks in spores and seeds

    DEFF Research Database (Denmark)

    Vesty, Eleanor F.; Saidi, Younousse; Moody, Laura A.

    2016-01-01

    , the role of abscisic acid and diterpenes (gibberellins) in germination assumed much greater importance as land plant evolution progressed. We conclude that the endogenous hormone signalling networks mediating germination in response to the environment may have evolved independently in spores and seeds...

  4. Journal of Chemical Sciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Abstract. Two metabolites featuring norcembranoid diterpene skeleton have been isolated from chloroform extract of soft coral of the genus sinularia, which was collected from the southern coast of India. The structures of the metabolites were determined by 1D, 2D NMR spectroscopic data and HRESIMS data analysis.

  5. A Review of the Secondary Metabolites and Biological Activities of ...

    African Journals Online (AJOL)

    Tinospora crispa Beumee, a herbaceous climber, has been widely used in traditional medicine for treating various ailments such as contusion, septicaemia, fever, fracture, scabies and other tropical ulcers. A wide range of secondary metabolites such as alkaloids, diterpenes, flavones, phenolics, and triterpenes have been ...

  6. Antimicrobial activity of seed extracts and bondenolide from Caesalpinia bonduc (L.) Roxb.

    Science.gov (United States)

    Simin, K; Khaliq-Uz-Zaman, S M; Ahmad, V U

    2001-08-01

    The antibacterial and antifungal activities, along with a phytotoxicity test of the newly isolated diterpene bondenolide (1), of a methanol extract, ethylacetate fraction and water soluble part of the methanol extract of Caesalpinia bonduc (L.) Roxb. were assayed. Copyright 2001 John Wiley & Sons, Ltd.

  7. Chemical Diversity and Biological Activity of the Volatiles of Five Artemisia Species from Far East Russia

    Science.gov (United States)

    2014-01-01

    primarily sesquiterpene lactones [4,5], diterpenes, coumarins [1], polyacetylenes [6] and flavonoids [1,7,8] as the main metabolites. Biological activity...liver injuries, Gen. Pharmacol. 32(6), 661-667. [62] B. Oomah and G. Mazza (1996). Flavonoids and antioxidative activities in buckwheat, J. Agric. Food

  8. SAPONIFICAÇÃO ASSISTIDA POR MICRO-ONDAS NA EXTRAÇÃO DE DITERPENOS EM CAFÉ ARÁBICA TORRADO

    Directory of Open Access Journals (Sweden)

    Mirelli Bianchin

    Full Text Available The extraction of kahweol and cafestol involves saponification reaction. This step is important for the efficiency of the extraction as the diterpenes are susceptible to structural changes during hydrolysis. The microwave-assisted saponification has been successfully used in different matrices, but there is no previous report of the use of this technique in the saponification of diterpenes. Therefore, the effect of microwave-assisted saponification on the extraction of kahweol and cafestol in roasted coffee was evaluated. A 32 factorial experimental design was used in order to evaluate the effect of temperature (70, 80, and 90 ºC and reaction time (4, 8, and 12 min. The quantification of diterpenes was performed by high-performance liquid chromatography and the results were compared to with those obtained by a method, which uses thermostatic bath for saponification. Temperature and time had a significant effect (p < 0.05 on diterpenes levels. For simultaneous saponification of kahweol and cafestol, the optimal reaction conditions were 80 ºC / 12 min. The use of microwave-assisted procedure lead to lower yields of kahweol (24% and cafestol (35% compared to reference method. However a significant reduction of reaction time (80% was achieved, and the procedure also has the advantage of controlled process conditions and the possibility of extended scale.

  9. A survey of bacterial, fungal and plant metabolites against Aedes aegypti (Diptera: Culicidae), the vector of yellow and dengue fevers and Zika virus

    OpenAIRE

    Masi Marco; Cimmino Alessio; Tabanca Nurhayat; Becnel James J.; Bloomquist Jeffrey R.; Evidente Antonio

    2017-01-01

    Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. Some bacterial, fungal and plant metabolites belonging to different chemical subgroups, including Amaryllidaceae alkaloids, anthracenes, azoxymethoxytetrahydropyrans, cytochalasans, 2,5-diketopiperazines, isochromanones, naphthoquinones, organic small acids and their methyl esters, sterols and terpenes including sesquiterpenes and diterpenes, were tested for their ...

  10. Extračné postupy pre izoláciu diterpénov z uhlia

    Czech Academy of Sciences Publication Activity Database

    Zubrik, A.; Lovás, M.; Dolinská, S.; Hredzák, S.; Turčeková, Ĺ.; Cvačka, Josef; Vrkoslav, Vladimír

    2013-01-01

    Roč. 107, č. 9 (2013), s. 723-728 ISSN 0009-2770 R&D Projects: GA ČR GAP206/12/1093 Grant - others:VEGA(SK) 2/0114/13 Institutional support: RVO:61388963 Keywords : Slovak brown coal * diterpenes * supercritical fluid extraction * microwave extraction Subject RIV: CC - Organic Chemistry Impact factor: 0.196, year: 2013

  11. Phytochemical and Ethno-Pharmacological Review of the Genus ...

    African Journals Online (AJOL)

    Distribution, traditional uses, isolated chemical constituents and pharmacological activities of some common species of the genus Araucaria are reviewed in this paper. Almost 19 species belong to the genus, Araucaria. It is indigenous to North. America. Biflavanoid, diterpene, phenyl propanoid and lignans are abundant in ...

  12. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown ...

  13. The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors

    NARCIS (Netherlands)

    Ricketts, Marie-Louise; Boekschoten, Mark V.; Kreeft, Arja J.; Hooiveld, Guido J. E. J.; Moen, Corina J. A.; Mueller, Michael; Frants, Rune R.; Kasanmoentalib, Soemini; Post, Sabine M.; Princen, Hans M. G.; Porter, J. Gordon; Katan, Martijn B.; Hofker, Marten H.; Moore, David D.

    Cafestol, a diterpene present in unfiltered coffee brews such as Scandinavian boiled, Turkish, and cafetiere coffee, is the most potent cholesterol-elevating compound-knownin the human diet. Several genes involved in cholesterol homeostasis have previously been shown to be targets of cafestol,

  14. Antileishmanial activity of piceatannol isolated from Euphorbia lagascae seeds

    NARCIS (Netherlands)

    Duarte, Noelia; Kayser, Oliver; Abreu, Pedro; Ferreira, Maria-Jose U.

    In the search for biologically active compounds from Euphorbia lagascae Spreng, an herbaceous plant native to southeast of Iberic Peninsula, a stilbene, two coumarins and two 1-2-deoxyphorbol diterpene esters were isolated by chromatographic methods, from the methanol extracts of its defatted seeds.

  15. Cafestol: a multi-faced compound kinetics and metabolic effects of cafestol in mice

    NARCIS (Netherlands)

    Cruchten, van S.T.J.

    2010-01-01

    Cafestol and kahweol are two diterpenes present in unfiltered coffees such as Scandinavian-style boiled coffee, French press coffee and espresso. The health effects of cafestol and kahweol can be positive but also potentially harmful. On the one hand cafestol shows chemo-preventive properties, which

  16. The hypercholesterolemic effect of cafestol in coffee oil in gerbils and rats

    NARCIS (Netherlands)

    Terpstra, A.H.M.; Katan, M.B.; Weusten-van, der M.P.M.E.; Roos, de B.; Beynen, A.C.

    2000-01-01

    Coffee beans contain the diterpene cafestol, which raises plasma cholesterol concentrations in humans. Daily consumption of 2 g coffee oil, which provides approximately 60 mg cafestol (equivalent to 5.7 mg cafestol/MJ), increases plasma cholesterol concentrations by 28%. We studied the effect of

  17. Pine needle abortion in cattle update: Metabolite detection in sera and fetal fluids from abortion case samples

    Science.gov (United States)

    Cattle abortions associated with consumption of pine needles during late gestation are a serious poisonous plant problem in the Western US. Most cases of abortion have been associated with consumption of ponderosa pine (Pinus ponderosa) and the causative agent was identified as the labdane diterpen...

  18. Cafestol, the cholesterol-raising factor in boiled coffee, suppresses bile acid synthesis by downregulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase in rat hepatocytes

    NARCIS (Netherlands)

    Post, S.M.; Wit, E.C.M. de; Princen, H.M.G.

    1997-01-01

    Consumption of boiled coffee raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol in boiled coffee have been found to be responsible for the increase. To investigate the biochemical background of this effect, we studied the effects of cafestol and a mixture of

  19. Antiparasitic, Nematicidal and Antifouling Constituents from Juniperus Berries

    Science.gov (United States)

    A bioassay-guided fractionation of Juniperus procera berries yielded antiparasitic, nematicidal and antifouling constituents, including a wide range of known abietane, pimarane and labdane diterpenes. Among these, abieta-7,13-diene (1) demonstrated in vitro antimalarial activity against Plasmodium f...

  20. Oxidation and cyclization of Casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L

    DEFF Research Database (Denmark)

    Luo, Dan; Callari, Roberta; Hamberger, Britta

    2016-01-01

    Ingenol mebutate is a diterpene ester with a highly complex macrocyclic structure that has been approved for the treatment of actinic keratosis, a precondition of skin cancer. The current production of ingenol mebutate through plant extraction or chemical synthesis is inefficient and costly. Here...

  1. Differences in ponderosa pine isocupressic acid concentrations across space and time

    Science.gov (United States)

    Ponderosa Pine (Pinus ponderosa) is distributed throughout the western half of North America, where it is the most widely adapted and ubiquitous conifer. Ponderosa Pine contains isocupressic acid, a diterpene acid, which has been shown to be responsible for its abortifacient activity. The objectiv...

  2. Investigating sesquiterpene biosynthesis in Ginkgo biloba: molecular cloning and functional characterization of (E,E)-farnesol and a-bisabolene synthases

    Science.gov (United States)

    Ginkgo biloba is one of the oldest living tree species and has been extensively investigated as a source of bioactive natural compounds, including flavonoids, diterpene lactones, terpenoids and polysaccharides which accumulate in leaf tissues. Relatively few genes associated with biosynthetic pathwa...

  3. Screening marine organisms for antimicrobial activity against clinical pathogens

    Digital Repository Service at National Institute of Oceanography (India)

    PrabhaDevi; Wahidullah, S.; Tonima, K.; DeSouza, L.

    , 37 (1982) 179. 15 Gonzalez, A. G., Estrada, D. M., Martin, J. D., Martin, S. W., Perez, C. & Perez, R., New antimicrobial diterpenes from the sponge Spongia officinalis, Tetrahedron, (1984) 4109. 16 Rinehart, K.L., Shaw, Jr P.D., Shield, L...

  4. Author Details

    African Journals Online (AJOL)

    Sondengam, B. L., Department of Organic Chemistry, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaounde, Cameroon. Vol 19, No 1 (2005) - Articles ERYTHROSUAVINE, A NEW DITERPENIC ALKALOID FROM ERYTHROPHLEUM SUAVEOLENS (GUILL. & PERR.) BRENAN Abstract PDF. ISSN: 1726-801X.

  5. A simple approach to the construction of the core structure present

    Indian Academy of Sciences (India)

    A convenient route for the synthesis of oxacyclobutapentalene, the tricyclic bridged core structure present in bioactive marine diterpene bielschowskysin and the polyketide hippolachnin A, is reported. The key steps involve ring closing metathesis of a triene derived from D-mannitol to produce selectively the dihydrofuran ...

  6. Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches.

    Science.gov (United States)

    Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B

    2018-01-01

    Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location of

  7. Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches

    Directory of Open Access Journals (Sweden)

    Max Hirte

    2018-04-01

    Full Text Available Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially

  8. Insights into the bifunctional Aphidicolan-16-ß-ol synthase through rapid biomolecular modelling approaches

    Science.gov (United States)

    Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B.

    2018-04-01

    Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modelling techniques offer an alternative route to study the enzyme’s reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modelling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modelling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789 and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modelling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location

  9. Physical characteristics of the paper filter and low cafestol content filter coffee brews.

    Science.gov (United States)

    Rendón, Mery Yovana; Dos Santos Scholz, Maria Brígida; Bragagnolo, Neura

    2018-06-01

    The results found in the literature concerning the effect of consuming filter coffee brews on increasing the blood cholesterol levels due to the presence of diterpenes, are divergent. Thus the present research evaluated the diterpene (cafestol and kahweol) concentrations in filter coffee brews prepared with paper filters of different sizes, colors and origins (Brazil, Japan, The United States of America, Germany, France and the Netherlands), with and without micro perforations. This is the first study that reports the physical characteristics of paper filter and its importance to obtain filter coffee brew with low cafestol content. Thus, a sample of Catuai cultivar coffee with high cafestol content was roasted to a medium-light degree and used to prepare the brews in a 1:10 ratio (coffee powder to water). The diterpenes were extracted by direct saponification and quantified and identified by HPLC-DAD-MS/MS. The paper filters were physically characterized by measuring their grammage, and the fat permeation rate calculated in order to better understand the differences between the filters which allow one to obtain higher or lower diterpene contents. The cafestol and kahweol concentrations in the brews varied from 1.62 to 2.98 mg/L and from 0.73 to 1.96 mg/L, respectively. The highest cafestol and kahweol concentrations were obtained using paper filters with micro perforations, considering similar sized paper filters. The paper filters showed high fat permeability and grammages between 50.46 and 67.48 g/m 2 . The diterpene retention capacities of the filters produced in the different countries were similar. The results showed that the porosity of the paper filter and the particle size of the ground roasted coffee were determinant factors in obtaining filter coffee brews with lower cafestol contents. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals.

    Science.gov (United States)

    Ebiloma, Godwin Unekwuojo; Igoli, John Ogbaji; Katsoulis, Evangelos; Donachie, Anne-Marie; Eze, Anthonius; Gray, Alexander Ian; de Koning, Harry P

    2017-04-18

    Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC 50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC 50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC 50 of 1.58µg/mL. None of the isolated compounds displayed toxicity

  11. Multi-targeting Andrographolide and its Natural Analogs as Potential Therapeutic Agents.

    Science.gov (United States)

    Kishore, V; Yarla, Nagendra Sastry; Bishayee, Anupam; Putta, Swathi; Malla, Ramarao; Neelapu, Nageswara Rao Reddy; Challa, Surekha; Das, Subhasish; Shiralgi, Yallappa; Hegde, Gurumurthy; Dhananjaya, Bhadrapura Lakkappa

    2017-01-01

    Andrographis paniculata (A. paniculata) is a medicinal plant used in the Indian and Chinese traditional medicinal systems for its various beneficial properties of therapeutics. This is due to the presence of a diterpene lactone called 'andrographolide'. Several biological activities like antiinflammatory, antitumour, anti-hyperglycaemic, anti-fertility, antiviral, cardio protective and hepatoprotective properties are attributed to andrographolide and its natural analogs. The studies have shown that not only this diterpene lactone (andrographolide), but also other related terpenoid analogs from A. paniculata could be exploited for disease prevention due to their structural similarity with diverse pharmacological activities. Several scientific groups are trying to unveil the underlying mechanisms involved in these biological actions brough aout by andrographolide and its analogs. This review aims at giving an overview on the therapeutical and/or pharmacological activities of andrographolide and its derivatives and also exemplify the underlying mechanisms involved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Synthesis of a new allelopathic agent from the biotransformation of ent-15α-hydroxy-16-kauren-19-oic acid with Fusarium proliferatum.

    Science.gov (United States)

    Rocha, A D; Vieira, H da S; Takahashi, J A; Boaventura, M A D

    2017-11-01

    The use of kaurane diterpenes as substrates in fungal biotransformation to achieve bioactive compounds has been widely reported. In this work, the natural product kaurenoic acid, a diterpene widely distributed in the plant Kingdom, was chemically converted into ent-15α-hydroxy-kaur-16-en-19-oic acid (1). Substrate 1 was subjected to biotransformation by the fungus Fusarium proliferatum, furnishing a new derivative, ent-2α,15α-dihydroxy-kaur-16-en-19-oic acid (2). The structure of metabolite 2 was deduced on the basis of spectroscopy and MS data. Derivative 2 showed allelopathic activity on germination and growth of root and stem of lettuce (Lactuca sativa), inhibiting 100% of germination and growth of roots and stem, at higher concentration assayed (10 -4  mol/L).

  13. New volatile constituents from leaves of Stemodia trifoliata (Link.) Reichb. (Schrophulariaceae)

    International Nuclear Information System (INIS)

    Silva, Wildson Max B. da; Assuncao, Joao Carlos da C.; Araujo, Renata M.; Silveira, Edilberto R.; Pessoa, Otilia D.L.

    2009-01-01

    The leaf essential oils of Stemodia trifoliata (Scrophulariaceae), collected at the same month of two different years (August 2005 and 2006), were analyzed by GC-MS and GC-FID. A total of 22 volatile components represented by sesquiterpenes and diterpenes was identified. β-Caryophyllene (9.4-15.4%) and caryophyllene oxide (6.2-9.0%) were the major compounds identified in the sesquiterpene fraction, while the diterpenoids 6α-acetoxymanoyl oxide (13.9-23.2%) and 6α-hydroxymanoyl oxide (25.1-29.7%) were the main constituents of the diterpene fraction. The two novel manoyl oxide derivatives had their structures established by means of spectroscopic methods, particularly 1D and 2D NMR. This work describes for the first time the chemical investigation on the volatile composition of S. trifoliata. (author)

  14. New volatile constituents from leaves of Stemodia trifoliata (Link.) Reichb. (Schrophulariaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Wildson Max B. da; Assuncao, Joao Carlos da C.; Araujo, Renata M.; Silveira, Edilberto R.; Pessoa, Otilia D.L. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica]. E-mail: opessoa@ufc.br

    2009-07-01

    The leaf essential oils of Stemodia trifoliata (Scrophulariaceae), collected at the same month of two different years (August 2005 and 2006), were analyzed by GC-MS and GC-FID. A total of 22 volatile components represented by sesquiterpenes and diterpenes was identified. {beta}-Caryophyllene (9.4-15.4%) and caryophyllene oxide (6.2-9.0%) were the major compounds identified in the sesquiterpene fraction, while the diterpenoids 6{alpha}-acetoxymanoyl oxide (13.9-23.2%) and 6{alpha}-hydroxymanoyl oxide (25.1-29.7%) were the main constituents of the diterpene fraction. The two novel manoyl oxide derivatives had their structures established by means of spectroscopic methods, particularly 1D and 2D NMR. This work describes for the first time the chemical investigation on the volatile composition of S. trifoliata. (author)

  15. Chemical profile of Taxodium distichum winter cones

    Directory of Open Access Journals (Sweden)

    Đapić Nina M.

    2017-01-01

    Full Text Available This work is concerned with the chemical profile of Taxodium distichum winter cones. The extract obtained after maceration in absolute ethanol was subjected to qualitative analysis by gas chromatography/mass spectrometry and quantification was done by gas chromatography/ flame ionization detector. The chromatogram revealed the presence of 53 compounds, of which 33 compounds were identified. The extract contained oxygenated monoterpenes (12.42%, sesquiterpenes (5.18%, oxygenated sesquiterpenes (17.41%, diterpenes (1.15%, and oxygenated diterpenes (30.87%, while the amount of retinoic acid was 0.32%. Monoacylglycerols were detected in the amount of 4.32%. The most abundant compounds were: caryophyllene oxide (14.27%, 6,7-dehydro-ferruginol (12.49%, bornyl acetate (10.96%, 6- deoxy-taxodione (9.50% and trans-caryophyllene (4.20%.

  16. ent-Rosane and abietane diterpenoids as cancer chemopreventive agents.

    Science.gov (United States)

    Núñez, Marvin J; Reyes, Carolina P; Jiménez, Ignacio A; Hayashi, Hirotaka; Tokuda, Harukuni; Bazzocchi, Isabel L

    2011-04-01

    Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Terpenes isolated of Coussarea platyphylla Muell. Arg. (Rubiaceae)

    International Nuclear Information System (INIS)

    Araujo, Francieli Casassa Vieira de; Marques, Fabio Goncalves; Silva, Cleuza Conceicao da; Santin, Silvana Maria de Oliveira; Nakamura, Celso Vataru; Zamuner, Maria Lucilia Motinha; Souza, Maria Conceicao de

    2009-01-01

    The phytochemical investigation of Coussarea platyphylla led to the isolation of triterpenes betulonic and betulinic acid, monoterpenes monotropein and monotropein salt, the diterpene trans-phytol and steroids. The structures of the isolated compounds were assigned on the basis of spectroscopic data, including two-dimensional NMR methods. The antiproliferative properties against human cancer cell lines and molluscicidal activity against Biomphalaria glabrata of the crude methanolic extract and of its fractions were investigated. (author)

  18. Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

    OpenAIRE

    Cunningham, Christopher W.; Rothman, Richard B.; Prisinzano, Thomas E.

    2011-01-01

    Salvia divinorum is a perennial sage native to Oaxaca, Mexico, that has been used traditionally in divination rituals and as a treatment for the “semimagical” disease panzón de borrego. Because of the intense “out-of-body” experiences reported after inhalation of the pyrolized smoke, S. divinorum has been gaining popularity as a recreational hallucinogen, and the United States and several other countries have regulated its use. Early studies isolated the neoclerodane diterpene salvinorin A as...

  19. Secondary Metabolites from Inula britannica L. and Their Biological Activities

    Directory of Open Access Journals (Sweden)

    Yoon-Ha Kim

    2010-03-01

    Full Text Available Inula britannica L., family Asteraceae, is used in traditional Chinese and Kampo Medicines for various diseases. Flowers or the aerial parts are a rich source of secondary metabolites. These consist mainly of terpenoids (sesquiterpene lactones and dimmers, diterpenes and triterpenoids and flavonoids. The isolated compounds have shown diverse biological activities: anticancer, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective activities. This review provides information on isolated bioactive phytochemicals and pharmacological potentials of I. britannica.

  20. Oxidative Lung Injury in Virus-Induced Wheezing

    Science.gov (United States)

    2013-05-01

    Flavonoids are a ubiquitous group of polyphenolic substances present in seeds, fruit skin or peel, and flowers of most plants. Among them, quercetin and...study investigating the effect of di- etary flavonoids , including quercetin and catechins, on the infectivity and replication of RSV. In this study... flavonoids quercetin and EGCG, the nonflavonoids curcumin and re- sveratrol, and the phenolic acid and diterpens rosmarinic and carnosic (carnasol) acids

  1. Cytochrome P-450 complex formation in rat liver by the antibiotic tiamulin.

    OpenAIRE

    Witkamp, R F; Nijmeijer, S M; van Miert, A S

    1996-01-01

    Tiamulin is a semisynthetic diterpene antibiotic frequently used in farm animals. The drug has been shown to produce clinically important--often lethal--interactions with other compounds. It has been suggested that this is caused by a selective inhibition of oxidative drug metabolism via the formation of a cytochrome P-450 metabolic intermediate complex. In the present study, rats were treated orally for 6 days with tiamulin at two different doses: 40 and 226 mg/kg of body weight. For compari...

  2. Semisynthetic Esters of 17-Hydroxycativic Acid with in Vitro Cytotoxic Activity against Leukemia Cell Lines

    Czech Academy of Sciences Publication Activity Database

    Cavallaro, V.; Řezníčková, Eva; Jorda, Radek; Alza, N.P.; Murray, A.P.; Kryštof, Vladimír

    2017-01-01

    Roč. 40, č. 11 (2017), s. 1923-1928 ISSN 0918-6158 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : biological evaluation * derivatives * andrographolide * apoptosis * cancer * agents * diterpenes * inhibition * activation * chemistry * diterpenoid * 17-hydroxycativic acid * cytotoxic activity * human cancer cell * apoptosis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Hematology Impact factor: 1.683, year: 2016

  3. Isolation and Structure Elucidation of Three New Dolastanes from the Brown Alga Dilophus spiralis

    Directory of Open Access Journals (Sweden)

    Vassilios Roussis

    2013-04-01

    Full Text Available Three new dolastane diterpenes (1–3 and five previously reported perhydroazulenes were isolated from the organic extracts of the brown alga Dilophus spiralis. The structure elucidation and the assignment of the relative configurations of the isolated natural products were based on extensive analyses of their spectroscopic data, whereas the absolute configuration of metabolite 2 was determined through its chemical conversion to a previously isolated compound of known configuration.

  4. Directions on the use of stevia leaves (Stevia Rebauidana) as an additive in food products.

    Science.gov (United States)

    Kobus-Moryson, Małgorzata; Gramza-Michałowska, Anna

    2015-01-01

    Due to the high intake of sugars, especially sucrose, global trends in food processing have encouraged producers to use sweeteners, particularly synthetic ones, to a wide extent. For several years, increasing attention has been paid in the literature to the stevia (Stevia rebauidana), containing glycosidic diterpenes, for which sweetening properties have been identified. Chemical composition, nutritional value and application of stevia leaves are briefl y summarized and presented.

  5. Terpenos isolados de Coussarea platyphylla Müll. Arg. (Rubiaceae Terpenes isolated of Coussarea platyphylla Müll. Arg. (Rubiaceae

    Directory of Open Access Journals (Sweden)

    Francieli Casassa Vieira de Araujo

    2009-01-01

    Full Text Available The phytochemical investigation of Coussarea platyphylla led to the isolation of triterpenes betulonic and betulinic acid, monoterpenes monotropein and monotropein salt, the diterpene trans-phytol and esteroids. The structures of the isolated compounds were assigned on the basis of spectroscopic data, including two-dimensional NMR methods. The antiproliferative properties against human cancer cell lines and molluscicidal activity against Biomphalaria glabrata of the crude methanolic extract and of its fractions were investigated.

  6. Structural studies and antimicrobial properties of norcembrane diterpenoid from an Indian soft coral Sinularia inelegans Tixier-Durivault

    Digital Repository Service at National Institute of Oceanography (India)

    Singh, K.S.; Kaminsky, W.H.; Rodrigues, C; Naik, C

    SARJIT SINGH 1, *, WERNER H KAMINSKY 2 , CELINA RODRIGUES 1 and C G NAIK 1 1 Bioorganic Chemistry Laboratory, National Institute of Oceanography (CSIR), Goa 403 004 2 Department of Chemistry, University of Washington, Seattle, Washington 98195, USA... from marine organisms, 21 here, we wish to report the isolation of two norcembranoid diterpenes (1 and 2) that are epimer at one carbon atom (C-9) from the soft coral of the genus sinularia. Bioassay of the compounds against some micro- organisms...

  7. Analgesic, diuretic, and anti-inflammatory principle from Scoparia dulcis.

    Science.gov (United States)

    Ahmed, M; Shikha, H A; Sadhu, S K; Rahman, M T; Datta, B K

    2001-08-01

    Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant analgesic (p < 0.001) and anti-inflammatory activity (p < 0.01) in animals. A sedative action of scoparinol was demonstrated by a marked potentiation of pentobarbital-induced sedation with a significant effect on both onset and duration of sleep (p < 0.05). Measurement of urine volume after administration of scoparinol indicated its significant diuretic action.

  8. The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial

    OpenAIRE

    Mena, Pedro; Tassotti, Michele; Martini, Daniela; Rosi, Alice; Brighenti, Furio; Del Rio, Daniele

    2017-01-01

    Background Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still ne...

  9. Some structures of marine natural products

    Energy Technology Data Exchange (ETDEWEB)

    Finer-Moore, J.S.

    1979-07-01

    Applications of x-ray crystallographic methods to marine chemistry are discussed. Results of research on a biosynthetic problem: diterpenes from Dictyotaceae are discussed under the following section headings: history of the problem; dictyoxepin; dictyodial; and dictyolactone. Studies on marine ecology are reported under the following headings: symbiosis and antibiosis; metabolites from opisthobranch molluscs, including, dolabelladiene, 9-isocyanopupukeanane and 2-isocyanopupukeanane, and crispatone; metabolites of goronians and soft corals, including zooxanthellae and the metabolism of coelenterates, ophirin, sinularene, and erectene. (JGB)

  10. 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.

  11. NMR study of the preparation of 6 {alpha}, 7 {beta}-dihydroxyvouacapan-17 beta-oic acid mannich base derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Flavio Jose Leite dos; Pilo-Veloso, Dorila [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Inst. de Ciencias Exatas. Dept. Quimica]. E-mail: dorila@zeus.qui.ufmg.br; Ferreira-Alves, Dalton L. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Inst. de Ciencias Biologicas. Dept. de Farmacologia

    2007-07-01

    This work presents four new Mannich base compounds obtained by the Mannich reaction of a {delta}-keto-lactone derivative of 6{alpha}, 7{beta}-dihydroxyvouacapan- 17{beta}-oic acid, a furano diterpene isolated from the hexane extract of Pterodon polygalaeflorus Benth fruits, which shows anti-inflammatory and analgesic activities. The use of 1D and 2D NMR (COSY, DEPT-135, HMBC, HMQC) spectroscopy made it possible to characterize the new compounds. (author)

  12. Chemical Composition and In Vitro Cytotoxic Activity of Essential Oil of Leaves of Malus domestica Growing in Western Himalaya (India)

    OpenAIRE

    Walia, Mayanka; Mann, Tavleen S.; Kumar, Dharmesh; Agnihotri, Vijai K.; Singh, Bikram

    2012-01-01

    Light pale-colored volatile oil was obtained from fresh leaves of Malus domestica tree, growing in Dhauladhar range of Himalaya (Himachal Pradesh, India), with characteristic eucalyptol dominant fragrance. The oil was found to be a complex mixture of mono-, sesqui-, di-terpenes, phenolics, and aliphatic hydrocarbons. Seventeen compounds accounting for nearly 95.3% of the oil were characterized with the help of capillary GC, GC-MS, and NMR. Major compounds of the oil were characterized as euca...

  13. Triterpenoids from Azorella trifurcata (Gaertn.) Pers and their effect against the enzyme acetylcholinesterase

    Energy Technology Data Exchange (ETDEWEB)

    Areche, Carlos; Cejas, Patricia; Thomas, Pablo; San-Martin, Aurelio [University of Chile, Santiago (Chile). Faculty of Sciences. Dept. of Chemistry], e-mail: aurelio@uchile.cl; Astudillo, Luis; Gutierrez, Margarita [University of Talca, Talca (Chile). Inst. of Chemistry of Natural Resource; Loyola, Luis A. [University of Antofagasta (Chile). Faculty of Basic Sciences. Dept. of Chemistry

    2009-07-01

    The inhibition of the enzyme acetylcholinesterase is considered as a strategy for the treatment of Alzheimer's disease, senile dementia, ataxia, and myasthenia gravis. Three lanostane- and two cycloartane-type triterpenes, together with two mulinane-type diterpenes were isolated from petroleum ether extract of the whole shrub of Azorella trifurcata (Gaertn.) Pers. Their effect on the enzyme acetylcholinesterase was assessed as well. In addition, this is the first report of these triterpenes in the genus Azorella. (author)

  14. Triterpenoids from Azorella trifurcata (Gaertn.) Pers and their effect against the enzyme acetylcholinesterase

    International Nuclear Information System (INIS)

    Areche, Carlos; Cejas, Patricia; Thomas, Pablo; San-Martin, Aurelio; Astudillo, Luis; Gutierrez, Margarita; Loyola, Luis A.

    2009-01-01

    The inhibition of the enzyme acetylcholinesterase is considered as a strategy for the treatment of Alzheimer's disease, senile dementia, ataxia, and myasthenia gravis. Three lanostane- and two cycloartane-type triterpenes, together with two mulinane-type diterpenes were isolated from petroleum ether extract of the whole shrub of Azorella trifurcata (Gaertn.) Pers. Their effect on the enzyme acetylcholinesterase was assessed as well. In addition, this is the first report of these triterpenes in the genus Azorella. (author)

  15. Separation and formation of ryanodine from dehydroryanodine. Preparation of tritium-labelled ryanodine

    International Nuclear Information System (INIS)

    Sutko, J.L.; Thompson, L.J.; Schlatterer, R.G.

    1986-01-01

    The commercially available preparation of the naturally occurring diterpene ester ryanodine contains several compounds in addition to ryanodine. These compounds were separated and purified using high performance liquid chromatography. The two major components, ryanodine and dehydroryanodine represented 90% of the material present. A method for the efficient reduction of dehydroryanodine to ryanodine was developed and used to produce ryanodine having tritium atoms at positions 19 and 20 and a specific activity of 60.8 Ci/mmole. (author)

  16. Terpenes isolated of Coussarea platyphylla Muell. Arg. (Rubiaceae); Terpenos isolados de Coussarea platyphylla Muell. Arg. (Rubiaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Francieli Casassa Vieira de; Marques, Fabio Goncalves; Silva, Cleuza Conceicao da; Santin, Silvana Maria de Oliveira [Universidade Estadual de Maringa, PR (Brazil). Dept. de Quimica], e-mail: smoliveira@uem.br; Nakamura, Celso Vataru [Universidade Estadual de Maringa, PR (Brazil). Dept. de Microbiologia; Zamuner, Maria Lucilia Motinha [Universidade Estadual de Maringa, PR (Brazil). Dept. de Farmacia e Farmacologia; Souza, Maria Conceicao de [Universidade Estadual de Maringa, PR (Brazil). Dept. de Biologia

    2009-07-01

    The phytochemical investigation of Coussarea platyphylla led to the isolation of triterpenes betulonic and betulinic acid, monoterpenes monotropein and monotropein salt, the diterpene trans-phytol and steroids. The structures of the isolated compounds were assigned on the basis of spectroscopic data, including two-dimensional NMR methods. The antiproliferative properties against human cancer cell lines and molluscicidal activity against Biomphalaria glabrata of the crude methanolic extract and of its fractions were investigated. (author)

  17. Erinacine S, a Rare Sesterterpene from the Mycelia of Hericium erinaceus.

    Science.gov (United States)

    Chen, Chien-Chih; Tzeng, Tsai-Teng; Chen, Chin-Chu; Ni, Ching-Li; Lee, Li-Ya; Chen, Wan-Ping; Shiao, Young-Ji; Shen, Chien-Chang

    2016-02-26

    A new sesterterpene, erinacine S, and one cyathane diterpene xyloside, erinacine A, were isolated from the ethanol extract of the mycelia of Hericium erinaceus. Their structures were elucidated by spectroscopic and X-ray analysis. A 30-day oral course of erinacines A and S attenuated Aβ plaque burden in the brains of 5-month-old female APP/PS1 transgenic mice. Moreover, erinacines A and S significantly increased the level of insulin-degrading enzyme in cerebral cortex.

  18. New Terpenes from the Egyptian Soft Coral Sarcophyton ehrenbergi

    Directory of Open Access Journals (Sweden)

    Ahmed Elkhateeb

    2014-04-01

    Full Text Available Chemical investigations of the Egyptian soft coral Sarcophyton ehrenbergi have led to the isolation of compounds 1–3 as well as the previously reported marine cembranoid diterpene sarcophine (4. Structures were elucidated by comprehensive NMR and HRMS experimentation. Isolated compounds were in vitro assayed for cytotoxic activity against human hepatocarcinoma (HepG2 and breast adenocarcinoma (MCF-7 cell lines.

  19. Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase.

    Science.gov (United States)

    Kudo, Fumitaka; Matsuura, Yasunori; Hayashi, Takaaki; Fukushima, Masayuki; Eguchi, Tadashi

    2016-07-01

    Sordarin is a glycoside antibiotic with a unique tetracyclic diterpene aglycone structure called sordaricin. To understand its intriguing biosynthetic pathway that may include a Diels-Alder-type [4+2]cycloaddition, genome mining of the gene cluster from the draft genome sequence of the producer strain, Sordaria araneosa Cain ATCC 36386, was carried out. A contiguous 67 kb gene cluster consisting of 20 open reading frames encoding a putative diterpene cyclase, a glycosyltransferase, a type I polyketide synthase, and six cytochrome P450 monooxygenases were identified. In vitro enzymatic analysis of the putative diterpene cyclase SdnA showed that it catalyzes the transformation of geranylgeranyl diphosphate to cycloaraneosene, a known biosynthetic intermediate of sordarin. Furthermore, a putative glycosyltransferase SdnJ was found to catalyze the glycosylation of sordaricin in the presence of GDP-6-deoxy-d-altrose to give 4'-O-demethylsordarin. These results suggest that the identified sdn gene cluster is responsible for the biosynthesis of sordarin. Based on the isolated potential biosynthetic intermediates and bioinformatics analysis, a plausible biosynthetic pathway for sordarin is proposed.

  20. Isolation and structure elucidation of some compounds of Solidago gigantea var. serotina (O. Kuntze) Cronquist

    International Nuclear Information System (INIS)

    Lichtenberger, E.

    1985-03-01

    Studies on plants of the genus Solidago used in folk medicine as a remedy against diseases of the urinary-system induced the investigation of Solidago gigantea Aiton var. serotina (O. Kuntze) Cronquist = S. serotina. A methanolic extract of the aerial parts was examined for the biologically active saponin complex. The most effective constituents were found to be a mixture of closely related triterpene glycosides named saponin G, H, I and saponin K. Fractionation over a series of silicagel columns and droplet countercurrent chromatographies resulted in pure saponin G and saponin H. The screening of the hydrolized glycosides afforded the genins bayogenin as major compound, oleanolic acid and three additional aglycones in trace quantities. The identy of bayogenin, oleanolic acid and bayogeninglucosid was established by mass-, 1 H-NMR- and 13 C-NMR-measurements and by direct comparison with authentic samples. Gas chromatographic analysis of the sugar moiety yielded rhamnose, xylose, glucose and 6-desoxyglucose after KILIANI-degradation in a ratio 3:3:1:1. Beside the triterpene derivatives, mentioned above, we found a diterpene, sterol and sterolglycosed as well. The diterpene structure was confirmed by UV-, IR-, mass-, 1 H-NMR- and 13 C-NMR-spectroscopy. This diterpene was not previously known to be present in S. serotina. The sterol-compounds could be determined as α-spinasterol and the respective hexosid. (Author)

  1. New Abietane and Kaurane Type Diterpenoids from the Stems of Tripterygium regelii

    Directory of Open Access Journals (Sweden)

    Dongsheng Fan

    2017-01-01

    Full Text Available Eleven new abietane type (1‒11, and one new kaurane (12, diterpenes, together with eleven known compounds (13–23, were isolated and identified from the stems of Tripterygium regelii, which has been used as a traditional folk Chinese medicine for the treatment of rheumatoid arthritis in China. The structures of new compounds were characterized by means of the interpretation of high-resolution electrospray ionization mass spectrometry (HRESIMS, extensive nuclear magnetic resonance (NMR spectroscopic data and comparisons of their experimental CD spectra with calculated electronic circular dichroism (ECD spectra. Compound 1 is the first abietane type diterpene with an 18→1 lactone ring. Compound 19 was isolated from the plants of the Tripterygium genus for the first time, and compounds 14–17 were isolated from T. regelii for the first time. Triregelin I (9 showed significant cytotoxicity against A2780 and HepG2 with IC50 values of 5.88 and 11.74 µM, respectively. It was found that this compound was inactive against MCF-7 cells. The discovery of these twelve new diterpenes not only provided information on chemical substances of T. regelii, but also contributed to the chemical diversity of natural terpenoids.

  2. Bifunctional cis-Abienol Synthase from Abies balsamea Discovered by Transcriptome Sequencing and Its Implications for Diterpenoid Fragrance Production*

    Science.gov (United States)

    Zerbe, Philipp; Chiang, Angela; Yuen, Macaire; Hamberger, Björn; Hamberger, Britta; Draper, Jason A.; Britton, Robert; Bohlmann, Jörg

    2012-01-01

    The labdanoid diterpene alcohol cis-abienol is a major component of the aromatic oleoresin of balsam fir (Abies balsamea) and serves as a valuable bioproduct material for the fragrance industry. Using high-throughput 454 transcriptome sequencing and metabolite profiling of balsam fir bark tissue, we identified candidate diterpene synthase sequences for full-length cDNA cloning and functional characterization. We discovered a bifunctional class I/II cis-abienol synthase (AbCAS), along with the paralogous levopimaradiene/abietadiene synthase and isopimaradiene synthase, all of which are members of the gymnosperm-specific TPS-d subfamily. The AbCAS-catalyzed formation of cis-abienol proceeds via cyclization and hydroxylation at carbon C-8 of a postulated carbocation intermediate in the class II active site, followed by cleavage of the diphosphate group and termination of the reaction sequence without further cyclization in the class I active site. This reaction mechanism is distinct from that of synthases of the isopimaradiene- or levopimaradiene/abietadiene synthase type, which employ deprotonation reactions in the class II active site and secondary cyclizations in the class I active site, leading to tricyclic diterpenes. Comparative homology modeling suggested the active site residues Asp-348, Leu-617, Phe-696, and Gly-723 as potentially important for the specificity of AbCAS. As a class I/II bifunctional enzyme, AbCAS is a promising target for metabolic engineering of cis-abienol production. PMID:22337889

  3. Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli

    Directory of Open Access Journals (Sweden)

    Emily J. Parker

    2013-08-01

    Full Text Available The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse. This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.

  4. Identification of Minor Secondary Metabolites from the Latex of Croton lechleri (Muell-Arg and Evaluation of Their Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Maria Iorizzi

    2008-06-01

    Full Text Available Dragon’s blood (Sangre de drago, a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae, is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-β-O-4’- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods (1H-, 13C- NMR and 2D-NMR experiments, ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex exhibited the highest antioxidant activity.

  5. Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus.

    Science.gov (United States)

    Heskes, Allison M; Sundram, Tamil C M; Boughton, Berin A; Jensen, Niels B; Hansen, Nikolaj L; Crocoll, Christoph; Cozzi, Federico; Rasmussen, Simon; Hamberger, Britta; Hamberger, Björn; Staerk, Dan; Møller, Birger L; Pateraki, Irini

    2018-03-01

    Vitex agnus-castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus-castus show that it contains an enormous array of structurally related diterpenoids and, as such, holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in V. agnus-castus. With the assistance of matrix-assisted laser desorption ionisation-mass spectrometry imaging (MALDI-MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome-specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs); three class I diTPSs; and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in V. agnus-castus. The identified CYP, VacCYP76BK1, was found to catalyse 16-hydroxylation of the diol-diterpene, peregrinol, to labd-13Z-ene-9,15,16-triol when expressed in Saccharomyces cerevisiae. Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan- and lactone-containing diterpenoids that are present in this species. © 2018 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  6. Further Mulinane and Azorellane Diterpenoids Isolated from Mulinum crassifolium and Azorella compacta

    Directory of Open Access Journals (Sweden)

    Jorge Bórquez

    2014-03-01

    Full Text Available The new mulinane diterpenoids 1 and 2 were isolated from the EtOAc extract of Mulinum crassifolium, while the rearranged mulinane 5, which was isolated for the first time from a natural source, was isolated from Azorella compacta. Compounds 1–2 were prepared by semi-synthesis thorough acetylation of the diterpene 17-acetoxymulinic acid (3. A mechanism of reaction was proposed, while the structures of the new compounds were elucidated on the basis of comprehensive spectroscopic analysis and computational methods.

  7. Catalytic Hydrogenation of the Sweet Principles of Stevia rebaudiana, Rebaudioside B, Rebaudioside C, and Rebaudioside D and Sensory Evaluation of Their Reduced Derivatives

    Science.gov (United States)

    Prakash, Indra; Campbell, Mary; Chaturvedula, Venkata Sai Prakash

    2012-01-01

    Catalytic hydrogenation of rebaudioside B, rebaudioside C, and rebaudioside D; the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana was carried out using Pd(OH)2. Reduction of steviol glycosides was performed using straightforward synthetic chemistry with the catalyst Pd(OH)2 and structures of the corresponding dihydro derivatives were characterized on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectral data indicating that all are novel compounds being reported for the first time. Also, the taste properties of all reduced compounds were evaluated against their corresponding original steviol glycosides and sucrose. PMID:23203115

  8. Chemical constituents of Sebastiania macrocarpa Muell. Arg. (Euphorbiaceae); Constituintes quimicos de Sebastiania macrocarpa Muell. Arg. (Euphorbiaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Michele A.A.; Lima, Jefferson Q.; Arriaga, Angela M.C.; Andrade-Neto, Manoel; Braz-Filho, Raimundo [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica; Santiago, Gilvandete M.P.; Bezerra, Beatriz P.; Fereira, Yana S.; Veras, Helenicy N.H. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Faculdade de Farmacia, Odontologia e Enfermagem. Dept. de Farmacia]. E-mail: gil@ufc.br

    2009-07-01

    The chemical investigation of the methanolic extract of the aerial part of Sebastiania macrocarpa allowed the isolation of the mixture of steroids {beta}-sitosterol and stigmasterol, gallic acid, and scopoletin. The hexane extract of the roots allowed the isolation of the triterpene lupeol and of the macrocyclic diterpene (+)-tonantzitlolone. The structures of all compounds isolated were identified on the basis of their spectral data and by comparison of their spectral data with values described in the literature. This is the first report involving the chemical investigation of this species (author)

  9. Essential oils of Pinus nigra J.F. Arnold subsp. laricio Maire: Chemical composition and study of their herbicidal potential

    OpenAIRE

    Ismail Amri; Mohsen Hanana; Bassem Jamoussi; Lamia Hamrouni

    2017-01-01

    The chemical composition of essential oils isolated by hydrodistillation from the needles of Tunisian Pinus nigra L. subsp. laricio was analyzed by GC and GC/MS. 27 compounds were identified, representing 97.9% of total oil, which was found to be rich in oxygenated diterpenes (38.5%) particularly manool oxide (38%) and sesquiterpene hydrocarbons (41.4%) that included germacrene D (16.7%), δ-cadinene (9%) and (E)-caryophyllene (8.9%). Results of the herbicidal effects of the oil when tested on...

  10. Isolation of diacyl glycerol acyl transferase (DGAT) inhibitors from Pachydictyon coriaceum.

    Science.gov (United States)

    Choi, Byoung Wook; Lee, Hyun Sun; Lee, Kyung Bok; Lee, Bong Ho

    2011-07-01

    The pharmacological inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) has emerged as a target for the treatment of obesity and type 2 diabetes. Chromatographic analysis of the brown alga, Pachydictyon coriaceum, led to the isolation of diterpene dictyol E and hydroxyisocrenulatin. Pharmacological assay of these compounds demonstrated DGAT inhibitory activity with IC₅₀ values of 46.0 μM and 23.3 μM, respectively. Copyright © 2011 John Wiley & Sons, Ltd.

  11. Heterologous expression of the isopimaric acid pathway in Nicotiana benthamiana and the effect of N-terminal modifications of the involved cytochrome P450 enzyme

    DEFF Research Database (Denmark)

    Gnanasekaran, Thiyagarajan; Vavitsas, Konstantinos; Andersen-Ranberg, Johan

    2015-01-01

    in the infiltrated leaves. Furthermore, we demonstrated that a modified membrane anchor is a prerequisite for a functional CYP720B4 enzyme when the chloroplast targeting peptide is added. We report the accumulation of 45-55 μg/g plant dry weight of isopimaric acid four days after the infiltration with the modified...... in the chloroplast and subsequently oxidized by a cytochrome P450, CYP720B4. RESULTS: We transiently expressed the isopimaric acid pathway in Nicotiana benthamiana leaves and enhanced its productivity by the expression of two rate-limiting steps in the pathway (providing the general precursor of diterpenes). This co...

  12. (3R,4S,5S,8S,10R,13R-3-Hydroxykaura-9(11,16-dien-18-oic acid

    Directory of Open Access Journals (Sweden)

    Karren D. Beattie

    2012-02-01

    Full Text Available The title compound, C20H28O3, was isolated during our investigation into the chemical composition and pharmacological activity of Centipeda cunninghamii (DC. A. Braun & Asch. (Asteraceae. The enantiopure compound, a diterpene with a carbon skeleton, is composed of three six- and one five-membered rings in chair, twist-boat, half-chair and envelope conformations, respectively. Each molecule makes one intra- and one intermolecular O—H...O hydrogen bond in the crystal lattice, forming hydrogen-bonded chains along [010]. The absolute configuration of the compound was assigned on the basis of optical rotation measurements.

  13. Catalytic Hydrogenation of the Sweet Principles of Stevia rebaudiana, Rebaudioside B, Rebaudioside C, and Rebaudioside D and Sensory Evaluation of Their Reduced Derivatives

    Directory of Open Access Journals (Sweden)

    Mary Campbell

    2012-11-01

    Full Text Available Catalytic hydrogenation of rebaudioside B, rebaudioside C, and rebaudioside D; the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana was carried out using Pd(OH2. Reduction of steviol glycosides was performed using straightforward synthetic chemistry with the catalyst Pd(OH2 and structures of the corresponding dihydro derivatives were characterized on the basis of 1D and 2D nuclear magnetic resonance (NMR spectral data indicating that all are novel compounds being reported for the first time. Also, the taste properties of all reduced compounds were evaluated against their corresponding original steviol glycosides and sucrose.

  14. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    Science.gov (United States)

    Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.; Simpson, Jeffrey; Fry, John C.; Yurttas, Nese; Biermann, Kari L.; Chen, Jie; Trout, Bernhardt L.; Myerson, Allan S.

    2015-12-01

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described.

  15. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    International Nuclear Information System (INIS)

    Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.; Chen, Jie; Trout, Bernhardt L.; Myerson, Allan S.; Simpson, Jeffrey; Fry, John C.; Biermann, Kari L.; Yurttas, Nese

    2015-01-01

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described

  16. Terpenos em cupins do gênero Nasutitermes (Isoptera, Termitidae, Nasutitermitinae

    Directory of Open Access Journals (Sweden)

    Márcia N. S. de la Cruz

    2014-01-01

    Full Text Available The chemical composition of the front gland of termites has been studied for over 40 years. The genus Nasutitermes, considered the most evolved of the Termitidae family, has a peculiarity that sets it apart from the others: a caste of soldiers that carry a terpenic mixture used in defense. This secretion is formed by mono, sesqui and diterpenes from trinervitane, kempane and rippertane skeletons, only found in termites. This article sought to review the scientific literature and contribute to the knowledge on the chemical composition of the secretion of the Nasutitermes soldiers from the interesting aspects of its behavior.

  17. Phytoconstituents from Vitex agnus-castus fruits.

    Science.gov (United States)

    Chen, Shao-Nong; Friesen, J Brent; Webster, Donna; Nikolic, Dejan; van Breemen, Richard B; Wang, Z Jim; Fong, Harry H S; Farnsworth, Norman R; Pauli, Guido F

    2011-06-01

    A new labdane-diterpene, viteagnusin I (1), together with 23 known phytoconstituents were isolated from the fruits of Vitex agnus-castus L, and their structures characterized by spectroscopic methods (NMR and MS). The known compounds include ten flavonoids, five terpenoids, three neolignans, and four phenolic compounds, as well as one glyceride. Biological evaluation identified apigenin, 3-methylkaempferol, luteolin, and casticin as weak ligands of delta and mu opioid receptors, exhibiting dose-dependent receptor binding. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Antifungal activity against postharvest fungi by extracts from Colombian propolis

    International Nuclear Information System (INIS)

    Meneses, Erick A.; Durango, Diego L.; Garcia, Carlos M.

    2009-01-01

    The aims of the present study were to evaluate the antifungal properties of Colombian propolis extracts against Colletotrichum gloeosporioides and Botryodiplodia theobromae, and to isolate and identify the main constituents from the active extracts. Therefore, propolis samples were thoroughly extracted with n-hexane/methanol (EPEM), dichloromethane, ethyl acetate, and methanol. Experimental results indicated that mycelial growth of all selected microorganisms was reduced in culture media containing EPEM and dichloromethane fractions. Furthermore, through antifungal bioassay-guided fractionation, three known labdane-type diterpenes: isocupressic acid (1), (+)-agathadiol (2) and epi-13-torulosol (3) were isolated as the main constituents from the active fractions. (author)

  19. Antifungal activity against postharvest fungi by extracts from Colombian propolis

    Energy Technology Data Exchange (ETDEWEB)

    Meneses, Erick A.; Durango, Diego L.; Garcia, Carlos M. [Universidad Nacional de Colombia, Medellin (Colombia). Facultad de Ciencias. Escuela de Quimica], e-mail: cmgarcia@unal.edu.co

    2009-07-01

    The aims of the present study were to evaluate the antifungal properties of Colombian propolis extracts against Colletotrichum gloeosporioides and Botryodiplodia theobromae, and to isolate and identify the main constituents from the active extracts. Therefore, propolis samples were thoroughly extracted with n-hexane/methanol (EPEM), dichloromethane, ethyl acetate, and methanol. Experimental results indicated that mycelial growth of all selected microorganisms was reduced in culture media containing EPEM and dichloromethane fractions. Furthermore, through antifungal bioassay-guided fractionation, three known labdane-type diterpenes: isocupressic acid (1), (+)-agathadiol (2) and epi-13-torulosol (3) were isolated as the main constituents from the active fractions. (author)

  20. Coffee: biochemistry and potential impact on health.

    Science.gov (United States)

    Ludwig, Iziar A; Clifford, Michael N; Lean, Michael E J; Ashihara, Hiroshi; Crozier, Alan

    2014-08-01

    This review provides details on the phytochemicals in green coffee beans and the changes that occur during roasting. Key compounds in the coffee beverage, produced from the ground, roasted beans, are volatile constituents responsible for the unique aroma, the alkaloids caffeine and trigonelline, chlorogenic acids, the diterpenes cafestol and kahweol, and melanoidins, which are Maillard reaction products. The fate of these compounds in the body following consumption of coffee is discussed along with evidence of the mechanisms by which they may impact on health. Finally, epidemiological findings linking coffee consumption to potential health benefits including prevention of several chronic and degenerative diseases, such as cancer, cardiovascular disorders, diabetes, and Parkinson's disease, are evaluated.

  1. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    Energy Technology Data Exchange (ETDEWEB)

    Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.; Chen, Jie; Trout, Bernhardt L.; Myerson, Allan S., E-mail: myerson@mit.edu [Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 66-568, Cambridge, Massachusetts 02139 (United States); Simpson, Jeffrey [Department of Chemistry Instrumentation Facility, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 18-0090, Cambridge, Massachusetts 02139 (United States); Fry, John C.; Biermann, Kari L. [Connect Consulting, 6 Hollands Field, Horsham RH123HQ (United Kingdom); Yurttas, Nese [Cargill, Inc., Global Food Technology, 2301 Crosby Road, Wayzata, Minnesota 55391 (United States)

    2015-12-28

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described.

  2. Quantitative chemical analysis for the standardization of copaiba oil by high resolution gas chromatography; Analise quimica quantitativa para a padronizacao do oleo de copaiba por cromatografia em fase gasosa de alta resolucao

    Energy Technology Data Exchange (ETDEWEB)

    Tappin, Marcelo R.R.; Pereira, Jislaine F.G.; Lima, Lucilene A.; Siani, Antonio C. [Farmanguinhos - Inst. de Tecnologia em Farmacos, Rio de Janeiro, RJ (Brazil)]. E-mail: siani@far.fiocruz.br; Mazzei, Jose L. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Escola de Quimica; Ramos, Monica F.S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Farmacia. Dept. de Medicamentos

    2004-04-01

    Quantitative GC-FID was evaluated for analysis of methylated copaiba oils, using trans-(-)-caryophyllene or methyl copalate as external standards. Analytical curves showed good linearity and reproducibility in terms of correlation coefficients (0.9992 and 0.996, respectively) and relative standard deviation (< 3%). Quantification of sesquiterpenes and diterpenic acids were performed with each standard, separately. When compared with the integrator response normalization, the standardization was statistically similar for the case of methyl copalate, but the response of trans-(-)-caryophyllene was statistically (P < 0.05) different. This method showed to be suitable for classification and quality control of commercial samples of the oils. (author)

  3. Quantitative chemical analysis for the standardization of copaiba oil by high resolution gas chromatography

    International Nuclear Information System (INIS)

    Tappin, Marcelo R.R.; Pereira, Jislaine F.G.; Lima, Lucilene A.; Siani, Antonio C.; Mazzei, Jose L.; Ramos, Monica F.S.

    2004-01-01

    Quantitative GC-FID was evaluated for analysis of methylated copaiba oils, using trans-(-)-caryophyllene or methyl copalate as external standards. Analytical curves showed good linearity and reproducibility in terms of correlation coefficients (0.9992 and 0.996, respectively) and relative standard deviation (< 3%). Quantification of sesquiterpenes and diterpenic acids were performed with each standard, separately. When compared with the integrator response normalization, the standardization was statistically similar for the case of methyl copalate, but the response of trans-(-)-caryophyllene was statistically (P < 0.05) different. This method showed to be suitable for classification and quality control of commercial samples of the oils. (author)

  4. Essential oils composition of Pinus peuce Griseb. (Pinaceae growing on Pelister Mtn., Republic of Macedonia

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    Marija Karapandzova

    2011-06-01

    Full Text Available The composition of essential oils obtained by hydrodistillation from needles, from branches without needles and from branches with needles of Pinus peuce Griseb. (Pinaceae from Pelister Mtn. (R. Macedonia was analyzed by GC/FID/MS. One hundred and seven components (40 monoterpenes, 37 sesquiterpenes, 9 diterpenes and 21 other components - aliphatic and cyclic hydrocarbons; aliphatic alcohols, aldehydes, and acids; phenols and other oxygenated benzene derivates were identified. The most abundant constituents were terpene hydrocarbons, encompassing the monoterpenes: α-pinene, β-pinene, limonene + β-phellandrene and bornyl acetate and the sesquiterpenes: trans (E-caryophyllene and germacrene D.

  5. Vinylogous Nicholas reactions in the synthesis of bi- and tricyclic cycloheptynedicobalt complexes.

    Science.gov (United States)

    Kolodziej, Izabela; Green, James R

    2015-11-28

    The Lewis acid mediated intramolecular Nicholas reactions of allylic acetate enyne-Co2(CO)6 complexes afford cycloheptenyne-Co2(CO)6 complexes in three manifestations. Electron rich aryl substituted alkyne complexes give tricyclic 6,7,x-benzocycloheptenyne complexes, with x = 5, 6, or 7. Allylsilane substituted complexes afford exo methylene bicyclic x,7-cycloheptenyne complexes (x = 6,7). The allyl acetate function may also be replaced by a benzylic acetate, to afford dibenzocycloheptyne-Co2(CO)6 complexes. Following reductive complexation, the methodology may be applied to the synthesis of the icetexane diterpene carbon framework.

  6. Gastroprotective effect of the Mapuche crude drug Araucaria araucana resin and its main constituents.

    Science.gov (United States)

    Schmeda-Hirschmann, Guillermo; Astudillo, Luis; Rodríguez, Jaime; Theoduloz, Cristina; Yáñez, Tania

    2005-10-03

    The resin from the tree Araucaria araucana (Araucariaceae) has been used since pre-columbian times by the Mapuche amerindians to treat ulcers. The gastroprotective effect of the resin was assessed in the ethanol-HCl-induced gastric ulcer in mice showing a dose-dependent gastroprotective activity at 100, 200 and 300 mg/kg per os. The main three diterpene constituents of the resin, namely imbricatolic acid, 15-hydroxyimbricatolal and 15-acetoxyimbricatolic acid were isolated and evaluated for gastroprotective effect at doses of 50, 100 and 200 mg/kg. A dose-related gastroprotective effect with highly significant activity (PMapuche culture.

  7. Mollebenzylanols A and B, Highly Modified and Functionalized Diterpenoids with a 9-Benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane Core from Rhododendron molle.

    Science.gov (United States)

    Zhou, Junfei; Liu, Junjun; Dang, Ting; Zhou, Haofeng; Zhang, Hanqi; Yao, Guangmin

    2018-04-06

    Two highly modified and functionalized diterpenoids, mollebenzylanols A (1) and B (2), and a known grayanane diterpenoid rhodojaponin III (3) were isolated from Rhododendron molle. Their structures were determined by spectroscopic data analysis, an electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis of the p-bromobenzoate ester of 1 (1a). Compounds 1 and 2 possess an unprecedented diterpene carbon skeleton featuring a unique 9-benzyl-8,10-dioxatricyclo[5.2.1.0 1,5 ]decane core, and their plausible biosynthetic pathways are proposed. Their PTP1B inhibitory activity and modes of action were investigated.

  8. Uprolides N, O and P from the Panamanian Octocoral Eunicea succinea

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    Daniel Torres-Mendoza

    2016-06-01

    Full Text Available Three new diterpenes, uprolide N (1, uprolide O (2, uprolide P (3 and a known one, dolabellane (4, were isolated from the CH2Cl2-MeOH extract of the gorgonian octocoral Eunicea succinea, collected from Bocas del Toro, on the Caribbean coast of Panama. Their structures were determined using spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HRMS together with molecular modeling studies. Compounds 1–3 displayed anti-inflammatory properties by inhibiting production of Tumor Necrosis Factor (TNF and Interleukin (IL-6 induced by lipopolysaccharide (LPS in murine macrophages.

  9. Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L.

    Science.gov (United States)

    Bosisio, E; Giavarini, F; Dell'Agli, M; Galli, G; Galli, C L

    2004-05-01

    Due to its liver toxicity, the medicinal use of germander (Teucrium chamaedrys L.) was banned in some countries. Nevertheless, alcoholic extracts are still permitted as flavour ingredients since they are fundamental in providing a bitter aromatic taste. Teucrin A represents the substance of major concern regarding the potential toxicity of germander. Hence, teucrin A represents the best analytical and toxicological marker of alcoholic extracts of T. chamaedrys. A sensitive high-performance liquid chromatography method to detect teucrin A in beverages is reported. Teucrin A was prepared by isolation from the plant extract using column chromatography and crystallization. The identity and purity (99%) were established by melting point, nuclear magnetic resonance and liquid chromatography-mass spectrometry. The high-performance liquid chromatography procedure was validated and its intra- and interday performance was established (relative standard deviation beverages not containing T. chamaedrys spiked with a range of concentrations of teucrin A. The limit of detection was 0.1 ppm and the limit of quantification was 0.3 ppm. Teucrin A accounted for about 70% of the neo-clerodane diterpenoids found in the total extract of a specimen of T. chamaedrys. The content (+/- standard deviation) in 18 batches of different geographical origin was 2338 +/- 740 ppm, per cent coefficient of variation = 32, minimum-maximum = 999 - 3445 ppm. The mean level of teucrin A in 10 bottles of the same brand was 6.1 +/- 0.8 ppm, per cent coefficient of variation = 12. In 10 different brands found on the Italian market, the content of teucrin A ranged from not detectable to 10 ppm.

  10. The release of organic compounds during biomass drying depends upon the feedstock and/or altering drying heating medium

    International Nuclear Information System (INIS)

    Rupar, K.; Sanati, M.

    2003-01-01

    The release of organic compounds during the drying of biomass is a potential environmental problem, it may contribute to air pollution or eutrophication. In many countries there are legal restrictions on the amounts of terpenes that may be released into the atmosphere. When considering bioenergy in future energy systems, it is important that information on the environmental effects is available. The emissions of organic compounds from different green and dried biofuels that have been dried in hot air and steam medium, were analyzed by using different techniques. Gas chromatography and gas chromatography mass spectrometry have been used to identify the organic matter. The terpene content was significantly affected by the following factors: changing of the drying medium and the way the same biomass was handled from different localities in Sweden. Comparison between spectra from dried and green fuels reveal that the main compounds emitted during drying are monoterpene and sesquiterpene hydrocarbons, while the emissions of diterpene hydrocarbons seem to be negligible. The relative proportionality between emitted monoterpene, diterpene and sesquiterpene change when the drying medium shifts from steam to hot air. The obtained result of this work implies a parameter optimization study of the dryer with regard to environmental impact. With assistance of this result it might be foreseen that choice of special drying medium, diversity of biomass and low temperature reduce the emissions. A thermo-gravimetric analyzer was used for investigating the biomass drying rate. (author)

  11. Antibacterial Activity of Daucus crinitus Essential Oils along the Vegetative Life of the Plant

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    Amel Bendiabdellah

    2013-01-01

    Full Text Available The essential oils from the aerial parts of Daucus crinitus Desf. were analyzed at three developmental stages (early vegetative, early flowering, and full flowering. Oil yield was found to vary depending on the stage of development, and the highest content of oil (0.15% w/w was obtained at full flowering. The chemical composition of essential oils studied by GC and GC-MS showed a total of 71 compounds: 27 aliphatic compounds, 18 sesquiterpene hydrocarbons, 9 hydrocarbons monoterpene, 5 oxygenated monoterpenes, 5 phenolic compounds, 4 oxygenated sesquiterpenes, 2 oxygenated diterpenes, and 01 diterpene hydrocarbons. Whatever the analyzed stage, phenolic compounds were the most abundant group. Their level significantly increased during ripening and varied from 36.4 to 82.1%. Antimicrobial activities of oils were tested on four different microorganisms. The oils of various phenological stages showed high activity against Candida albicans (30 mm and Staphylococcus aureus (11–28 mm bacteria strains which are deemed very dangerous and very difficult to eliminate. Thus, they represent an inexpensive source of natural antibacterial substances that may potentially be used in pathogenic systems.

  12. Transcriptome mining, functional characterization, and phylogeny of a large terpene synthase gene family in spruce (Picea spp.

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    Dullat Harpreet K

    2011-03-01

    Full Text Available Abstract Background In conifers, terpene synthases (TPSs of the gymnosperm-specific TPS-d subfamily form a diverse array of mono-, sesqui-, and diterpenoid compounds, which are components of the oleoresin secretions and volatile emissions. These compounds contribute to defence against herbivores and pathogens and perhaps also protect against abiotic stress. Results The availability of extensive transcriptome resources in the form of expressed sequence tags (ESTs and full-length cDNAs in several spruce (Picea species allowed us to estimate that a conifer genome contains at least 69 unique and transcriptionally active TPS genes. This number is comparable to the number of TPSs found in any of the sequenced and well-annotated angiosperm genomes. We functionally characterized a total of 21 spruce TPSs: 12 from Sitka spruce (P. sitchensis, 5 from white spruce (P. glauca, and 4 from hybrid white spruce (P. glauca × P. engelmannii, which included 15 monoterpene synthases, 4 sesquiterpene synthases, and 2 diterpene synthases. Conclusions The functional diversity of these characterized TPSs parallels the diversity of terpenoids found in the oleoresin and volatile emissions of Sitka spruce and provides a context for understanding this chemical diversity at the molecular and mechanistic levels. The comparative characterization of Sitka spruce and Norway spruce diterpene synthases revealed the natural occurrence of TPS sequence variants between closely related spruce species, confirming a previous prediction from site-directed mutagenesis and modelling.

  13. A screening method for cardiovascular active compounds in marine algae.

    Science.gov (United States)

    Agatonovic-Kustrin, S; Kustrin, E; Angove, M J; Morton, D W

    2018-05-18

    The interaction of bioactive compounds from ethanolic extracts of selected marine algae samples, separated on chromatographic plates, with nitric/nitrous acid was investigated. The nature of bioactive compounds in the marine algae extracts was characterised using UV absorption spectra before and after reaction with diluted nitric acid, and from the characteristic colour reaction after derivatization with anisaldehyde. It was found that diterpenes from Dictyota dichotoma, an edible brown algae, and sterols from green algae Caulerpa brachypus, bind nitric oxide and may act as a nitric oxide carrier. Although the carotenoid fucoxanthin, found in all brown marine algae also binds nitric oxide, the bonds between nitrogen and the fucoxanthin molecule are much stronger. Further studies are required to evaluate the effects of diterpenes from Dictyota dichotoma and sterols from green algae Caulerpa brachypus to see if they have beneficial cardiovascular effects. The method reported here should prove useful in screening large numbers of algae species for compounds with cardiovascular activity. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Proteomic Analysis of the Endosperm Ontogeny of Jatropha curcas L. Seeds.

    Science.gov (United States)

    Shah, Mohibullah; Soares, Emanoella L; Carvalho, Paulo C; Soares, Arlete A; Domont, Gilberto B; Nogueira, Fábio C S; Campos, Francisco A P

    2015-06-05

    Seeds of Jatropha curcas L. represent a potential source of raw material for the production of biodiesel. However, this use is hampered by the lack of basic information on the biosynthetic pathways associated with synthesis of toxic diterpenes, fatty acids, and triacylglycerols, as well as the pattern of deposition of storage proteins during seed development. In this study, we performed an in-depth proteome analysis of the endosperm isolated from five developmental stages which resulted in the identification of 1517, 1256, 1033, 752, and 307 proteins, respectively, summing up 1760 different proteins. Proteins with similar label free quantitation expression pattern were grouped into five clusters. The biological significance of these identifications is discussed with special focus on the analysis of seed storage proteins, proteins involved in the metabolism of fatty acids, carbohydrates, toxic components and proteolytic processing. Although several enzymes belonging to the biosynthesis of diterpenoid precursors were identified, we were unable to find any terpene synthase/cyclase, indicating that the synthesis of phorbol esters, the main toxic diterpenes, does not occur in seeds. The strategy used enabled us to provide a first in depth proteome analysis of the developing endosperm of this biodiesel plant, providing an important glimpse into the enzymatic machinery devoted to the production of C and N sources to sustain seed development.

  15. Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content.

    Science.gov (United States)

    Farag, Mohamed A; Al-Mahdy, Dalia A; Meyer, Achim; Westphal, Hildegard; Wessjohann, Ludger A

    2017-04-05

    The effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl 2 , glutathione and β-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coral Sarcophyton ehrenbergi were assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggesting the absence of a remarkable stress on primary production. Chemometric analyses of UPLC-MS data showed clear segregation of SA and ZnCl 2 elicited samples at 24 and 48 h post elicitation. Levels of acetylated diterpene and sterol viz., sarcophytonolide I and cholesteryl acetate, was increased in ZnCl 2 and SA groups, respectively, suggesting an activation of specific acetyl transferases. Post elicitation, sarcophytonolide I level increased 132 and 17-folds at 48 h in 0.1 mM SA and 1 mM ZnCl 2 groups, respectively. Interestingly, decrease in sarcophine, a major diterpene was observed only in response to ZnCl 2 , whereas no change was observed in sesquiterpene content following treatments. To the best of our knowledge, this study provides the first documentation for elicitation effects on a soft corals secondary metabolome and suggests that SA could be applied to increase diterpenoid levels in corals.

  16. Composition and Chemical Variability of the Needle Oil from Pinus halepensis growing in Corsica.

    Science.gov (United States)

    Nam, Anne-Marie; Tomi, Félix; Gibernau, Marc; Casanova, Joseph; Bighelli, Ange

    2016-04-01

    The composition of oil samples isolated from needles of Pinus halepensis growing in three locations in Corsica (Saleccia, Capo di Feno, and Tre Padule) has been investigated by combination of chromatographic (GC with retention indices) and spectroscopic (MS and (13)C-NMR) techniques. In total, 35 compounds that accounted for 77 - 100% of the whole composition have been identified. α-Pinene, myrcene, and (E)-β-caryophyllene were the major component followed by α-humulene and 2-phenylethyl isovalerate. Various diterpenes have been identified as minor components. 47 Oil samples isolated from pine needles have been analyzed and were differentiated in two groups. Oil samples of the first group (15 samples) contained myrcene (M = 28.1 g/100 g; SD = 10.6) and (E)-β-caryophyllene (M = 19.0 g/100 g; SD = 2.2) as major components and diterpenes were absent. All these oil samples were isolated from pine needles harvested in Saleccia. Oil samples of the second group (32 samples) contained mostly (E)-β-caryophyllene (M = 28.7 g/100 g; SD = 7.9), α-pinene (M = 12.3 g/100 g; SD = 3.6), and myrcene (M = 11.7 g/100 g; SD = 7.3). All these oil samples were isolated from pine needles harvested in Capo di Feno and Tre Padule. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

  17. In vivo evaluation of the mutagenic potential and phytochemical characterization of oleoresin from Copaifera duckei Dwyer

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    Edson Luis Maistro

    2005-12-01

    Full Text Available We characterized the chemical constituents of Copaifera duckei oleoresin and used dermal application to Wistar rats to evaluated its possible mutagenic and cytotoxic activities on peripheral blood reticulocytes and bone marrow cells. Chemical characterization of the oleoresin revealed the presence of sesquiterpene hydrocarbons, an unidentified neutral diterpene and diterpene acids. To evaluate mutagenicity evaluation the rats were treated with 10, 25 and 50% of the LD50 dose of the oleoresin for three consecutive days and peripheral blood collected after 0, 24, 48 and 72 h for micronucleus analysis. The rats were humanly sacrificed 24 hours after the last treatment and chromosome preparations made using standard techniques. At the three concentrations and the three time intervals tested we found that there were no statistically significant differences in either the mean number of micronucleated reticulocytes (MNRETs or the number of chromosomal aberrations as to the negative control. However, at 25 and 50% of the LD50 dose of the oleoresin there was a significant decrease in the mitotic index (MI as compared to the negative control. Under our experimental conditions, C. duckei V11 oleoresin produced no mutagenic effects on bone marrow cells or in peripheral reticulocytes as assessed by chromosome aberrations and the micronucleus test respectively, but showed cytotoxic activity at high doses.

  18. Profiling secondary metabolites of needles of ozone-fumigated white pine (Pinus strobus) clones by thermally assisted hydrolysis/methylation GC/MS.

    Science.gov (United States)

    Shadkami, F; Helleur, R J; Cox, R M

    2007-07-01

    Plant secondary metabolites have an important role in defense responses against herbivores and pathogens, and as a chemical barrier to elevated levels of harmful air pollutants. This study involves the rapid chemical profiling of phenolic and diterpene resin acids in needles of two (ozone-tolerant and ozone-sensitive) white pine (Pinus strobus) clones, fumigated with different ozone levels (control, and daily events peaking at 80 and 200 ppb) for 40 days. The phenolic and resin acids were measured using thermally assisted hydrolysis and methylation (THM) gas chromatography/mass spectrometry. Short-term fumigation affected the levels of two phenolic acids, i.e., 3-hydroxybenzoic and 3,4-dihydroxybenzoic acids, in that both showed a substantial decrease in concentration with increased ozone dose. The decrease in concentration of these THM products may be caused by inhibition of the plant's shikimate biochemical pathway caused by ozone exposure. The combined occurrence of these two ozone-sensitive indicators has a role in biomonitoring of ozone levels and its impact on forest productivity. In addition, chromatographic profile differences in the major diterpene resin acid components were observed between ozone-tolerant and ozone-sensitive clones. The resin acids anticopalic, 3-oxoanticopalic, 3beta-hydroxyanticopalic, and 3,4-cycloanticopalic acids were present in the ozone-sensitive pine; however, only anticopalic acid was present in the ozone-tolerant clone. This phenotypic variation in resin acid composition may be useful in distinguishing populations that are differentially adapted to air pollutants.

  19. Known and novel terpenes from Buddleja globosa displaying selective antifungal activity against dermatophytes.

    Science.gov (United States)

    Mensah, A Y; Houghton, P J; Bloomfield, S; Vlietinck, A; Vanden Berghe, D

    2000-09-01

    Lipophilic extracts of the stembark of Buddleja globosa were found to have antifungal activity at 125 microg/mL against three dermatophytic fungal species but had no activity at 1000 microg/mL against four other fungal species or two yeast species. Bioassay-guided fractionation of Si gel column eluates using the sensitive fungal species resulted in active fractions from which were isolated five compounds that were characterized by spectroscopic methods as one novel and four known compounds. The known compounds were the diterpene buddlejone (1), the bisditerpene maytenone, and the two sesquiterpenes buddledin A and buddledin B, while the novel compound was characterized as the diterpene deoxybuddlejone (2). The minimum inhibitory concentration of all the compounds was determined against all the microorganisms under test, and buddledins A and B were shown to exhibit the greatest antifungal activity, with values of 43 microM and 51 microM, respectively, against the sensitive fungi Trichophyton rubrum, Tricophyton interdigitale, and Epidermophyton floccosum.

  20. PECULIARITIES OF SECONDARY METABOLITES BIOSYNTHESIS IN PLANT CELL CULTURES

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    A.M. NOSOV

    2014-06-01

    Full Text Available metabolites formation in plant cell cultures of Panax spp., (ginsenosides; Dioscorea deltoidea (steroid glycosides; Ajuga reptans, Serratula coronata, Rhaponticum carthamoides (ecdisteroids; Polyscias spp., (triterpene glycosides, Taxus spp. (taxoids, Stevia rebaudiana (diterpene steviol-glycosides, Stephania glabra (alkaloids. They are some regular trends of secondary metabolites synthesis in the plant cell culture:It can be noted the stable synthesis of the compound promoting cell proliferation. Indeed, cell cultures of Dioscorea deltoidea were demonstrated to accumulate only furostanol glycosides, which promoted cell division. Furostanol glycoside content of Dioscorea strain DM-0.5 was up to 6 - 12% by dry biomass.Panax ginseng and P. japonicus plant cell cultures synthesize as minimum seven triterpene glycosides (ginsenosides, the productivity of these compounds was up to 6.0 - 8.0% on dry biomass.By contrast, the detectable synthesis of diterpene steviol-glycosides in cultivated cells of Stevia rebaudiana initiated in the mixotrophic cultures during chloroplast formation only.Despite these differences, or mainly due to them, plant cell cultures have become an attractive source of phytochemicals in alternative to collecting wild plants. It provides a guideline to bioreactor-based production of isoprenoids using undifferentiated plant cell cultures. 

  1. Currencies of Mutualisms: Sources of Alkaloid Genes in Vertically Transmitted Epichloae

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    Christopher L. Schardl

    2013-06-01

    Full Text Available The epichloae (Epichloë and Neotyphodium species, a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae. Most epichloae are vertically transmitted in seeds (endophytes, and most produce alkaloids that attack nervous systems of potential herbivores. These protective metabolites include ergot alkaloids and indole-diterpenes (tremorgens, which are active in vertebrate systems, and lolines and peramine, which are more specific against invertebrates. Several Epichloë species have been described which are sexual and capable of horizontal transmission, and most are vertically transmissible also. Asexual epichloae are mainly or exclusively vertically transmitted, and many are interspecific hybrids with genomic contributions from two or three ancestral Epichloë species. Here we employ genome-scale analyses to investigate the origins of biosynthesis gene clusters for ergot alkaloids (EAS, indole-diterpenes (IDT, and lolines (LOL in 12 hybrid species. In each hybrid, the alkaloid-gene and housekeeping-gene relationships were congruent. Interestingly, hybrids frequently had alkaloid clusters that were rare in their sexual ancestors. Also, in those hybrids that had multiple EAS, IDT or LOL clusters, one cluster lacked some genes, usually for late pathway steps. Possible implications of these findings for the alkaloid profiles and endophyte ecology are discussed.

  2. Currencies of Mutualisms: Sources of Alkaloid Genes in Vertically Transmitted Epichloae

    Science.gov (United States)

    Schardl, Christopher L.; Young, Carolyn A.; Pan, Juan; Florea, Simona; Takach, Johanna E.; Panaccione, Daniel G.; Farman, Mark L.; Webb, Jennifer S.; Jaromczyk, Jolanta; Charlton, Nikki D.; Nagabhyru, Padmaja; Chen, Li; Shi, Chong; Leuchtmann, Adrian

    2013-01-01

    The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of potential herbivores. These protective metabolites include ergot alkaloids and indole-diterpenes (tremorgens), which are active in vertebrate systems, and lolines and peramine, which are more specific against invertebrates. Several Epichloë species have been described which are sexual and capable of horizontal transmission, and most are vertically transmissible also. Asexual epichloae are mainly or exclusively vertically transmitted, and many are interspecific hybrids with genomic contributions from two or three ancestral Epichloë species. Here we employ genome-scale analyses to investigate the origins of biosynthesis gene clusters for ergot alkaloids (EAS), indole-diterpenes (IDT), and lolines (LOL) in 12 hybrid species. In each hybrid, the alkaloid-gene and housekeeping-gene relationships were congruent. Interestingly, hybrids frequently had alkaloid clusters that were rare in their sexual ancestors. Also, in those hybrids that had multiple EAS, IDT or LOL clusters, one cluster lacked some genes, usually for late pathway steps. Possible implications of these findings for the alkaloid profiles and endophyte ecology are discussed. PMID:23744053

  3. In planta functions of cytochrome P450 monooxygenase genes in the phytocassane biosynthetic gene cluster on rice chromosome 2.

    Science.gov (United States)

    Ye, Zhongfeng; Yamazaki, Kohei; Minoda, Hiromi; Miyamoto, Koji; Miyazaki, Sho; Kawaide, Hiroshi; Yajima, Arata; Nojiri, Hideaki; Yamane, Hisakazu; Okada, Kazunori

    2018-06-01

    In response to environmental stressors such as blast fungal infections, rice produces phytoalexins, an antimicrobial diterpenoid compound. Together with momilactones, phytocassanes are among the major diterpenoid phytoalexins. The biosynthetic genes of diterpenoid phytoalexin are organized on the chromosome in functional gene clusters, comprising diterpene cyclase, dehydrogenase, and cytochrome P450 monooxygenase genes. Their functions have been studied extensively using in vitro enzyme assay systems. Specifically, P450 genes (CYP71Z6, Z7; CYP76M5, M6, M7, M8) on rice chromosome 2 have multifunctional activities associated with ent-copalyl diphosphate-related diterpene hydrocarbons, but the in planta contribution of these genes to diterpenoid phytoalexin production remains unknown. Here, we characterized cyp71z7 T-DNA mutant and CYP76M7/M8 RNAi lines to find that potential phytoalexin intermediates accumulated in these P450-suppressed rice plants. The results suggested that in planta, CYP71Z7 is responsible for C2-hydroxylation of phytocassanes and that CYP76M7/M8 is involved in C11α-hydroxylation of 3-hydroxy-cassadiene. Based on these results, we proposed potential routes of phytocassane biosynthesis in planta.

  4. Currencies of mutualisms: sources of alkaloid genes in vertically transmitted epichloae.

    Science.gov (United States)

    Schardl, Christopher L; Young, Carolyn A; Pan, Juan; Florea, Simona; Takach, Johanna E; Panaccione, Daniel G; Farman, Mark L; Webb, Jennifer S; Jaromczyk, Jolanta; Charlton, Nikki D; Nagabhyru, Padmaja; Chen, Li; Shi, Chong; Leuchtmann, Adrian

    2013-06-06

    The epichloae (Epichloë and Neotyphodium species), a monophyletic group of fungi in the family Clavicipitaceae, are systemic symbionts of cool-season grasses (Poaceae subfamily Poöideae). Most epichloae are vertically transmitted in seeds (endophytes), and most produce alkaloids that attack nervous systems of potential herbivores. These protective metabolites include ergot alkaloids and indole-diterpenes (tremorgens), which are active in vertebrate systems, and lolines and peramine, which are more specific against invertebrates. Several Epichloë species have been described which are sexual and capable of horizontal transmission, and most are vertically transmissible also. Asexual epichloae are mainly or exclusively vertically transmitted, and many are interspecific hybrids with genomic contributions from two or three ancestral Epichloë species. Here we employ genome-scale analyses to investigate the origins of biosynthesis gene clusters for ergot alkaloids (EAS), indole-diterpenes (IDT), and lolines (LOL) in 12 hybrid species. In each hybrid, the alkaloid-gene and housekeeping-gene relationships were congruent. Interestingly, hybrids frequently had alkaloid clusters that were rare in their sexual ancestors. Also, in those hybrids that had multiple EAS, IDT or LOL clusters, one cluster lacked some genes, usually for late pathway steps. Possible implications of these findings for the alkaloid profiles and endophyte ecology are discussed.

  5. Effect of sous vide processing on physicochemical, ultrastructural, microbial and sensory changes in vacuum packaged chicken sausages.

    Science.gov (United States)

    Naveena, B M; Khansole, Panjab S; Shashi Kumar, M; Krishnaiah, N; Kulkarni, Vinayak V; Deepak, S J

    2017-01-01

    The processing of sous vide chicken sausages was optimized under vacuum packaging condition and cooking at 100 ℃ for 30 min (SV30), 60 min (SV60) and 120 min (SV120) and compared with aerobically cooked control at 100 ℃ for 30 min. Sous vide processing of chicken sausages (SV30) produced higher (p emulsion ultra-structure due to SV30 processing relative to control sausages. Sous vide processing of chicken sausages enriched with rosemary diterpene phenols retained the freshness and quality up to 120 days during storage at 4 ± 1 ℃ relative to control sausages that were spoiled on 20th day. Lipid oxidation and microbial growth remained below the spoilage levels for all the SV-processed sausages throughout the storage and addition of rosemary diterpene mixture at 0.02% v/w reduced the microbial growth and improved (p < 0.05) the sensory attributes. Our results demonstrate that sous vide processing minimizes lipid oxidation and microbial growth of chicken sausages with improved product quality and shelf-life at 4 ± 1 ℃. © The Author(s) 2016.

  6. Bioactive Natural Products from Two Sudanese Medicinal Plants Diospyros mespiliformis and Croton zambesicus

    Directory of Open Access Journals (Sweden)

    Ietidal E. Mohamed

    2009-10-01

    Full Text Available Phytochemical investigations were performed in two plant species used in Sudanese traditional medicines to treat different illnesses, Diospyros mespiliformis and Croton zambesicus. The investigations revealed compounds of triterpenes (lupane series, one trihydroxyflavone and one diterpene. The compounds have been isolated and identified using various chromatographic and spectroscopic techniques. These were lupeol (1, betulinic acid (2, betulin (3 and lupenone (4 from Diospyros mespiliformis. Compounds 1, 2, 3 in addition to diterpene ent -kaurane-3β, 16β, 17-triol (5 and vitexin (6 were re-isolated from Croton zambesicus. However,compound 5 and 6 were isolated for the first time from this source.The pure isolated compounds and semi-synthesized acetates 1Ac, 2Ac and 3Ac, which were prepared from compounds 1, 2 and 3 respectively, were subjected to two bioassays: α- glucosidase enzyme inhibition assay and antioxidant activity. Compounds, 1, 1Ac, 3 and 4 showed a marked α-glucosidase inhibitory potential, while compound 6 exhibited strong antioxidant activity.

  7. Synthesis, Antiproliferative and Antifungal Activities of 1,2,3-Triazole-Substituted Carnosic Acid and Carnosol Derivatives

    Directory of Open Access Journals (Sweden)

    Mariano Walter Pertino

    2015-05-01

    Full Text Available Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1–3 were the most active antiproliferative compounds of the series, with IC50 values in the range of 43.4–46.9 μM and 39.2–48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL−1. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition at 250 µg∙mL−1 In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL−1.

  8. Identification of two aflatrem biosynthesis gene loci in Aspergillus flavus and metabolic engineering of Penicillium paxilli to elucidate their function.

    Science.gov (United States)

    Nicholson, Matthew J; Koulman, Albert; Monahan, Brendon J; Pritchard, Beth L; Payne, Gary A; Scott, Barry

    2009-12-01

    Aflatrem is a potent tremorgenic toxin produced by the soil fungus Aspergillus flavus, and a member of a structurally diverse group of fungal secondary metabolites known as indole-diterpenes. Gene clusters for indole-diterpene biosynthesis have recently been described in several species of filamentous fungi. A search of Aspergillus complete genome sequence data identified putative aflatrem gene clusters in the genomes of A. flavus and Aspergillus oryzae. In both species the genes for aflatrem biosynthesis cluster at two discrete loci; the first, ATM1, is telomere proximal on chromosome 5 and contains a cluster of three genes, atmG, atmC, and atmM, and the second, ATM2, is telomere distal on chromosome 7 and contains five genes, atmD, atmQ, atmB, atmA, and atmP. Reverse transcriptase PCR in A. flavus demonstrated that aflatrem biosynthesis transcript levels increased with the onset of aflatrem production. Transfer of atmP and atmQ into Penicillium paxilli paxP and paxQ deletion mutants, known to accumulate paxilline intermediates paspaline and 13-desoxypaxilline, respectively, showed that AtmP is a functional homolog of PaxP and that AtmQ utilizes 13-desoxypaxilline as a substrate to synthesize aflatrem pathway-specific intermediates, paspalicine and paspalinine. We propose a scheme for aflatrem biosynthesis in A. flavus based on these reconstitution experiments in P. paxilli and identification of putative intermediates in wild-type cultures of A. flavus.

  9. Isolation and evaluation of antiglycation potential of polyalthic acid (furano-terpene from Daniella oliveri

    Directory of Open Access Journals (Sweden)

    Olubunmi Atolani

    2014-12-01

    Full Text Available A furano-diterpene (polyalthic acid was isolated as a major stable compound for the first time from the oleoresin of the Daniella oliveri of the family Caesalpiniacea through column chromatography fractionation. Polyalthic acid was characterized using data obtained from EIMS, HREIMS, ESI-MS, MALDI-MS as well as 1D and 2D NMR and it was evaluated for its potential to inhibit the formation of advanced glycation end-products (AGEs using a standard in vitro antiglycation procedure. Polyalthic acid indicated a negative antiglycation potential compared to standard inhibitor that has 85% inhibition, which is an indication that polyalthic acid may not contribute to the antiglycation activity of the plant as acclaimed in folkloric medicine. The negative antiglycation observed could indicate that the polyalthic acid could trigger glycation, thereby subjecting users to various degrees of complications. The bioactivity evaluation on molinspiration evaluator indicated that polyalthic acid could be a potential drug candidate. The biological and chemical insights gained on polyalthic acid provide a good basis for future research. Keywords: Daniella oliveria, Polyalthic acid, Furano-diterpene, Antiglycation, Matrix assisted laser desorption/ionization (MALDI

  10. Antiproliferative Activity of Flavonoids from Croton sphaerogynus Baill. (Euphorbiaceae

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    Kátia Pereira dos Santos

    2015-01-01

    Full Text Available Croton sphaerogynus is a shrub from the Atlantic Rain Forest in southeastern Brazil. A lyophilized crude EtOH extract from leaves of C. sphaerogynus, obtained by maceration at room temperature (seven days, was suspended in methanol and partitioned with hexane. The purified MeOH phase was fractionated over Sephadex LH-20 yielding five fractions (F1–F5 containing flavonoids, as characterized by HPLC-DAD and HPLC-MS analyses. The antiproliferative activity of the crude EtOH extract, MeOH and hexane phases, and fractions F1–F5 was evaluated on in vitro cell lines NCI-H460 (nonsmall cell lung, MCF-7 (breast cancer, and U251 (glioma. The MeOH phase showed activity (mean log GI50 0.54 higher than the hexane phase and EtOH extract (mean log GI50 1.13 and 1.19, resp.. F1 exhibited activity against NCI-H460 (nonsmall cell lung (GI50 1.2 μg/mL, which could be accounted for the presence of flavonoids and/or diterpenes. F4 showed moderate activity (mean log GI50 1.05, while F5 showed weak activity (mean log GI50 1.36. It is suggested that the antiproliferative activity of the crude EtOH extract and MeOH phase is accounted for a synergistic combination of flavonoids and diterpenes.

  11. Environmentally Friendly Procedure Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking for the Discovery of Potent Antiviral Compounds from Euphorbia semiperfoliata.

    Science.gov (United States)

    Nothias, Louis-Félix; Boutet-Mercey, Stéphanie; Cachet, Xavier; De La Torre, Erick; Laboureur, Laurent; Gallard, Jean-François; Retailleau, Pascal; Brunelle, Alain; Dorrestein, Pieter C; Costa, Jean; Bedoya, Luis M; Roussi, Fanny; Leyssen, Pieter; Alcami, José; Paolini, Julien; Litaudon, Marc; Touboul, David

    2017-10-27

    A supercritical fluid chromatography-based targeted purification procedure using tandem mass spectrometry and molecular networking was developed to analyze, annotate, and isolate secondary metabolites from complex plant extract mixture. This approach was applied for the targeted isolation of new antiviral diterpene esters from Euphorbia semiperfoliata whole plant extract. The analysis of bioactive fractions revealed that unknown diterpene esters, including jatrophane esters and phorbol esters, were present in the samples. The purification procedure using semipreparative supercritical fluid chromatography led to the isolation and identification of two new jatrophane esters (13 and 14) and one known (15) and three new 4-deoxyphorbol esters (16-18). The structure and absolute configuration of compound 16 were confirmed by X-ray crystallography. This compound was found to display antiviral activity against Chikungunya virus (EC 50 = 0.45 μM), while compound 15 proved to be a potent and selective inhibitor of HIV-1 replication in a recombinant virus assay (EC 50 = 13 nM). This study showed that a supercritical fluid chromatography-based protocol and molecular networking can facilitate and accelerate the discovery of bioactive small molecules by targeting molecules of interest, while minimizing the use of toxic solvents.

  12. Temporal effects of prescribed burning on terpene production in Mediterranean pines.

    Science.gov (United States)

    Valor, Teresa; Ormeño, Elena; Casals, Pere

    2017-12-01

    Prescribed burning is used to reduce fuel hazard but underburning can damage standing trees. The effect of burning on needle terpene storage, a proxy for secondary metabolism, in fire-damaged pines is poorly understood despite the protection terpenes confer against biotic and abiotic stressors. We investigated variation in needle terpene storage after burning in three Mediterranean pine species featuring different adaptations to fire regimes. In two pure-stands of Pinus halepensis Mill. and two mixed-stands of Pinus sylvestris L. and Pinus nigra ssp. salzmanni (Dunal) Franco, we compared 24 h and 1 year post-burning concentrations with pre-burning concentrations in 20 trees per species, and evaluated the relative contribution of tree fire severity and physiological condition (δ13C and N concentration) on temporal terpene dynamics (for mono- sesqui- and diterpenes). Twenty-four hours post-burning, monoterpene concentrations were slightly higher in P. halepensis than at pre-burning, while values were similar in P. sylvestris. Differently, in the more fire-resistant P. nigra monoterpene concentrations were lower at 24 h, compared with pre-burning. One year post-burning, concentrations were always lower compared with pre- or 24 h post-burning, regardless of the terpene group. Mono- and sesquiterpene variations were negatively related to pre-burning δ13C, while diterpene variations were associated with fire-induced changes in needle δ13C and N concentration. At both post-burning times, mono- and diterpene concentrations increased significantly with crown scorch volume in all species. Differences in post-burning terpene contents as a function of the pine species' sensitivity to fire suggest that terpenic metabolites could have adaptive importance in fire-prone ecosystems in terms of flammability or defence against biotic agents post-burning. One year post-burning, our results suggest that in a context of fire-induced resource availability, pines likely prioritize

  13. Isogermacrene A, a proposed intermediate in sesquiterpene biosynthesis.

    Science.gov (United States)

    Hackl, Thomas; König, Wilfried A; Muhle, Hermann

    2004-08-01

    In the essential oil of the liverwort Saccogyna viticulosa, collected on the island of Madeira, the new sesquiterpene hydrocarbons isogermacrene A (5) and its Cope rearrangement product iso-beta-elemene (6) were identified. 5 is proposed to act as the biogenetic precursor of several new sesquiterpenes identified in the volatiles of S. viticulosa. These include iso-alpha-humulene, alpha-gorgonene, gorgona-1,4(15), 11-triene and gorgon- 11-en-4-ol. In addition, the Cope product of zierene, isozierene, allo-aromadendra-4(15),10(14)-diene, aromadendra-4(15),10(14)-dien-1-ol and a prenylguaiane diterpene alcohol, named viticulol, were identified as new natural products.

  14. Terpenes and fatty acids from Dipteryx lacunifera Ducke; Terpenos e acidos graxos de Dipteryx lacunifera Ducke

    Energy Technology Data Exchange (ETDEWEB)

    Vieira Junior, Gerardo Magela; Silva, Hilris Rocha e; Bittencourt, Thais Chaves; Chaves, Mariana H. [Universidade Federal do Piaui (UFPI), Teresina (Brazil). Dept. de Quimica]. E-mail: mariana@ufpi.br; Simone, Carlos Alberto de [Universidade Federal do Alagoas (UFAL), Maceio, AL (Brazil). Inst. de Quimica e Biotecnologia

    2007-07-01

    This paper describes the isolation of the furanocassane-type diterpene, named vinhaticoic acid, along with b-farnesene and spatulenol from fruit shells of D. lacunifera. Structural determinations were accomplished by chemical derivatization and spectral analysis, including 1D and 2D NMR and X-ray crystallography. The fatty portion was extracted from the fruit kernels, transesterfied and analysed by HRGC/MS. Oleic acid (75.8 +- 4.3%) was the major component. Essential oil extracted from the fruit shells of D. lacunifera was analysed by HRGC/MS and nine sesquiterpenes were identified; beta-farnesene (48.6%) and spatulenol (21.61%) were the major constituents. (author)

  15. Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases

    Science.gov (United States)

    Itoh, Takayuki; Tokunaga, Kinya; Matsuda, Yudai; Fujii, Isao; Abe, Ikuro; Ebizuka, Yutaka; Kushiro, Tetsuo

    2010-10-01

    Meroterpenoids are hybrid natural products of both terpenoid and polyketide origin. We identified a biosynthetic gene cluster that is responsible for the production of the meroterpenoid pyripyropene in the fungus Aspergillus fumigatus through reconstituted biosynthesis of up to five steps in a heterologous fungal expression system. The cluster revealed a previously unknown terpene cyclase with an unusual sequence and protein primary structure. The wide occurrence of this sequence in other meroterpenoid and indole-diterpene biosynthetic gene clusters indicates the involvement of these enzymes in the biosynthesis of various terpenoid-bearing metabolites produced by fungi and bacteria. In addition, a novel polyketide synthase that incorporated nicotinyl-CoA as the starter unit and a prenyltransferase, similar to that in ubiquinone biosynthesis, was found to be involved in the pyripyropene biosynthesis. The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities.

  16. Possibilities and limitations of sup 1 H and sup 13 C nuclear magnetic resonance spectroscopy for the identification and the quantitative determination of some naturally occurring carcinogenic risk factors. [Senecio vulgaris; Senecio vernalis; Senecio jacobaea; Euphorbia ingens

    Energy Technology Data Exchange (ETDEWEB)

    Pieters, L.

    1988-01-01

    The aim of this work was to develop a phytochemical screening method for some selected carcinogenic or tumor-promoting principles in higher plants. The pyrrolizidine alkaloids from some Senecio species (Compositae or Asteraceae), and the diterpene ester from Croton tiglium L. and Euphorbia ingens E. Mey (Euphorbiaceae) were chosen as representatives of both groups. The possibilities and limitations of {sup 1}H and {sup 13}C nuclear magnetic resonance spectroscopy ({sup 1}H and {sup 13}C NMR) for the analysis of mixtures of carcinogenic pyrrolizidine alkaloids were compared with high performance liquid chromatography, and gas chromatography with high performance liquid chromatography, and gas chromatography was well as gas chromatography - mass spectrometry. Senecio vulgaris L., Senecio vernalis Waldst. and Kit. and Senecio jacobaea L. were investigated.

  17. A Dereplication and Bioguided Discovery Approach to Reveal New Compounds from a Marine-Derived Fungus Stilbella fimetaria

    DEFF Research Database (Denmark)

    Kildgaard, Sara; Subko, Karolina; Phillips, Emma

    2017-01-01

    towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues......A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection...... aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity...

  18. Therapeutic Potential of Andrographolide Isolated from the Leaves of Andrographis paniculata Nees for Treating Lung Adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Yu-Tang Tung

    2013-01-01

    Full Text Available Andrographolide is one of the major diterpene lactones found in Andrographis paniculata Nees and exhibits remarkable inhibitory effects on various cancers. In this study, the antipulmonary cancer effects of andrographolide were studied in a lung tumor mouse model induced by human vascular endothelial growth factor A165 (hVEGF-A165. These results demonstrated that andrographolide significantly reduced the expression of hVEGF-A165 compared with a mock group in the Clara cells of the lungs. In addition, andrographolide also decreased tumor formation by reducing VEGF, EGFR, Cyclin A, and Cyclin B expression on the transcriptional and translational levels. These results indicated that andrographolide treatment on the overexpression of VEGF can arrest the cell cycle, which induced pulmonary tumors in transgenic mice. In conclusion, the antiangiogenesis and chemotherapeutic potential of andrographolide may provide a cure for pulmonary tumors in the future.

  19. Essential oils of Pinus nigra J.F. Arnold subsp. laricio Maire: Chemical composition and study of their herbicidal potential

    Directory of Open Access Journals (Sweden)

    Ismail Amri

    2017-05-01

    Full Text Available The chemical composition of essential oils isolated by hydrodistillation from the needles of Tunisian Pinus nigra L. subsp. laricio was analyzed by GC and GC/MS. 27 compounds were identified, representing 97.9% of total oil, which was found to be rich in oxygenated diterpenes (38.5% particularly manool oxide (38% and sesquiterpene hydrocarbons (41.4% that included germacrene D (16.7%, δ-cadinene (9% and (E-caryophyllene (8.9%. Results of the herbicidal effects of the oil when tested on Phalaris canariensis L., Trifolium campestre Schreb. and Sinapis arvensis L., indicated that the oil completely inhibited germination and seedling growth at a high concentration (5 μL/mL−1, while at low doses the oil acted by decreasing germination and partially inhibiting seedling growth of all tested weeds.

  20. Molecular Interactions at Membranes

    DEFF Research Database (Denmark)

    Jagalski, Vivien

    . Today, we know more than ever before about the properties of biological membranes. Advanced biophysical techniques and sophisticated membrane models allow us to answer specific questions about the structure of the components within membranes and their interactions. However, many detailed structural...... the surface-immobilization of LeuT by exchanging the detergent with natural phosphatidylcholine (PC) lipids. Various surface sensitive techniques, including neutron reflectometry (NR), are employed and finally enabled us to confirm the gross structure of LeuT in a lipid environment as predicted by molecular...... dynamic simulations. In a second study, the co-localization of three toxic plant-derived diterpene resin acids (RAs) within DPPC membranes was investigated. These compounds are reported to disrupt the membrane and increase its fluidity. The RAs used in this study vary in their toxicity while...

  1. Greek Salvia sclarea L. Essential Oils: Effect of Hydrodistillation Time, Comparison of the Aroma Chemicals Using Hydrodistillation and HS-SPME Techniques

    Directory of Open Access Journals (Sweden)

    Aikaterini Koutsaviti

    2016-05-01

    Full Text Available Since the essential oil of Salvia sclarea is used as a flavouring agent, the effect of different extraction techniques (hydrodistillation & HS-SPME and duration of hydrodistillation (2, 3 and 4 h with respect to yield, composition and identification rate of extracted essential oils from Greek cultivated S. sclarea aerial blooming parts were investigated. Linalool and linalyl acetate levels seemed to decrease with increasing duration of hydrodistillation, while diterpenes increased dramatically, while the head space analysis showed significantly lower levels of linalool in comparison to its ester. Thus, linalool (5.1-35.8%, linalyl acetate (11.3-37.6% and sclareol (0.0-41.8%, concerning the oils obtained by hydrodistillation, were the most important metabolites. Solid-phase microextraction yielded mainly oxygenated monoterpenes, especially linalyl acetate (59.3%, followed by cis-linalool oxide (8.6% and linalool (7.8%.

  2. Antifungal isopimaranes from Hypoestes serpens.

    Science.gov (United States)

    Rasoamiaranjanahary, L; Guilet, D; Marston, A; Randimbivololona, F; Hostettmann, K

    2003-09-01

    Five isopimarane diterpenes (7beta-hydroxyisopimara-8,15-dien-14-one, 14alpha-hydroxyisopimara-7,15-dien-1-one, 1beta,14alpha-dihydroxyisopimara-7,15-diene, 7beta-hydroxyisopimara-8(14),15-dien-1-one and 7beta-acetoxyisopimara-8(14),15-dien-1-one) have been isolated from the leaves of Hypoestes serpens (Acanthaceae). All compounds exhibited antifungal activity against both the plant pathogenic fungus Cladosporium cucumerinum and the yeast Candida albicans; two of them also displayed an acetylcholinesterase inhibition. The structures of the compounds were determined by means of spectrometric methods, including 1D and 2D NMR experiments and MS analysis.

  3. 2012 David W. Robertson Award for Excellence in Medicinal Chemistry: Neoclerodanes as Atypical Opioid Receptor Ligands⊥

    Science.gov (United States)

    Prisinzano, Thomas E.

    2013-01-01

    The neoclerodane diterpene salvinorin A is the major active component of the hallucinogenic mint plant Salvia divinorum Epling & Játiva (Lamiaceae). Since the finding that salvinorin A exerts its potent psychotropic actions through the activation of opioid receptors, the site of action of morphine and related analogues, there has been much interest in elucidating the underlying mechanisms behind its effects. These effects are particularly remarkable, because (1) salvinorin A is the first reported non-nitrogenous opioid receptor agonist, and (2) its effects are not mediated through the previously investigated targets of psychotomimetics. This perspective outlines our research program, illustrating a new direction to the development of tools to further elucidate the biological mechanisms of drug tolerance and dependence. The information gained from these efforts is expected to facilitate the design of novel agents to treat pain, drug abuse, and other CNS disorders. PMID:23548164

  4. Comparison between several techniques of olive tree bark extraction (Tunisian Chemlali variety).

    Science.gov (United States)

    Issaoui, Aimen; Ksibi, Hatem; Ksibi, Mohamed

    2017-01-01

    In order to better understand the chemical composition of the olive tree bark of Tunisian chemlali variety (Olea europaea cv. 'Chemlali'), this material was extracted by different ways. Compositions of extracts were used at best-selected conditions for each technique, and characterised using HPLC, LC/MS and GC-MS techniques. Analyses are conducted to an important variety of high carbon number compounds such as aliphatic compounds as nanocosane and heptacosane, and molecules with high value added tax (VAT) which can be classified as follows: diterpenes as phytol, triterpenes as squalene and also esters as Benzyl cinnamate. Hydrodistillation at high pressure seems to be a very common method to get a wide variety of compounds, the results are better than the ones obtained using supercritical fluid extraction and solvent extraction.

  5. STEVIOSIDE SYNTHESIS IN STEVIA (Stevia rebaudiana Bert

    Directory of Open Access Journals (Sweden)

    Alfredo Jarma Orozco

    2010-01-01

    Full Text Available Stevia rebaudiana Bert. is a subtropical wild plant of Paraguay, that possesses a potent sweetener up to 300 times higher than sucrose and has no calories. The molecules responsible for these characteristics are diterpen glycosides, found in leaves and synthesized at least, at initial states, which use the same pathway of the gibberellic acid in which the shiquimic acid gives origin to many aromatic compounds. The acetate is the precursor of the terpens or isoprenoids through the acetate-mevalonate pathway, where steviosides are found. Although in this article, an alternative route is discussed. This updating pretends to contribute tools for the understanding of the main pathways of steviol glycosides synthesis.

  6. Antifouling Metabolites from the Mangrove Plant Ceriops tagal

    Directory of Open Access Journals (Sweden)

    Yi Ming Lin

    2008-01-01

    Full Text Available The new diterpene methoxy-ent-8(14-pimarenely-15-one (1 and three knownmetabolites: ent-8(14-pimarene-15R,16-diol (2, stigmasterol (3 and β-sitosterol (4, wereisolated from the roots of the mangrove plant Ceriops tagal. Their structures and relativestereochemistry were elucidated by means of extensive NMR, IR and MS analysis.Compounds 1, 2, 3 and 4 exhibited significant antifouling activities against cyprid larvaeof the barnacle Balanus albicostatus Pilsbry, with EC50 values of 0.32 ± 0.01, 0.04 ± 0.00,4.05 ± 0.15 and 18.47 ± 0.40 μg/cm2, respectively, whereas their toxicities towards cypridswere very low, with LC50 values all above 10 μg/cm2.

  7. Terpenos e ácidos graxos de Dipteryx lacunifera Ducke Terpenes and fatty acids from Dipteryx lacunifera Ducke

    Directory of Open Access Journals (Sweden)

    Gerardo Magela Vieira Júnior

    2007-01-01

    Full Text Available This paper describes the isolation of the furanocassane-type diterpene, named vinhaticoic acid, along with beta-farnesene and spatulenol from fruit shells of D. lacunifera. Structural determinations were accomplished by chemical derivatization and spectral analysis, including 1D and 2D NMR and X-ray crystallography. The fatty portion was extracted from the fruit kernels, transesterfied and analysed by HRGC/MS. Oleic acid (75.8 ± 4.3% was the major component. Essential oil extracted from the fruit shells of D. lacunifera was analysed by HRGC/MS and nine sesquiterpenes were identified; beta-farnesene (48.6% and spatulenol (21.61% were the major constituents.

  8. [Vitex Agnus Castus in the treatment of hyperprolactinemia and menstrual disorders - a case report].

    Science.gov (United States)

    Męczekalski, Błażej; Czyżyk, Adam

    2015-07-01

    We describe a patient with mild hyperprolactinemia and menstrual disorders (oligomenorrhea). She presented relative hypoestrogenism in laboratory tests. Magnetic resonans excluded the presence of pituitary adenoma. Because patient developed a bromocriptine intolerance, the Vitex Agnus Castus (VAC) extract has been introduced. The VAC therapy was effective, with symptoms relief and improvement of hormonal tests. The VAC medicines are indicated for the treatment of premenstrual syndrome (PMS), mastalgia, menstrual disorders and mild hyperprolactinemia. The mechanism of action is not fully understood, but it is related to dopaniergic activity of diterpenes and castacin in VAC. The randomized clinical trials revealed efficacy of VAC extract in the treatmet of hyperprolactinemia, menstrual disorders, PMS and mastalgia. Good tolerability, lack of serious side-effects and drug interactions are the advantages of the VAC preparations. © 2015 MEDPRESS.

  9. Polyphenols from the Mediterranean herb rosemary (Rosmarinus officinalis for prostate cancer

    Directory of Open Access Journals (Sweden)

    Sakina M Petiwala

    2013-03-01

    Full Text Available The Mediterranean diet is rich in fruits and vegetables and has been associated with a variety of health benefits including cancer prevention. One aspect of the diet that has not received enough attention is Mediterranean herbs. Specifically, rosemary and its polyphenolic diterpenes (carnosic acid and carnosol are known to possess antioxidant activity that may be beneficial for cancer control. Herein, we describe the in vitro and in vivo studies carried out towards understanding the molecular mechanisms of carnosic acid and carnosol leading to inhibition of prostate cancer. The reported findings suggest that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Further work is required to understand its potential for health promotion and potential drug discovery for prostate cancer chemoprevention.

  10. Terpenoids, flavonoids and other constituents of Eupatorium betonicaeforme (Asteraceae)

    Energy Technology Data Exchange (ETDEWEB)

    Albuquerque, Maria Rose Jane R.; Pires, Andreza Maria L.; Pessoa, Otilia Deusdenia L.; Silveira, Edilberto R. [Ceara Univ., Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica. Curso de Pos-Graduacao em Quimica Organica]. E-mail: opessoa@ufc.br

    2006-01-15

    A new acylated kaurene diterpene, characterized as 15{alpha}-decanoyloxy-kaur-16-en-19-oic acid, along with nine known compounds: pentacosanoic acid, 24{alpha}-ethyl-5{alpha}-cholesta-7,22E-dien-3{beta}-ol, 15{alpha}-hydroxy-kaur-16-en-19-oic acid, 8{beta}-angeloyloxy-9{beta},10{beta}-dihydroxy-1-oxogermacra-4E,11(13)dien-12,6{alpha}-olide, 3{beta}-hydroxyeicosan-1,5{beta}-olide, taraxasteryl acetate, 7-Omethylkaempferol, kaempferol, and nepetin were isolated from the flowers of Eupatorium betonicaeforme (Asteraceae). In addition, from the aerial parts were isolated taraxasteryl acetate and {alpha}- and {beta}-amyrin, while the mixture of {beta}-sitosterol and stigmasterol, and 6-acetyl-2,2-dimethylchroman-4-one were isolated from the roots. The structure elucidation of all compounds was performed by spectroscopic analysis and comparison with published data from literature. (author)

  11. Terpenoids, flavonoids and other constituents of Eupatorium betonicaeforme (Asteraceae)

    International Nuclear Information System (INIS)

    Albuquerque, Maria Rose Jane R.; Pires, Andreza Maria L.; Pessoa, Otilia Deusdenia L.; Silveira, Edilberto R.

    2006-01-01

    A new acylated kaurene diterpene, characterized as 15α-decanoyloxy-kaur-16-en-19-oic acid, along with nine known compounds: pentacosanoic acid, 24α-ethyl-5α-cholesta-7,22E-dien-3β-ol, 15α-hydroxy-kaur-16-en-19-oic acid, 8β-angeloyloxy-9β,10β-dihydroxy-1-oxogermacra-4E,11(13)dien-12,6α-olide, 3β-hydroxyeicosan-1,5β-olide, taraxasteryl acetate, 7-Omethylkaempferol, kaempferol, and nepetin were isolated from the flowers of Eupatorium betonicaeforme (Asteraceae). In addition, from the aerial parts were isolated taraxasteryl acetate and α- and β-amyrin, while the mixture of β-sitosterol and stigmasterol, and 6-acetyl-2,2-dimethylchroman-4-one were isolated from the roots. The structure elucidation of all compounds was performed by spectroscopic analysis and comparison with published data from literature. (author)

  12. Partial chemical composition and antimicrobial activity of Daucus crinitus Desf. extracts

    Energy Technology Data Exchange (ETDEWEB)

    Dib, M. A.; Bendahou, M.; Bendiabdellah, A.; Djabou, N.; Allali, H.; Tabti, B.; Paolini, J.; Costa, J.

    2010-07-01

    The chemical composition of fatty acids and the unsaponifiable fraction of the roots, leaves and stems from Daucus crinitus Desf. were, determined using gas chromatography (GC) and gas chromatography-Mass Spectrometry (GC-MS). The fatty acid fractions of different organs (leaves, stems and roots) were characterized by lauric acid (17.9, 17.5 and 18.1 % respectively) and other long chain fatty acids (until C22). Qualitative and quantitative differences were reported between the unsaponifiable fractions of different organs from D. crinitus. The unsaponifiable fractions of the leaves, roots and stem showed high amounts of aliphatic components (83.4%, 87.2% and 91.4%, respectively). The monoterpen, diterpen and sesquiterpen components were only present in small percentages. The antimicrobial properties of the D. critinus extracts were tested on four different microorganisms. These extracts were found to be active against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Candida albicans. (Author) 35 refs.

  13. Improved Properties and Microbiological Safety of Novel Cottage Cheese Containing Spices

    Directory of Open Access Journals (Sweden)

    Zvonimira Medverec Knežević

    2015-01-01

    Full Text Available The study focuses on developing novel cott age cheese containing spices with acceptable sensory properties, increased biological value and extended shelf life. Thirty types of cheese with added fresh or dried parsley, dill, pepper, garlic and rosemary were produced. Characterisation of phenolic compounds, antioxidant capacity and antibacterial activity of spices and cheese samples were evaluated. The cheese containing fresh pepper and fresh and dried herbs showed excellent sensory properties, with the best results obtained with fresh sweet red pepper. Dry rosemary had the highest antioxidant and antibacterial activity due to high mass fractions of caffeic and rosmarinic acids as well as high mass fractions of flavones and phenolic diterpenes. The plant extracts examined in vitro and in situ effectively reduce numbers of foodborne pathogens like Salmonella typhimurium, Escherichia coli, Staphylococcus aureus and Listeria monocytogenes, and therefore have potential as natural preservatives and antioxidants.

  14. Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis.

    Science.gov (United States)

    Hayashi, T; Kawasaki, M; Okamura, K; Tamada, Y; Morita, N; Tezuka, Y; Kikuchi, T; Miwa, Y; Taga, T

    1992-12-01

    The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta-glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor.

  15. Halogenated Terpenes and a C15-Acetogenin from the Marine Red Alga Laurencia saitoi

    Directory of Open Access Journals (Sweden)

    Xiao-Ming Li

    2008-11-01

    Full Text Available Seven parguerane diterpenes: 15-bromo-2,7,19-triacetoxyparguer-9(11-en-16-ol (1, 15-bromo-2,7,16,19-tetraacetoxyparguer-9(11-ene (2, 15-bromo-2,19-diacetoxyparguer-9(11-en-7,16-diol (3, 15-bromo-2,16,19-triacetoxyparguer-9(11-en-7-ol (4, 15-bromo-2,16-diacetoxyparguer-9(11-en-7-ol (5, 15-bromoparguer-9(11-en-16-ol (6, 15-bromoparguer-7-en-16-ol (7, two polyether triterpenes: thyrsiferol (8 and thyrsiferyl 23-acetate (9, and one C15-acetogenin, neolaurallene (10, were isolated from a sample of marine red alga Laurencia saitoi collected off the coast of Yantai. Their structures were established by detailed NMR spectroscopic analysis and comparison with literature data.

  16. Microbial transformation of isosteviol and inhibitory effects on Epstein-Barr virus activation of the transformation products.

    Science.gov (United States)

    Akihisa, Toshihiro; Hamasaki, Yusuke; Tokuda, Harukuni; Ukiya, Motohiko; Kimura, Yumiko; Nishino, Hoyoku

    2004-03-01

    Microbial transformation of isosteviol (2), a beyerane-type diterpenoid obtained from stevioside (1) by acid hydrolysis, yielded 7beta-hydroxyisosteviol (3), 11beta-hydroxyisosteviol (5), and 12beta-hydroxyisosteviol (6) by the fungus Aspergillus niger, 17-hydroxyisosteviol (7) by the fungus Glomerella cingulata, and 3 and 7-oxoisosteviol (4) by the fungus Mortierella elongate. The five metabolites, 3-7, along with 1 and 2 were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the diterpenes tested showed potent inhibitory effects, with the five metabolites 3-7 exhibiting more potent effects.

  17. Isolation of Bioactive Compounds from Sunflower Leaves (Helianthus annuus L.) Extracted with Supercritical Carbon Dioxide.

    Science.gov (United States)

    El Marsni, Zouhir; Torres, Ascension; Varela, Rosa M; Molinillo, José M G; Casas, Lourdes; Mantell, Casimiro; Martinez de la Ossa, Enrique J; Macias, Francisco A

    2015-07-22

    The work described herein is a continuation of our initial studies on the supercritical fluid extraction (SFE) with CO2 of bioactive substances from Helianthus annuus L. var. Arianna. The selected SFE extract showed high activity in the wheat coleoptile bioassay, in Petri dish phytotoxicity bioassays, and in the hydroponic culture of tomato seeds. Chromatographic fractionations of the extracts and a spectroscopic analysis of the isolated compounds showed 52 substances belonging to 10 different chemical classes, which were mainly sesquiterpene lactones, diterpenes, and flavonoids. Heliannuol M (31), helivypolides K and L (36, 37), and helieudesmanolide B (38) are described for the first time in the literature. Metabolites have been tested in the etiolated wheat coleoptile bioassay with good results in a noteworthy effect on germination. The most active compounds were also tested on tomato seeds, heliannuol A (30) and leptocarpin (45) being the most active, with values similar to those of the commercial herbicide.

  18. Chirospecific analysis of plant volatiles

    International Nuclear Information System (INIS)

    Tkachev, A V

    2007-01-01

    Characteristic features of the analysis of plant volatiles by enantioselective gas (gas-liquid) chromatography and gas chromatography/mass spectrometry are discussed. The most recent advances in the design of enantioselective stationary phases are surveyed. Examples of the preparation of the most efficient phases based on modified cyclodextrins are given. Current knowledge on the successful analytical resolution of different types of plant volatiles (aliphatic and aromatic compounds and mono-, sesqui- and diterpene derivatives) into optical antipodes is systematically described. Chiral stationary phases used for these purposes, temperature conditions and enantiomer separation factors are summarised. Examples of the enantiomeric resolution of fragrance compounds and components of plant extracts, wines and essential oils are given.

  19. Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland.

    Science.gov (United States)

    Giroud, C; Felber, F; Augsburger, M; Horisberger, B; Rivier, L; Mangin, P

    2000-08-14

    Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana substitute. Recently, two S. divinorum specimens were seized in a large-scale illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin A, a trans-neoclerodane diterpene, was identified in several organic solvent extracts by gas chromatography-mass spectrometry. The botanical identity of the plant was confirmed by comparing it to an authentic herbarium specimen. More plants were then discovered in Swiss horticulturists greenhouses. All these data taken together suggest that many attempts exist in Switzerland to use S. divinorum as a recreational drug. This phenomenon may be enhanced because neither the magic mint, nor its active compound are banned substances listed in the Swiss narcotic law.

  20. Pharmacological activity of salvinorin A, the major component of Salvia divinorum.

    Science.gov (United States)

    Listos, Joanna; Merska, Alicja; Fidecka, Sylwia

    2011-01-01

    The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the Mazatecs. Today, S. divinorum has become increasingly popular as a recreational drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A, the major active component of S. divinorum, is responsible for the hallucinogenic effect of this plant. Here, we described the behavioral effects of salvinorin A in animals including the addictive, antinociception and antidepressant properties of the drug. The present paper also demonstrates the not well recognized (or unclear) mechanisms of action of salvinorin A. The last part of the paper presents information about the legal status of S. divinorum and its derivatives. Taking into account the increasing popularity and consumption of salvinorin A and S. divinorum today, it is important to collect all data on the pharmacological profile of this plant and its products.

  1. Chemical composition and evaluation of the antimicrobial activity of the essential oil from leaves of Eugenia platysema.

    Science.gov (United States)

    Tenfen, Adrielli; Siebert, Diogo Alexandre; Yamanaka, Celina Noriko; Mendes de Córdova, Caio Maurício; Scharf, Dilamara Riva; Simionatto, Edésio Luiz; Alberton, Michele Debiasi

    2016-09-01

    This study describes the qualitative and quantitative chemical composition and evaluates the antibacterial activity of essential oil from Eugenia platysema leaves. Analysis by GC-FID and GC-MS allowed the identification of 22 compounds. Different from the other species of the Eugenia genus, the major compound found in the essential oil was the diterpene phytol (66.05%), being this the first report of the presence of this compound in the essential oils from Eugenia genus. The sesquiterpene elixene was the second most concentrated compound in the studied essential oil (9.16%). The essential oil from E. platysema was tested for its antibacterial activity against cell-walled bacteria and mollicute strains of clinical interest using the microdilution broth assay. The results showed that the essential oil of E. platysema was inactive until 1000 μg mL(-1) against tested bacteria.

  2. Stereochemical Analysis of Leubethanol, an Anti-TB Active Serrulatane, from Leucophyllum frutescens

    Science.gov (United States)

    Molina-Salinas, Gloria M.; Rivas-Galindo, Verónica M.; Said-Fernández, Salvador; Lankin, David C.; Muñoz, Marcelo A.; Joseph-Nathan, Pedro; Pauli, Guido F.; Waksman, Noemí

    2013-01-01

    Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens (Berl.) I.M. Johnst. led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25–12.50 µg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, 1H-NMR full spin analysis, as well as by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers. PMID:21859082

  3. Diterpenoids from the Endophytic Fungus Botryosphaeria sp. P483 of the Chinese Herbal Medicine Huperzia serrata

    Directory of Open Access Journals (Sweden)

    Yan-Mei Chen

    2015-09-01

    Full Text Available Two new tetranorlabdane diterpenoids, named botryosphaerins G (1 and H (2, were isolated from the solid fermentation products of Botryosphaeria sp. P483 along with seven known tetranorlabdane diterpenes (3–9. Their structures were elucidated by extensive analysis, including 1D and 2D nuclear magnetic resonance (NMR spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS. Their absolute configuration was confirmed by single-crystal X-ray diffraction analyses using the anomalous scattering of Cu Kα radiation. All of the isolated compounds were tested for activity against phytopathogenic fungi and nematodes. Compounds 2 and 3 showed antifungal activity and compound 2 showed weak nematicidal activity.

  4. Antiplasmodial Natural Products

    Directory of Open Access Journals (Sweden)

    Cláudio R. Nogueira

    2011-03-01

    Full Text Available Malaria is a human infectious disease that is caused by four species of Plasmodium. It is responsible for more than 1 million deaths per year. Natural products contain a great variety of chemical structures and have been screened for antiplasmodial activity as potential sources of new antimalarial drugs. This review highlights studies on natural products with antimalarial and antiplasmodial activity reported in the literature from January 2009 to November 2010. A total of 360 antiplasmodial natural products comprised of terpenes, including iridoids, sesquiterpenes, diterpenes, terpenoid benzoquinones, steroids, quassinoids, limonoids, curcubitacins, and lanostanes; flavonoids; alkaloids; peptides; phenylalkanoids; xanthones; naphthopyrones; polyketides, including halenaquinones, peroxides, polyacetylenes, and resorcylic acids; depsidones; benzophenones; macrolides; and miscellaneous compounds, including halogenated compounds and chromenes are listed in this review.

  5. Chemical constituents from three medicinal plants: Piper renitens, Siparuna guianensis and Alternanthera brasiliana

    Directory of Open Access Journals (Sweden)

    Valdir A. Facundo

    2012-10-01

    Full Text Available Chemical study of three medicinal plants: from leaves of Piper renitens (Miq. Yunck, Piperaceae, and Siparuna guianensis Aubl., Siparunaceae, and from flowers of Alternanthera brasiliana (L. Kuntze, Amaranthaceae, resulted in isolation of nine compounds: three steroids, β-sitosterol, stigmasterol from P. renitens and sitosterol-3-O-β-D-glucopyranoside from A. brasiliana, the diterpene kaurane ent-kauran-16α,17-diol from P. renitens, two derivatives kaempferol-methylether, kumatakenine (kaempferol-3,7-dimethylether and kaempferol-3,7,3'-trimethylether from S. guianensis and three flavones, crysoeriol (5,7,4'-trihydroxy-3'-methoxyflavone, tricin (5,7,4'-trihydroxy-3',5'-dimethoxyflavone and 7-O-β-D-glucopyranoside-5,4'-dihydroxy-3'-methoxyflavone from A. brasiliana. Compounds structures were determinate using 1D and 2D ¹H NMR and 13C spectral data, mass and IR spectra, comparing with literature data.

  6. Chemical constituents from three medicinal plants: Piper renitens, Siparuna guianensis and Alternanthera brasiliana

    Directory of Open Access Journals (Sweden)

    Valdir A. Facundo

    2012-04-01

    Full Text Available Chemical study of three medicinal plants: from leaves of Piper renitens (Miq. Yunck, Piperaceae, and Siparuna guianensis Aubl., Siparunaceae, and from flowers of Alternanthera brasiliana (L. Kuntze, Amaranthaceae, resulted in isolation of nine compounds: three steroids, β-sitosterol, stigmasterol from P. renitens and sitosterol-3-O-β-D-glucopyranoside from A. brasiliana, the diterpene kaurane ent-kauran-16α,17-diol from P. renitens, two derivatives kaempferol-methylether, kumatakenine (kaempferol-3,7-dimethylether and kaempferol-3,7,3'-trimethylether from S. guianensis and three flavones, crysoeriol (5,7,4'-trihydroxy-3'-methoxyflavone, tricin (5,7,4'-trihydroxy-3',5'-dimethoxyflavone and 7-O-β-D-glucopyranoside-5,4'-dihydroxy-3'-methoxyflavone from A. brasiliana. Compounds structures were determinate using 1D and 2D ¹H NMR and 13C spectral data, mass and IR spectra, comparing with literature data.

  7. (4bS,8aS-1-Isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octahydrophenanthren-2-yl acetate

    Directory of Open Access Journals (Sweden)

    Radouane Oubabi

    2014-03-01

    Full Text Available The hemisynthesis of the title compound, C22H32O2, was carried out through direct acetylation reaction of the naturally occurring diterpene totarol [systematic name: (4bS,8aS-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-ol]. The molecule is built up from three fused six membered rings, one saturated and two unsaturated. The central unsaturated ring has a half-chair conformation, whereas the other unsaturated ring displays a chair conformation. The absolute configuration is deduced from the chemical pathway. The value of the Hooft parameter [−0.10 (6] allowed this absolute configuration to be confirmed.

  8. Separation of glycosidic catiomers by TWIM-MS using CO2 as a drift gas.

    Science.gov (United States)

    Bataglion, Giovana A; Souza, Gustavo Henrique Martins Ferreira; Heerdt, Gabriel; Morgon, Nelson H; Dutra, José Diogo Lisboa; Freire, Ricardo Oliveira; Eberlin, Marcos N; Tata, Alessandra

    2015-02-01

    Traveling wave ion mobility mass spectrometry (TWIM-MS) is shown to be able to separate and characterize several isomeric forms of diterpene glycosides stevioside (Stv) and rebaudioside A (RebA) that are cationized by Na(+) and K(+) at different sites. Determination and characterization of these coexisting isomeric species, herein termed catiomers, arising from cationization at different and highly competitive coordinating sites, is particularly challenging for glycosides. To achieve this goal, the advantage of using CO2 as a more massive and polarizable drift gas, over N2, was demonstrated. Post-TWIM-MS/MS experiments were used to confirm the separation. Optimization of the possible geometries and cross-sectional calculations for mobility peak assignments were also performed. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Chirospecific analysis of plant volatiles

    Energy Technology Data Exchange (ETDEWEB)

    Tkachev, A V [N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk (Russian Federation)

    2007-10-31

    Characteristic features of the analysis of plant volatiles by enantioselective gas (gas-liquid) chromatography and gas chromatography/mass spectrometry are discussed. The most recent advances in the design of enantioselective stationary phases are surveyed. Examples of the preparation of the most efficient phases based on modified cyclodextrins are given. Current knowledge on the successful analytical resolution of different types of plant volatiles (aliphatic and aromatic compounds and mono-, sesqui- and diterpene derivatives) into optical antipodes is systematically described. Chiral stationary phases used for these purposes, temperature conditions and enantiomer separation factors are summarised. Examples of the enantiomeric resolution of fragrance compounds and components of plant extracts, wines and essential oils are given.

  10. Characterization and differentiation of monovarietal grape pomace distillate from native varieties of Galicia.

    Science.gov (United States)

    López-Vázquez, Cristina; Bollaín, María Herminia; Moser, Sergio; Orriols, Ignacio

    2010-09-08

    Monovarietal grape pomace distillates (orujo) of six native varieties of Vitis vinifera L. from Galicia (Albarino, Treixadura, Godello, Loureira, Dona Branca, and Torrontes) have been thoroughly analyzed considering esters, alcohols, major aldehydes, monoterpenes, sesquiterpenes, norisoprenoids, and diterpenes. Albarino and Loureira distillates showed similar profiles of terpenic compounds, with the Loureira products having higher contents of monoterpenols. Native Torrontes distillate from Galicia is principally characterized by marked levels of some sesquiterpenes such as cadinene isomers and epizonarene. On the other hand, Treixadura, Godello, and Dona Branca grape pomace distillates seem not to have any marked terpenic content, and their single separation is difficult. PCA data treatments showed a good separation among the terpenic-rich varieties. Also, the p-menthen-9-al isomers, typical flavors in honey citrus and dill herb (derived from 8-hydroxylinalool), are reported for the first time in grape pomace distillate.

  11. Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

    Science.gov (United States)

    Bailey, Andy M.; Alberti, Fabrizio; Kilaru, Sreedhar; Collins, Catherine M.; de Mattos-Shipley, Kate; Hartley, Amanda J.; Hayes, Patrick; Griffin, Alison; Lazarus, Colin M.; Cox, Russell J.; Willis, Christine L.; O'Dwyer, Karen; Spence, David W.; Foster, Gary D.

    2016-05-01

    Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi.

  12. Introduction of distillate rosemary leaves into the diet of the Murciano-Granadina goat: transfer of polyphenolic compounds to goats' milk and the plasma of suckling goat kids.

    Science.gov (United States)

    Jordán, Maria José; Moñino, María Inmaculada; Martínez, Cristina; Lafuente, Arturo; Sotomayor, José Antonio

    2010-07-28

    The effect of the introduction of distilled rosemary leaves into the diet of the Murciano-Granadina goat on the polyphenolic profile of the goats' milk during the physiological stages of gestation and lactation was studied. The inclusion of rosemary leaves into the animal diet modified neither animal productivity (milk yield) nor milk quality. The following components were found in increased concentration (P goats' milk after the introduction of rosemary leaves into their diet: flavonoids hesperidin, naringin, and genkwanin; gallic acid; and phenolic diterpenes carnosol and carnosic acid. With regard to the transfer of polyphenols to the plasma of the suckling goat kid, a statistically significant increase (P goats' milk and allow for an increased concentration of polyphenolic components in the goats' milk and in the plasma of the suckling goat kid.

  13. Exploring two plant hosts for expression of diterpenoid pathway genes

    DEFF Research Database (Denmark)

    Bach, Søren Spanner

    Plants produce more than 10.000 diterpenoid compounds of which the large majority is involved in specialized metabolism, while a few are involved in general metabolism. Specialized metabolism diterpenoids have functions in interactions of plants with other organisms and selected ones are utilized....... Since only small changes in the amino acid sequence can influence the roduct outcome of a diterpene synthase (diTPS), prediction of the catalytic activity diTPS of a is not possible purely based on phylogenetic relationship. Thus, functional characterization is required in to determine the catalytic...... and aracterization of diTPSs deriving from the plant kingdom, a plant expression host offers several advantages such as the presence of all relevant compartments (plastids and endoplasmic reticulum) and the universal C5 building blocks for isoprenoid biosynthesis. In addition, a plant based xpression host...

  14. Chemical composition and biological activities of the essential oils from two Pereskia species grown in Brazil.

    Science.gov (United States)

    Souza, Lucéia Fatima; De Barros, Ingrid Bergman Inchausti; Mancini, Emilia; De Martino, Laura; Scandolera, Elia; De Feo, Vincenzo

    2014-12-01

    The chemical composition of the essential oils of Pereskia aculeata Mill. and P. grandifolia Haw. (Cactaceae), grown in Brazil, was studied by means of GC and GC-MS. In all, 37 compounds were identified, 30 for P. aculeata and 15 for P. grandifolia. Oxygenated diterpenes are the main constituents, both in the oil ofP. grandifolia (55.5%) and in that ofP. aculeata (29.4%). The essential oils were evaluated for their in vitro phytotoxic activity against germination and initial radicle growth of Raphanus sativus L., Sinapis arvensis L., and Phalaris canariensis L. seeds. The essential oil of P. grandifolia, at all doses tested, significantly inhibited the radicle elongation of R. sativus. Moreover, the antimicrobial activity of the essential oils was assayed against ten bacterial strains. The essential oils showed weak inhibitory activity against the Gram-positive pathogens.

  15. Terpenes and fatty acids from Dipteryx lacunifera Ducke

    International Nuclear Information System (INIS)

    Vieira Junior, Gerardo Magela; Silva, Hilris Rocha e; Bittencourt, Thais Chaves; Chaves, Mariana H.; Simone, Carlos Alberto de

    2007-01-01

    This paper describes the isolation of the furanocassane-type diterpene, named vinhaticoic acid, along with b-farnesene and spatulenol from fruit shells of D. lacunifera. Structural determinations were accomplished by chemical derivatization and spectral analysis, including 1D and 2D NMR and X-ray crystallography. The fatty portion was extracted from the fruit kernels, transesterfied and analysed by HRGC/MS. Oleic acid (75.8 +- 4.3%) was the major component. Essential oil extracted from the fruit shells of D. lacunifera was analysed by HRGC/MS and nine sesquiterpenes were identified; beta-farnesene (48.6%) and spatulenol (21.61%) were the major constituents. (author)

  16. Analgesic, anti-inflammatory, antipyretic and haematological effects of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives.

    Science.gov (United States)

    Hernández-Pérez, M; Rabanal, R M; de la Torre, M C; Rodríguez, B

    1995-12-01

    Aethiopinone (1), an o-naphthoquinone diterpene from Salvia aethiopis L. roots and two hemisynthetic derivatives 2 and 3 have been evaluated for toxicity, anti-inflammatory, analgesic, antipyretic, and haemostatic activities. The compounds tested showed low toxicity and a pharmacological profile similar to other NSAI substances on reducing the edema induced by carrageenan and contractions induced by phenyl-p-quinone; the most active compounds were 1 and 2. In the same way and as expected with these types of substances, the bleeding time increased. In the TPA-induced ear inflammation model, the three compounds showed a moderate reduction of edema, and 1 produced a significant increase in the reaction time against thermal painful stimuli in the tail immersion test. The results demonstrated strong anti-inflammatory, peripheral and central analgesic properties for 1, as well as antiedematose topical action and peripheral analgesic properties for 2 and 3.

  17. Characterization and evolutionary analysis of ent-kaurene synthase like genes from the wild rice species Oryza rufipogon.

    Science.gov (United States)

    Toyomasu, Tomonobu; Miyamoto, Koji; Shenton, Matthew R; Sakai, Arisa; Sugawara, Chizu; Horie, Kiyotaka; Kawaide, Hiroshi; Hasegawa, Morifumi; Chuba, Masaru; Mitsuhashi, Wataru; Yamane, Hisakazu; Kurata, Nori; Okada, Kazunori

    2016-11-18

    Cultivated rice (Oryza sativa) possesses various labdane-related diterpene synthase genes, homologs of ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS) that are responsible for the biosynthesis of phytohormone gibberellins. The CPS homologs and KS like (KSL) homologs successively converted geranylgeranyl diphosphate to cyclic diterpene hydrocarbons via ent-copalyl diphosphate or syn-copalyl diphosphate in O. sativa. Consequently, a variety of labdane-related diterpenoids, including phytoalexin phytocassanes, momilactones and oryzalexins, have been identified from cultivated rice. Our previous report indicated that the biosynthesis of phytocassanes and momilactones is conserved in Oryza rufipogon, the progenitor of Asian cultivated rice. Moreover, their biosynthetic gene clusters, containing OsCPS2 and OsKSL7 for phytocassane biosynthesis and OsCPS4 and OsKSL4 for momilactone biosynthesis, are also present in the O. rufipogon genome. We herein characterized O. rufipogon homologs of OsKSL5, OsKSL6, OsKSL8 responsible for oryzalexin S biosynthesis, and OsKSL10 responsible for oryzalexins A-F biosynthesis, to obtain more evolutionary insight into diterpenoid biosynthesis in O. sativa. Our phytoalexin analyses showed that no accumulation of oryzalexins was detected in extracts from O. rufipogon leaf blades. In vitro functional analyses indicated that unlike OsKSL10, O. rufipogon KSL10 functions as an ent-miltiradiene synthase, which explains the lack of accumulation of oryzalexins A-F in O. rufipogon. The different functions of KSL5 and KSL8 in O. sativa japonica to those in indica are conserved in each type of O. rufipogon, while KSL6 functions (ent-isokaurene synthases) are well conserved. Our study suggests that O. sativa japonica has evolved distinct specialized diterpenoid metabolism, including the biosynthesis of oryzalexins. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes

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    Joseph Schwager

    2016-04-01

    Full Text Available Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL, carnosic acid (CA, carnosic acid-12-methylether (CAME, 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT in murine macrophages (RAW264.7 cells and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO and prostaglandin E2 (PGE2 production in LPS-stimulated macrophages (i.e., acute inflammation. They significantly blunted gene expression levels of iNOS, cytokines/interleukins (IL-1α, IL-6 and chemokines including CCL5/RANTES, CXCL10/IP-10. The substances modulated the expression of catabolic and anabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes that were stimulated by IL-1β (i.e., chronic inflammation In SW1353, catabolic genes like MMP-13 and ADAMTS-4 that contribute to cartilage erosion were down-regulated, while expression of anabolic genes including Col2A1 and aggrecan were shifted towards pre-pathophysiological homeostasis. CL had the strongest overall effect on inflammatory mediators, as well as on macrophage and chondrocyte gene expression. Conversely, CAME mainly affected catabolic gene expression, whereas ABTT had a more selectively altered interleukin and chemokine gene exprssion. CL inhibited the IL-1β induced nuclear translocation of NF-κBp65, suggesting that it primarily regulated via the NF-κB signalling pathway. Collectively, CL had the strongest effects on inflammatory mediators and chondrocyte gene expression. The data show that the phenolic diterpenes altered activity pattern of genes that regulate acute and chronic inflammatory processes. Since the substances affected catabolic and anabolic gene expression in cartilage cells in vitro, they may beneficially act on the aetiology of osteoarthritis.

  19. Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.

    Science.gov (United States)

    Areche, Carlos; Theoduloz, Cristina; Yáñez, Tania; Souza-Brito, Alba R M; Barbastefano, Víctor; de Paula, Débora; Ferreira, Anderson L; Schmeda-Hirschmann, Guillermo; Rodríguez, Jaime A

    2008-02-01

    The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE(2) content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg(-1)) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg(-1)) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg(-1)) increased gastric PGE(2) content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg(-1) ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE(2) synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels.

  20. Ecological Roles and Biological Activities of Specialized Metabolites from the Genus Nicotiana.

    Science.gov (United States)

    Jassbi, Amir Reza; Zare, Somayeh; Asadollahi, Mojtaba; Schuman, Meredith C

    2017-10-11

    Species of Nicotiana grow naturally in different parts of the world and have long been used both medicinally and recreationally by human societies. More recently in our history, Nicotiana tabacum has attracted interest as one of the most economically important industrial crops. Nicotiana species are frequently investigated for their bioactive natural products, and the ecological role of their specialized metabolites in responses to abiotic stress or biotic stress factors like pathogens and herbivores. The interest of tobacco companies in genetic information as well as the success of a few wild tobacco species as experimental model organisms have resulted in growing knowledge about the molecular biology and ecology of these plants and functional studies of the plant's natural products. Although a large number of reviews and books on biologically active natural products already exists, mostly from N. tabacum, we focus our attention on the ecological roles and biological activity of natural products, versus products from cured and processed material, in this Review. The studied compounds include alkaloids, aromatic compounds, flavonoids, volatiles, sesquiterpenoids, diterpenes alcohols, and sugar esters from trichomes of the plants, and recently characterized acyclic hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). In this Review (1800s-2017), we describe the above-mentioned classes of natural products, emphasizing their biological activities and functions as they have been determined either in bioassay-guided purification approaches or in bioassays with plants in which the expression of specific biosynthetic genes has been genetically manipulated. Additionally, a review on the history, taxonomy, ecology, and medicinal application of different Nicotiana species growing around the globe presented in this Review may be of interest for pharmacognosists, natural products, and ecological chemists.

  1. Screening and Identification for Immunological Active Components from Andrographis Herba Using Macrophage Biospecific Extraction Coupled with UPLC/Q-TOF-MS

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    Yaqi Wang

    2018-04-01

    Full Text Available The method of cell biospecific extraction coupled with UPLC/Q-TOF-MS has been developed as a tool for the screening and identification of potential immunological active components from Andrographis Herba (AH. In our study, a macrophage cell line (RAW264.7 was used to extract cell-combining compounds from the ethanol extract of AH. The cell binding system was then analyzed and identified by UPLC/Q-TOF-MS analysis. Finally, nine compounds, which could combine with macrophages, in an ethanol extract of AH were detected by comparing basic peak intensity (BPI profiles of macrophages before and after treatment with AH. Then they were identified as Andrographidine E (1, Andrographidine D (2, Neoandrographolide (3, Dehydroandrographolide (4, 5, 7, 2′, 3′-tetramethoxyflavone (5, β-sitosterol (7, 5-hydroxy-7, 2′, 3′-trimethoxyflavone (8 and 5-hydroxy-7, 8, 2′, 3′-tetramethoxyflavone (9, which could classified into five flavonoids, three diterpene lactones, and one sterol. Their structures were recognized by their characteristic fragment ions and fragmentations pattern of diterpene lactones and flavonoids. Additionally, the activity of compounds 3, 4, and 7 was tested in vitro. Results showed that these three compounds could decrease the release of NO (p < 0.01 in macrophages remarkably. Moreover, 3, 4, and 7 showed satisfactory dose-effect relationships and their IC50 values were 9.03, 18.18, and 13.76 μg/mL, respectively. This study is the first reported work on the screening of immunological active components from AH. The potential immunological activity of flavonoids from AH has not been reported previously.

  2. Comparison of total phenolic content, scavenging activity and HPLC-ESI-MS/MS profiles of both young and mature leaves and stems of Andrographis paniculata.

    Science.gov (United States)

    Chua, Lee Suan; Yap, Ken Choy; Jaganath, Indu Bala

    2013-12-01

    The total phenolic content and radical scavenging activity of Andrographis paniculata has been investigated to estimate the amount of phenolic compounds and diterpene lactones, respectively in the plant extracts. The stem extracts exhibited higher total phenolic content and scavenging activity than those of the leaf extracts from both young and mature plants. A range of 19.6-47.8 mg extract of A. paniculata from different parts of the plant is equivalent to the scavenging activity exhibited by one mg of standard Trolox. HPLC-ESI-MS/MS was also used to identify simultaneously the phytochemicals from the leaves and stems of both young and mature plant samples. Of the identified compounds, seven of the sixteen diterpene lactones, three of the six flavonoids, five of the six phenolic acids and two cyclic acids are reported here for the first time for this species. Multivariate statistical approaches such as Hierarchiral Component Analysis (HCA) and Principle Component Analysis (PCA) have clustered the plant extracts into the leaf and stem groups, regardless of plant age. Further classification based on the phytochemical profiles revealed that mostly phenolic acids and flavonoids were from the young leaf extracts, and diterpenoids and their glycosides from the mature leaf extracts. However, the phytochemical profiles for the stems of both young and mature plants were not significantly different as presented in the dendrogram of HCA and the score plot of PCA. The marker for mature plants might be the m/z 557 ion (dihydroxyl dimethyl 19-[(beta-D-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide), whereas the m/z 521 ion (propyl neoandrographolide) could be the marker for leaf extracts.

  3. Two distinct Epichloë species symbiotic with Achnatherum inebrians, drunken horse grass.

    Science.gov (United States)

    Chen, Li; Li, Xiuzhang; Li, Chunjie; Swoboda, Ginger A; Young, Carolyn A; Sugawara, Koya; Leuchtmann, Adrian; Schardl, Christopher L

    2015-01-01

    Achnatherum inebrians, colloquially known as drunken horse grass, is associated with livestock toxicity in northern China. Epichloë gansuensis (Eg) was described from endophyte isolates from A. inebrians in Sunan County, Gansu Province, whereas a morphologically distinct variety, E. gansuensis var. inebrians (Ei), was described based on two isolates from A. inebrians seeds collected in Urumqi County, Xinjiang Province. Genome sequencing and alkaloid analyses also distinguish these taxa; the Ei isolates produce neurotropic lysergic acid amides (ergot alkaloids), and an Eg isolate produces paxilline (an indole-diterpene alkaloid). To better elucidate the taxonomic diversity of Epichloë spp. symbiotic with A. inebrians, we surveyed eight populations in Xinjiang, Gansu and Inner Mongolia provinces of China and analyzed their genotypes by multiplex PCR for alkaloid biosynthesis genes and mating-type genes. Genotypes consistent with Ei were present in all eight populations, of which they dominated seven. The Ei isolates were all mating type A and tested positive for the ergot alkaloid gene, dmaW. In contrast Eg isolates were all mating type B and had the indole-diterpene gene, idtG. The genome was sequenced from an Ei isolate from seeds collected in Xiahe County, Gansu, and compared to that of the varietal ex type isolate from Urumqi. Alkaloid genes and four different housekeeping genes were nearly identical between the two sequenced Ei isolates and were distinct from a sequenced Eg isolate. Phylogenetic analysis placed Ei, Eg and Epichloë sibirica into respective subclades of a clade that emanated from the base of the Epichloë phylogeny. Given its chemotypic, genotypic, morphological and phylogenetic distinctiveness, its widespread occurrence in rangelands of northern China, and its importance in livestock toxicity, we propose raising Ei to species rank as Epichloë inebrians. © 2015 by The Mycological Society of America.

  4. Manduca sexta recognition and resistance among allopolyploid Nicotiana host plants

    Science.gov (United States)

    Lou, Yonggen; Baldwin, Ian T.

    2003-01-01

    Allopolyploid speciation occurs instantly when the genomes of different species combine to produce self-fertile offspring and has played a central role in the evolution of higher plants, but its consequences for adaptive responses are unknown. We compare herbivore-recognition and -resistance responses of the diploid species and putative ancestral parent Nicotiana attenuata with those of the two derived allopolyploid species Nicotiana clevelandii and Nicotiana bigelovii. Manduca sexta larvae attack all three species, and in N. attenuata attack is recognized when larval oral secretions are introduced to wounds during feeding, resulting in a jasmonate burst, a systemic amplification of trypsin inhibitor accumulation, and a release of volatile organic compounds, which function as a coordinated defense response that slows caterpillar growth and increases the probability of their being attacked. Most aspects of this recognition response are retained with modifications in one allotetraploid (N. bigelovii) but lost in the other (N. clevelandii). Differences between diploid and tetraploid species were apparent in delays (maximum 1 and 0.5 h, respectively) in the jasmonate burst, the elicitation of trypsin inhibitors and release of volatile organic compounds, and the constitutive levels of nicotine, trypsin inhibitors, diterpene glycosides, rutin, and caffeoylputrescine in the leaves. Resistance to M. sexta larvae attack was most strongly associated with diterpene glycosides, which were higher in the diploid than in the two allotetraploid species. Because M. sexta elicitors differentially regulate a large proportion of the N. attenuata transcriptome, we propose that these species are suited for the study of the evolution of adaptive responses requiring trans-activation mechanisms. PMID:14530394

  5. Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction.

    Science.gov (United States)

    Li, Shenghong; Qiu, Shengxiang; Yao, Ping; Sun, Handong; Fong, Harry H S; Zhang, Hongjie

    2013-01-01

    As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits of Vitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1), were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing an α , β -unsaturated γ -lactam moiety. Structurally, they were elucidated to be 9 α -hydroxy-13(14)-labden-16,15-amide (2) and 6 β -acetoxy-9 α -hydroxy-13(14)-labden-15,16-amide (3), which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4), rotundifuran (5), 8-epi-manoyl oxide (6), vitetrifolin D (7), spathulenol (8), cis-dihydro-dehydro-diconiferylalcohol-9-O- β -D-glucoside (9), luteolin-7-O-glucoside (10), 5-hydroxy-3,6,7,4'-tetramethoxyflavone (11), casticin (12), artemetin (13), aucubin (14), agnuside (15), β -sitosterol (16), p-hydroxybenzoic acid (17), and p-hydroxybenzoic acid glucose ester (18). All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds 6, 8, 9, and 18 were reported from a Vitex spieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H):quinone oxidoreductase type 1 (QR1) induction activity. Compound 7 demonstrated promising QR1 induction effect, while the new compound vitexlactam (3) was only slightly active.

  6. The inhibitory effect of Mesembryanthemum edule (L.) bolus essential oil on some pathogenic fungal isolates

    Science.gov (United States)

    2014-01-01

    Background Mesembryanthemum edule is a medicinal plant which has been indicated by Xhosa traditional healers in the treatment HIV associated diseases such as tuberculosis, dysentery, diabetic mellitus, laryngitis, mouth infections, ringworm eczema and vaginal infections. The investigation of the essential oil of this plant could help to verify the rationale behind the use of the plant as a cure for these illnesses. Methods The essential oil from M. edule was analysed by GC/MS. Concentration ranging from 0.005 - 5 mg/ml of the hydro-distilled essential oil was tested against some fungal strains, using micro-dilution method. The plant minimum inhibitory activity on the fungal strains was determined. Result GC/MS analysis of the essential oil resulted in the identification of 28 compounds representing 99.99% of the total essential oil. A total amount of 10.6 and 36.61% constituents were obtained as monoterpenes and oxygenated monoterpenes. The amount of sesquiterpene hydrocarbons (3.58%) was low compared to the oxygenated sesquiterpenes with pick area of 9.28%. Total oil content of diterpenes and oxygenated diterpenes detected from the essential oil were 1.43% and 19.24%. The fatty acids and their methyl esters content present in the essential oil extract were found to be 19.25%. Antifungal activity of the essential oil extract tested against the pathogenic fungal, inhibited C. albican, C. krusei, C. rugosa, C. glabrata and C. neoformans with MICs range of 0.02-0.31 mg/ml. the activity of the essential oil was found competing with nystatin and amphotericin B used as control. Conclusion Having accounted the profile chemical constituent found in M. edule oil and its important antifungal properties, we consider that its essential oil might be useful in pharmaceutical and food industry as natural antibiotic and food preservative. PMID:24885234

  7. In vitro antiproliferative effect of fractions from the caribbean marine sponge Myrmekioderma gyroderma

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    Diana Márquez Fernández

    Full Text Available Introduction: studies performed to Myrmekioderma genus sponges show phospholipid fatty acids, volatile compounds, sterols, bioactive cyclic diterpenes, sesquiterpenes, lineal diterpenes and glycolipid ethers. Objetive: to evaluate the antiproliferative effect of seven fractions (F1-F7 obtained by flash column chromatography from the most bioactive extract of the sponge Myrmekioderma gyroderma, and to analyze the chemical composition of the most active fraction. Methods: samples of dried sponge were extracted with two different solvents: CH2Cl2 (2 x 50 mL, and CH3OH (2 x 50 mL. Each fraction was evaluated on tumor cell derived cell lines; and the cell growth, and viability were determined by a colorimeter assay using sulforhodamine B. Fatty acids structure of the most active fraction was possible by GC-MS analysis of the methyl ester, and pyrrolidine derivatives. Results: the fraction with higher activity on the assessed tumor cell lines is F4 due to it totally inhibited MDA-MB-231, and HT29 cell line growth to 5, and 25 µg/mL concentration (IC50< 1 µg/mL. Fatty acids identified in bioactive F4 fraction of the M. gyroderma sponge can be classified on the following groups: lineal chain saturated, branched-saturated, unsaturated, and a 3-hydroxy acid. Conclusions: 43 fatty acids among saturated, branched-saturated, and unsaturated were identified out of the F4 fraction with activity on the cell lines derived of breast cancer MDA-MB-231, colon carcinoma HT29, and lung carcinoma cells A-549. These results show the growth inhibitory effect shown by the fractions, on the tumor cell lines, depends on the dose.

  8. The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

    Energy Technology Data Exchange (ETDEWEB)

    Simplicio, Janaina A. [Programa de Pós-Graduação em Farmacologia - Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP (Brazil); Departamento de Enfermagem Psiquiátrica e Ciências Humanas - Laboratório de Farmacologia - Escola de Enfermagem de Ribeirão Preto (USP), Ribeirão Preto, SP (Brazil); Simão, Marilia R.; Ambrosio, Sergio R. [Núcleo de Pesquisa em Ciências e Tecnologia - Universidade de Franca (UNIFRAN), Franca, SP (Brazil); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Departamento de Enfermagem Psiquiátrica e Ciências Humanas - Laboratório de Farmacologia - Escola de Enfermagem de Ribeirão Preto (USP), Ribeirão Preto, SP (Brazil)

    2016-06-15

    Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.

  9. Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H:Quinone Oxidoreductase Type 1 Induction

    Directory of Open Access Journals (Sweden)

    Shenghong Li

    2013-01-01

    Full Text Available As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits of Vitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1, were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing an α, β-unsaturated γ-lactam moiety. Structurally, they were elucidated to be 9α-hydroxy-13(14-labden-16,15-amide (2 and 6β-acetoxy-9α-hydroxy-13(14-labden-15,16-amide (3, which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4, rotundifuran (5, 8-epi-manoyl oxide (6, vitetrifolin D (7, spathulenol (8, cis-dihydro-dehydro-diconiferylalcohol-9-O-β-D-glucoside (9, luteolin-7-O-glucoside (10, 5-hydroxy-3,6,7,4′-tetramethoxyflavone (11, casticin (12, artemetin (13, aucubin (14, agnuside (15, β-sitosterol (16, p-hydroxybenzoic acid (17, and p-hydroxybenzoic acid glucose ester (18. All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds 6, 8, 9, and 18 were reported from a Vitex spieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H:quinone oxidoreductase type 1 (QR1 induction activity. Compound 7 demonstrated promising QR1 induction effect, while the new compound vitexlactam (3 was only slightly active.

  10. Marrubium vulgare L.: A review on phytochemical and pharmacological aspects

    Directory of Open Access Journals (Sweden)

    Santram Lodhi

    2017-12-01

    Full Text Available Marrubium vulgare L. (family: Lamiaceae, also known as white horehound, is widely used as herbal remedy for chronic coughs and colds. It is used in various disorders related to skin, liver, gastric, heart and immune system. This review abridges phytochemical, pharmacological studies and medicinal uses of M. vulgare and provides scientific proof for various ethnobotanical claims in order to identify gaps, which will give impulsion for novel research on M. vulgare based herbal medicines. This review summarizes selected scientific evidence on phytochemistry and pharmacological properties of M. vulgare over the past 48 years (1968 to 2016. The work reported on M. vulgare was reviewed from various sources like books, internet source i.e. google search engine, pubmed, sciencedirect and chemical abstract. The exhaustive literature was studied and critical analysis was done according to their phytochemical and pharmacological properties. Phytochemical investigations on different parts of M. vulgare have been reported the presence of flavonoids, steroids, terpenoids, tannins, saponins and volatile oils (0.05%. The aerial parts contain marrubiin, together with ursolic acid and choline. Pharmacological activities like, anti-nociceptive, anti-spasmodic, anti-hypertensive, anti-diabetic, gastroprotective, anti-inflammatory, anti-microbial, anti-cancer, antioxidant, and anti-hepatotoxic activity have been reported. M. vulgare has therapeutic potential in the treatment of inflammatory conditions, liver disorders, pain, cardiovascular, gastric and diabetic conditions. Aerial parts of M. vulgare is a good source of labdane type diterpene especially marrubiin which is present in high concentrations. However, further scientific studies are needed to explore clinical efficacy, toxicity and to explore the therapeutic effect of major secondary metabolites like diterpenes, phenylpropanoid and phenylethanoid glycosides of M. vulgare. [J Complement Med Res 2017; 6

  11. Identification of Two Aflatrem Biosynthesis Gene Loci in Aspergillus flavus and Metabolic Engineering of Penicillium paxilli To Elucidate Their Function ▿

    Science.gov (United States)

    Nicholson, Matthew J.; Koulman, Albert; Monahan, Brendon J.; Pritchard, Beth L.; Payne, Gary A.; Scott, Barry

    2009-01-01

    Aflatrem is a potent tremorgenic toxin produced by the soil fungus Aspergillus flavus, and a member of a structurally diverse group of fungal secondary metabolites known as indole-diterpenes. Gene clusters for indole-diterpene biosynthesis have recently been described in several species of filamentous fungi. A search of Aspergillus complete genome sequence data identified putative aflatrem gene clusters in the genomes of A. flavus and Aspergillus oryzae. In both species the genes for aflatrem biosynthesis cluster at two discrete loci; the first, ATM1, is telomere proximal on chromosome 5 and contains a cluster of three genes, atmG, atmC, and atmM, and the second, ATM2, is telomere distal on chromosome 7 and contains five genes, atmD, atmQ, atmB, atmA, and atmP. Reverse transcriptase PCR in A. flavus demonstrated that aflatrem biosynthesis transcript levels increased with the onset of aflatrem production. Transfer of atmP and atmQ into Penicillium paxilli paxP and paxQ deletion mutants, known to accumulate paxilline intermediates paspaline and 13-desoxypaxilline, respectively, showed that AtmP is a functional homolog of PaxP and that AtmQ utilizes 13-desoxypaxilline as a substrate to synthesize aflatrem pathway-specific intermediates, paspalicine and paspalinine. We propose a scheme for aflatrem biosynthesis in A. flavus based on these reconstitution experiments in P. paxilli and identification of putative intermediates in wild-type cultures of A. flavus. PMID:19801473

  12. Comparative Phenolic Fingerprint and LC-ESI+QTOF-MS Composition of Oregano and Rosemary Hydrophilic Extracts in Relation to their Antibacterial Effect

    Directory of Open Access Journals (Sweden)

    Florina Bunghez

    2015-05-01

    Full Text Available Rosemary (Rosmarinus officinalis and oregano (Origanum vulgare are known aromatic plants used as spice, with good flavoring, preservative, antioxidant and antibacterial activity. Beside their known terpenoid content responsible for the antibacterial activity, the water-soluble compounds (phenolic derivatives are of high interest not only for their antioxidant activity but as a good alternative or as a hydrophilic new antibacterial solution. Two hydrophilic extracts from each plant were obtained (15% plant in hot water and the phytochemicals were fingerprinted by UV-Vis and FTIR spectrometry and quantified. The total phenolic content was higher in case of oregano (54.2 mg GAE/g DW comparing to rosemary (54.25 vs 15.35 mg GAE/g dry matter. By LC-ESI+QTOF-MS analysis there were identified mainly, in both extracts, flavonoid and diterpene derivatives, mainly carnosol, carnosic acid, rosmarinic acid, kaempferol 3-O-glucuronide. Other flavonoid glucuronides were more specific to one or the other plant, e.g. Luteolin 3'-(4''-acetylglucuronide for rosemary and Apigenin 7-O-glucuronide for oregano. Water favorized increased extraction of flavonoid derivatives and soluble diterpenes, but not non-soluble  terpenes. The antibacterial activity of both extracts was tested against B.cereus, L. monocytogenes, Salmonella, S. aureus and E.coli. Both oregano and rosemary extracts showed a slight antibacterial activity, which can be related to the low concentration of terpenoids, known to have the most important antibacterial activity in these plants. Nevertheless, the antibacterial activity seems to be strain dependent, Bacillus cereus being the most sensitive bacterial strain comparing with the other four bacteria, the oregano extract having a slightly superior activity comparing to the rosemary extract.

  13. Chemical and Antimicrobial Evaluation of Supercritical and Conventional Sideritis scardica Griseb., Lamiaceae Extracts

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    Marko Stamenić

    2012-03-01

    Full Text Available Sideritis scardica Griseb., Lamiaceae (ironwort, mountain tea, an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of antimicrobial infections, gastrointestinal complaints, inflammation and rheumatic disorders. This study reports a comparison between conventional (hydrodistillation HD and solvent extraction SE and alternative (supercritical carbon dioxide SC CO2 extraction methods regarding the qualitative and quantitative composition of the obtained extracts as analyzed by GC and GC-MS techniques and their anitimicrobial activity. Different types of extracts were tested, the essential oil EO obtained by HD, EO-CO2 and AO-CO2 obtained by SC CO2 at different preasures 10 and 30 MPa, at 40 °C, respectively, and the fractions A, B, C and D obtained by successive solvent extraction (SE A: ethanol, B: diethyl ether, C: ethyl acetate and D: n-butanol. While EO was characterized by the presence of the high percentage of oxygenated monoterpenes and sesquiterpenes (30.01 and 25.54%, respectively, the rest of the investigated samples were the most abundant in fatty acids and their esters and diterpenes (from 16.72 to 71.07% for fatty acids and their esters, and from 23.30 to 72.76%, for diterpenes. Microbial susceptibility tests revealed the strong to moderate activity of all investigated extracts against the tested microorganisms (MIC from 40 to 2,560 μg/mL. Although differences in the chemical compositions determined by GC and GC-MS analysis were established, the displayed antimicrobial activity was similar for the all investigated extracts.

  14. Mutational, Phylogeny and Evolution Analyses of Salvia Copalyl Diphosphate Synthase

    International Nuclear Information System (INIS)

    Hao, D. C.; Thimmappa, R. B.; Xiao, P. G.

    2016-01-01

    The cyclization of geranylgeranyl diphosphate (GGPP) is catalyzed by copalyl diphosphate synthase (CPS), a class II diterpene synthase (diTPS), to form copalyl diphosphate (CPP), which is an essential substrate of a variety of diterpenes in secondary metabolism of angiosperm including Salvia medicinal plants. The protein environment of the N-terminal class II active site stabilizes the carbocation intermediates and maintains the catalytic activity of angiosperm class II diTPS. The virtual modeling and mutagenesis of the class II diTPS of Salvia miltiorrhiza (SmCPS) were accomplished to illuminate the catalytic activity of SmCPS. Terminal truncations and point mutations established the role of the Beta-Gamma domain and Alpha domain, i.e., they facilitate the flexible conformational change of the class II active site after substrate binding. E203 and K238 in the N-ter Gamma domain of SmCPS1 are functional in the substrate binding and conformational transition and might be essential in catalysis. Similar to other CPSs, the ensuing protonation of the GGPP substrate and coordination of the diphosphate group are governed by highly conserved residues in the DxDD motif of SmCPS, e.g., D372 of CPS1. Moreover, F256 and Y505 stabilize the carbocation and control the enzymatic activity during CPP formation. The amino acids of the predicted active sites, despite under purifying selection, vary greatly, corresponding to the functional flexibility of angiosperm CPSs. Molecular phylogeny and evolution analyses suggest early and ongoing evolution of labdane-related diterpenoid metabolism in angiosperm. (author)

  15. Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal A. Rich (Annonaceae and the major constituent, xylopic acid in murine models

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    Eric Woode

    2012-01-01

    Full Text Available Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE and xylopic acid (XA, in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests, thermal (Tail-flick and Hargreaves thermal hyperalgesia tests, and mechanical (Randall-Selitto paw pressure test pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg -1 , p.o. and XA (10-100 mg kg -1 , p.o. inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory, thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg -1 , i.p. and diclofenac (1-10 mg kg -1 , i.p., used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

  16. Chemical composition profiling and antifungal activity of the essential oil and plant extracts of Mesembryanthemum edule (L.) bolus leaves.

    Science.gov (United States)

    Omoruyi, Beauty Etinosa; Afolayan, Anthony Jide; Bradley, Graeme

    2014-01-01

    Essential oil from Mesembryanthemum edule leaves have been used by the Eastern Cape traditional healers for the treatment of respiratory tract infections, tuberculosis, dysentery, diabetic mellitus, laryngitis and vaginal infections. The investigation of bioactive compounds in the essential oil of this plant could help to verify the efficacy of the plant in the management or treatment of these illnesses. Various concentrations of the hydro-distilled essential oil, ranging from 0.005-5 mg/ml, were tested against some fungal strains, using the micro-dilution method. Minimum inhibitory activity was compared with four other different crude extracts of hexane, acetone, ethanol and aqueous samples from the same plant. The chemical composition of the essential oil, hexane, acetone and ethanol extracts was determined using GC-MS. GC/MS analysis of the essential oil resulted in the identification of 28 compounds, representing 99.99% of the total oil. Phytoconstituents of hexane, acetone and ethanol extracts yielded a total peak chromatogram of fifty nine compounds. A total amount of 10.6% and 36.61% of the constituents were obtained as monoterpenes and oxygenated monoterpenes. Sesquiterpene hydrocarbons (3.58%) were relatively low compared to the oxygenated sesquiterpenes (9.28%), while the major concentrated diterpenes and oxygenated diterpenes were 1.43% and 19.24 %, respectively and phytol 12.41%. Total amount of fatty acids and their methyl esters content, present in the oil extract, were found to be 19.25 %. Antifungal activity of the oil extract and four solvent extracts were tested against five pathogenic fungal strains. The oil extract showed antifungal activity against Candida albican, Candida krusei, Candida rugosa, Candida glabrata and Cryptococcus neoformans with MIC ranges of 0.02 0.31 mg/ml. Hexane extract was active against the five fungal strains with MICs ranging between 0.02-1.25 mg/ml. Acetone extracts were active against C. krusei only at 0.04mg/ml. No

  17. Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Kotowski, Ulana; Heiduschka, Gregor; Eckl-Dorna, Julia; Kranebitter, Veronika; Stanisz, Isabella; Brunner, Markus; Lill, Claudia; Thurnher, Dietmar [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Seemann, Rudolf [Medical University of Vienna, Departement of Cranio-, Maxillofacial- and Oral Surgery, Vienna (Austria); Schmid, Rainer [Medical University of Vienna, Department of Radiotherapy, Vienna (Austria)

    2015-01-10

    Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation. (orig.) [German] Cafestol ist ein Diterpen, das in der Kaffeebohne vorkommt und antikanzerogene Eigenschaften besitzt. Ziel der Studie war, die Wirkung von Cafestol auf Kopf-Hals-Tumorzelllinien zu untersuchen. Drei Kopf-Hals-Tumorzelllinien (SCC25, CAL27 und FaDu) wurden mit steigenden Cafestol-Dosen behandelt. Anschliessend fanden Kombinationsexperimente mit Cisplatin und Bestrahlung statt. Die Wechselwirkung zwischen den Substanzen und moegliche synergistische Wirkungen wurden mit dem Combination-Index analysiert. Koloniebildungstests wurden nach Bestrahlung mit 2, 4, 6 und 8 Gy durchgefuehrt. Apoptose wurde mittels Durchflusszytometrie gemessen. Die Behandlung der Kopf-Hals-Tumorzelllinien mit Cafestol fuehrt zu einer dosisabhaengigen Abnahme des Zellueberlebens und zur Induktion von Apoptose. Die Kombination von Cafestol mit Bestrahlung zeigt eine geringere

  18. Carbonaceous aerosol particles from common vegetation in the Grand Canyon

    International Nuclear Information System (INIS)

    Hallock, K.A.; Mazurek, M.A.; Cass, G.R.

    1992-05-01

    The problem of visibility reduction in the Grand Canyon due to fine organic aerosol particles in the atmosphere has become an area of increased environmental concern. Aerosol particles can be derived from many emission sources. In this report, we focus on identifying organic aerosols derived from common vegetation in the Grand Canyon. These aerosols are expected to be significant contributors to the total atmospheric organic aerosol content. Aerosol samples from living vegetation were collected by resuspension of surface wax and resin components liberated from the leaves of vegetation common to areas of the Grand Canyon. The samples were analyzed using high-resolution gas chromatography/mass spectrometry (GC/MS). Probable identification of compounds was made by comparison of sample spectra with National Institute of Standards and Technology (NIST) mass spectral references and positive identification of compounds was made when possible by comparison with authentic standards as well as NIST references. Using these references, we have been able to positively identify the presence of n-alkane and n-alkanoic acid homolog series in the surface waxes of the vegetation sampled. Several monoterpenes, sesquiterpenes, and diterpenes were identified also as possible biogenic aerosols which may contribute to the total organic aerosol abundance leading to visibility reduction in the Grand Canyon

  19. Spearmint R2R3-MYB transcription factor MsMYB negatively regulates monoterpene production and suppresses the expression of geranyl diphosphate synthase large subunit (MsGPPS.LSU).

    Science.gov (United States)

    Reddy, Vaishnavi Amarr; Wang, Qian; Dhar, Niha; Kumar, Nadimuthu; Venkatesh, Prasanna Nori; Rajan, Chakravarthy; Panicker, Deepa; Sridhar, Vishweshwaran; Mao, Hui-Zhu; Sarojam, Rajani

    2017-09-01

    Many aromatic plants, such as spearmint, produce valuable essential oils in specialized structures called peltate glandular trichomes (PGTs). Understanding the regulatory mechanisms behind the production of these important secondary metabolites will help design new approaches to engineer them. Here, we identified a PGT-specific R2R3-MYB gene, MsMYB, from comparative RNA-Seq data of spearmint and functionally characterized it. Analysis of MsMYB-RNAi transgenic lines showed increased levels of monoterpenes, and MsMYB-overexpressing lines exhibited decreased levels of monoterpenes. These results suggest that MsMYB is a novel negative regulator of monoterpene biosynthesis. Ectopic expression of MsMYB, in sweet basil and tobacco, perturbed sesquiterpene- and diterpene-derived metabolite production. In addition, we found that MsMYB binds to cis-elements of MsGPPS.LSU and suppresses its expression. Phylogenetic analysis placed MsMYB in subgroup 7 of R2R3-MYBs whose members govern phenylpropanoid pathway and are regulated by miR858. Analysis of transgenic lines showed that MsMYB is more specific to terpene biosynthesis as it did not affect metabolites derived from phenylpropanoid pathway. Further, our results indicate that MsMYB is probably not regulated by miR858, like other members of subgroup 7. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  20. Multi-substrate terpene synthases: their occurrence and physiological significance

    Directory of Open Access Journals (Sweden)

    Leila Pazouki

    2016-07-01

    Full Text Available Terpene synthases are responsible for synthesis of a large number of terpenes in plants using substrates provided by two distinct metabolic pathways, the mevalonate-dependent pathway that is located in cytosol and has been suggested to be responsible for synthesis of sesquiterpenes (C15, and 2-C-methyl-D-erythritol-4-phosphate pathway located in plastids and suggested to be responsible for the synthesis of hemi- (C5, mono- (C10 and diterpenes (C20. Recent advances in characterization of genes and enzymes responsible for substrate and end product biosynthesis as well as efforts in metabolic engineering have demonstrated existence of a number of multi-substrate terpene synthases. This review summarizes the progress in the characterization of such multi-substrate terpene synthases and suggests that the presence of multi-substrate use might have been significantly underestimated. Multi-substrate use could lead to important changes in terpene product profiles upon substrate profile changes under perturbation of metabolism in stressed plants as well as under certain developmental stages. We therefore argue that multi-substrate use can be significant under physiological conditions and can result in complicate modifications in terpene profiles.

  1. Identification, Functional Characterization, and Evolution of Terpene Synthases from a Basal Dicot1[OPEN

    Science.gov (United States)

    Yahyaa, Mosaab; Matsuba, Yuki; Brandt, Wolfgang; Doron-Faigenboim, Adi; Bar, Einat; McClain, Alan; Davidovich-Rikanati, Rachel; Lewinsohn, Efraim; Pichersky, Eran; Ibdah, Mwafaq

    2015-01-01

    Bay laurel (Laurus nobilis) is an agriculturally and economically important dioecious tree in the basal dicot family Lauraceae used in food and drugs and in the cosmetics industry. Bay leaves, with their abundant monoterpenes and sesquiterpenes, are used to impart flavor and aroma to food, and have also drawn attention in recent years because of their potential pharmaceutical applications. To identify terpene synthases (TPSs) involved in the production of these volatile terpenes, we performed RNA sequencing to profile the transcriptome of L. nobilis leaves. Bioinformatic analysis led to the identification of eight TPS complementary DNAs. We characterized the enzymes encoded by three of these complementary DNAs: a monoterpene synthase that belongs to the TPS-b clade catalyzes the formation of mostly 1,8-cineole; a sesquiterpene synthase belonging to the TPS-a clade catalyzes the formation of mainly cadinenes; and a diterpene synthase of the TPS-e/f clade catalyzes the formation of geranyllinalool. Comparison of the sequences of these three TPSs indicated that the TPS-a and TPS-b clades of the TPS gene family evolved early in the evolution of the angiosperm lineage, and that geranyllinalool synthase activity is the likely ancestral function in angiosperms of genes belonging to an ancient TPS-e/f subclade that diverged from the kaurene synthase gene lineages before the split of angiosperms and gymnosperms. PMID:26157114

  2. Andrographolide and analogues in cancer prevention.

    Science.gov (United States)

    Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

    2015-01-01

    Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

  3. Multi-Targeting Andrographolide, a Novel NF-κB Inhibitor, as a Potential Therapeutic Agent for Stroke.

    Science.gov (United States)

    Yang, Chih-Hao; Yen, Ting-Lin; Hsu, Chia-Yuan; Thomas, Philip-Aloysius; Sheu, Joen-Rong; Jayakumar, Thanasekaran

    2017-07-27

    A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury. Conferring to the pharmacological mechanisms underlying neuroprotection, a study found that androgapholide, a diterpene lactone compound, exhibits varying degrees of neuroprotective activities in both in vitro and in vivo experimental models of stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I) increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1) expression through p38-mitogen activated protein kinase (MAPK) regulation, (II) inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation, (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV) inhibiting hydroxyl radical (OH - ) formation, and activating transcription factor NF-κB signaling pathways. Recently, several researchers have also been trying to unveil the principal mechanisms involved in the neuroprotective effects of andrographolide. Therefore, this review aims to summarize an overview on the neuroprotective effects of andrographolide and exemplifies the essential mechanisms involved. This paper can provide information that andrographolide drug discovery may be a promising strategy for the development of a novel class of neuroprotective drug.

  4. Transdermal delivery of forskolin from emulsions differing in droplet size.

    Science.gov (United States)

    Sikora, Elżbieta; Llinas, Meritxell; Garcia-Celma, Maria Jose; Escribano, Elvira; Solans, Conxita

    2015-02-01

    The skin permeation of forskolin, a diterpene isolated from Coleus forsholii, was studied using oil in water (O/W) emulsions as delivery formulations and also an oil solution for comparative purposes. Two forskolin-loaded emulsions of water/Brij 72:Symperonic A7/Miglyol 812:Isohexadecane, at 0.075 wt% forskolin concentration were prepared with the same composition and only differing in droplet size (0.38 μm and 10 μm). The emulsions showed high kinetic stability at 25 °C. In vitro study of forskolin penetration through human skin was carried out using the MicroettePlus(®) system. The concentration of the active in the receptor solution (i.e. ethanol/phosphate buffer 40/60, v/v) was analyzed by high performance liquid chromatography with UV detection. The obtained results showed that forskolin permeation from the emulsions and the oil solution, through human skin, was very high (up to 72.10%), and no effect of droplet size was observed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Do Coffee Polyphenols Have a Preventive Action on Metabolic Syndrome Associated Endothelial Dysfunctions? An Assessment of the Current Evidence.

    Science.gov (United States)

    Yamagata, Kazuo

    2018-02-04

    Epidemiologic studies from several countries have found that mortality rates associated with the metabolic syndrome are inversely associated with coffee consumption. Metabolic syndrome can lead to arteriosclerosis by endothelial dysfunction, and increases the risk for myocardial and cerebral infarction. Accordingly, it is important to understand the possible protective effects of coffee against components of the metabolic syndrome, including vascular endothelial function impairment, obesity and diabetes. Coffee contains many components, including caffeine, chlorogenic acid, diterpenes and trigonelline. Studies have found that coffee polyphenols, such as chlorogenic acids, have many health-promoting properties, such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetes, and antihypertensive properties. Chlorogenic acids may exert protective effects against metabolic syndrome risk through their antioxidant properties, in particular toward vascular endothelial cells, in which nitric oxide production may be enhanced, by promoting endothelial nitric oxide synthase expression. These effects indicate that coffee components may support the maintenance of normal endothelial function and play an important role in the prevention of metabolic syndrome. However, results related to coffee consumption and the metabolic syndrome are heterogeneous among studies, and the mechanisms of its functions and corresponding molecular targets remain largely elusive. This review describes the results of studies exploring the putative effects of coffee components, especially in protecting vascular endothelial function and preventing metabolic syndrome.

  6. Nrf2 activation ameliorates cytotoxic effects of arsenic trioxide in acute promyelocytic leukemia cells through increased glutathione levels and arsenic efflux from cells

    Energy Technology Data Exchange (ETDEWEB)

    Nishimoto, Shoichi; Suzuki, Toshihiro; Koike, Shin [Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588 (Japan); Yuan, Bo; Takagi, Norio [Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392 (Japan); Ogasawara, Yuki, E-mail: yo@my-pharm.ac.jp [Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588 (Japan)

    2016-08-15

    Carnosic acid (CA), a phenolic diterpene isolated from Rosmarinus officinalis, has been shown to activate nuclear transcription factor E2-related factor 2 (Nrf2), which plays a central role in cytoprotective responses to oxidative and electrophilic stress. Recently, the Nrf2-Kelch ECH associating protein 1 (Keap1) pathway has been associated with cancer drug resistance attributable to modulation of the expression and activation of antioxidant and detoxification enzymes. However, the exact mechanisms by which Nrf2 activation results in chemoresistance are insufficiently understood to date. This study investigated the mechanisms by which the cytotoxic effects of arsenic trioxide (ATO), an anticancer drug, were decreased in acute promyelocytic leukemia cells treated with CA, a typical activator of Nrf2 used to stimulate the Nrf2/Keap1 system. Our findings suggest that arsenic is non-enzymatically incorporated into NB4 cells and forms complexes that are dependent on intracellular glutathione (GSH) concentrations. In addition, the arsenic complexes are recognized as substrates by multidrug resistance proteins and subsequently excreted from the cells. Therefore, Nrf2-associated activation of the GSH biosynthetic pathway, followed by increased levels of intracellular GSH, are key mechanisms underlying accelerated arsenic efflux and attenuation of the cytotoxic effects of ATO. - Highlights: • Nrf2 activation attenuates the effect of arsenic trioxide to acute promyelocytic leukemia cells. • The sensitivity of arsenic trioxide to NB4 cells was dependent on efflux rate of arsenic. • Activation of the GSH biosynthesis is essential in Nrf2-regulated responses for arsenic efflux.

  7. Scientific basis of botanical medicine as alternative remedies for rheumatoid arthritis.

    Science.gov (United States)

    Yang, Cindy L H; Or, Terry C T; Ho, Marco H K; Lau, Allan S Y

    2013-06-01

    Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder that causes permanent disability and mortality to approximately 1 to 100 people in the world. Patients with RA not only suffer from pain, stiffness, swelling, and loss of function in their joints, but also have a higher risk of cardiovascular disease and lymphoma. Typically prescribed medications, including pain-relieving drugs, nonsteroidal anti-inflammatory drugs (NSAID), and disease-modifying antirheumatic drugs, can help to relieve pain, reduce inflammation and slow the course of disease progression in RA patients. However, the general effectiveness of the drugs has been far from satisfactory. Other therapeutic modalities like TNF-alpha (TNF-α) inhibitors and interleukin-1 receptor antagonists targeting precise pathways within the immune system are expensive and may be associated with serious side effects. Recently, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years experience in treating patients. In this review, we will summarize recent evidence for pharmacological effects of herbs including Black cohosh, Angelica sinensis, Licorice, Tripterygium wilfordii, Centella asiatica, and Urtica dioica. Scientific research has demonstrated that these herbs have strong anti-inflammatory and anti-arthritic effects. A wide range of phytochemicals including phenolic acids, phenylpropanoid ester, triterpene glycosides, phthalide, flavonoids, triterpenoid saponin, diterpene and triterpene have been isolated and demonstrated to be responsible for the biological effects of the herbs. Understanding the mechanisms of action of the herbs may provide new treatment opportunities for RA patients.

  8. BdorCSP2 is important for antifeed and oviposition-deterring activities induced by Rhodojaponin-III against Bactrocera dorsalis.

    Directory of Open Access Journals (Sweden)

    Xin Yi

    Full Text Available Rhodojaponin-III is a nonvolatile botanical grayanoid diterpene compound, which has antifeedant and oviposition deterrence effects against many kinds of insects. However, the molecular mechanism of the chemoreception process remains unknown. In this study, the important role of BdorCSP2 in the recognition of Rhodojaponin-III was identified. The full length cDNA encoding BdorCSP2 was cloned from legs of Bactrocera dorsalis. The results of expression pattern revealed that BdorCSP2 was abundantly expressed in the legs of adult B. dorsalis. Moreover, the expression of BdorCSP2 could be up-regulated by Rhodojaponin-III. In order to gain comprehensive understanding of the recognition process, the binding affinity between BdorCSP2 and Rhodojaponin-III was measured by fluorescence binding assay. Silencing the expression of BdorCSP2 through the ingestion of dsRNA could weaken the effect of oviposition deterrence and antifeedant of Rhodojaponin-III. These results suggested that BdorCSP2 of B. dorsalis could be involved in chemoreception of Rhodojaponin-III and played a critical role in antifeedant and oviposition behaviors induced by Rhodojaponin-III.

  9. Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiang; Zhao, Fang [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Lv, Zhong-ming; Shi, Wei-qin [Jiangsu Provincial Center for Disease Control and Prevention, Nanjing (China); Zhang, Lu-yong, E-mail: lyzhang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing (China); State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Yan, Ming, E-mail: brookming@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)

    2016-11-01

    Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

  10. Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

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    Mariano Walter Pertino

    2014-02-01

    Full Text Available Dehydroabietic acid (DHA is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid, and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol, four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM.

  11. In vitro thrombolytic, anthelmintic, anti-oxidant and cytotoxic activity with phytochemical screening of methanolic extract of Xanthium indicum leaves

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    Antara Ghosh

    2015-12-01

    Full Text Available Xanthium indicum is an important medicinal plant traditionally used in Bangladesh as a folkloric treatment. The current study was undertaken to evaluate thrombolytic, anthelmintic, anti-oxidant, cytotoxic properties with phytochemical screening of methanolic extract of X. indicum leaves. The analysis of phytochemical screening confirmed the existence of phytosetrols and diterpenes. In thrombolytic assay, a significant clot lysis was observed at four concentrations of plant extract compare to the positive control streptokinase (30,000 IU, 15,000 IU and negative control normal saline. The extract revealed potent anthelmintic activity at different concentrations. In anti-oxidant activity evaluation by two potential experiments namely total phenolic content determination and free radical scavenging assay by 2, 2-diphenylpicrylhydrazyl (DPPH, the leaves extract possess good anti-oxidant property. In the brine shrimp lethality bioassay, the crude extract showed potent (LC50 1.3 μg/mL cytotoxic activity compare to the vincristine sulfate as a positive control (LC50 0.8 μg/mL.

  12. Una revisión sobre la producción de taxoides anticancerígenos en cultivos in vitro de callos y células de Taxus spp.

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    Hebert Jair Barrales Cureño

    2013-07-01

    Palabras clave: cáncer, biotecnología, metabolismo secundario, taxol, Taxaceae.  Abstract: The taxoids are polioxigenated diterpenes from the metabolic pathway of the 2-methyl-erythritol 4-phosphate whose biosynthesis is generated in the plastides. The importance of the taxoides including taxol, in the area of human medicine is very valuable due to the use in oncology, drug used against breast, lung and ovarian cancer. The species of trees of Taxus spp. are in danger of extinction due to logging immoderate, to the low reproduction rate, slow growth; therefore, the plant tissue culture in vitro is a biotechnological alternative high-impact and a great help to the knowledge of the production of the taxoides to level in vitro and above all, for the conservation of this valuable natural resource. The objectives of this article are to determine some general information about the geographical distribution of Taxus spp.; chemical characteristics of taxoids, biological mechanism of action of taxol; path of biosynthesis, methods of extraction and analysis of the taxoids and a current review of the production of taxoids in situ and in vitro cultures and cells of Taxus spp.  Key words: cancer, biotechnology, secondary metabolism, taxol, Taxaceae.

  13. Immunochemical Analysis of Paxilline and Ergot Alkaloid Mycotoxins in Grass Seeds and Plants.

    Science.gov (United States)

    Bauer, Julia I; Gross, Madeleine; Cramer, Benedikt; Humpf, Hans-Ulrich; Hamscher, Gerd; Usleber, Ewald

    2018-01-10

    Limited availability of toxin standards for lolitrem B and ergovaline impedes routine control of grasses for endophyte toxins. This study aimed at assessing the applicability of an enzyme immunoassay (EIA) for the indole-diterpene mycotoxin paxilline, in combination with a generic EIA for ergot alkaloids, as alternative parameters for screening purposes. Analysis of grass seeds and model pastures of four different grass species showed that both EIAs yielded highly positive results for paxilline and ergot alkaloids in perennial ryegrass seeds. Furthermore, evidence for natural occurrence of paxilline in grass in Germany was obtained. High performance liquid chromatography-tandem mass spectrometry analysis qualitatively confirmed the paxilline EIA results but showed that paxilline analogues 1'-O-acetylpaxilline and 13-desoxypaxilline were the predominant compounds in seeds and grass. In the absence of easily accessible reference standards for specific analysis of some major endophyte toxins, analysis of paxilline and ergot alkaloids by EIA may be suitable substitute parameters. The major advantage of this approach is its ease of use and speed, providing an analytical tool which could enhance routine screening for endophyte toxins in pasture.

  14. Changes in the essential oil composition of leaves of Echinodorus macrophyllus exposed to

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    Thiago M. Silva

    2013-08-01

    Full Text Available Leaves of Echinodorus macrophyllus (Kunth Micheli, Alismataceae, were exposed to different doses of γ-radiation (0.00, 1.00, 3.00, 5.00, 10.00, and 20.00 kGy and the chemical composition of their essential oils was investigated. The extractive process of the essential oil was more favored when the leaves were irradiated. The essential oil components were identified by correlation between GC-FID data and retention parameters obtained from the Kováts method. Moreover, GC-MS analyses of the essential oils were correlated with fragmentation profiles in the NIST standard mass fragmentation data bank. The essential oil of E. macrophyllus contains biologically active constituents of different chemical classes. Acyclic monoterpenes and sesquiterpenes showed increase in concentration when the leaves were exposed to γ-radiation. On the other hand, the component concentrations of some chemical classes were lightly decreased, i.e., for bicyclic monoterpenes, diterpenes, triterpenes, carboxylic esters, and carotenoid derivatives.

  15. Screening of the odour-activity and bioactivity of the essential oils of leaves and flowers of Hyptis Passerina Mart. from the Brazilian Cerrado

    Energy Technology Data Exchange (ETDEWEB)

    Zellner, Barbara D.; Amorim, Ana Carolina L.; Rezende, Claudia M. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Centro de Tecnologia. Inst. de Quimica]. E-mail: crezende@iq.ufrj.br; Miranda, Ana Luisa P. de [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Faculdade de Farmacia; Alves, Ruy J.V. [Museu Nacional, Rio de Janeiro, RJ (Brazil). Dept. de Botanica. Herbario; Barbosa, Jussara P.; Costa, Gisela L. da [Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Lab. de Taxonomia, Bioquimica e Bioprospeccao de Fungos

    2009-07-01

    The chemical profile of the essential oils obtained from the leaves and flowers of Hyptis passerina Mart., a rare species of the Brazilian Cerrado, has been determined for the first time. Analyses by GC-MS showed sesquiterpenes as major compounds. {beta}-epi-acorenol (35.7% and 32.8%, respectively from leaf and flower essential oils), was isolated and identified by 1D and 2D NMR. The flower-derived oil presented a higher concentration of hydrocarbon and oxygenated monoterpenes, while the leaf-oil was richer in diterpenes. The global odour impressions of both oils were given by direct analysis and GC-MS-O and were characterized as herbaceous with tea notes, and green, cooked and woody impressions for leaf-oil; herbaceous, with spicy, woody and minty notes for flower-oil. {beta}-epi-acorenol, spathulenol, {beta}-caryophyllene, and caryophyllene oxide were relevant for the odour-activity of both oils, as well as minor constituents, such as linalool. The antimicrobial activity was investigated by means of agar diffusion disc method and contact bioautography, against Gram-positive and negative bacteria and yeast. Both oils presented to be bioactive against the tested microorganisms with significant inhibition level. (author)

  16. Differential Timing of Spider Mite-Induced Direct and Indirect Defenses in Tomato Plants1[w

    Science.gov (United States)

    Kant, Merijn R.; Ament, Kai; Sabelis, Maurice W.; Haring, Michel A.; Schuurink, Robert C.

    2004-01-01

    Through a combined metabolomics and transcriptomics approach we analyzed the events that took place during the first 5 d of infesting intact tomato (Lycopersicon esculentum) plants with spider mites (Tetranychus urticae). Although the spider mites had caused little visible damage to the leaves after 1 d, they had already induced direct defense responses. For example, proteinase inhibitor activity had doubled and the transcription of genes involved in jasmonate-, salicylate-, and ethylene-regulated defenses had been activated. On day four, proteinase inhibitor activity and particularly transcript levels of salicylate-regulated genes were still maintained. In addition, genes involved in phospholipid metabolism were up-regulated on day one and those in the secondary metabolism on day four. Although transcriptional up-regulation of the enzymes involved in the biosynthesis of monoterpenes and diterpenes already occurred on day one, a significant increase in the emission of volatile terpenoids was delayed until day four. This increase in volatile production coincided with the increased olfactory preference of predatory mites (Phytoseiulus persimilis) for infested plants. Our results indicate that tomato activates its indirect defenses (volatile production) to complement the direct defense response against spider mites. PMID:15122016

  17. Anti-ulcer activity of Synadenium grantii latex

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    Larissa L. G. Costa

    2012-10-01

    Full Text Available Synadenium grantii Hook f., Euphorbiaceae, is popularly known as leitosinha or janaúba. The diluted latex (18 drops/L of water is commonly used in the south of Brazil to treat gastric disturbances. This study evaluated phytochemical screening and toxicity using Artemia salina Leach of crude bark extract and also latex. The toxicity and the anti-ulcer activity of S. grantii latex were also tested in rats. Phytochemical results showed presence of tannins, terpenes, unsaponificable substances, coumarins and anthraquinones in the crude bark extract and terpenes in the latex. Gas chromatography-mass spectrometry (GC-MS analysis demonstrated the presence of diterpene tigliane esters in the latex, identified as 12-deoxyphorbol-13-(2-metilpropionate and phorbol 12,13,20-triacetate. The toxicity results using A. salina presented CL50 26.58μg/mL and CL50 778.66μg/mL, for the latex and the crude bark extract respectively. The toxicological hepatic parameters of the diluted latex were not different to the control group (p<0.05. The eosinophils cells showed an increase in both the diluted and pure latex groups. The pure latex showed gastric protection of 90% (p<0.05 and the diluted latex showed 6% compared to the negative control. Therefore, our data indicate that S. grantii latex, under research conditions presented gastric protection. Pure latex showed more toxicity than the diluted latex.

  18. Induction of the pi class of glutathione S-transferase by carnosic acid in rat Clone 9 cells via the p38/Nrf2 pathway.

    Science.gov (United States)

    Lin, Chia-Yuan; Wu, Chi-Rei; Chang, Shu-Wei; Wang, Yu-Jung; Wu, Jia-Jiuan; Tsai, Chia-Wen

    2015-06-01

    Induction of phase II enzymes is important in cancer chemoprevention. We compared the effect of rosemary diterpenes on the expression of the pi class of glutathione S-transferase (GSTP) in rat liver Clone 9 cells and the signaling pathways involved. Culturing cells with 1, 5, 10, or 20 μM carnosic acid (CA) or carnosol (CS) for 24 h in a dose-dependent manner increased the GSTP expression. CA was more potent than CS. The RNA level and the enzyme activity of GSTP were also enhanced by CA treatment. Treatment with 10 μM CA highly induced the reporter activity of the enhancer element GPEI. Furthermore, CA markedly increased the translocation of nuclear factor erythroid-2 related factor 2 (Nrf2) from the cytosol to the nucleus after 30 to 60 min. CA the stimulated the protein induction of p38, nuclear Nrf2, and GSTP was diminished in the presence of SB203580 (a p38 inhibitor). In addition, SB203580 pretreatment or silencing of Nrf2 by siRNA suppressed the CA-induced GPEI-DNA binding activity and GSTP protein expression. Knockdown of p38 or Nrf2 by siRNA abolished the activation of p38 and Nrf2 as well as the protein induction and enzyme activity of GSTP by CA. These results suggest that CA up-regulates the expression and enzyme activity of GSTP via the p38/Nrf2/GPEI pathway.

  19. Phenolic Content and Antioxidant Capacity of Essential Oil Obtained from Sawdust of Chamaecyparis obtusa by Microwave-Assisted Hydrodistillation

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    Vivek K. Bajpai

    2013-01-01

    Full Text Available Reactive oxygen species and free radicals play a major role in food deterioration. Current research is directed towards finding naturally occurring antioxidants of plant origin. In the present study, the chemical composition analysis of the essential oil obtained from sawdust of Chamaecyparis obtusa (COEO was conducted by gas chromatography coupled with mass spectroscopy (GC-MS. Further, the phenolic content and antioxidant capacity of the COEO were investigated using different radical scavenging assays. The COEO obtained from the dried sawdust material using a microwave-assisted hydrodistillation technique resulted in the determination of 46 different compounds by GC-MS analysis, representing 98.94 % of total oil content. The COEO was characterised by the presence of mono- and sesquiterpene hydrocarbons, oxygenated mono- and sesquiterpenes, steroids, diterpenes and indole derivatives. At the highest tested concentration range, the COEO showed antioxidant capacity, i.e. the inhibition of DPPH, nitric oxide, superoxide and hydroxyl radicals of 80.16, 82.93, 72.99 and 71.62 %, respectively. Moreover, the COEO displayed concentration-dependent reducing power ability and remarkable inhibitory effect on ferric ion-induced lipid peroxidation in bovine brain extract. In addition, the COEO yielded (6.13±0.05 mg of gallic acid per g of dry mass. The present study confirms that the C. obtusa essential oil has potent antioxidant, lipid peroxidation inhibition and radical scavenging abilities; therefore, it might be used as a natural antioxidant to prevent food deterioration.

  20. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology

    Directory of Open Access Journals (Sweden)

    Agbonlahor Okhuarobo

    2014-06-01

    Full Text Available Andrographis paniculata Wall (family Acanthaceae is one of the most popular medicinal plants used traditionally for the treatment of array of diseases such as cancer, diabetes, high blood pressure, ulcer, leprosy, bronchitis, skin diseases, flatulence, colic, influenza, dysentery, dyspepsia and malaria for centuries in Asia, America and Africa continents. It possesses several photochemical constituents with unique and interesting biological properties. This review describes the past and present state of research on Andrographis paniculata with respect to the medicinal usage, phytochemistry, pharmacological activities, toxicity profile and therapeutic usage, in order to bridge the gap requiring future research opportunities. This review is based on literature study on scientific journals and books from library and electronic sources. Diterpenes, flavonoids, xanthones, noriridoides and other miscellaneous compounds have been isolated from the plant. Extract and pure compounds of the plant have been reported for their antimicrobial, cytotoxicity, anti-protozoan, anti-inflammatory, anti-oxidant, immunostimulant, anti-diabetic, anti-infective, anti-angiogenic, hepato-renal protective, sex hormone/sexual function modulation, liver enzymes modulation insecticidal and toxicity activities. The results of numerous toxicity evaluations of extracts and metabolites isolated from this plant did not show any significant acute toxicity in experimental animals. Detailed and more comprehensive toxicity profile on mammalian tissues and organs is needed in future studies.

  1. Elicitation of andrographolide in the suspension cultures of Andrographis paniculata.

    Science.gov (United States)

    Gandi, Suryakala; Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Giri, Archana

    2012-12-01

    Andrographis paniculata belonging to the family Acanthaceae produces a group of diterpene lactones, one of which is the pharmaceutically important-andrographolide. It is known to possess various important biological properties like anticancer, anti-HIV, anti-inflammatory, etc. This is the first report on the production of andrographolide in the cell suspension cultures of Andrographis paniculata by 'elicitation'. Elicitation was attempted to enhance the andrographolide content in the suspension cultures of Andrographis paniculata and also to ascertain its stimulation under stress conditions or in response to pathogen attack. The maximum andrographolide production was found to be 1.53 mg/g dry cell weight (DCW) at the end of stationary phase during the growth curve. The biotic elicitors (yeast, Escherichia coli, Bacillus subtilis, Agrobacterium rhizogenes 532 and Agrobacterium tumefaciens C 58) were more effective in eliciting the response when compared to the abiotic elicitors (CdCl(2), AgNO(3), CuCl(2) and HgCl(2)). Yeast has shown to stimulate maximum accumulation of 13.5 mg/g DCW andrographolide, which was found to be 8.82-fold higher than the untreated cultures.

  2. Infrared-metabolomics approach in detecting changes in Andrographis paniculata metabolites due to different harvesting ages and times.

    Science.gov (United States)

    Yusof, Nur A'thifah; Isha, Azizul; Ismail, Intan Safinar; Khatib, Alfi; Shaari, Khozirah; Abas, Faridah; Rukayadi, Yaya

    2015-09-01

    The metabolite changes in three germplasm accessions of Malaysia Andrographis paniculata (Burm. F.) Nees, viz. 11265 (H), 11341 (P) and 11248 (T), due to their different harvesting ages and times were successfully evaluated by attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy and translated through multivariate data analysis of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). This present study revealed the feasibility of ATR-FTIR in detecting the trend changes of the major metabolites - andrographolide and neoandrographolide - functional groups in A. paniculata leaves of different accessions. The harvesting parameter was set at three different ages of 120, 150 and 180 days after transplanting (DAT) and at two different time sessions of morning (7:30-10:30 am) and evening (2:30-5.30 pm). OPLS-DA successfully discriminated the A. paniculata crude extracts into groups of which the main constituents - andrographolide and neoandrographolide - could be mainly observed in the morning session of 120 DAT for P and T, while H gave the highest intensities of these constituents at 150 DAT. The information extracted from ATR-FTIR data through OPLS-DA could be useful in tailoring this plant harvest stage in relation to the content of its two major diterpene lactones: andrographolide and neoandrographolide. © 2014 Society of Chemical Industry.

  3. Preferentially Cytotoxic Constituents of Andrographis paniculata and their Preferential Cytotoxicity against Human Pancreatic Cancer Cell Lines.

    Science.gov (United States)

    Lee, Sullim; Morita, Hiroyuki; Tezuka, Yasuhiro

    2015-07-01

    In the course of our search for anticancer agents based on a novel anti-austerity strategy, we found that the 70% EtOH extract of the crude drug Andrographis Herba (aerial parts of Andrographis paniculata), used in Japanese Kampo medicines, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation of the 70% EtOH extract led to the isolation of 21 known compounds consisting of six labdane-type diterpenes (11, 15, 17-19, 21), six flavones (5, 7, 10, 12, 14, 20), three flavanones (2, 6, 16), two sterols (3, 8), a fatty acid (1), a phthalate (4), a triterpene (9), and a monoterpene (13). Among them, 14-deoxy-11,12-didehydroandrographolide (17) displayed the most potent preferential cytotoxicity against PANC-1 and PSN-1 cells with PC50 values of 10.0 μM and 9.27 μM, respectively. Microscopical observation, double staining with ethidium bromide (EB) and acridine orange (AO), and flow cytometry with propidium iodide/annexin V double staining indicated that 14-deoxy-11,12-didehydroandrographolide (17) triggered apoptosis-like cell death in NDM with an amino acids and/or serum-sensitive mode.

  4. Review on liver inflammation and antiinflammatory activity of Andrographis paniculata for hepatoprotection.

    Science.gov (United States)

    Chua, Lee Suan

    2014-11-01

    Till to date, the advancement of medical science and technology is still unable to provide inclusive treatment to liver inflammation caused by neither microbial invasion nor antibiotics nor environmental toxins. Therefore, this article provides the basic knowledge of liver inflammation up to the cellular level and its current medical treatment for inflammatory symptom suppression. Because of the adverse effects of drug treatment, people start looking for comprehensive alternative nowadays. Herbal medicine is believed to be the best of choice because it is being practiced until now for centuries. Although numerous herbal plants have been reported for their efficacies in liver protection, Andrographis paniculata is the most widely used herb for hepatoprotection, particularly in Ayurveda and traditional Chinese medicine. This review covers the significant observation on the biochemical responses due to the experimental induction of liver damage in vitro and in vivo using the marker compound of the herb, namely andrographolide and its derivatives. The standardized extract of A. paniculata with the right phytochemical composition of diterpenic labdanes is likely to have tremendous potential for the development of hepatoprotective medicine. This standardized herbal medicine may not provide immediate remedy, but it can be considered as a comprehensive therapy for liver inflammation. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology

    Science.gov (United States)

    Okhuarobo, Agbonlahor; Falodun, Joyce Ehizogie; Erharuyi, Osayemwenre; Imieje, Vincent; Falodun, Abiodun; Langer, Peter

    2014-01-01

    Andrographis paniculata Wall (family Acanthaceae) is one of the most popular medicinal plants used traditionally for the treatment of array of diseases such as cancer, diabetes, high blood pressure, ulcer, leprosy, bronchitis, skin diseases, flatulence, colic, influenza, dysentery, dyspepsia and malaria for centuries in Asia, America and Africa continents. It possesses several photochemical constituents with unique and interesting biological properties. This review describes the past and present state of research on Andrographis paniculata with respect to the medicinal usage, phytochemistry, pharmacological activities, toxicity profile and therapeutic usage, in order to bridge the gap requiring future research opportunities. This review is based on literature study on scientific journals and books from library and electronic sources. Diterpenes, flavonoids, xanthones, noriridoides and other miscellaneous compounds have been isolated from the plant. Extract and pure compounds of the plant have been reported for their anti-microbial, cytotoxicity, anti-protozoan, anti-inflammatory, anti-oxidant, immunostimulant, anti-diabetic, anti-infective, anti-angiogenic, hepato-renal protective, sex hormone/sexual function modulation, liver enzymes modulation insecticidal and toxicity activities. The results of numerous toxicity evaluations of extracts and metabolites isolated from this plant did not show any significant acute toxicity in experimental animals. Detailed and more comprehensive toxicity profile on mammalian tissues and organs is needed in future studies.

  6. A Validated Method for the Quality Control of Andrographis paniculata Preparations.

    Science.gov (United States)

    Karioti, Anastasia; Timoteo, Patricia; Bergonzi, Maria Camilla; Bilia, Anna Rita

    2017-10-01

    Andrographis paniculata is a herbal drug of Asian traditional medicine largely employed for the treatment of several diseases. Recently, it has been introduced in Europe for the prophylactic and symptomatic treatment of common cold and as an ingredient of dietary supplements. The active principles are diterpenes with andrographolide as the main representative. In the present study, an analytical protocol was developed for the determination of the main constituents in the herb and preparations of A. paniculata . Three different extraction protocols (methanol extraction using a modified Soxhlet procedure, maceration under ultrasonication, and decoction) were tested. Ultrasonication achieved the highest content of analytes. HPLC conditions were optimized in terms of solvent mixtures, time course, and temperature. A reversed phase C18 column eluted with a gradient system consisting of acetonitrile and acidified water and including an isocratic step at 30 °C was used. The HPLC method was validated for linearity, limits of quantitation and detection, repeatability, precision, and accuracy. The overall method was validated for precision and accuracy over at least three different concentration levels. Relative standard deviation was less than 1.13%, whereas recovery was between 95.50% and 97.19%. The method also proved to be suitable for the determination of a large number of commercial samples and was proposed to the European Pharmacopoeia for the quality control of Andrographidis herba. Georg Thieme Verlag KG Stuttgart · New York.

  7. The essential oil qualitative and quantitative composition in the needles of Pinus sylvestris L. growing along industrial transects.

    Science.gov (United States)

    Kupcinskiene, Eugenija; Stikliene, Aida; Judzentiene, Asta

    2008-10-01

    The aim of this study was to evaluate composition of the essential oils in the needles of Pinus sylvestris growing in the areas affected by a cement factory (CF), and an oil refinery (OR). Volatile components of the needles were analyzed by GC and GC/MS. The most heavily polluted CF stand had significantly higher concentration of gamma-Terpinene, Caryophyllene oxide in the current-year needles, while higher concentration of delta-3-Carene, alpha-Terpinene, gamma-Terpinene and Terpinolene was documented for 1-year-old needles. The most heavily polluted OR stand had a significantly higher concentration of Sabinene+beta-Pinene, 1-epi-Cubenol in the current-year needles and a significantly higher concentration of Camphene, Sabinene+beta-Pinene, Myrcene, alpha-Cadinene, 1-epi-Cubenol in the 1-year-old needles than the least polluted site. Along transects an increase in the amount of some diterpenes and a decrease in the components of the shorter chain essential oils was observed. These effects could be at least partially attributed to SO(2).

  8. Antimicrobial activity of needle essential oil of Pinus peuce Griseb. (Pinaceae from Macedonian flora

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    Marija Karapandzova

    2012-03-01

    Full Text Available Chemical composition and antimicrobial activity of needle essential oil, obtained by hydrodistillation from wild Pinus peuce Griseb. (Pinaceae, growing on three different locations in R. Macedonia were investigated in period 2008/2009. Carried out GC/FID/MS analysis, one hundred and three constituents were identified belonging to the six different classes of components: monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, diterpenes and other non-terpene components, representing 88.61/94.04% of the entire oil. The most abundant constituents were α-pinene (12.89/27.34%, β-pinene (6.16/13.13%, limonene + β-phellandrene (2.09/6.64% and bornyl acetate (2.92/11.67% as well as trans-(E-caryophyllene (4.63/7.13% and germacrene D (8.75/20.14%. Antimicrobial screening of Pinus peuce needle essential oil was made by hole-plate diffusion and broth dilution method against 13 bacterial isolates of Gram positive and Gram negative bacteria and one strain of Candida albicans. The most sensitive bacteria against tested Pinus peuce essential oils were Streptococcus pneumonia encompassing Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Acinetobacter spp. and Streptococcus pyogenes. Minimal inhibitory concentrations (MICs of the oils ranged from 7.5- 62.5 µl/ml.

  9. Chemical Composition of the Essential Oils from Different Morphological Parts of Pinus cembra L.

    Science.gov (United States)

    Lis, Anna; Kalinowska, Aleksandra; Krajewska, Agnieszka; Mellor, Karolina

    2017-04-01

    The essential oils from needles, twigs, bark, wood, and cones of Pinus cembra were analyzed by GC-FID, GC/MS, and 1 H-NMR spectroscopy. More than 130 compounds were identified. The oils differed in the quantitative composition. The principal components of the oil from twigs with needles were α-pinene (36.3%), limonene (22.7%) and β-phellandrene (12.0%). The needle oil was dominated by α-pinene (48.4%), whereas in the oil from bark and in the oil from twigs without needles there were limonene (36.2% and 33.6%, resp.) and β-phellandrene (18.8% and 17.1%, resp.). The main constituents of the wood oil as well as cone oil were α-pinene (35.2% and 39.0%, resp.) and β-pinene (10.4% and 18.9%, resp.). The wood oil and the cone oil contained large amounts of oxygenated diterpenes in comparison with needle, twig, and bark oils. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  10. Composition and chemical variability of Corsican Pinus halepensis cone oil.

    Science.gov (United States)

    Nam, Anne-Marie; Casanova, Joseph; Tomi, Félix; Bighelli, Ange

    2014-09-01

    The composition of the essential oil isolated from cones of Pinus halepensis grown in Corsica has been investigated by a combination of chromatographic (CC, GC) and spectroscopic (MS, 13C NMR) techniques. In total, 48 compounds that accounted for 95.5% of the whole composition have been identified. α-Pinene (47.5%) was the major component followed by myrcene (11.0%), (E)-β-caryophyllene (8.3%) and caryophyllene oxide (5.9%). Various diterpenes have been identified by 13C NMR in the fractions of CC. Fifteen oil samples isolated from cones harvested in three forests have been analyzed and two groups of similar importance have been differentiated within the 15 compositions. Oil samples of the first group contained α-pinene (mean 45.0 g/100 g, SD = 5.5) as the major component. The composition of samples of the second group was dominated by myrcene (mean 30.3 g/100g, SD = 9.0) and α-pinene (mean 24.6 g/100 g, SD = 3.1).

  11. The essential oil qualitative and quantitative composition in the needles of Pinus sylvestris L. growing along industrial transects

    Energy Technology Data Exchange (ETDEWEB)

    Kupcinskiene, Eugenija [Department of Biology, Vytautas Magnus University, Vileikos 8, LT-44404 Kaunas (Lithuania)], E-mail: e.kupcinskiene@gmail.com; Stikliene, Aida [Department of Ecology, Lithuanian University of Agriculture, Studentu 11, LT-53361 Kaunas, Akademija (Lithuania); Judzentiene, Asta [Institute of Chemistry, A. Gostauto 9, LT-01108 Vilnius (Lithuania)

    2008-10-15

    The aim of this study was to evaluate composition of the essential oils in the needles of Pinus sylvestris growing in the areas affected by a cement factory (CF), and an oil refinery (OR). Volatile components of the needles were analyzed by GC and GC/MS. The most heavily polluted CF stand had significantly higher concentration of {gamma}-Terpinene, Caryophyllene oxide in the current-year needles, while higher concentration of {delta}-3-Carene, {alpha}-Terpinene, {gamma}-Terpinene and Terpinolene was documented for 1-year-old needles. The most heavily polluted OR stand had a significantly higher concentration of Sabinene + {beta}-Pinene, 1-epi-Cubenol in the current-year needles and a significantly higher concentration of Camphene, Sabinene + {beta}-Pinene, Myrcene, {alpha}-Cadinene, 1-epi-Cubenol in the 1-year-old needles than the least polluted site. Along transects an increase in the amount of some diterpenes and a decrease in the components of the shorter chain essential oils was observed. These effects could be at least partially attributed to SO{sub 2}. - Quantities of components of essential oil in the needles of Scots pine growing around two factories are described in relation to pollution.

  12. Phytochemicals attenuating aberrant activation of β-catenin in cancer cells.

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    Dan Wang

    Full Text Available Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/β-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of β-catenin, a key causative step in a broad spectrum of cancers. Here we report the modulation of lithium chloride-activated canonical Wnt/β-catenin signaling by phytochemicals that have antioxidant, anti-inflammatory or chemopreventive properties. The compounds were first screened with a cervical cancer-derived stable Wnt signaling reporter HeLa cell line. Positive hits were subsequently evaluated for β-catenin degradation, suppression of β-catenin nuclear localization and down-regulation of downstream oncogenic targets of Wnt/β-catenin pathway. Our study shows a novel degradation path of β-catenin protein in HeLa cells by Avenanthramide 2p (a polyphenol and Triptolide (a diterpene triepoxide, respectively from oats and a Chinese medicinal plant. The findings present Avenanthramide 2p as a potential chemopreventive dietary compound that merits further study using in vivo models of cancers; they also provide a new perspective on the mechanism of action of Triptolide.

  13. Cafestol Inhibits Cyclic-Strain-Induced Interleukin-8, Intercellular Adhesion Molecule-1, and Monocyte Chemoattractant Protein-1 Production in Vascular Endothelial Cells

    Science.gov (United States)

    Hao, Wen-Rui; Sung, Li-Chin; Chen, Chun-Chao; Chen, Jin-Jer

    2018-01-01

    Moderate coffee consumption is inversely associated with cardiovascular disease mortality; however, mechanisms underlying this causal effect remain unclear. Cafestol, a diterpene found in coffee, has various properties, including an anti-inflammatory property. This study investigated the effect of cafestol on cyclic-strain-induced inflammatory molecule secretion in vascular endothelial cells. Cells were cultured under static or cyclic strain conditions, and the secretion of inflammatory molecules was determined using enzyme-linked immunosorbent assay. The effects of cafestol on mitogen-activated protein kinases (MAPK), heme oxygenase-1 (HO-1), and sirtuin 1 (Sirt1) signaling pathways were examined using Western blotting and specific inhibitors. Cafestol attenuated cyclic-strain-stimulated intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein- (MCP-) 1, and interleukin- (IL-) 8 secretion. Cafestol inhibited the cyclic-strain-induced phosphorylation of extracellular signal-regulated kinase and p38 MAPK. By contrast, cafestol upregulated cyclic-strain-induced HO-1 and Sirt1 expression. The addition of zinc protoporphyrin IX, sirtinol, or Sirt1 silencing (transfected with Sirt1 siRNA) significantly attenuated cafestol-mediated modulatory effects on cyclic-strain-stimulated ICAM-1, MCP-1, and IL-8 secretion. This is the first study to report that cafestol inhibited cyclic-strain-induced inflammatory molecule secretion, possibly through the activation of HO-1 and Sirt1 in endothelial cells. The results provide valuable insights into molecular pathways that may contribute to the effects of cafestol. PMID:29854096

  14. Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

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    Jueun Oh

    2012-01-01

    Full Text Available Carnosic acid (CA is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS and retinoic acid (RA. In addition, CA blocked the release of nitric oxide (NO, tumor necrosis factor (TNF-α, and prostaglandin E2 (PGE2 from RAW264.7 cells activated by the toll-like receptor (TLR-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS. CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms such Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K, Akt, inhibitor of κBα (IκBα kinase (IKK, and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties.

  15. Feeding preferences of the endemic gastropod Astraea latispina in relation to chemical defenses of Brazilian tropical seaweeds

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    PEREIRA R. C.

    2002-01-01

    Full Text Available Seaweed preference by the Brazilian endemic gastropod Astraea latispina was examined in the laboratory to evaluate the role of secondary metabolites in determining food choice. Of three species of seaweeds examined, Plocamium brasiliense was highly preferred; less so were Sargassum furcatum and Dictyota cervicornis were preferred less. Extracts and/or pure major metabolites of the two potentially chemically-defended seaweeds (P. brasiliense and D. cervicornis were tested as feeding deterrents against A. latispina. Algal extract assays demonstrated that three concentrations of crude organic extract of the red alga P. brasiliense (50%, 100%: natural concentration, and 200% of dry weight: dw did not affect feeding of this gastropod. In contrast, the three concentrations of crude organic extract of the brown alga D. cervicornis (50%, 100% and 200% dw inhibited feeding by A. latispina. The chemical deterrent property of D. cervicornis extract against the gastropod A. latispina occurred due to a mixture of the secodolastane diterpenes isolinearol/linearol (4:1 -- 0.08% dry weight. This is the first report showing that Dictyota cervicornis produces a chemical defense against herbivores using secodolastane diterpenoid. In addition, these results widen the action spectrum of secondary metabolites found in seaweed belonging to this brown algal genus.

  16. NaJAZh Regulates a Subset of Defense Responses against Herbivores and Spontaneous Leaf Necrosis in Nicotiana attenuata Plants[C][W][OA

    Science.gov (United States)

    Oh, Youngjoo; Baldwin, Ian T.; Gális, Ivan

    2012-01-01

    The JASMONATE ZIM DOMAIN (JAZ) proteins function as negative regulators of jasmonic acid signaling in plants. We cloned 12 JAZ genes from native tobacco (Nicotiana attenuata), including nine novel JAZs in tobacco, and examined their expression in plants that had leaves elicited by wounding or simulated herbivory. Most JAZ genes showed strong expression in the elicited leaves, but NaJAZg was mainly expressed in roots. Another novel herbivory-elicited gene, NaJAZh, was analyzed in detail. RNA interference suppression of this gene in inverted-repeat (ir)JAZh plants deregulated a specific branch of jasmonic acid-dependent direct and indirect defenses: irJAZh plants showed greater trypsin protease inhibitor activity, 17-hydroxygeranyllinalool diterpene glycosides accumulation, and emission of volatile organic compounds from leaves. Silencing of NaJAZh also revealed a novel cross talk in JAZ-regulated secondary metabolism, as irJAZh plants had significantly reduced nicotine levels. In addition, irJAZh spontaneously developed leaf necrosis during the transition to flowering. Because the lesions closely correlated with the elevated expression of programmed cell death genes and the accumulations of salicylic acid and hydrogen peroxide in the leaves, we propose a novel role of the NaJAZh protein as a repressor of necrosis and/or programmed cell death during plant development. PMID:22496510

  17. Phytochemicals from Kaempferia angustifolia Rosc. and Their Cytotoxic and Antimicrobial Activities

    Directory of Open Access Journals (Sweden)

    Sook Wah Tang

    2014-01-01

    Full Text Available Phytochemical investigation on rhizomes of Kaempferia angustifolia has afforded a new abietene diterpene, kaempfolienol (1 along with crotepoxide (2, boesenboxide (3, 2′-hydroxy-4,4′,6′-trimethoxychalcone (4, zeylenol (5, 6-methylzeylenol (6, (24S-24-methyl-5α-lanosta-9(11, 25-dien-3β-ol (7, sucrose, β-sitosterol, and its glycoside (8. The structures of the compounds were elucidated on the basis of spectroscopic methods (IR, MS, and NMR. Isolation of 6-methylzeylenol (6, (24S-24-methyl-5α-lanosta-9(11, 25-dien-3β-ol (7, and β-sitosterol-3-O-β-D-glucopyranoside (8 from this plant species has never been reported previously. The spectroscopic data of (7 is firstly described in this paper. Cytotoxic screening indicated that most of the pure compounds tested showed significant activity with (4 showing the most potent activity against HL-60 (human promyelocytic leukemia and MCF-7 (human breast cancer cell lines. However, all extracts and most of the pure compounds tested were found to be inactive against HT-29 (human colon cancer and HeLa (human cervical cancer cell lines. Similarly, none of the extracts or compounds showed activity in the antimicrobial testing.

  18. Effect-directed analysis via hyphenated high-performance thin-layer chromatography for bioanalytical profiling of sunflower leaves.

    Science.gov (United States)

    Móricz, Ágnes M; Ott, Péter G; Yüce, Imanuel; Darcsi, András; Béni, Szabolcs; Morlock, Gertrud E

    2018-01-19

    High-performance thin-layer chromatography (HPTLC) coupled with effect-directed analysis was used for non-targeted screening of sunflower leaf extract for components exhibiting antioxidant, antibacterial and/or cholinesterase enzyme inhibitory effects. The active compounds were characterized by HPTLC-electrospray ionization-high resolution mass spectrometry (ESI-HRMS) and HPTLC-Direct Analysis in Real Time (DART)-MS/MS. The latter ambient ionization technique (less soft than ESI) resulted in oxidation and fragmentation products and characteristic fragment ions. NMR spectroscopy after targeted isolation via preparative normal phase flash chromatography and semi-preparative reversed phase high-performance liquid chromatography supported the identification of two diterpenes to be (-)-kaur-16-en-19-oic acid and 15-α-angeloyloxy-ent-kaur-16-en-19-oic acid. Both compounds found to be multi-potent as they inhibited acetylcholinesterase and butyrylcholinesterase and showed antibacterial effects against Gram-positive Bacillus subtilis and Gram-negative Aliivibrio fischeri bacteria. Kaurenoic acid was also active against the Gram-negative pepper pathogenic Xanthomonas euvesicatoria bacteria. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides.

    Science.gov (United States)

    Dos Santos, Cintia Miranda; Campos, Jaqueline Ferreira; Dos Santos, Helder Freitas; Balestieri, José Benedito Perrella; Silva, Denise Brentan; de Picoli Souza, Kely; Carollo, Carlos Alexandre; Estevinho, Leticia M; Dos Santos, Edson Lucas

    2017-01-01

    Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG) included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies of S. cerevisiae . The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential of M. q. anthidioides geopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.

  20. Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides

    Directory of Open Access Journals (Sweden)

    Cintia Miranda dos Santos

    2017-01-01

    Full Text Available Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies of S. cerevisiae. The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential of M. q. anthidioides geopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.

  1. Seasonal variation of the essential oil from two Brazilian native Aldama La Llave (Asteraceae) species.

    Science.gov (United States)

    Oliveira, Tuane S DE; Bombo, Aline B; Oliveira, Adriana S S DE; Garcia, Vera L; Appezzato-DA-Glória, Beatriz

    2016-01-01

    Aldama arenaria and A. robusta are morphologically similar aromatic species that have seasonal development. The yield and chemical composition of essential oils from aerial and underground vegetative organs of these species were compared to verify the production of volatile metabolites in flowering and dormant phases of development and to identify if there are unique compounds for either species. The major compound in the essential oils from A. arenaria leaves was palustrol (16.22%) and for aerial stems was limonene (15.3%), whereas limonene (11.16%) and α-pinene (19.64%) were the major compounds for leaves and aerial stems from A. robusta, respectively. The major compound for the underground organs was α-pinene, in both species and phenological stages. High amounts of diterpenes were found especially for A. arenaria essential oils. Each analyzed species presented unique compounds, which can provide a characteristic chemical profile for both species helping to solve their taxonomic problems. This study characterized for the first time the yield and essential oil composition of A. arenaria and A. robusta, which have medicinal potential, and some of the compounds in their essential oils are unique to each one and may be useful in helping the correct identification of them.

  2. Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems.

    Science.gov (United States)

    Kemper, Katarina; Hirte, Max; Reinbold, Markus; Fuchs, Monika; Brück, Thomas

    2017-01-01

    With over 50.000 identified compounds terpenes are the largest and most structurally diverse group of natural products. They are ubiquitous in bacteria, plants, animals and fungi, conducting several biological functions such as cell wall components or defense mechanisms. Industrial applications entail among others pharmaceuticals, food additives, vitamins, fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isoprenoids that is quite amenable for genetic engineering. Together with recombinant terpene biosynthesis modules, they are very suitable hosts for heterologous production of high value terpenes. Yet, in contrast to the number of extracted and characterized terpenes, little is known about the specific biosynthetic enzymes that are involved especially in the formation of highly functionalized compounds. Novel approaches discussed in this review include metabolic engineering as well as site-directed mutagenesis to expand the natural terpene landscape. Focusing mainly on the validation of successful integration of engineered biosynthetic pathways into optimized terpene producing Escherichia coli , this review shall give an insight in recent progresses regarding manipulation of mostly diterpene synthases.

  3. Discovery of Natural Products as Novel and Potent FXR Antagonists by Virtual Screening

    Science.gov (United States)

    Diao, Yanyan; Jiang, Jing; Zhang, Shoude; Li, Shiliang; Shan, Lei; Huang, Jin; Zhang, Weidong; Li, Honglin

    2018-04-01

    Farnesoid X receptor (FXR) is a member of nuclear receptor family involved in multiple physiological processes through regulating specific target genes. The critical role of FXR as a transcriptional regulator makes it a promising target for diverse diseases, especially those related to metabolic disorders such as diabetes and cholestasis. However, the underlying activation mechanism of FXR is still a blur owing to the absence of proper FXR modulators. To identify potential FXR modulators, an in-house natural product database (NPD) containing over 4000 compounds was screened by structure-based virtual screening strategy and subsequent hit-based similarity searching method. After the yeast two-hybrid (Y2H) assay, six natural products were identified as FXR antagonists which blocked the CDCA-induced SRC-1 association. The IC50 values of compounds 2a, a diterpene bearing polycyclic skeleton, and 3a, named daphneone with chain scaffold, are as low as 1.29 μM and 1.79 μM, respectively. Compared to the control compound guggulsterone (IC50 = 6.47 μM), compounds 2a and 3a displayed 5-fold and 3-fold higher antagonistic activities against FXR, respectively. Remarkably, the two representative compounds shared low topological similarities with other reported FXR antagonists. According to the putative binding poses, the molecular basis of these antagonists against FXR was also elucidated in this report.

  4. Tiamulin-nitrovin interaction in pigs: a case report and experimental reproduction.

    Science.gov (United States)

    Noa, M; Bulnes, C; Valcárcel, L; Abeledo, M A; Figueredo, J M; Toraño, M E

    2000-10-01

    Tiamulin is a diterpenic veterinary drug widely used in swine for the control of infectious diseases, including swine dysentery and enzootic pneumonia. Tiamulin is well tolerated and only a few drug interactions have been reported with some ionophore antibiotics. A case of tiamulin adverse drug interaction with nitrovin, a nitrofuranic growth promoter, in fattening pigs from a commercial farm is described. To confirm the diagnosis, experimental reproduction was conducted using 20 healthy female pigs. The animals were randomly divided into 4 groups: 1 of them receiving feed medicated with 100 mg tiamulin hydrogen fumarate/kg, another received 20 mg nitrovin/kg to establish the harmlessness of the drugs alone. The other 2 groups received feeds containing both drugs at the previous concentrations, one of which came from the farm. In the last 2 groups clinical signs appeared 72-96 h after initially feeding pigs the tiamulin hydrogen fumarate + nitrovin-containing feed. The animals had uneasiness, anxiety, skin erythema, and rash on snout, vulva and abdomen, and increased body temperatures. No mortality occurred, and there were no characteristic findings during pathological examination. The signs disappeared after 96 h of consuming the medicated feed, leaving a slight skin thickening of the affected regions. All signs disappeared spontaneously 4-5 d after ceasing medication.

  5. The activity and compatibility of the antibiotic tiamulin with other drugs in poultry medicine--A review.

    Science.gov (United States)

    Islam, K M S; Klein, U; Burch, D G S

    2009-11-01

    Tiamulin hydrogen fumarate is a semisynthetic derivative of the diterpene antibiotic pleuromutilin used in poultry medicine to treat mainly Mycoplasma- and Brachyspira-related diseases. Its use over 30 yr has not generally increased the development of resistance to these pathogens but occasionally resistant isolates are encountered. Tiamulin administered at therapeutic levels is relatively quickly absorbed, metabolized in the liver, and eliminated from the body of the bird after a withdrawal period of 72 h, and as a result, meat products can be safely consumed. A zero withdrawal period for eggs has been granted in several European Union states. When administered with different drugs, tiamulin has been shown to have an enhanced activity with the tetracyclines. There is a strong interaction, even death, with the ionophore anticoccidials monensin, narasin, and salinomycin when tiamulin is used at therapeutic levels, but this is dose-related and low doses do not interact. It is thought to be caused by the preferential metabolism of tiamulin in the liver resulting in a build up of the ionophore leading to clinical signs of overdosage. Tiamulin shows a milder interaction, such as temporary growth depression, with maduramicin and semduramicin but is compatible with lasalocid. Although tiamulin shows small benefits in improving performance in healthy animals, its main production benefit is in the face of infection, as a true therapeutic antibiotic.

  6. 2-Methyl-3-buten-2-ol (MBO) synthase expression in Nostoc punctiforme leads to over production of phytols.

    Science.gov (United States)

    Gupta, Dinesh; Ip, Tina; Summers, Michael L; Basu, Chhandak

    2015-01-01

    Phytol is a diterpene alcohol of medicinal importance and it also has potential to be used as biofuel. We found over production of phytol in Nostoc punctiforme by expressing a 2-Methyl-3-buten-2-ol (MBO) synthase gene. MBO synthase catalyzes the conversion of dimethylallyl pyrophosphate (DMAPP) into MBO, a volatile hemiterpene alcohol, in Pinus sabiniana. The result of enhanced phytol production in N. punctiforme, instead of MBO, could be explained by one of the 2 models: either the presence of a native prenyltransferase enzyme with a broad substrate specificity, or appropriation of a MBO synthase metabolic intermediate by a native geranyl diphosphate (GDP) synthase. In this work, an expression vector with an indigenous petE promoter for gene expression in the cyanobacterium N. punctiforme was constructed and MBO synthase gene expression was successfully shown using reverse transcriptase (RT)-PCR and SDS-PAGE. Gas chromatography--mass spectrophotometry (GC-MS) was performed to confirm phytol production from the transgenic N. punctiforme strains. We conclude that the expression of MBO synthase in N. punctiforme leads to overproduction of an economically important compound, phytol. This study provides insights about metabolic channeling of isoprenoids in cyanobacteria and also illustrates the challenges of bioengineering non-native hosts to produce economically important compounds.

  7. Screening and fractionation of plant extracts with antiproliferative activity on human peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Souza-Fagundes Elaine M

    2002-01-01

    Full Text Available Three hundred and thirteen extracts from 136 Brazilian plant species belonging to 36 families were tested for their suppressive activity on phytohemaglutinin (PHA stimulated proliferation of human peripheral blood mononuclear cells (PBMC. The proliferation was evaluated by the amount of [³H]-thymidine incorporated by the cells. Twenty extracts inhibited or strongly reduced the proliferation in a dose-dependent manner at doses between 10 and 100 µg/ml. Three of these extracts appeared to be non-toxic to lymphocytes, according to the trypan blue permeability assay and visual inspection using optical microscopy. Bioassay-guided fractionation of Alomia myriadenia extract showed that myriadenolide, a labdane diterpene known to occur in this species, could account for the observed activity of the crude extract. Using a similar protocol, an active fraction of the extract from Gaylussacia brasiliensis was obtained. Analysis of the ¹H and13C NMR spectra of this fraction indicates the presence of an acetylated triterpene whose characterization is underway. The extract of Himatanthus obovatus is currently under investigation.

  8. Evaluation of the potential use of rebaudioside-A as sweetener for diet jam

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    Ana Cláudia Guilhen de Carvalho

    2013-09-01

    Full Text Available Sweeteners based on stevia extract contain a series of diterpene glycosides derivatives from steviol, standing out the rebaudioside-A. There is no tabletop sweeteners in the market formulated purely with rebaudioside-A yet, so its use in foods depends on the development of new products followed by physicochemical and sensory evaluations. This work presents the formulation of a diet strawberry jam dyed with cranberry juice and sweetened with rebaudioside-A purified from stevia plants of the lineage UEM-320 developed in the Centro de Estudos de Produtos Naturais da Universidade Estadual de Maringá. Evaluations of physicochemical properties, microbiological and sensory characteristics were carried out for the product in comparison with a control sweetened with equal amount of sucralose. The results showed that the physicochemical characteristics of the sample and the control are not significantly different and the supplementation with cranberry juice increased both color and total phenolic content in both samples. The sensory acceptability indicated a significant preference for the formulation sweetened with 100% of rebaudioside-A, only in the items flavor and purchase intent. We concluded that rebaudioside-A has a better sensory performance than sucralose, even this last one being 1.33 fold sweeter than rebaudioside-A.

  9. Screening of acetylcholinesterase inhibitors in marine organisms from the Caribbean Sea.

    Science.gov (United States)

    Castellanos, Fabio; Amaya-García, Fabián; Tello, Edisson; Ramos, Freddy Alejandro; Umaña, Adriana; Puyana, Mónica; Resende, Jackson A L C; Castellanos, Leonardo

    2018-06-04

    The acetylcholinesterase inhibitory activity of 89 organic extracts from marine organisms was evaluated through a TLC bioautography methodology. Extracts from soft corals (Eunicea and Plexaura) were the most active compared with extracts from sponges. The bioguided chemical study of the most active extract, obtained from Pseudoplexaura porosa, led to the isolation of a diterpene with spectroscopic properties consistent to those published to the cembrane Steylolide. However, further analysis by X-ray diffraction indicated that the compound was the 14-acetoxycrassine (1), correcting the structure reported to the Styelolide. Additionally, the acetylcholinesterase inhibitory activity of fourteen cembranoids (2-15) isolated from soft corals Eunicea knighti and Pseudoplexaura flagellosa was evaluated. Cembranoids 2, 3 and 4 were the most active compounds in the TLC bioassay. Then, the most promising cembranoids, 14-acetoxycrassine (1) and asperdiol (2), were tested quantitatively and they exhibited IC 50 values of 1.40 ± 0.113 and 0.358 ± 0.130 μM, respectively.

  10. Synthesis of rebaudioside-A by enzymatic transglycosylation of stevioside present in the leaves of Stevia rebaudiana Bertoni.

    Science.gov (United States)

    Adari, Bhaskar Rao; Alavala, Sateesh; George, Sara A; Meshram, Harshadas M; Tiwari, Ashok K; Sarma, Akella V S

    2016-06-01

    Rebaudioside-A is the second most abundant sweet diterpene glycoside (1-3%) present in the leaves of Stevia rebaudiana Bertoni, and is now being considered as a possible sucrose substitute due to its pleasant organoleptic properties and associated health benefits. In the present study, a novel in situ enzymatic transglycosylation of stevioside has been developed by pre-treating the stevia leaves with cellulase and adding soluble starch as the glucosyl donor. The results confirm that the transglycosylation of stevioside led to an enrichment in the rebaudioside-A content from 4% to 66%. This was further purified by multiple column chromatography to obtain 95% pure rebaudioside-A. The isolated rebaudioside-A showed concentration-dependent α-glucosidase inhibitory activity with IC50=35.01 μg/ml. Thus the study highlights the biotransformation of stevioside present in stevia leaves to rebaudioside-A by a simple, inexpensive and eco-friendly process that has commercial potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Base substitution mutations in uridinediphosphate-dependent glycosyltransferase 76G1 gene of Stevia rebaudiana causes the low levels of rebaudioside A: mutations in UGT76G1, a key gene of steviol glycosides synthesis.

    Science.gov (United States)

    Yang, Yong-Heng; Huang, Su-Zhen; Han, Yu-Lin; Yuan, Hai-Yan; Gu, Chun-Sun; Zhao, Yan-Hai

    2014-07-01

    Steviol glycosides, extracted from the leaves of Stevia rebaudiana (Bert) Bertoni, are calorie-free sugar substitute of natural origin with intensely sweet (Boileau et al., 2012). Stevioside and rebaudioside A are the two main kinds of the diterpenic glycosides. We analyzed the concentration of stevioside and rebaudioside A in Stevia leaves of about 500 samples (hybrid progenies) and discovered a mutation plant "Z05" with very low levels of rebaudioside A. Because UGT76G1, a uridinediphosphate-dependent glycosyltransferases, is responsible for the conversion from stevioside to rebaudioside A (Richman et al., 2005), so mutation identification was done by sequencing the candidate gene, UGT76G1. In this study molecular analysis of two strains revealed a heterozygotic nonsense mutation of c.389T > G (p.L121X) in UGT76G1. Meanwhile, we found some amino acid substitutions significant change the protein structure. And the difference of enzyme activity between two strains proved the lack of functionality of UGT76G1 of the mutation "Z05". So the nonsense mutation and amino acid substitution mutation resulted in the low levels of rebaudioside A. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Authentication of the botanical origin of Western herbal products using Cimicifuga and Vitex products as examples.

    Science.gov (United States)

    Masada, Sayaka

    2016-07-01

    Various herbal medicines have been developed and used in various parts of the world for thousands of years. Although locally grown indigenous plants were originally used for traditional herbal preparations, Western herbal products are now becoming popular in Japan with the increasing interest in health. At the same time, there are growing concerns about the substitution of ingredients and adulteration of herbal products, highlighting the need for the authentication of the origin of plants used in herbal products. This review describes studies on Cimicifuga and Vitex products developed in Europe and Japan, focusing on establishing analytical methods to evaluate the origins of material plants and finished products. These methods include a polymerase chain reaction-restriction fragment length polymorphism method and a multiplex amplification refractory mutation system method. A genome-based authentication method and liquid chromatography-mass spectrometry-based authentication for black cohosh products, and the identification of two characteristic diterpenes of agnus castus fruit and a shrub chaste tree fruit-specific triterpene derivative are also described.

  13. Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents.

    Science.gov (United States)

    Hajdú, Zsuzsanna; Hohmann, Judit; Forgo, Peter; Martinek, Tamás; Dervarics, Máté; Zupkó, István; Falkay, György; Cossuta, Daniel; Máthé, Imre

    2007-04-01

    From the n-hexane fraction of the fruits of Vitex agnus-castus, two labdane-type diterpenes, vitetrifolin B and C, were isolated by means of multiple chromatographic separations, together with the previously identified rotundifuran, vitexilactone and the sesquiterpene spathulenol. From the EtOAc fraction, eupatorin was identified for the first time, besides the known casticin, penduletin, vitexin and orientin. The n-hexane, EtOAc and MeOH-H(2)O fractions of the MeOH extract of Agni-casti fructus were subjected to in vitro antioxidant assays. The EtOAc extract displayed a significant concentration-dependent effect when tested by 1,1-diphenyl-2-picrylhydrasyl (DPPH) free radical assay (IC(50) = 68 microg/mL) and against the autooxidation of a standard rat brain homogenate (IC(50) = 14 microg/mL). The MeOH-H(2)O fraction was less active with 3643 microg/mL (DPPH test) and IC(50) = 125 microg/mL (rat brain homogenate), while the n-hexane phase proved to be inactive. The main flavonoid constituents of the EtOAc extract, casticin, vitexin and orientin were assayed for antioxidant activity and found that only casticin possesses a marked lipid peroxidation inhibitory effect (IC(50) = 0.049 mm) compared with that of the positive control ascorbic acid (IC(50) = 0.703 mm).

  14. Pharmacological activities of Vitex agnus-castus extracts in vitro.

    Science.gov (United States)

    Meier, B; Berger, D; Hoberg, E; Sticher, O; Schaffner, W

    2000-10-01

    The pharmacological effects of ethanolic Vitex agnus-castus fruit-extracts (especially Ze 440) and various extract fractions of different polarities were evaluated both by radioligand binding studies and by superfusion experiments. A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL. Binding, neither to the histamine H1, benzodiazepine and OFQ receptor, nor to the binding-site of the serotonin (5-HT) transporter, was significantly inhibited. The lipophilic fractions contained the diterpenes rotun-difuran and 6beta,7beta-diacetoxy-13-hydroxy-labda-8,14-dien . They exhibited inhibitory actions on dopamine D2 receptor binding. While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction. Standardised Ze 440 extracts of different batches were of constant pharmacological quality according to their potential to inhibit the binding to D2 receptors. In superfusion experiments, the aqueous fraction of a methanolic extract inhibited the release of acetylcholine in a concentration-dependent manner. In addition, the potent D2 receptor antagonist spiperone antagonised the effect of the extract suggesting a dopaminergic action mediated by D2 receptor activation. Our results indicate a dopaminergic effect of Vitex agnus-castus extracts and suggest additional pharmacological actions via opioid receptors.

  15. Funktionelle in vitro-Effekte CAMP/CGMP-modulierender Pharmaka am humanen Detrusormuskel

    Directory of Open Access Journals (Sweden)

    Ückert St

    2002-01-01

    Full Text Available Die zyklischen Nukleotidmonophosphate cAMP und cGMP regulieren als intrazelluläre Second Messenger zahlreiche Gewebe- und Organfunktionen. cAMP und cGMP werden von zellulären Adenylat- und Guanylatzyklasen synthetisiert und von Phosphodiesterasen degradiert, die somit Schlüsselenzyme im Prozeß der Tonusregulation glatter Muskulatur sind. Die Markteinführung des PDE5-Inhibitors Sildenafil (Viagra hat dem Konzept der PDE-Inhibition auch in der Urologie breite Akzeptanz verschafft. Eigene Arbeiten der vergangenen Jahre beschreiben die Präsenz der PDE-Isoenzyme 1, 2, 3, 4 und 5 in der Muskulatur des humanen Detrusors und zeigen das klinische Potential des PDE1-Inhibitors Vinpocetin in der Behandlung der motorischen Dranginkontinenz. Mit dem Ziel der Charakterisierung geeigneter Substanzen für die Pharmakotherapie der Detrusorhyperaktivität haben wir die in vitro-Effekte neuer, selektiver Inhibitoren der PDE des Typs 2, 3 und 5 auf isolierte humane Detrusormuskulatur untersucht und mit denen des Diterpens Forskolin (Aktivator der Adenylatzyklase und der Stickoxid (NO-Donatoren Dihydropyridin (DHP und Na+Nitroprussid (NNP verglichen.

  16. Pinus halepensis, Pinus pinaster, Pinus pinea and Pinus sylvestris Essential Oils Chemotypes and Monoterpene Hydrocarbon Enantiomers, before and after Inoculation with the Pinewood Nematode Bursaphelenchus xylophilus.

    Science.gov (United States)

    Rodrigues, Ana M; Mendes, Marta D; Lima, Ana S; Barbosa, Pedro M; Ascensão, Lia; Barroso, José G; Pedro, Luis G; Mota, Manuel M; Figueiredo, A Cristina

    2017-01-01

    Pinewood nematode (PWN), Bursaphelenchus xylophilus, is the causal agent of pine wilt disease, a serious threat to global forest populations of conifers, especially Pinus spp. A time-course study of the essential oils (EOs) of 2-year-old Pinus halepensis, Pinus pinaster, Pinus pinea and Pinus sylvestris following inoculation with the PWN was performed. The constitutive and nematode inoculation induced EOs components were analyzed at both the wounding or inoculation areas and at the whole plant level. The enantiomeric ratio of optically active main EOs components was also evaluated. External symptoms of infection were observed only in P. pinaster and P. sylvestris 21 and 15 days after inoculation, respectively. The EO composition analysis of uninoculated and unwounded plants revealed the occurrence of chemotypes for P. pinaster, P. halepensis and P. sylvestris, whereas P. pinea showed a homogenous EO composition. When whole plants were evaluated for EO and monoterpene hydrocarbon enantiomeric chemical composition, no relevant qualitative and quantitative differences were found. Instead, EO analysis of inoculated and uninoculated wounded areas revealed an increase of sesquiterpenes and diterpenic compounds, especially in P. pinea and P. halepensis, comparatively to healthy whole plants EOs. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  17. Rosemary Extracts Upregulate Nrf2, Sestrin2, and MRP2 Protein Level in Human Hepatoma HepG2 Cells

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    Xiao-pei Tong

    2017-01-01

    Full Text Available In the past few decades, the incidence of liver cancer has been rapidly rising across the world. Rosemary is known to possess antioxidant activity and is used as natural antioxidant food preservative. It is proposed to have anticancer activity in treating different tumor models. In this study, we try to explore the impact of rosemary extracts on upregulating the level of Nrf2 and Nrf2-regulatory proteins, Sestrin2 and MRP2 in HepG2 cells, and to speculate its potential mechanism. The anticancer activity of rosemary extract, including its polyphenolic diterpenes carnosic acid and carnosol, was evaluated to understand the potential effect on HepG2 cells. Rosemary extract, carnosic acid, and carnosol induced the expression of Sestrin2 and MRP2 associate with enhancement of Nrf2 protein level in HepG2 cells, in which carnosic acid showed most obvious effect. Although the activation pathway of Nrf2/ARE was not exactly assessed, it can be assumed that the enhancement of expression of Sestrin2 and MRP2 may result from upregulation of Nrf2.

  18. A survey of bacterial, fungal and plant metabolites against Aedes aegypti (Diptera: Culicidae, the vector of yellow and dengue fevers and Zika virus

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    Masi Marco

    2017-06-01

    Full Text Available Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. Some bacterial, fungal and plant metabolites belonging to different chemical subgroups, including Amaryllidaceae alkaloids, anthracenes, azoxymethoxytetrahydropyrans, cytochalasans, 2,5-diketopiperazines, isochromanones, naphthoquinones, organic small acids and their methyl esters, sterols and terpenes including sesquiterpenes and diterpenes, were tested for their larvicidal and adulticidal activity against Ae. aegypti. Out of 23 compounds tested, gliotoxin exhibited mosquitocidal activity in both bioassays with an LC50 value of 0.0257 ± 0.001 µg/µL against 1st instar Ae. aegypti and LD50 value of 2.79 ± 0.1197 µg/mosquito against adult female Ae. aegypti. 2-Methoxy-1,4-naphthoquinone and cytochalasin A showed LC50 values of 0.0851 ± 0.0012 µg/µL and 0.0854 ± 0.0019 µg/µL, respectively, against Ae. aegypti larvae. In adult bioassays, fusaric acid (LD50= 0.8349 ± 0.0118 µg/mosquito, 3-nitropropionic acid (LD50 = 1.6641 ± 0.0494 µg/mosquito and α-costic acid (LD50 = 2.547 ± 0.0835 µg/mosquito exhibited adulticidal activity. Results from the current study confirm that compounds belonging to cytochalsin, diketopiperazine, naphthoquinone and low molecular weight organic acid groups are active and may stimulate further SAR investigations.

  19. Plants as natural antioxidants for meat products

    Science.gov (United States)

    Tomović, V.; Jokanović, M.; Šojić, B.; Škaljac, S.; Ivić, M.

    2017-09-01

    The meat industry is demanding antioxidants from natural sources to replace synthetic antioxidants because of the negative health consequences or beliefs regarding some synthetic ones. Plants materials provide good alternatives. Spices and herbs, generally used for their flavouring characteristics, can be added to meat products in various forms: whole, ground, or as isolates from their extracts. These natural antioxidants contain some active compounds, which exert antioxidative potential in meat products. This antioxidant activity is most often due to phenolic acids, phenolic diterpenes, flavonoids and volatile oils. Each of these compounds often has strong H-donating activity, thus making them extremely effective antioxidants; some compounds can chelate metals and donate H to oxygen radicals, thus slowing oxidation via two mechanisms. Numerous studies have demonstrated the efficacy of natural antioxidants when used in meat products. Based on this literature review, it can be concluded that natural antioxidants are added to fresh and processed meat and meat products to delay, retard, or prevent lipid oxidation, retard development of off-flavours (rancidity), improve colour stability, improve microbiological quality and extend shelf-life, without any damage to the sensory or nutritional properties.

  20. Biochemical Studies on Rosemary Extracts as an Antioxidant in Irradiated Rats

    International Nuclear Information System (INIS)

    Abady, M.M.; Zahran, A.M.; Mansour, S.Z.; Ragab, E.A.

    2003-01-01

    The antioxidant properties of rosemary (Rosmarinus officinalis) essential oil and crude ethanolic extract, have been attributed to its phenolic diterpene, carnosol, carnosic acid, caffeic acid and its derivatives such as rosmarinic acid. These aroma compounds were identified to protect biological membranes from oxidative stress in addition to divers pharmacological and therapeutic activities. This study was undertaken to investigate the effect of natural extract derived from rosemary herb, as an antioxidant defensive element in irradiated rats. Mixture of essential oil and hydroalcoholic extract was orally administered to rats by gavage (150 mg/kg B.w.) for 35 days before exposure to the first fraction of irradiation exposure and during the whole period of irradiation treatment (12 days). Whole body irradiation was delivered as fractionated doses at 1 Gy increment every other day up to total cumulative dose of 6 Gy. Changes in the content of reduced glutathion (GSH), glutathion peroxidase (GSHPx), glucose -6- phosphate dehydrogenase (G-6-PD), superoxide dismutase (SOD) and catalase (Cat.) in blood, liver and spleen were evaluated in different rat groups. The results revealed that transient noticeable increase during the 1st hour post irradiation in the aforementioned parameters, followed by significant decrease recorded after 7 days. Rats supplemented rosemary extract before irradiation have significantly ameliorate the radiation induced depletion in the antioxidant component system

  1. Rosmarinus Officinalis Leaves as a Natural Source of Bioactive Compounds

    Directory of Open Access Journals (Sweden)

    Isabel Borrás-Linares

    2014-11-01

    Full Text Available In an extensive search for bioactive compounds from plant sources, the composition of different extracts of rosemary leaves collected from different geographical zones of Serbia was studied. The qualitative and quantitative characterization of 20 rosemary (Rosmarinus officinalis samples, obtained by microwave-assisted extraction (MAE, was determined by high performance liquid chromatography coupled to electrospray quadrupole-time of flight mass spectrometry (HPLC–ESI-QTOF-MS. The high mass accuracy and true isotopic pattern in both MS and MS/MS spectra provided by the QTOF-MS analyzer enabled the characterization of a wide range of phenolic compounds in the extracts, including flavonoids, phenolic diterpenes and abietan-type triterpenoids, among others. According to the data compiled, rosemary samples from Sokobanja presented the highest levels in flavonoids and other compounds such as carnosol, rosmaridiphenol, rosmadial, rosmarinic acid, and carnosic acid. On the other hand, higher contents in triterpenes were found in the extracts of rosemary from Gložan (Vojvodina.

  2. Secondary metabolites from marine microorganisms.

    Science.gov (United States)

    Kelecom, Alphonse

    2002-03-01

    After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  3. Secondary metabolites from marine microorganisms

    Directory of Open Access Journals (Sweden)

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  4. The Genome of the Generalist Plant Pathogen Fusarium avenaceum Is Enriched with Genes Involved in Redox, Signaling and Secondary Metabolism

    Science.gov (United States)

    Lysøe, Erik; Harris, Linda J.; Walkowiak, Sean; Subramaniam, Rajagopal; Divon, Hege H.; Riiser, Even S.; Llorens, Carlos; Gabaldón, Toni; Kistler, H. Corby; Jonkers, Wilfried; Kolseth, Anna-Karin; Nielsen, Kristian F.; Thrane, Ulf; Frandsen, Rasmus J. N.

    2014-01-01

    Fusarium avenaceum is a fungus commonly isolated from soil and associated with a wide range of host plants. We present here three genome sequences of F. avenaceum, one isolated from barley in Finland and two from spring and winter wheat in Canada. The sizes of the three genomes range from 41.6–43.1 MB, with 13217–13445 predicted protein-coding genes. Whole-genome analysis showed that the three genomes are highly syntenic, and share>95% gene orthologs. Comparative analysis to other sequenced Fusaria shows that F. avenaceum has a very large potential for producing secondary metabolites, with between 75 and 80 key enzymes belonging to the polyketide, non-ribosomal peptide, terpene, alkaloid and indole-diterpene synthase classes. In addition to known metabolites from F. avenaceum, fuscofusarin and JM-47 were detected for the first time in this species. Many protein families are expanded in F. avenaceum, such as transcription factors, and proteins involved in redox reactions and signal transduction, suggesting evolutionary adaptation to a diverse and cosmopolitan ecology. We found that 20% of all predicted proteins were considered to be secreted, supporting a life in the extracellular space during interaction with plant hosts. PMID:25409087

  5. Feeding preferences of the endemic gastropod Astraea latispina in relation to chemical defenses of Brazilian tropical seaweeds

    Directory of Open Access Journals (Sweden)

    R. C. PEREIRA

    Full Text Available Seaweed preference by the Brazilian endemic gastropod Astraea latispina was examined in the laboratory to evaluate the role of secondary metabolites in determining food choice. Of three species of seaweeds examined, Plocamium brasiliense was highly preferred; less so were Sargassum furcatum and Dictyota cervicornis were preferred less. Extracts and/or pure major metabolites of the two potentially chemically-defended seaweeds (P. brasiliense and D. cervicornis were tested as feeding deterrents against A. latispina. Algal extract assays demonstrated that three concentrations of crude organic extract of the red alga P. brasiliense (50%, 100%: natural concentration, and 200% of dry weight: dw did not affect feeding of this gastropod. In contrast, the three concentrations of crude organic extract of the brown alga D. cervicornis (50%, 100% and 200% dw inhibited feeding by A. latispina. The chemical deterrent property of D. cervicornis extract against the gastropod A. latispina occurred due to a mixture of the secodolastane diterpenes isolinearol/linearol (4:1 -- 0.08% dry weight. This is the first report showing that Dictyota cervicornis produces a chemical defense against herbivores using secodolastane diterpenoid. In addition, these results widen the action spectrum of secondary metabolites found in seaweed belonging to this brown algal genus.

  6. Lipophilic Fraction of Cultivated Bifurcaria bifurcata R. Ross: Detailed Composition and In Vitro Prospection of Current Challenging Bioactive Properties

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    Sónia A. O. Santos

    2017-11-01

    Full Text Available Macroalgae have been seen as an alternative source of molecules with promising bioactivities to use in the prevention and treatment of current lifestyle diseases. In this vein, the lipophilic fraction of short-term (three weeks cultivated Bifurcaria bifurcata was characterized in detail by gas chromatography–mass spectrometry (GC-MS. B. bifurcata dichloromethane extract was composed mainly by diterpenes (1892.78 ± 133.97 mg kg−1 dry weight (DW, followed by fatty acids, both saturated (550.35 ± 15.67 mg kg−1 DW and unsaturated (397.06 ± 18.44 mg kg−1 DW. Considerable amounts of sterols, namely fucosterol (317.68 ± 26.11 mg kg−1 DW were also found. In vitro tests demonstrated that the B. bifurcata lipophilic extract show antioxidant, anti-inflammatory and antibacterial activities (against both Gram-positive and Gram-negative bacteria, using low extract concentrations (in the order of µg mL−1. Enhancement of antibiotic activity of drug families of major clinical importance was observed by the use of B. bifurcata extract. This enhancement of antibiotic activity depends on the microbial strain and on the antibiotic. This work represents the first detailed phytochemical study of the lipophilic extract of B. bifurcata and is, therefore, an important contribution for the valorization of B. bifurcata macroalgae, with promising applications in functional foods, nutraceutical, cosmetic and biomedical fields.

  7. Geranylgeranyl diphosphate synthase from Scoparia dulcis and Croton sublyratus. Plastid localization and conversion to a farnesyl diphosphate synthase by mutagenesis.

    Science.gov (United States)

    Sitthithaworn, W; Kojima, N; Viroonchatapan, E; Suh, D Y; Iwanami, N; Hayashi, T; Noji, M; Saito, K; Niwa, Y; Sankawa, U

    2001-02-01

    cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene-producing plants, Scoparia dulcis and Croton sublyratus, have been isolated using the homology-based polymerase chain reaction (PCR) method. Both clones contained highly conserved aspartate-rich motifs (DDXX(XX)D) and their N-terminal residues exhibited the characteristics of chloroplast targeting sequence. When expressed in Escherichia coli, both the full-length and truncated proteins in which the putative targeting sequence was deleted catalyzed the condensation of farnesyl diphosphate and isopentenyl diphosphate to produce geranylgeranyl diphosphate (GGPP). The structural factors determining the product length in plant GGPPSs were investigated by constructing S. dulcis GGPPS mutants on the basis of sequence comparison with the first aspartate-rich motif (FARM) of plant farnesyl diphosphate synthase. The result indicated that in plant GGPPSs small amino acids, Met and Ser, at the fourth and fifth positions before FARM and Pro and Cys insertion in FARM play essential roles in determination of product length. Further, when a chimeric gene comprised of the putative transit peptide of the S. dulcis GGPPS gene and a green fluorescent protein was introduced into Arabidopsis leaves by particle gun bombardment, the chimeric protein was localized in chloroplasts, indicating that the cloned S. dulcis GGPPS is a chloroplast protein.

  8. Geranylgeranyl diphosphate synthases from Scoparia dulcis and Croton sublyratus. cDNA cloning, functional expression, and conversion to a farnesyl diphosphate synthase.

    Science.gov (United States)

    Kojima, N; Sitthithaworn, W; Viroonchatapan, E; Suh, D Y; Iwanami, N; Hayashi, T; Sankaw, U

    2000-07-01

    cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene producing plants, Scoparia dulcis and Croton sublyratus, were isolated using the homology-based polymerase chain reaction method. Both cloned genes showed high amino acid sequence homology (60-70%) to other plant GGPPSs and contained highly conserved aspartate-rich motifs. The obtained clones were functionally expressed in Escherichia coli and showed sufficient GGPPS activity to catalyze the condensation of farnesyl diphosphate (FPP) and isopentenyl diphosphate to form geranylgeranyl diphosphate. To investigate the factor determining the product chain length of plant GGPPSs, S. dulcis GGPPS mutants in which either the small amino acids at the fourth and fifth positions before the first aspartate-rich motif (FARM) were replaced with aromatic amino acids or in which two additional amino acids in FARM were deleted were constructed. Both mutants behaved like FPPS-like enzymes and almost exclusively produced FPP when dimethylallyl diphosphate was used as a primer substrate, and failed to accept FPP as a primer substrate. These results indicate that both small amino acids at the fourth and fifth positions before FARM and the amino acid insertion in FARM play essential roles in product length determination in plant GGPPSs.

  9. [Coffee as hepatoprotective factor].

    Science.gov (United States)

    Szántová, Mária; Ďurkovičová, Zuzana

    The mind about the coffee did change upon the recent studies and metaanalysis of the last years. Consensual protective effect of coffee on the progression of chronic liver diseases (NASH, viral hepatitis, liver cirrhosis, hepatocelullar carcinoma) was detected in experimental, clinical and large population studies together with decrease of mortality. Antioxidant, antifibrotic, insulinsensitizing and anticarcinogenic effect of coffee were detected. Modulation of genetic expression of key enzymes of fatty acid synthesis, modulation of mRNA included in autophagia, reduction of stress of endoplasmatic reticulum together with decrease of proinflammatory cytokines and decrease of fibrogenesis are main mechanisms. Chlorogenic acids, diterpens (cafestol, kahweol), caffein, polyfenols and melanoidins are key protective components of coffee. Inverse dose-dependent correlation of coffee consumption with liver diseases was found in clinical and population studies. Coffee is non-pharmacological tool of primary and secondary prevention of chronic liver diseases. Review of published data together with supposed mechanisms of hepatoprotection are given.Key words: coffee - hepatoprotective effect - metaanalysis.

  10. How coffee affects metabolic syndrome and its components.

    Science.gov (United States)

    Baspinar, B; Eskici, G; Ozcelik, A O

    2017-06-21

    Metabolic syndrome, with its increasing prevalence, is becoming a major public health problem throughout the world. Many risk factors including nutrition play a role in the emergence of metabolic syndrome. Of the most-consumed beverages in the world, coffee contains more than 1000 components such as caffeine, chlorogenic acid, diterpenes and trigonelline. It has been proven in many studies that coffee consumption has a positive effect on chronic diseases. In this review, starting from the beneficial effects of coffee on health, the relationship between coffee consumption and metabolic syndrome and its components has been investigated. There are few studies investigating the relationship between coffee and metabolic syndrome, and the existing ones put forward different findings. The factors leading to the differences are thought to stem from coffee variety, the physiological effects of coffee elements, and the nutritional ingredients (such as milk and sugar) added to coffee. It is reported that consumption of coffee in adults up to three cups a day reduces the risk of Type-2 diabetes and metabolic syndrome.

  11. [Coffee in Cancer Chemoprevention].

    Science.gov (United States)

    Neuwirthová, J; Gál, B; Smilek, P; Urbánková, P

    Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process. Maximum antioxidant activity is observed for medium-roasted coffee. The roasting process leads to the formation of several components, e.g., melanoidins, which have antioxidant and anti-inflammatory properties. Coffee also contains two specific diterpenes, cafestol and kahweol, which have anticarcinogenic properties. Roasted coffee is a complex mixture of various chemicals. Previous studies have reported that the chemopreventive components present in coffee induce apoptosis, inhibit growth and metastasis of tumor cells, and elicit antiangiogenic effects. A meta-analysis of epidemiological studies showed that coffee consumption is associated with a lower risk of developing various malignant tumors. This review summarizes the molecular mechanisms and the experimental and epidemiological evidence supporting the chemopreventive effect of coffee.Key words: coffee - chemoprevention - antioxidative enzyme - detoxification enzyme - anti-inflammatory effect The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 9. 2016Accepted: 24. 11. 2016.

  12. Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Kotowski, Ulana; Heiduschka, Gregor; Eckl-Dorna, Julia; Kranebitter, Veronika; Stanisz, Isabella; Brunner, Markus; Lill, Claudia; Thurnher, Dietmar; Seemann, Rudolf; Schmid, Rainer

    2015-01-01

    Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation. (orig.) [de

  13. Coffee and liver health.

    Science.gov (United States)

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients.

  14. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    International Nuclear Information System (INIS)

    Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel Ángel

    2014-01-01

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells

  15. Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

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    Gaetan eMaertens

    2015-01-01

    Full Text Available We present a review of natural product syntheses accomplished in our laboratory during the last five years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the aromatic ring umpolung concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol, a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor, acetylaspidoalbidine (an antitumor agent, fortucine (antiviral and antitumor, erysotramidine (curare-like effect, platensimycin (an antibiotic, and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis. These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

  16. Do Coffee Polyphenols Have a Preventive Action on Metabolic Syndrome Associated Endothelial Dysfunctions? An Assessment of the Current Evidence

    Science.gov (United States)

    Yamagata, Kazuo

    2018-01-01

    Epidemiologic studies from several countries have found that mortality rates associated with the metabolic syndrome are inversely associated with coffee consumption. Metabolic syndrome can lead to arteriosclerosis by endothelial dysfunction, and increases the risk for myocardial and cerebral infarction. Accordingly, it is important to understand the possible protective effects of coffee against components of the metabolic syndrome, including vascular endothelial function impairment, obesity and diabetes. Coffee contains many components, including caffeine, chlorogenic acid, diterpenes and trigonelline. Studies have found that coffee polyphenols, such as chlorogenic acids, have many health-promoting properties, such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetes, and antihypertensive properties. Chlorogenic acids may exert protective effects against metabolic syndrome risk through their antioxidant properties, in particular toward vascular endothelial cells, in which nitric oxide production may be enhanced, by promoting endothelial nitric oxide synthase expression. These effects indicate that coffee components may support the maintenance of normal endothelial function and play an important role in the prevention of metabolic syndrome. However, results related to coffee consumption and the metabolic syndrome are heterogeneous among studies, and the mechanisms of its functions and corresponding molecular targets remain largely elusive. This review describes the results of studies exploring the putative effects of coffee components, especially in protecting vascular endothelial function and preventing metabolic syndrome. PMID:29401716

  17. Coffee consumption and human health--beneficial or detrimental?--Mechanisms for effects of coffee consumption on different risk factors for cardiovascular disease and type 2 diabetes mellitus.

    Science.gov (United States)

    Ranheim, Trine; Halvorsen, Bente

    2005-03-01

    Coffee is probably the most frequently ingested beverage worldwide. Especially Scandinavia has a high prevalence of coffee-drinkers, and they traditionally make their coffee by boiling ground coffee beans and water. Because of its consumption in most countries in the world, it is interesting, from both a public and a scientific perspective, to discuss its potential benefits or adverse aspects in relation to especially two main health problems, namely cardiovascular disease and type 2 diabetes mellitus. Epidemiological studies suggest that consumption of boiled coffee is associated with elevated risk for cardiovascular disease. This is mainly due to the two diterpenes identified in the lipid fraction of coffee grounds, cafestol and kahweol. These compounds promote increased plasma concentration of cholesterol in humans. Coffee is also a rich source of many other ingredients that may contribute to its biological activity, like heterocyclic compounds that exhibit strong antioxidant activity. Based on the literature reviewed, it is apparent that moderate daily filtered, coffee intake is not associated with any adverse effects on cardiovascular outcome. On the contrary, the data shows that coffee has a significant antioxidant activity, and may have an inverse association with the risk of type 2 diabetes mellitus.

  18. Identification of antibacterial constituents from the indigenous Australian medicinal plant Eremophila duttonii F. Muell. (Myoporaceae).

    Science.gov (United States)

    Smith, Joshua E; Tucker, David; Watson, Kenneth; Jones, Graham Lloyd

    2007-06-13

    This paper reports on the isolation and identification of antibacterial constituents from the indigenous Australian medicinal plant Eremophila duttonii F. Muell. (Myoporaceae). Preparations derived from this plant are used by indigenous populations in the topical treatment of minor wounds, otitis and ocular complaints, and as a gargle for sore throat. Several authors have reported extracts of this plant to effect rapid bacteriolysis and inhibit growth of a wide range of Gram-positive micro-organisms. In other studies involving screening of native medicinal plants for antibacterial activity, extracts of Eremophila duttonii have been reported to consistently exhibit the highest potency amongst all species included. From a hexane extract, we identified two diterpenes of the serrulatane class, the principal constituents responsible for antibacterial activity and present as major constituents of the resinous leaf cuticle: serrulat-14-en-7,8,20-triol (1) and serrulat-14-en-3,7,8,20-tetraol (2). In addition, a hydroxylated furanosesquiterpene with mild antibacterial activity which appeared to be a novel compound was isolated from the extract and tentatively identified as 4-hydroxy-4-methyl-1-(2,3,4,5-tetrahydro-5-methyl[2,3'-bifuran]-5-yl) pentan-2-one. Minimum inhibitory concentrations for each of the compounds against three Gram-positive bacteria: Staphylococcus aureus (ATCC 29213), Staphylococcus epidermidis (ATCC 12228) and Streptococcus pneumoniae (ARL 10582), were determined using a micro-titre plate broth dilution assay.

  19. Chemical Composition and Biological Activity of Essential Oils of Sempervivum brevipilum Muirhead

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    Nuran Kahriman

    2015-06-01

    Full Text Available The essential oils of the fresh flower, leaf, and stem of Sempervivum brevipilum Muirhead. (Crassulaceae were isolated by hydrodistillation in a modified Clevenger-type apparatus, and characterized by GC-FID and GC-MS. A total of fifty, fourty-three, and thirty-one compounds were identified, constituting over 92.6%, 92.6%, and 94.3% of oil composition of the flower, leaf, and stem of S. brevipilum, respectively. The chemical profile reveals the dominance of hydrocarbons (flower: 65.3%, leaf: 47.6%, stem: 71.1%. The major compounds of essential oils from S. brevipilum were tetracosane (20.2% in flower, 1,2-diphenyl ethandione (16.1% in leaf and docosane (30.5% in stem. Monoterpene hydrocarbons were the major class of terpenoids in flower (2.2% and in stem (1.8%, oxygenated diterpene was the major class of terpenoids in leaf (4.5%. Oxygenated monoterpenes were in minor amounts in all parts (flower: 0.3%, leaf: 0.7%, stem: 0.1% of the plant. In addition, antimicrobial activities of the essential oils of S. brevipilum were investigated. The oils didn’t show any antibacterial and antifungal activity against tested bacteria, but showed high antituberculostatic activity against Mycobacterium smegmatis.

  20. Profiling of lipophilic and phenolic phytochemicals of four cultivars from cherimoya (Annona cherimola Mill.).

    Science.gov (United States)

    Santos, Sónia A O; Vilela, Carla; Camacho, João F; Cordeiro, Nereida; Gouveia, Manuela; Freire, Carmen S R; Silvestre, Armando J D

    2016-11-15

    The lipophilic and phenolic extractives of the ripe mesocarp of four cherimoya cultivars ('Perry Vidal', 'Mateus I', 'Mateus III' and 'Funchal') from Madeira Island, were studied for the first time. The predominant lipophilic compounds are kaurene diterpenes (42.2-59.6%), fatty acids (18.0-35.6%) and sterols (9.6-23.7%). Kaur-16-en-19-oic acid is the major lipophilic component of all cultivars accounting between 554 and 1350mgkg(-1) of dry material. The studied fruits also contain a high variety of flavan-3-ols, including galloylated and non-galloylated compounds. Five phenolic compounds were identified for the first time: catechin, (epi)catechin-(epi)gallocatechin, (epi)gallocatechin, (epi)afzelechin-(epi)catechin and procyanidin tetramer. 'Mateus I' and 'Mateus III' cultivars present the highest content of phenolic compounds (6299 and 9603mgkg(-1) of dry weight, respectively). These results support the use of this fruit as a rich source of health-promoting components, with the capacity to prevent or delay the progress of oxidative-stress related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Lipophilic Fraction of Cultivated Bifurcaria bifurcata R. Ross: Detailed Composition and In Vitro Prospection of Current Challenging Bioactive Properties.

    Science.gov (United States)

    Santos, Sónia A O; Trindade, Stephanie S; Oliveira, Catia S D; Parreira, Paula; Rosa, Daniela; Duarte, Maria F; Ferreira, Isabel; Cruz, Maria T; Rego, Andreia M; Abreu, Maria H; Rocha, Silvia M; Silvestre, Armando J D

    2017-11-01

    Macroalgae have been seen as an alternative source of molecules with promising bioactivities to use in the prevention and treatment of current lifestyle diseases. In this vein, the lipophilic fraction of short-term (three weeks) cultivated Bifurcaria bifurcata was characterized in detail by gas chromatography-mass spectrometry (GC-MS). B. bifurcata dichloromethane extract was composed mainly by diterpenes (1892.78 ± 133.97 mg kg -1 dry weight (DW)), followed by fatty acids, both saturated (550.35 ± 15.67 mg kg -1 DW) and unsaturated (397.06 ± 18.44 mg kg -1 DW). Considerable amounts of sterols, namely fucosterol (317.68 ± 26.11 mg kg -1 DW) were also found. In vitro tests demonstrated that the B. bifurcata lipophilic extract show antioxidant, anti-inflammatory and antibacterial activities (against both Gram-positive and Gram-negative bacteria), using low extract concentrations (in the order of µg mL -1 ). Enhancement of antibiotic activity of drug families of major clinical importance was observed by the use of B. bifurcata extract. This enhancement of antibiotic activity depends on the microbial strain and on the antibiotic. This work represents the first detailed phytochemical study of the lipophilic extract of B. bifurcata and is, therefore, an important contribution for the valorization of B. bifurcata macroalgae, with promising applications in functional foods, nutraceutical, cosmetic and biomedical fields.

  2. Picomolar dichotomous activity of gnidimacrin against HIV-1.

    Directory of Open Access Journals (Sweden)

    Li Huang

    Full Text Available Highly active antiretroviral therapy (HAART has offered a promising approach for controlling HIV-1 replication in infected individuals. However, with HARRT, HIV-1 is suppressed rather than eradicated due to persistence of HIV-1 in latent viral reservoirs. Thus, purging the virus from latent reservoirs is an important strategy toward eradicating HIV-1 infection. In this study, we discovered that the daphnane diterpene gnidimacrin, which was previously reported to have potent anti-cancer cell activity, activated HIV-1 replication and killed persistently-infected cells at picomolar concentrations. In addition to its potential to purge HIV-1 from latently infected cells, gnidimacrin potently inhibited a panel of HIV-1 R5 virus infection of peripheral blood mononuclear cells (PBMCs at an average concentration lower than 10 pM. In contrast, gnidimacrin only partially inhibited HIV-1 ×4 virus infection of PBMCs. The strong anti-HIV-1 R5 virus activity of gnidimacrin was correlated with its effect on down-regulation of the HIV-1 coreceptor CCR5. The anti-R5 virus activity of gnidimacrin was completely abrogated by a selective protein kinase C beta inhibitor enzastaurin, which suggests that protein kinase C beta plays a key role in the potent anti-HIV-1 activity of gnidimacrin in PBMCs. In summary, these results suggest that gnidimacrin could activate latent HIV-1, specifically kill HIV-1 persistently infected cells, and inhibit R5 viruses at picomolar concentrations.

  3. Active Component of Danshen (Salvia miltiorrhiza Bunge, Tanshinone I, Attenuates Lung Tumorigenesis via Inhibitions of VEGF, Cyclin A, and Cyclin B Expressions

    Directory of Open Access Journals (Sweden)

    Yu-Tang Tung

    2013-01-01

    Full Text Available Tanshinone I (T1 and tanshinone II (T2 are the major diterpenes isolated from Danshen (Salvia miltiorrhiza Bunge. Three human lung adenocarcinoma cell lines, A549, CL1-0, and CL1-5, were treated with T1 and T2 for the in vitro antitumor test. Results showed that T1 was more effective than T2 in inhibiting the growth of lung cancer cells via suppressing the expression of VEGF, Cyclin A, and Cyclin B proteins in a dose-dependent manner. Moreover, a transgenic mice model of the human vascular endothelial growth factor-A165 (hVEGF-A165 gene-induced pulmonary tumor was further treated with T1 for the in vivo lung cancer therapy test. T1 significantly attenuated hVEGF-A165 overexpression to normal levels of the transgenic mice (Tg that were pretreated with human monocytic leukemia THP-1 cell-derived conditioned medium (CM. It also suppressed the formation of lung adenocarcinoma tumors (16.7% compared with two placebo groups (50% for Tg/Placebo and 83.3% for Tg/CM/Placebo; P<0.01. This antitumor effect is likely to slow the progression of cells through the S and G2/M phases of the cell cycle. Blocking of the tumor-activated cell cycle pathway may be a critical mechanism for the observed antitumorigenic effects of T1 treatment on vasculogenesis and angiogenesis.

  4. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas, Casimiro [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); Research Support Central Services (SCAI) of the University of Málaga, E-29071 Málaga (Spain); Quesada, Ana R. [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain); Medina, Miguel Ángel, E-mail: medina@uma.es [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain)

    2014-05-09

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

  5. Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

    Science.gov (United States)

    Shi, Bin; Wang, Li-Fang; Meng, Wen-Shu; Chen, Liang; Meng, Zi-Li

    2017-06-01

    Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, which is generated by many species from Lamiaceae family. Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different vegetables and fruits. Fisetin has been reported to have various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Lung cancer is reported as the most common neoplasm in human world-wide. In the present study, the possible benefits of carnosic acid combined with fisetin on lung cancer in vitro and in vivo was explored. Carnosic acid and fisetin combination led to apoptosis in lung cancer cells. Caspase-3 signaling pathway was promoted in carnosic acid and fisetin co-treatment, which was accompanied by anti-apoptotic proteins of Bcl-2 and Bcl-xl decreasing and pro-apoptotic signals of Bax and Bad increasing. The death receptor (DR) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was enhanced in carnosic acid and fisetin combined treatment. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and fisetin combined treatment inhibited lung cancer growth in comparison to the carnosic acid or fisetin monotherapy. This study supplies a novel therapy to induce apoptosis to inhibit lung cancer through caspase-3 activation.

  6. The essential oil qualitative and quantitative composition in the needles of Pinus sylvestris L. growing along industrial transects

    International Nuclear Information System (INIS)

    Kupcinskiene, Eugenija; Stikliene, Aida; Judzentiene, Asta

    2008-01-01

    The aim of this study was to evaluate composition of the essential oils in the needles of Pinus sylvestris growing in the areas affected by a cement factory (CF), and an oil refinery (OR). Volatile components of the needles were analyzed by GC and GC/MS. The most heavily polluted CF stand had significantly higher concentration of γ-Terpinene, Caryophyllene oxide in the current-year needles, while higher concentration of δ-3-Carene, α-Terpinene, γ-Terpinene and Terpinolene was documented for 1-year-old needles. The most heavily polluted OR stand had a significantly higher concentration of Sabinene + β-Pinene, 1-epi-Cubenol in the current-year needles and a significantly higher concentration of Camphene, Sabinene + β-Pinene, Myrcene, α-Cadinene, 1-epi-Cubenol in the 1-year-old needles than the least polluted site. Along transects an increase in the amount of some diterpenes and a decrease in the components of the shorter chain essential oils was observed. These effects could be at least partially attributed to SO 2 . - Quantities of components of essential oil in the needles of Scots pine growing around two factories are described in relation to pollution

  7. MIDAS: A Modular DNA Assembly System for Synthetic Biology.

    Science.gov (United States)

    van Dolleweerd, Craig J; Kessans, Sarah A; Van de Bittner, Kyle C; Bustamante, Leyla Y; Bundela, Rudranuj; Scott, Barry; Nicholson, Matthew J; Parker, Emily J

    2018-04-20

    A modular and hierarchical DNA assembly platform for synthetic biology based on Golden Gate (Type IIS restriction enzyme) cloning is described. This enabling technology, termed MIDAS (for Modular Idempotent DNA Assembly System), can be used to precisely assemble multiple DNA fragments in a single reaction using a standardized assembly design. It can be used to build genes from libraries of sequence-verified, reusable parts and to assemble multiple genes in a single vector, with full user control over gene order and orientation, as well as control of the direction of growth (polarity) of the multigene assembly, a feature that allows genes to be nested between other genes or genetic elements. We describe the detailed design and use of MIDAS, exemplified by the reconstruction, in the filamentous fungus Penicillium paxilli, of the metabolic pathway for production of paspaline and paxilline, key intermediates in the biosynthesis of a range of indole diterpenes-a class of secondary metabolites produced by several species of filamentous fungi. MIDAS was used to efficiently assemble a 25.2 kb plasmid from 21 different modules (seven genes, each composed of three basic parts). By using a parts library-based system for construction of complex assemblies, and a unique set of vectors, MIDAS can provide a flexible route to assembling tailored combinations of genes and other genetic elements, thereby supporting synthetic biology applications in a wide range of expression hosts.

  8. Annonalide and derivatives: Semisynthesis, cytotoxic activities and studies on interaction of annonalide with DNA.

    Science.gov (United States)

    Marques, Ricardo A; Gomes, Akenaton O C V; de Brito, Maria V; Dos Santos, Ana L P; da Silva, Gladyane S; de Lima, Leandro B; Nunes, Fátima M; de Mattos, Marcos C; de Oliveira, Fátima C E; do Ó Pessoa, Cláudia; de Moraes, Manoel O; de Fátima, Ângelo; Franco, Lucas L; Silva, Marina de M; Dantas, Maria Dayanne de A; Santos, Josué C C; Figueiredo, Isis M; da Silva-Júnior, Edeíldo F; de Aquino, Thiago M; de Araújo-Júnior, João X; de Oliveira, Maria C F; Leslie Gunatilaka, A A

    2018-02-01

    The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2-10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma) and HCT-116 (colon cancer), and normal mouse fibroblast (L929) cells. The preparation of 2-10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives are being reported for the first time. Most of the tested compounds presented IC 50 s below 4.0 μM, being considered potential antitumor agents. The structures of all new compounds were elucidated by spectroscopic analyses including 2D NMR and HRMS. Additionally, the interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques, and the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacts preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA). The ΔG value was calculated as -28.24 kJ mol -1 , and indicated that the interaction process occurs spontaneously. Docking studies revealed that van der Walls is the most important interaction in 1-DNA and EB-DNA complexes, and that both ligands (1 and EB) interact with the same DNA residues (DA6, DA17 and DT19). Copyright © 2018. Published by Elsevier B.V.

  9. Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology.

    Science.gov (United States)

    Karchesy, Joseph J; Kelsey, Rick G; González-Hernández, M P

    2018-05-01

    Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of southeast Alaska, western Canada, and inland forests along the Cascades to northern California, USA. These trees have few microbial or animal pests, attributable in part to the distinct groups of biologically active secondary metabolites their tissues store for chemical defense. Here we summarize the new yellow-cedar compounds identified and their biological activities, plus new or expanded activities for tissues, extracts, essential oils and previously known compounds since the last review more than 40 years ago. Monoterpene hydrocarbons are the most abundant compounds in foliage, while heartwood contains substantial quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins have been isolated from inner bark. Biological activities expressed by one or more compounds in these groups include fungicide, bactericide, sporicide, acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer. The diversity of organisms impacted by whole tissues, essential oils, extracts, or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes, bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood component with sufficient activity against arthropods to warrant research focused toward potential development as a commercial repellent and biopesticide for ticks, mosquitoes and possibly other arthropods that vector human and animal pathogens.

  10. Screening of the odour-activity and bioactivity of the essential oils of leaves and flowers of Hyptis Passerina Mart. from the Brazilian Cerrado

    International Nuclear Information System (INIS)

    Zellner, Barbara D.; Amorim, Ana Carolina L.; Rezende, Claudia M.; Miranda, Ana Luisa P. de; Alves, Ruy J.V.; Barbosa, Jussara P.; Costa, Gisela L. da

    2009-01-01

    The chemical profile of the essential oils obtained from the leaves and flowers of Hyptis passerina Mart., a rare species of the Brazilian Cerrado, has been determined for the first time. Analyses by GC-MS showed sesquiterpenes as major compounds. β-epi-acorenol (35.7% and 32.8%, respectively from leaf and flower essential oils), was isolated and identified by 1D and 2D NMR. The flower-derived oil presented a higher concentration of hydrocarbon and oxygenated monoterpenes, while the leaf-oil was richer in diterpenes. The global odour impressions of both oils were given by direct analysis and GC-MS-O and were characterized as herbaceous with tea notes, and green, cooked and woody impressions for leaf-oil; herbaceous, with spicy, woody and minty notes for flower-oil. β-epi-acorenol, spathulenol, β-caryophyllene, and caryophyllene oxide were relevant for the odour-activity of both oils, as well as minor constituents, such as linalool. The antimicrobial activity was investigated by means of agar diffusion disc method and contact bioautography, against Gram-positive and negative bacteria and yeast. Both oils presented to be bioactive against the tested microorganisms with significant inhibition level. (author)

  11. Essential oil from the leaves of Xylopia langsdorfiana (Annonaceae) as a possible spasmolytic agent.

    Science.gov (United States)

    Correia, Ana Carolina de C; Ferreira, Tamyris F; Martins, Italo Rossi R; Macêdo, Cibério L; Monteiro, Fabio de S; Costa, Vicente Carlos O; Tavares, Josean F; Silva, Marcelo S; Paredes-Gamero, Edgar J; Buri, Marcus V; Rigoni, Vera L S; Nouailhetas, Viviane L A; Da Silva, Bagnólia A

    2015-01-01

    Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 μg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 μg/mL) inhibited carbachol or histamine-induced phasic contractions (1 μM) in a significant and concentration-dependent manner. In addition, XL-OE (81 μg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration.

  12. The genus Eremophila (Scrophulariaceae): an ethnobotanical, biological and phytochemical review.

    Science.gov (United States)

    Singab, Abdel Nasser; Youssef, Fadia S; Ashour, Mohamed L; Wink, Michael

    2013-09-01

    Eremophila (Scrophulariaceae) is an endemic Australian genus with 214 species, which is commonly known as Fuchsia bush, Emu bush or Poverty bush. Plants of this genus played an important role for the Australian Aborigines who used them widely for medicinal and ceremonial purposes. Many studies have been carried out on many species of this genus and have generated immense data about the chemical composition and corresponding biological activity of extracts and isolated secondary metabolites. Thorough phytochemical investigations of different Eremophila species have resulted in the isolation of more than 200 secondary metabolites of different classes with diterpenes as major constituents. Biological studies and traditional clinical practice demonstrated that Eremophila and its bioactive compounds possess various pharmacological properties. Plants were employed especially as a cardiotonic drug and also as potent anti-inflammatory, antimicrobial and antiviral agents. Further investigations are required to explore other Eremophila species, to evaluate the different biological activities of either their extracts or the isolated compounds and the possible underlying modes of action. © 2013 Royal Pharmaceutical Society.

  13. Coffee and health: a review of recent human research.

    Science.gov (United States)

    Higdon, Jane V; Frei, Balz

    2006-01-01

    Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterol-raising effects of coffee. The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson's disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3-4 cups/d providing 300-400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine. In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth.

  14. Overview of the taxonomy and of the major secondary metabolites and their biological activities related to human health of the Laurencia complex (Ceramiales, Rhodophyta from Brazil

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    Mutue T. Fujii

    2011-04-01

    Full Text Available In Brazil, the Laurencia complex is represented by twenty taxa: Laurencia s.s. with twelve species, Palisada with four species (including Chondrophycus furcatus now that the proposal of its transference to Palisada is in process, and Osmundea and Yuzurua with two species each. The majority of the Brazilian species of the Laurencia complex have been phylogenetically analyzed by 54 rbcL sequences, including five other Rhodomelacean species as outgroups. The analysis showed that the Laurencia complex is monophyletic with high posterior probability value. The complex was separated into five clades, corresponding to the genera: Chondrophycus, Laurencia, Osmundea, Palisada, and Yuzurua. A bibliographical survey of the terpenoids produced by Brazilian species showed that only six species of Laurencia and five of Palisada (including C. furcatcus have been submitted to chemical analysis with 48 terpenoids (47 sesquiterpenes and one triterpene isolated. No diterpenes were found. Of the total, 23 sesquiterpenes belong to the bisabolane class and eighteen to the chamigrene type, whose biochemical precursor is bisabolane, two are derived from lauranes and four are triquinols. Despite the considerable number of known terpenes and their ecological and pharmacological importance, few experimental biological studies have been performed. In this review, only bioactivities related to human health were considered.

  15. Inhibition of bone resorption by Tanshinone VI isolated from Salvia miltiorrhiza Bunge

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    V. Nicolin

    2010-05-01

    Full Text Available During the last decade, a more detailed knowledge of molecular mechanisms involved in osteoclastogenesis has driven research efforts in the development and screening of compound libraries of several small molecules that specifically inhibit the pathway involved in the commitment of the osteoclast precursor cells. Natural compounds that suppress osteoclast differentiation may have therapeutic value in treating osteoporosis and other bone erosive diseases such as rheumatoid arthritis or metastasis associated with bone loss. In ongoing investigation into anti-osteoporotic compounds from natural products we have analyzed the effect of Tanshinone VI on osteoclasts differentiation, using a physiologic three-dimensional osteoblast/bone marrow model of cell co-culture. Tanshinone VI is an abietane diterpene extracted from the root of Salvia miltiorrhiza Bunge (Labiatae, a Chinese traditional crude drug, ‘’Tan-Shen’’. Tashinone has been widely used in clinical practice for the prevention of cardiac diseases, arthritis and other inflammation-related disorders based on its pharmacological actions in multiple tissues. Although Tanshinone VI A has been used as a medicinal agent in the treatment of many diseases, its role in osteoclast-related bone diseases remains unknown. We showed previously that Tanshinone VI greatly inhibits osteoclast differentiation and suppresses bone resorption through disruption of the actin ring; subsequently, we intended to examine the precise inhibitory mechanism of Tanshinone VI on osteoclast differentiating factor. This study shows, for the first time, that Tanshinone VI prevents osteoclast differentiation by inhibiting RANKL expression and NFkB induction.

  16. High Amounts of n-Alkanes in the Composition of Asphodelus aestivus Brot. Flower Essential Oil from Cyprus.

    Science.gov (United States)

    Polatoğlu, Kaan; Demirci, Betül; Can Başer, Kemal Hüsnü

    2016-10-01

    There is only a couple of reports indicating essential oil composition of Asphodelus species in the literature. However, from the members of this genus many non-volatile secondary metabolites were isolated. In Cyprus, Asphodelus aestivus Brot. can be found abundantly in all regions of the island. This plant has various ethnobotanical uses in Cyprus. There is no report on the volatiles nor the essential oil composition of A. aestivus. The smell of A. aestivus flowers resembles that of a cat pee which caught our attention. Therefore, we have carried out GC, GC/MS analysis of the essential oil (yield: 0.01 v/w) obtained from Asphodelus aestivus flowers. Seventeen compounds were identified in the essential oil comprising 96.2% of the oil. The major components of the essential oil were hexadecanoic acid 35.6%, pentacosane 17.4%, tricosane 13.4% and heptacosane 8.4%. In our results, we expected to see sulfur containing cat pee odorants due to the odor of the flower whereas high amounts of n-alkanes, saturated fatty acids and minor amounts of acyclic diterpenes were observed.

  17. The effect of 60Co-gamma radio-sterilization on Boswellia carterii essential oil composition

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    P. Badr

    2016-10-01

    Full Text Available Background and objectives:Gamma-irradiation is used vastly for both decontamination and sterilization of natural products; but these high-energy rays can affect heat-sensitive essential oils. Methods: The oleo-gum-resin of Boswellia carterii (Burseraceae was sterilized by γ-irradiation at dose 30 KGy. The essential oils obtained by hydrodistillation of non-irradiated Boswellia (NIB and irradiated Boswellia (IB were analyzed by GC/MS and the changes were compared. The structure of octyl acetate as the major component and marker of B. carterii was confirmed by MS/MS. Results: Twenty-five compounds comprising 99.55% of NIB oil and nineteen compounds comprising 98.61% of IB oil were identified. Major constituents which were common for both oils were octyl acetate (52.67 % in NIB, 76.51 % in IB, 1-octanol (6.37 % in NIB, 5.19 % in IB, duva-4, 8, 13-triene-1,3α diol (5.52 % in NIB, 3.94 % in IB, verticiol (13.63 % in NIB and verticillane type diterpene (5.4 % in IB they made up 78.19% and 91.04% of NIB and IB, respectively. Conclusion: Gamma irradiation was an efficient method for sterilization of Boswellia carterii oleo-gum resin, but it resulted in change in the essential oil composition particularly octyl acetate changed from 52.67% to 76.51%.

  18. NpPDR1, a Pleiotropic Drug Resistance-Type ATP-Binding Cassette Transporter from Nicotiana plumbaginifolia, Plays a Major Role in Plant Pathogen Defense1

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    Stukkens, Yvan; Bultreys, Alain; Grec, Sébastien; Trombik, Tomasz; Vanham, Delphine; Boutry, Marc

    2005-01-01

    Nicotiana plumbaginifolia NpPDR1, a plasma membrane pleiotropic drug resistance-type ATP-binding cassette transporter formerly named NpABC1, has been suggested to transport the diterpene sclareol, an antifungal compound. However, direct evidence for a role of pleiotropic drug resistance transporters in the plant defense is still lacking. In situ immunolocalization and histochemical analysis using the gusA reporter gene showed that NpPDR1 was constitutively expressed in the whole root, in the leaf glandular trichomes, and in the flower petals. However, NpPDR1 expression was induced in the whole leaf following infection with the fungus Botrytis cinerea, and the bacteria Pseudomonas syringae pv tabaci, Pseudomonas fluorescens, and Pseudomonas marginalis pv marginalis, which do not induce a hypersensitive response in N. plumbaginifolia, whereas a weaker response was observed using P. syringae pv syringae, which does induce a hypersensitive response. Induced NpPDR1 expression was more associated with the jasmonic acid than the salicylic acid signaling pathway. These data suggest that NpPDR1 is involved in both constitutive and jasmonic acid-dependent induced defense. Transgenic plants in which NpPDR1 expression was prevented by RNA interference showed increased sensitivity to sclareol and reduced resistance to B. cinerea. These data show that NpPDR1 is involved in pathogen resistance and thus demonstrate a new role for the ATP-binding cassette transporter family. PMID:16126865

  19. NpPDR1, a pleiotropic drug resistance-type ATP-binding cassette transporter from Nicotiana plumbaginifolia, plays a major role in plant pathogen defense.

    Science.gov (United States)

    Stukkens, Yvan; Bultreys, Alain; Grec, Sébastien; Trombik, Tomasz; Vanham, Delphine; Boutry, Marc

    2005-09-01

    Nicotiana plumbaginifolia NpPDR1, a plasma membrane pleiotropic drug resistance-type ATP-binding cassette transporter formerly named NpABC1, has been suggested to transport the diterpene sclareol, an antifungal compound. However, direct evidence for a role of pleiotropic drug resistance transporters in the plant defense is still lacking. In situ immunolocalization and histochemical analysis using the gusA reporter gene showed that NpPDR1 was constitutively expressed in the whole root, in the leaf glandular trichomes, and in the flower petals. However, NpPDR1 expression was induced in the whole leaf following infection with the fungus Botrytis cinerea, and the bacteria Pseudomonas syringae pv tabaci, Pseudomonas fluorescens, and Pseudomonas marginalis pv marginalis, which do not induce a hypersensitive response in N. plumbaginifolia, whereas a weaker response was observed using P. syringae pv syringae, which does induce a hypersensitive response. Induced NpPDR1 expression was more associated with the jasmonic acid than the salicylic acid signaling pathway. These data suggest that NpPDR1 is involved in both constitutive and jasmonic acid-dependent induced defense. Transgenic plants in which NpPDR1 expression was prevented by RNA interference showed increased sensitivity to sclareol and reduced resistance to B. cinerea. These data show that NpPDR1 is involved in pathogen resistance and thus demonstrate a new role for the ATP-binding cassette transporter family.

  20. Nutraceutical Antioxidants as Novel Neuroprotective Agents

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    Daniel A. Linseman

    2010-11-01

    Full Text Available A variety of antioxidant compounds derived from natural products (nutraceuticals have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1 flavonoid polyphenols like epigallocatechin 3-gallate (EGCG from green tea and quercetin from apples; (2 non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3 phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4 organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2 transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.

  1. A high-resolution peak fractionation approach for streamlined screening of nuclear-factor-E2-related factor-2 activators in Salvia miltiorrhiza.

    Science.gov (United States)

    Zhang, Hui; Luo, Li-Ping; Song, Hui-Peng; Hao, Hai-Ping; Zhou, Ping; Qi, Lian-Wen; Li, Ping; Chen, Jun

    2014-01-24

    Generation of a high-purity fraction library for efficiently screening active compounds from natural products is challenging because of their chemical diversity and complex matrices. In this work, a strategy combining high-resolution peak fractionation (HRPF) with a cell-based assay was proposed for target screening of bioactive constituents from natural products. In this approach, peak fractionation was conducted under chromatographic conditions optimized for high-resolution separation of the natural product extract. The HRPF approach was automatically performed according to the predefinition of certain peaks based on their retention times from a reference chromatographic profile. The corresponding HRPF database was collected with a parallel mass spectrometer to ensure purity and characterize the structures of compounds in the various fractions. Using this approach, a set of 75 peak fractions on the microgram scale was generated from 4mg of the extract of Salvia miltiorrhiza. After screening by an ARE-luciferase reporter gene assay, 20 diterpene quinones were selected and identified, and 16 of these compounds were reported to possess novel Nrf2 activation activity. Compared with conventional fixed-time interval fractionation, the HRPF approach could significantly improve the efficiency of bioactive compound discovery and facilitate the uncovering of minor active components. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Identification of the finishing technique of an early eighteenth century musical instrument using FTIR spectromicroscopy.

    Science.gov (United States)

    Bertrand, Loïc; Robinet, Laurianne; Cohen, Serge X; Sandt, Christophe; Le Hô, Anne-Solenn; Soulier, Balthazar; Lattuati-Derieux, Agnès; Echard, Jean-Philippe

    2011-03-01

    The study of varnishes from musical instruments presents the difficulty of analysing very thin layers of heterogeneous materials on samples most of which are generally brittle and difficult to prepare. Such study is crucial to the understanding of historical musical instrument varnishing practices since written sources before 1800 are very rare and not precise. Fourier-transform infrared (FTIR) spectroscopy and imaging methods were applied to identify the major chemical components within the build-up of the varnish layers on a cello made by one of the most prominent French violin-makers of the eighteenth century (Jacques Boquay, ca. 1680-1730). Two types of FTIR imaging methods were used: scanning with a synchrotron-based microscope and full-field imaging using a 2D imager with a conventional source. An interpretation of the results obtained from these studies on the Boquay cello is that the maker first applied a proteinaceous layer, probably gelatine-based animal glue. He later applied a second layer based on a mixture of a drying oil and diterpenic resin from Pinaceae sp. From an historical perspective, the results complement previous studies by describing a second technique used for musical instrument finishes at the beginning of the eighteenth century in Europe.

  3. Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L. extract polyphenols and terpenoids in Caco-2 cell monolayers.

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    Almudena Pérez-Sánchez

    Full Text Available Rosemary (Rosmarinus officinalis is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids of a rosemary extract (RE, obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS, and the apparent permeability values (Papp were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability; therefore, RE itself should also be classified into this category.

  4. Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae).

    Science.gov (United States)

    Brinker, Anita M; Ma, Jun; Lipsky, Peter E; Raskin, Ilya

    2007-03-01

    Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook.f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-gamma). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

  5. Converting environmental risks to benefits by using spent coffee grounds (SCG) as a valuable resource.

    Science.gov (United States)

    Stylianou, Marinos; Agapiou, Agapios; Omirou, Michalis; Vyrides, Ioannis; Ioannides, Ioannis M; Maratheftis, Grivas; Fasoula, Dionysia

    2018-06-02

    Coffee is perhaps one of the most vital ingredients in humans' daily life in modern world. However, this causes the production of million tons of relevant wastes, i.e., plastic cups, aluminum capsules, coffee chaff (silver skin), and spent coffee grounds (SCG), all thrown untreated into landfills. It is estimated that 1 kg of instant coffee generates around 2 kg of wet SCG; a relatively unique organic waste stream, with little to no contamination, separated directly in the source by the coffee shops. The produced waste has been under researchers' microscope as a useful feedstock for a number of promising applications. SCG is considered a valuable, nutrients rich source of bioactive compounds (e.g., phenolics, flavonoids, carotenoids, lipids, chlorogenic and protocatechuic acid, melanoidins, diterpenes, xanthines, vitamin precursors, etc.) and a useful resource material in other processes (e.g., soil improver and compost, heavy metals absorbent, biochar, biodiesel, pellets, cosmetics, food, and deodorization products). This paper aims to provide a holistic approach for the SCG waste management, highlighting a series of processes and applications in environmental solutions, food industry, and agricultural sector. Thus, the latest developments and approaches of SCG waste management are reviewed and discussed.

  6. Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

    International Nuclear Information System (INIS)

    Wang, Xiang; Zhao, Fang; Lv, Zhong-ming; Shi, Wei-qin; Zhang, Lu-yong; Yan, Ming

    2016-01-01

    Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

  7. Characterization and differentiation of monovarietal grape marc distillates on the basis of varietal aroma compound composition.

    Science.gov (United States)

    Lukić, Igor; Milicević, Borislav; Banović, Mara; Tomas, Srećko; Radeka, Sanja; Persurić, Dordano

    2010-06-23

    To investigate the varietal aroma compound composition of monovarietal grape marc distillates made from six different varieties (Vitis vinifera L.) in the region of Istria (Croatia), 30 samples were subjected to GC/MS and GC/FID analysis. A total of 73 compounds were identified: 45 monoterpenes, 20 sesquiterpenes, 3 diterpenes, and 5 C(13)-norisoprenoids. The largest number and the highest concentration of monoterpenes were found in Muscat Blanc, followed by Rose Muscat of Porec (Muskat ruza porecki) distillates, which were both characterized as highly aromatic. Lower, but still significant monoterpenol content was determined in distillates made from Istrian Malvasia (Malvazija istarska) grape marc. Chardonnay, Cabernet Sauvignon, and Teran distillates exhibited poorer monoterpene profiles, while Teran distillates contained elevated sesquiterpene concentrations. It was concluded that investigated monovarietal grape marc distillates significantly differ in varietal aroma compound composition. Stepwise linear discriminant analysis provided efficient discrimination models, and extracted various monoterpenes, sesquiterpenes and C(13)-norisoprenoids as important differentiators of distillates according to varietal origin.

  8. Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

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    Katarina Kemper

    2017-05-01

    Full Text Available With over 50.000 identified compounds terpenes are the largest and most structurally diverse group of natural products. They are ubiquitous in bacteria, plants, animals and fungi, conducting several biological functions such as cell wall components or defense mechanisms. Industrial applications entail among others pharmaceuticals, food additives, vitamins, fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isoprenoids that is quite amenable for genetic engineering. Together with recombinant terpene biosynthesis modules, they are very suitable hosts for heterologous production of high value terpenes. Yet, in contrast to the number of extracted and characterized terpenes, little is known about the specific biosynthetic enzymes that are involved especially in the formation of highly functionalized compounds. Novel approaches discussed in this review include metabolic engineering as well as site-directed mutagenesis to expand the natural terpene landscape. Focusing mainly on the validation of successful integration of engineered biosynthetic pathways into optimized terpene producing Escherichia coli, this review shall give an insight in recent progresses regarding manipulation of mostly diterpene synthases.

  9. Chemosystematic Value of the Essential Oil Composition of Thuja species Cultivated in Poland—Antimicrobial Activity

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    Caroline Spyropoulos

    2009-11-01

    Full Text Available In the framework of the correlation between chemotaxonomy and chemical analysis studies, the chemical composition of the essential oils of four varieties of Thuja species cultivated in Poland − T. occidentalis ‘globosa’, T. occidentalis ‘aurea’, T. plicata and T. plicata ‘gracialis’ − were investigated by GC and GC-MS. Thirty-one compounds were identified from T. occidentalis ‘globosa’, representing 96.92% of the total oil; twenty-seven from T. occidentalis ‘aurea’ (94.34%; thirty-one from T. plicata (94.75%; and thirty compounds from T. plicata ‘gracialis’ (96.36%. The main constituents in all samples were the monoterpene ketones α- and β-thujone, fenchone and sabinene, as well as the diterpenes beyerene and rimuene.The chemosystematic value of the total ketone content of all samples (which varied from 54.30–69.18% has been discussed and investigated. The constituents, beyerene and the mixture of α- and β-thujone, were isolated from the oils and tested against six Gram-positive and -negative bacteria and three pathogenic fungi. The oils of the two T. plicata species exhibited significant antimicrobial activity, while the mixture of α- and β-thujone showed very strong activity as well.

  10. Essential oil composition of wild growing Sage from R. Macedonia

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    Gjoshe Stefkov

    2012-03-01

    Full Text Available The main objective of this study was to analyze and identify the essential oil composition of S. officinalis populations growing in Republic of Macedonia and to evaluate these data according to different standards’ requirements for, commercially most utilized, Dalmatian sage. The essential oil yield, obtained after hydrodestilation from leaves, of three different populations of Salvia officinalis L. from Republic of Macedonia was determined, varying from 1.40 to 3.46%. The GC/FID/MS analysis of the composition of the essential oils revealed 63, 57 and 51 components in Galicica Mtn., Jablanica Mtn. and Karaorman Mtn. sage populations, respectively. The main components of the oil, in all three samples, were the terpene hydrocarbons, encompassing the monoterpenes: camphor (13.15 - 25.91%, α-thujone (19.25 - 26.33%, β-thujone (2.03 - 5.28%, 1,8-cineole (6.51 – 13.60%, α-pinene (0.93 – 1.47%, borneol (1.07 – 4.67%, then sesquiterpenes: trans (E-caryophyllene (1.72 – 5.33%, α-humulene (2.89 – 7.99%, viridiflorol (4.27 – 7.99%, and the diterpene manool (2.13 - 3.79%. Thus, our results for the essential oil composition of sage complied with the reference values specified in the DAC 86 monograph for Salvia essential oil.

  11. GC Analyses of Salvia Seeds as Valuable Essential Oil Source

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    Mouna Ben Taârit

    2014-01-01

    Full Text Available The essential oils of seeds of Salvia verbenaca, Salvia officinalis, and Salvia sclarea were obtained by hydrodistillation and analyzed by gas chromatography (GC and GC-mass spectrometry. The oil yields (w/w were 0.050, 0.047, and 0.045% in S. verbenaca, S. sclarea, and S. officinalis, respectively. Seventy-five compounds were identified. The essential oil composition of S. verbenaca seeds showed that over 57% of the detected compounds were oxygenated monoterpenes followed by sesquiterpenes (24.04% and labdane type diterpenes (5.61%. The main essential oil constituents were camphor (38.94%, caryophyllene oxide (7.28%, and 13-epi-manool (5.61%, while those of essential oil of S. officinalis were α-thujone (14.77%, camphor (13.08%, and 1,8-cineole (6.66%. In samples of S. sclarea, essential oil consists mainly of linalool (24.25%, α-thujene (7.48%, linalyl acetate (6.90%, germacrene-D (5.88%, bicyclogermacrene (4.29%, and α-copaene (4.08%. This variability leads to a large range of naturally occurring volatile compounds with valuable industrial and pharmaceutical outlets.

  12. REGULATION OF CHLOROPHY LL DEGRADATION IN PLANT TISSUES

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    Syvash O. O.

    2017-06-01

    Full Text Available The purpose of the review was to analyze the basic biochemical processes leading to the chlorophyll degradation and ways to control this process in plant product storage. First of all, this is a complex of enzymatic reactions starting with the hydrolysis of chlorophyll with the formation of acyclic diterpene phytol and water-soluble chlorophyllide. An alternative primary reaction is the removal of magnesium from the chlorophyll tetrapyrrole ring to form pheophytin with the participation of Mg2+-dechelatase and/or low-molecular Mg2+-dechelating substances. The chlorophyll breakdown can also be caused by free radicals formed in the peroxidase-catalyzed reaction of Н2О2 with phenolic compounds or fatty acids. The unstable product of chlorophyll peroxidation, C132 –hydroxychlorophyll a decomposes to colorless low-molecular compounds. Expression of the genes of chlorophyll catabolism enzymes is controlled by phytohormones. Methods for controlling the pigment decomposition during storage of plant products are associated with the use of activators and inhibitors of chlorophyll decomposition. The best known inductor of the synthesis of catabolic enzymes is ethylene, widely used to accelerate fruit ripening. Gibberellins, cytokinins and nitric oxide, on the contrary, slow down the loss of chlorophyll.

  13. Mining chemodiversity from biodiversity: pharmacophylogeny of medicinal plants of Ranunculaceae.

    Science.gov (United States)

    Hao, Da-Cheng; Xiao, Pei-Gen; Ma, Hong-Ying; Peng, Yong; He, Chun-Nian

    2015-07-01

    This paper reports a pharmacophylogenetic study of a medicinal plant family, Ranunculaceae, investigating the correlations between their phylogeny, chemical constituents, and pharmaceutical properties. Phytochemical, ethnopharmacological, and pharmacological data were integrated in the context of the systematics and molecular phylogeny of the Ranunculaceae. The chemical components of this family included several representative metabolic groups: benzylisoquinoline alkaloids, ranunculin, triterpenoid saponin, and diterpene alkaloids, among others. Ranunculin and magnoflorine were found to coexist in some genera. The pharmacophylogenetic analysis, integrated with therapeutic information, agreed with the taxonomy proposed previously, in which the family Ranunculaceae was divided into five sub-families: Ranunculoideae, Thalictroideae, Coptidoideae, Hydrastidoideae, and Glaucidioideae. It was plausible to organize the sub-family Ranunculoideae into ten tribes. The chemical constituents and therapeutic efficacy of each taxonomic group were reviewed, revealing the underlying connections between phylogeny, chemical diversity, and clinical use, which should facilitate the conservation and sustainable utilization of the pharmaceutical resources derived from the Ranunculaceae. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  14. Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L.) extract polyphenols and terpenoids in Caco-2 cell monolayers

    Science.gov (United States)

    Arráez-Román, David; González-Álvarez, Isabel; Ibáñez, Elena; Segura-Carretero, Antonio; Bermejo, Marival; Micol, Vicente

    2017-01-01

    Rosemary (Rosmarinus officinalis) is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids) of a rosemary extract (RE), obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS), and the apparent permeability values (Papp) were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS) of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability); therefore, RE itself should also be classified into this category. PMID:28234919

  15. Principes toxiques, toxicité et technologie de détoxification de la graine de Jatropha curcas L. (synthèse bibliographique

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    Nesseim, TDT.

    2012-01-01

    Full Text Available Toxic principles, toxicity and technology of detoxification of Jatropha curcas L. seed: a review. The use of meal from the crushing of Jatropha curcas seed for livestock feed is limited owing to the variable amounts of seed available. This availability depends on the level and variety of toxic and antinutritional compounds contained in the seed at a given time; the most important of these compounds are phorbol esters and curcin. The phorbol esters present in J. curcas seed are Euphorbiaceae diterpenes, known for their inflammatory action resulting in irritation and toxicity to insects, fish and mammals. These compounds are sometimes completely degraded in soil and they may be reduced by physical, chemical or biological processes, with a reduction ratio of between 50 and 95%. Curcin is an irritating toxalbumin with lectin activity; it is inactivated by heat treatment at 121 °C for 30 min. Other antinutritional compounds are also present in J. curcas seed, such as saponins and an inhibitor of trypsin activity. This trypsin-inhibiting compound interferes with the digestion process and its reduction is achieved through thermal, chemical or biological treatments. The elimination of, or at least a reduction in the levels of, these molecules represents a prerequisite for using J. curcas meal in the livestock feed sector.

  16. Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum

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    Zeljka Rupcic

    2018-03-01

    Full Text Available Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF or (as established more recently brain-derived neurotrophic factor (BDNF in cell-based bioassays. The present study reports on the metabolite profiles of a Lion’s Mane mushroom (Hericium erinaceus strain and a strain of the rare species, Hericium flagellum (synonym H. alpestre. While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act on BDNF, which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well on NGF expression, which is consistent with the literature.

  17. Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion's Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds.

    Science.gov (United States)

    Friedman, Mendel

    2015-08-19

    The culinary and medicinal mushroom Hericium erinaceus is widely consumed in Asian countries, but apparently not in the United States, for its nutritional and health benefits. To stimulate broader interest in the reported beneficial properties, this overview surveys and consolidates the widely scattered literature on the chemistry (isolation and structural characterization) of polysaccharides and secondary metabolites such as erinacines, hericerins, hericenones, resorcinols, steroids, mono- and diterpenes, and volatile aroma compounds, nutritional composition, food and industrial uses, and exceptional nutritional and health-promoting aspects of H. erinaceus. The reported health-promoting properties of the mushroom fruit bodies, mycelia, and bioactive pure compounds include antibiotic, anticarcinogenic, antidiabetic, antifatigue, antihypertensive, antihyperlipodemic, antisenescence, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties and improvement of anxiety, cognitive function, and depression. The described anti-inflammatory, antioxidative, and immunostimulating properties in cells, animals, and humans seem to be responsible for the multiple health-promoting properties. A wide range of research advances and techniques are described and evaluated. The collated information and suggestion for further research might facilitate and guide further studies to optimize the use of the whole mushrooms and about 70 characterized actual and potential bioactive secondary metabolites to help prevent or treat human chronic, cognitive, and neurological diseases.

  18. Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum.

    Science.gov (United States)

    Rupcic, Zeljka; Rascher, Monique; Kanaki, Sae; Köster, Reinhard W; Stadler, Marc; Wittstein, Kathrin

    2018-03-06

    Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor ( NGF ) or (as established more recently) brain-derived neurotrophic factor ( BDNF ) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion's Mane mushroom ( Hericium erinaceus ) strain and a strain of the rare species, Hericium flagellum (synonym H. alpestre ). While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act on BDNF , which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well on NGF expression, which is consistent with the literature.

  19. Design, synthesis and structure-activity relationships studies on the D ring of the natural product triptolide.

    Science.gov (United States)

    Xu, Hongtao; Tang, Huanyu; Feng, Huijin; Li, Yuanchao

    2014-02-01

    Triptolide is a diterpene triepoxide natural product isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal herb. Triptolide has previously been shown to possess antitumor, anti-inflammatory, immunosuppressive, and antifertility activities. Earlier reports suggested that the five-membered unsaturated lactone ring (D ring) is essential for potent cytotoxicity, however, to the best of our knowledge, systematic structure-activity relationship studies have not yet been reported. Here, four types of D ring-modified triptolide analogues were designed, synthesized and evaluated against human ovarian (SKOV-3) and prostate (PC-3) carcinoma cell lines. The results suggest that the D ring is essential to potency, however it can be modified, for example to C18 hydrogen bond acceptor and/or donor furan ring analogues, without complete loss of cytotoxic activity. Interestingly, evaluation of the key series of C19 analogues showed that this site is exquisitely sensitive to polarity. Together, these results will guide further optimization of this natural product lead compound for the development of potent and potentially clinically useful triptolide analogues. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Ethnobotany, chemistry, and biological activities of the genus Tithonia (Asteraceae).

    Science.gov (United States)

    Chagas-Paula, Daniela A; Oliveira, Rejane B; Rocha, Bruno A; Da Costa, Fernando B

    2012-02-01

    The genus Tithonia is an important source of diverse natural products, particularly sesquiterpene lactones, diterpenes, and flavonoids. The collected information in this review attempts to summarize the recent developments in the ethnobotany, biological activities, and secondary metabolite chemistry of this genus. More than 100 structures of natural products from Tithonia are reported in this review. The species that has been most investigated in this genus is T. diversifolia, from which ca. 150 compounds were isolated. Biological studies are described to evaluate the anti-inflammatory, analgesic, antimalarial, antiviral, antidiabetic, antidiarrhoeal, antimicrobial, antispasmodic, vasorelaxant, cancer-chemopreventive, cytotoxic, toxicological, bioinsecticide, and repellent activities. A few of these studies have been carried out with isolated compounds from Tithonia species, but the majority has been conducted with different extracts. The relationship between the biological activity and the toxicity of compounds isolated from the plants of this genus as well as T. diversifolia extracts still remains unclear, and mechanisms of action remain to be determined. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  1. Platycladus orientalis leaves: a systemic review on botany, phytochemistry and pharmacology.

    Science.gov (United States)

    Shan, Ming-Qiu; Shang, Jing; Ding, An-Wei

    2014-01-01

    Platycladus orientalis leaves (Cebaiye) have been used for thousands of years as traditional Chinese medicine (TCM). According to the theory of TCM, they are categorized as a blood-cooling and hematostatic herb. In clinical practice, they were usually prescribed with heat-clearing herbs to reinforce the efficacy of hemostasis. The review provides the up-to-date information from 1980 to present that is available on the botany, processing research, phytochemistry, pharmacology and toxicology of the leaves. The information is collected from scientific journals, books, theses and reports via library and electronic search (Google Scholar, Pubmed and CNKI). Through literature reports, we can find that the leaves show a wide spectrum of pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, disinsection, anticancer, diuretic, hair growth-promoting, neuroprotective and antifibrotic activities. Diterpene and flavonoids would be active constituents in P. orientalis leaves. Many studies have provided evidence for various traditional uses. However, there is a great need for additional studies to elucidate the mechanism of blood-cooling and hematostatic activity of the leaves. Therefore, the present review on the botany, traditional uses, phytochemistry and toxicity has provided preliminary information for further studies of this herb.

  2. Euclea undulata Thunb.: Review of its botany, ethnomedicinal uses, phytochemistry and biological activities.

    Science.gov (United States)

    Maroyi, Alfred

    2017-11-01

    Euclea undulata (E. undulata) is traditionally used for the treatment of body pains, chest complaints, cough, diabetes, diarrhoea, headaches, heart diseases and toothaches in southern Africa. This study was aimed at reviewing the botany, ethnopharmacology and biological activities of E. undulata in southern Africa. Results presented in this study are based on review of literature using search engines such as Science Direct, Springerlink, Scopus, PubMed, Web of Science, BioMed Central and Google Scholar. Herbal medicine is prepared from the decoctions of the roots, bark and leaves, and extracts of these plant parts have demonstrated anticholinesterase, anti-inflammatory, antimicrobial, antimycobacterial, antiplasmodial, antioxidant and hypoglycaemic activities. Multiple classes of phytochemical compounds such alkaloids, diterpenes, fatty acids, flavonoids, glycosides, naphthoquinones, phenolics, phytosterols, reducing sugars, saponins and tannins have been isolated from the species. E. undulata has a lot of potential as herbal medicine in tropical Africa, and advanced research is required aimed at correlating its medicinal uses with the phytochemistry and pharmacological properties. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  3. The ent-15α-Acetoxykaur-16-en-19-oic Acid Relaxes Rat Artery Mesenteric Superior via Endothelium-Dependent and Endothelium-Independent Mechanisms

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    Êurica Adélia Nogueira Ribeiro

    2012-01-01

    Full Text Available The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy. In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS, indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release.

  4. Directed C-H Bond Oxidation of (+)-Pleuromutilin.

    Science.gov (United States)

    Ma, Xiaoshen; Kucera, Roman; Goethe, Olivia F; Murphy, Stephen K; Herzon, Seth B

    2018-05-01

    Antibiotics derived from the diterpene fungal metabolite (+)-pleuromutilin (1) are useful agents for the treatment Gram-positive infections in humans and farm animals. Pleuromutilins elicit slow rates of resistance development and minimal cross-resistance with existing antibiotics. Despite efforts aimed at producing new derivatives by semisynthesis, modification of the tricyclic core is underexplored, in part due to a limited number of functional group handles. Herein, we report methods to selectively functionalize the methyl groups of (+)-pleuromutilin (1) by hydroxyl-directed iridium-catalyzed C-H silylation, followed by Tamao-Fleming oxidation. These reactions provided access to C16, C17, and C18 monooxidized products, as well as C15/C16 and C17/C18 dioxidized products. Four new functionalized derivatives were prepared from the protected C17 oxidation product. C6 carboxylic acid, aldehyde, and normethyl derivatives were prepared from the C16 oxidation product. Many of these sequences were executed on gram scales. The efficiency and practicality of these routes provides an easy method to rapidly interrogate structure-activity relationships that were previously beyond reach. This study will inform the design of fully synthetic approaches to novel pleuromutilins and underscores the power of the hydroxyl-directed iridium-catalyzed C-H silylation reaction.

  5. "Wild cannabis": A review of the traditional use and phytochemistry of Leonotis leonurus.

    Science.gov (United States)

    Nsuala, Baudry N; Enslin, Gill; Viljoen, Alvaro

    2015-11-04

    Leonotis leonurus, locally commonly known as "wilde dagga" (=wild cannabis), is traditionally used as a decoction, both topically and orally, in the treatment of a wide variety of conditions such as haemorrhoids, eczema, skin rashes, boils, itching, muscular cramps, headache, epilepsy, chest infections, constipation, spider and snake bites. The dried leaves and flowers are also smoked to relieve epilepsy. The leaves and flowers are reported to produce a mild euphoric effect when smoked and have been said to have a similar, although less potent, psychoactive effect to cannabis. To amalgamate the botanical aspects, ethnopharmacology, phytochemistry, biological activity, toxicity and commercial aspects of the scientific literature available on L. leonurus. An extensive review of the literature from 1900 to 2015 was carried out. Electronic databases including Scopus, SciFinder, Pubmed, Google Scholar and Google were used as data sources. All abstracts, full-text articles and books written in English were considered. The phytochemistry of particularly the non-volatile constituents of L. leonurus has been comprehensively investigated due to interest generated as a result of the wide variety of biological effects reported for this plant. More than 50 compounds have been isolated and characterised. L. leonurus contains mainly terpenoids, particularly labdane diterpenes, the major diterpene reported is marrubiin. Various other compounds have been reported by some authors to have been isolated from the plant, including, in the popular literature only, the mildly psychoactive alkaloid, leonurine. Leonurine has however, never been reported by any scientific analysis of the extracts of L. leonurus. Despite the publication of various papers on L. leonurus, there is still, however, the need for definitive research and clarification of other compounds, including alkaloids and essential oils from L. leonurus, as well as from other plant parts, such as the roots which are

  6. Physicochemical and antimicrobial properties of copaiba oil: implications on product quality control.

    Science.gov (United States)

    Fonseca, Renata G; Barros, Francisco M; Apel, Miriam A; Poser, Gilsane L von; Andriolli, Jo O L; Filho, Pedro C Campos; Sousa, Dhierlate F; Lobo, Ivon P; Conceiç O, Aline O

    2015-01-01

    The copaiba oil is a common natural product used in cosmetic industry and as a nutraceutical product. However, lack of quality control and scarce knowledge about its antimicrobial activity is a point of concern. The proposal of this study was to investigate the physicochemical properties and the antimicrobial activity of five commercial brands of copaiba oil. Acidity and ester index, refractory index, solubility in alcohol, and thin layer chromatography were performed to verify the physicochemical properties of five commercial copaiba oils sold in local pharmacies. Ultra performance liquid chromatography coupled with diode-array detection and electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-DAD/ESI-Q-TOF-MS) was used to investigate diterpene acids while the volatile compounds were analysed by gas chromatography-mass spectrometry (GC-MS). Antibacterial and antifungal activities were also evaluated by agar diffusion technique; and minimal inhibitory concentration and maximal bactericidal concentration were defined for each sample and bacteria. The physical-chemical analysis revealed heterogeneity between all samples analysed. The A1 sample showed characteristics of copaiba oil and was mainly composed by hydrocarbon sesquiterpenes (29.95% β-bisabolene, 25.65% Z-α-bergamotene and 10.27% β-cariophyllene). Among diterpene acids, the UPLCDAD/ESI-Q-TOF-MS data are compatible with presence of copalic and/or kolavenic acid (m/z 305 [M + H]+). Candida albicans was sensitive to almost all samples at high concentration and Saccaromyces. Cerevisiae showed sensitivity to A1 sample at 100 mg/mL. Although variable, all samples showed antibacterial activity. Significant activity was seen for A3 (19.0 ±0 and 15.6 ±0.5 mm), A4 (16.6 ±0.5 and 15.6 ±0 mm), and A5 (17.1 ±0 and 17.1 ±0 mm) on Staphylococcus saprophyticus and S. aureus, respectively. All samples were active against Klebsiella pneumoniae showing ≥15 mm diameter halo inhibition; and only A

  7. Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition

    International Nuclear Information System (INIS)

    Wang, Wenwen; Yang, Yanqin; Xiong, Zhewen; Kong, Jiamin; Fu, Xinlu; Shen, Feihai; Huang, Zhiying

    2016-01-01

    Triptolide (TP), a diterpene triepoxide, is a major active component of Tripterygium wilfordii extracts, which are prepared as tablets and has been used clinically for the treatment of inflammation and autoimmune disorders. However, TP's therapeutic potential is limited by severe adverse effects. In a previous study, we reported that TP induced mitochondria dependent apoptosis in cardiomyocytes. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays important roles in the necrosis and apoptosis of cardiomyocytes. Our study aimed to investigate the role of GSK-3β in TP-induced cardiotoxicity. Inhibition of GSK-3β activity by SB 216763, a potent and selective GSK-3 inhibitor, prominently ameliorated the detrimental effects in C57BL/6J mice with TP administration, which was associated with a correction of GSK-3β overactivity. Consistently, in TP-treated H9c2 cells, SB 216763 treatment counteracted GSK-3β overactivity, improved cell viability, and prevented apoptosis by modulating the expression of Bcl-2 family proteins. Mechanistically, GSK-3β interacted with and phosphorylated cyclophilin F (Cyp-F), a key regulator of mitochondrial permeability transition pore (mPTP). GSK-3β inhibition prevented the phosphorylation and activation of Cyp-F, and desensitized mPTP. Our findings suggest that pharmacological targeting of GSK-3β could represent a promising therapeutic strategy for protecting against cardiotoxicity induced by TP. - Highlights: • GSK-3β inhibition ameliorates TP-induced cardiotoxicity in vitro and in vivo. • GSK-3β controls Cyp-F activation, and regulates mPTP and apoptosis in H9c2 cells. • The protective effect is attributed to GSK-3β activity rather than to protein level. • GSK-3β may be a promising target against TP-induced cardiotoxicity.

  8. The Tomato Terpene Synthase Gene Family1[W][OA

    Science.gov (United States)

    Falara, Vasiliki; Akhtar, Tariq A.; Nguyen, Thuong T.H.; Spyropoulou, Eleni A.; Bleeker, Petra M.; Schauvinhold, Ines; Matsuba, Yuki; Bonini, Megan E.; Schilmiller, Anthony L.; Last, Robert L.; Schuurink, Robert C.; Pichersky, Eran

    2011-01-01

    Compounds of the terpenoid class play numerous roles in the interactions of plants with their environment, such as attracting pollinators and defending the plant against pests. We show here that the genome of cultivated tomato (Solanum lycopersicum) contains 44 terpene synthase (TPS) genes, including 29 that are functional or potentially functional. Of these 29 TPS genes, 26 were expressed in at least some organs or tissues of the plant. The enzymatic functions of eight of the TPS proteins were previously reported, and here we report the specific in vitro catalytic activity of 10 additional tomato terpene synthases. Many of the tomato TPS genes are found in clusters, notably on chromosomes 1, 2, 6, 8, and 10. All TPS family clades previously identified in angiosperms are also present in tomato. The largest clade of functional TPS genes found in tomato, with 12 members, is the TPS-a clade, and it appears to encode only sesquiterpene synthases, one of which is localized to the mitochondria, while the rest are likely cytosolic. A few additional sesquiterpene synthases are encoded by TPS-b clade genes. Some of the tomato sesquiterpene synthases use z,z-farnesyl diphosphate in vitro as well, or more efficiently than, the e,e-farnesyl diphosphate substrate. Genes encoding monoterpene synthases are also prevalent, and they fall into three clades: TPS-b, TPS-g, and TPS-e/f. With the exception of two enzymes involved in the synthesis of ent-kaurene, the precursor of gibberellins, no other tomato TPS genes could be demonstrated to encode diterpene synthases so far. PMID:21813655

  9. The Effects of Vitex agnus castus Total Extract on Spermatogenesis of Balb/C Mice

    Directory of Open Access Journals (Sweden)

    M Ramezani

    2008-12-01

    Full Text Available ABSTRACT Introduction & Objective: Vitex agnus castus (Verbenaceae is a phytoestrogeic herb native to the Middle East and southern Europe. It has clinical usage in so many countries. In this research, the effects of Vitex agnus castus extract was investigated on spermatogenesis of male Balb/C mice. Materials & Methods: This is an experimental study in which adult male mice were chosen and divided into 3 groups: control, vehicle, and experimental. Animals were daily injected (i.p. with 65, 165 265, 365, and 465 mg/kg of seed extract for ten consecutive days. Then the animals were weighed and eventually killed by cervical dislocation 2 weeks after the last injection. The caudal part of the right epididymis was used for sperm counting. After macroscopic investigation (weight, diameter and volume of testes tissues were fixed in Buin's fixative. Tissues were cut at 5 µm, stained with Hematoxylin and Eosin (H& E.Ccollected data was analyzed by the SPSS software by using one-way ANOVA. Results: No significant differences in body weight, volume, weight and diameter of testes was seen. Light microscopic studies showed a significant reduction in germinal epithelium in doses of 265 and 365 mg/kg and increased of interstitial tissue area in doses of 265, 365, and 465 mg/kg of extract. There was no significant difference in epithelium thickness and of the diameter of the epididymis. Germinal cells contained pyknotic nuclei and several holes that were found scattered in the tubules. Testis also showed a general disarrangement in various germinal elements of seminiferous tubules. Result of sperms count indicated a significant decreasing of spermatozoa in animals which received 265 and 365 mg/kg of extract. Conclusion: Vitex agnus castus contains essential oils, iridoid glycosides, flavonoids diterpenes, and essential fatty acids. The results suggest that its contraceptive effects is related to its flavonoids and essential fatty acids but further studies is

  10. A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis.

    Science.gov (United States)

    Yen, Ting-Lin; Hsu, Wen-Hsien; Huang, Steven Kuan-Hua; Lu, Wan-Jung; Chang, Chao-Chien; Lien, Li-Ming; Hsiao, George; Sheu, Joen-Rong; Lin, Kuan-Hung

    2013-09-01

    Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs. This study investigated a novel bioactivity of andrographolide on cerebral ischemia/reperfusion-induced brain injury. CECs were treated with andrographolide (20-100 µΜ) for the indicated times (0-24 h). After the reactions, cell survival rate and cytotoxicity were tested by the MTT assay and the lactate dehydrogenase (LDH) test, respectively. Western blotting was used to detect caspase-3 expression. In addition, analysis of cell cycle and apoptosis using PI staining and annexin V-FITC/PI labeling, respectively, was performed by flow cytometry. We also investigated the effect of andrographolide on middle cerebral artery occlusion (MCAO)/reperfusion-induced brain injury in a rat model. In the present study, we found that andrographolide (50-100 µΜ) markedly inhibited CEC growth according to an MTT assay and caused CEC damage according to a LDH test. Our data also revealed that andrographolide (50 µM) induced CEC apoptosis and caspase-3 activation as respectively detected by PI/annexin-V double staining and western blotting. Moreover, andrographolide arrested the CEC cell cycle at the G0/G1 phase by PI staining. In addition, andrographolide (5 mg/kg) caused deterioration of MCAO/reperfusion-induced brain injury in a rat model. These data suggest that andrographolide may disrupt BBB integrity, thereby deteriorating MCAO/reperfusion-induced brain injury, which are, in part, associated with its capacity to arrest cell-cycle and induce CEC

  11. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-05

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights

  12. In vitro and in vivo antimalarial potential of oleoresin obtained from Copaifera reticulata Ducke (Fabaceae) in the Brazilian Amazon rainforest.

    Science.gov (United States)

    de Souza, Giovana A G; da Silva, Nazaré C; de Souza, Juarez; de Oliveira, Karen R M; da Fonseca, Amanda L; Baratto, Leopoldo C; de Oliveira, Elaine C P; Varotti, Fernando de Pilla; Moraes, Waldiney P

    2017-01-15

    In view of the wide variety of the flora of the Amazon region, many plants have been studied in the search for new antimalarial agents. Copaifera reticulata is a tree distributed throughout the Amazon region which contains an oleoresin rich in sesquiterpenes and diterpenes with β-caryophyllene as the major compound. The oleoresin has demonstrated antiparasitic activity against Leishmania amazonensis. Because of this previously reported activity, this oleoresin would be expected to also have antimalarial activity. In this study we evaluated the in vitro and in vivo antimalarial potential of C. reticulata oleoresin. In vitro assays were done using P. falciparum W2 and 3D7 strains and the human fibroblast cell line 26VA Wi-4. For in vivo analysis, BALB/c mice were infected with approximately 10 6 erythrocytes parasitized by P. berghei and their parasitemia levels were observed over 7 days of treatment with C. reticulata; hematological and biochemical parameters were analyzed at the end of experiment. The oleoresin of C. reticulata containing the sesquiterpenes β-caryophyllene (41.7%) and β-bisabolene (18.6%) was active against the P. falciparum W2 and 3D7 strains (IC 50  = 1.66 and 2.54 µg/ml, respectively) and showed low cytotoxicity against the 26VA Wi-4 cell line (IC 50  > 100 µg/ml). The C. reticulata oleoresin reduced the parasitemia levels of infected animals and doses of 200 and 100 mg/kg/day reached a rate of parasitemia elimination resembling that obtained with artemisinin 100 mg/kg/day. In addition, treatment with oleoresin improved the hypoglycemic, hematologic, hepatic and renal parameters of the infected animals. The oleoresin of C. reticulata has antimalarial properties and future investigations are necessary to elucidate its mechanism of action. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Identification of Potential Biomarkers from Aconitum carmichaelii, a Traditional Chinese Medicine, Using a Metabolomic Approach.

    Science.gov (United States)

    Zhao, Dake; Shi, Yana; Zhu, Xinyan; Liu, Li; Ji, Pengzhang; Long, Chunlin; Shen, Yong; Kennelly, Edward J

    2018-04-01

    Despite their well-known toxicity, Aconitum species are important traditional medicines worldwide. Aconitum carmichaelii , known in Chinese as (fuzi), is an officially recognized traditional Chinese medicine with characteristic analgesic and anti-inflammatory activities, whose principal pharmacological ingredients are considered as aconitine-type diterpene alkaloids. Notwithstanding the long-recorded use of A. carmichaelii in traditional Chinese medicine, no single-entity aconitum alkaloid drug has been developed for clinical use. UPLC-Q-TOF-MS was used to investigate the marker compounds that can be used to differentiate A. carmichaelii from seven other Aconitum species collected in Yunnan Province. Nontargeted principle component analysis scores plots found that all the tested Aconitum species clustered into three distinct groups, and A. carmichaelii was significantly different chemically than the other seven species. Furthermore, the primary and lateral roots of A. carmichaelii also showed significant differences. Using orthogonal partial least squares discriminate analysis analysis, eight marker compounds were identified, including 14-acetylkarakoline, aconitine, carmichaeline, fuziline, hypaconitine, mesaconitine, neoline, and talatisamine. Four of these aconitum alkaloids, fuziline, hypaconitine, mesaconitine, and neoline, showed significant analgesic activity in a dose-dependent manner compared to the negative and positive controls. However, hypaconitine, mesaconitine, and neoline exhibited significant acute toxicity activity, while fuziline showed no acute toxicity in mice, suggesting the relative safety of this alkaloid. This study provides a good example of how to differentiate an authentic medicinal plant from common adulterants using a metabolomics approach, and to identify compounds that may be developed into new drugs. Georg Thieme Verlag KG Stuttgart · New York.

  14. Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wenwen; Yang, Yanqin; Xiong, Zhewen; Kong, Jiamin [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Fu, Xinlu [Laboratory Animals Center, Sun Yat-sen University, Guangzhou 510006 (China); Shen, Feihai, E-mail: shenfh3@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Huang, Zhiying, E-mail: hzhiying@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China)

    2016-12-15

    Triptolide (TP), a diterpene triepoxide, is a major active component of Tripterygium wilfordii extracts, which are prepared as tablets and has been used clinically for the treatment of inflammation and autoimmune disorders. However, TP's therapeutic potential is limited by severe adverse effects. In a previous study, we reported that TP induced mitochondria dependent apoptosis in cardiomyocytes. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays important roles in the necrosis and apoptosis of cardiomyocytes. Our study aimed to investigate the role of GSK-3β in TP-induced cardiotoxicity. Inhibition of GSK-3β activity by SB 216763, a potent and selective GSK-3 inhibitor, prominently ameliorated the detrimental effects in C57BL/6J mice with TP administration, which was associated with a correction of GSK-3β overactivity. Consistently, in TP-treated H9c2 cells, SB 216763 treatment counteracted GSK-3β overactivity, improved cell viability, and prevented apoptosis by modulating the expression of Bcl-2 family proteins. Mechanistically, GSK-3β interacted with and phosphorylated cyclophilin F (Cyp-F), a key regulator of mitochondrial permeability transition pore (mPTP). GSK-3β inhibition prevented the phosphorylation and activation of Cyp-F, and desensitized mPTP. Our findings suggest that pharmacological targeting of GSK-3β could represent a promising therapeutic strategy for protecting against cardiotoxicity induced by TP. - Highlights: • GSK-3β inhibition ameliorates TP-induced cardiotoxicity in vitro and in vivo. • GSK-3β controls Cyp-F activation, and regulates mPTP and apoptosis in H9c2 cells. • The protective effect is attributed to GSK-3β activity rather than to protein level. • GSK-3β may be a promising target against TP-induced cardiotoxicity.

  15. Wild Sicilian rosemary: phytochemical and morphological screening and antioxidant activity evaluation of extracts and essential oils.

    Science.gov (United States)

    Napoli, Edoardo M; Siracusa, Laura; Saija, Antonella; Speciale, Antonio; Trombetta, Domenico; Tuttolomondo, Teresa; La Bella, Salvatore; Licata, Mario; Virga, Giuseppe; Leone, Raffaele; Leto, Claudio; Rubino, Laura; Ruberto, Giuseppe

    2015-07-01

    To identify the best biotypes, an extensive survey of Sicilian wild rosemary was carried out by collecting 57 samples from various sites, followed by taxonomic characterization from an agronomic perspective. All the biotypes collected were classified as Rosmarinus officinalis L. A cluster analysis based on the morphological characteristics of the plants allowed the division of the biotypes into seven main groups, although the characteristics examined were found to be highly similar and not area-dependent. Moreover, all samples were analyzed for their phytochemical content, applying an extraction protocol to obtain the nonvolatile components and hydrodistillation to collect the essential oils for the volatile components. The extracts were characterized by LC-UV-DAD/ESI-MS, and the essential oils by GC-FID and GC/MS analyses. In the nonvolatile fractions, 18 components were identified, namely, 13 flavones, two organic acids, and three diterpenes. In the volatile fractions, a total of 82 components were found, with as predominant components α-pinene and camphene among the monoterpene hydrocarbons and 1,8-cineole, camphor, borneol, and verbenone among the oxygenated monoterpenes. Cluster analyses were carried out on both phytochemical profiles, allowing the separation of the rosemary samples into different chemical groups. Finally, the total phenol content and the antioxidant activity of the essential oils and extracts were determined with the Folin-Ciocalteu (FC) colorimetric assay, the UV radiation-induced peroxidation in liposomal membranes (UV-IP test), and the scavenging activity of the superoxide radical (O$\\rm{{_{2}^{{^\\cdot} -}}}$). The present study confirmed that the essential oils and organic extracts of the Sicilian rosemary samples analyzed showed a considerable antioxidant/free radical-scavenging activity. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

  16. Cloning and Functional Characterization of Cycloartenol Synthase from the Red Seaweed Laurencia dendroidea.

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    Gabriela Calegario

    Full Text Available The red seaweed Laurencia dendroidea belongs to the Rhodophyta, a phylum of eukaryotic algae that is widely distributed across the oceans and that constitute an important source of bioactive specialized metabolites. Laurencia species have been studied since 1950 and were found to contain a plethora of specialized metabolites, mainly halogenated sesquiterpenes, diterpenes and triterpenes that possess a broad spectrum of pharmacological and ecological activities. The first committed step in the biosynthesis of triterpenes is the cyclization of 2,3-oxidosqualene, an enzymatic reaction carried out by oxidosqualene cyclases (OSCs, giving rise to a broad range of different compounds, such as the sterol precursors cycloartenol and lanosterol, or triterpene precursors such as cucurbitadienol and β-amyrin. Here, we cloned and characterized the first OSC from a red seaweed. The OSC gene was identified through mining of a L. dendroidea transcriptome dataset and subsequently cloned and heterologously expressed in yeast for functional characterization, which indicated that the corresponding enzyme cyclizes 2,3-oxidosqualene to the sterol precursor cycloartenol. Accordingly, the gene was named L. dendroidea cycloartenol synthase (LdCAS. A phylogenetic analysis using OSCs genes from plants, fungi and algae revealed that LdCAS grouped together with OSCs from other red algae, suggesting that cycloartenol could be the common product of the OSC in red seaweeds. Furthermore, profiling of L. dendroidea revealed cholesterol as the major sterol accumulating in this species, implicating red seaweeds contain a 'hybrid' sterol synthesis pathway in which the phytosterol precursor cycloartenol is converted into the major animal sterol cholesterol.

  17. Transcription Factor SmWRKY1 Positively Promotes the Biosynthesis of Tanshinones in Salvia miltiorrhiza

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    Wenzhi Cao

    2018-04-01

    Full Text Available Tanshinones, one group of bioactive diterpenes, were widely used in the treatment of cardiovascular diseases. WRKYs play important roles in plant metabolism, but their regulation mechanism in Salvia miltiorrhiza remains elusive. In this study, one WRKY transcription factor SmWRKY1 was isolated and functionally characterized from S. miltiorrhiza. Multiple sequence alignment and phylogenetic tree analysis showed SmWRKY1 shared high homology with other plant WRKYs such as CrWRKY1. SmWRKY1 was found predominantly expressed in leaves and stems, and was responsive to salicylic acid (SA, methyl jasmonate (MeJA, and nitric oxide (NO treatment. Subcellular localization analysis found that SmWRKY1 was localized in the nucleus. Over-expression of SmWRKY1 significantly elevated the transcripts of genes coding for enzymes in the MEP pathway especially 1-deoxy-D-xylulose-5-phosphate synthase (SmDXS and 1-deoxy-D-xylulose-5-phosphate reductoisomerase (SmDXR, resulted in over fivefold increase in tanshinones production in transgenic lines (up to 13.7 mg/g DW compared with the control lines. A dual-luciferase (Dual-LUC assay showed that SmWRKY1 can positively regulate SmDXR expression by binding to its promoter. Our work revealed that SmWRKY1 participated in the regulation of tanshinones biosynthesis and acted as a positive regulator through activating SmDXR in the MEP pathway, thus provided a new insight to further explore the regulation mechanism of tanshinones biosynthesis.

  18. A Classical Genetic Solution to Enhance the Biosynthesis of Anticancer Phytochemicals in Andrographis paniculata Nees

    Science.gov (United States)

    Talei, Daryush; Abdul Kadir, Mihdzar; Rafii, Mohd Yusop; Sagineedu, Sreenivasa Rao

    2014-01-01

    Andrographolides, the diterpene lactones, are major bioactive phytochemicals which could be found in different parts of the medicinal herb Andrographis paniculata. A number of such compounds namely andrographolide (AG), neoandrographolide (NAG), and 14-deoxy-11,12-didehydroandrographolide (DDAG) have already attracted a great deal of attention due to their potential therapeutic effects in hard-to-treat diseases such as cancers and HIV. Recently, they have also been considered as substrates for the discovery of novel pharmaceutical compounds. Nevertheless, there is still a huge gap in knowledge on the genetic pattern of the biosynthesis of these bioactive compounds. Hence, the present study aimed to investigate the genetic mechanisms controlling the biosynthesis of these phytochemicals using a diallel analysis. The high performance liquid chromatography analysis of the three andrographolides in 210 F1 progenies confirmed that the biosynthesis of these andrographolides was considerably increased via intraspecific hybridization. The results revealed high, moderate and low heterosis for DDAG, AG and NAG, respectively. Furthermore, the preponderance of non-additive gene actions was affirmed in the enhancement of the three andrographolides contents. The consequence of this type of gene action was the occurrence of high broad-sense and low narrow-sense heritabilities for the above mentioned andrographolides. The prevalence of non-additive gene action suggests the suitability of heterosis breeding and hybrid seed production as a preferred option to produce new plant varieties with higher andrographolide contents using the wild accessions of A. paniculata. Moreover, from an evolutionary point of view, the occurrence of population bottlenecks in the Malaysian accessions of A. paniculata was unveiled by observing a low level of additive genetic variance (VA) for all the andrographolides. PMID:24586262

  19. Digestibility of solvent-treated Jatropha curcas kernel by broiler chickens in Senegal.

    Science.gov (United States)

    Nesseim, Thierry Daniel Tamsir; Dieng, Abdoulaye; Mergeai, Guy; Ndiaye, Saliou; Hornick, Jean-Luc

    2015-12-01

    Jatropha curcas is a drought-resistant shrub belonging to the Euphorbiaceae family. The kernel contains approximately 60 % lipid in dry matter, and the meal obtained after oil extraction could be an exceptional source of protein for family poultry farming, in the absence of curcin and, especially, some diterpene derivatives phorbol esters that are partially lipophilic. The nutrient digestibility of J. curcas kernel meal (JKM), obtained after partial physicochemical deoiling was thus evaluated in broiler chickens. Twenty broiler chickens, 6 weeks old, were maintained in individual metabolic cages and divided into four groups of five animals, according to a 4 × 4 Latin square design where deoiled JKM was incorporated into grinded corn at 0, 4, 8, and 12 % levels (diets 0, 4, 8, and 12 J), allowing measurement of nutrient digestibility by the differential method. The dry matter (DM) and organic matter (OM) digestibility of diets was affected to a low extent by JKM (85 and 86 % in 0 J and 81 % in 12 J, respectively) in such a way that DM and OM digestibility of JKM was estimated to be close to 50 %. The ether extract (EE) digestibility of JKM remained high, at about 90 %, while crude protein (CP) and crude fiber (CF) digestibility were largely impacted by JKM, with values closed to 40 % at the highest levels of incorporation. J. curcas kernel presents various nutrient digestibilities but has adverse effects on CP and CF digestibility of the diet. The effects of an additional heat or biological treatment on JKM remain to be assessed.

  20. A classical genetic solution to enhance the biosynthesis of anticancer phytochemicals in Andrographis paniculata Nees.

    Directory of Open Access Journals (Sweden)

    Alireza Valdiani

    Full Text Available Andrographolides, the diterpene lactones, are major bioactive phytochemicals which could be found in different parts of the medicinal herb Andrographis paniculata. A number of such compounds namely andrographolide (AG, neoandrographolide (NAG, and 14-deoxy-11,12-didehydroandrographolide (DDAG have already attracted a great deal of attention due to their potential therapeutic effects in hard-to-treat diseases such as cancers and HIV. Recently, they have also been considered as substrates for the discovery of novel pharmaceutical compounds. Nevertheless, there is still a huge gap in knowledge on the genetic pattern of the biosynthesis of these bioactive compounds. Hence, the present study aimed to investigate the genetic mechanisms controlling the biosynthesis of these phytochemicals using a diallel analysis. The high performance liquid chromatography analysis of the three andrographolides in 210 F1 progenies confirmed that the biosynthesis of these andrographolides was considerably increased via intraspecific hybridization. The results revealed high, moderate and low heterosis for DDAG, AG and NAG, respectively. Furthermore, the preponderance of non-additive gene actions was affirmed in the enhancement of the three andrographolides contents. The consequence of this type of gene action was the occurrence of high broad-sense and low narrow-sense heritabilities for the above mentioned andrographolides. The prevalence of non-additive gene action suggests the suitability of heterosis breeding and hybrid seed production as a preferred option to produce new plant varieties with higher andrographolide contents using the wild accessions of A. paniculata. Moreover, from an evolutionary point of view, the occurrence of population bottlenecks in the Malaysian accessions of A. paniculata was unveiled by observing a low level of additive genetic variance (VA for all the andrographolides.