Antiproliferative Diterpenes from a Malleastrum sp. from the Madagascar dry forest[1

PubMed Central

Liu, Yixi; Wiedle, C. Houston; Brodie, Peggy J.; Callmander, Martin W.; Rakotondrajaona, R.; Rakotobe, Etienne; Rasamison, Vincent E.

2015-01-01

An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (−)-kolavenol (4), and the known labdane diterpene 3-oxo-ent-Iabda-8(17),13-dien-15,16-olide (5). Compounds 1, 3, and 4 showed moderate antiproliferative activities against the A2780 ovarian cancer cell line, with the IC50 values of 3.01 ± 0.8, 7.84 ± 0.2, and 17.9 ± 3 μM, respectively. The structure elucidations of all compounds were carried out based on analysis of NMR and mass spectroscopic data. The relative stereochemistry of compound 1 was determined by NOESY NMR spectrum. PMID:26594745

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

PubMed Central

Simplicio, Janaina A.; Simão, Marilia R.; Ambrosio, Sergio R.; Tirapelli, Carlos R.

2016-01-01

Background 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. Objective 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. Methods 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. Results 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. Conclusion The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats. PMID:27096521

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

PubMed

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.

A complete 1H and 13C NMR data assignment for the diterpene methyl (-)-zanzibarate by 2D spectroscopy and NOE experiments.

PubMed

Imamura, P M; Miranda, P C M L; Giacomini, R A

2004-06-01

The 1H and 13C NMR spectra of methyl (-)-zanzibarate (1), an ent-labdanic diterpene isolated from the epicarp of Hymenaea courbaril var. altissima (Leguminosaea, Cesalpinoideae, Detariae), was fully assigned by COSY experiments, 13C/1H shift correlation diagrams and NOE experiments. Copyright 2004 John Wiley & Sons, Ltd.

Diterpenes from Xylopia langsdorffiana inhibit cell growth and induce differentiation in human leukemia cells.

PubMed

Castello Branco, Marianna V S; Anazetti, Maristella C; Silva, Marcelo S; Tavares, Josean F; Diniz, Margareth F F Melo; Frungillo, Lucas; Haun, Marcela; Melo, Patrícia S

2009-01-01

Two new diterpenes were isolated from stems and leaves of Xylopia langsdorffiana, ent-atisane-7alpha,16alpha-diol (xylodiol) and ent-7alpha-acetoxytrachyloban-18-oic acid (trachylobane), along with the known 8(17),12E,14-labdatrien-18-oic acid (labdane). We investigated their antitumour effects on HL60, U937 and K562 human leukemia cell lines. We found that xylodiol was the most potent diterpene in inhibiting cell proliferation of HL60, U937 and K562 cells, with mean IC50 values of 90, 80 and 50 microM, respectively. Based on the nitroblue tetrazolium (NBT) reduction assay, all the diterpenes were found to induce terminal differentiation in HL60 and K562 cells, with xylodiol being the most effective. NBT reduction was increased by almost 120% after 12 h exposure of HL60 cells to xylodiol at a concentration lower than the IC50 (50 microM). Thus, xylodiol inhibited human leukemia cell growth in vitro partly by inducing cell differentiation, and merits further studies to examine its mechanism of action as a potential antitumoural agent.

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

PubMed

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.

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

PubMed Central

2012-01-01

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 specialized metabolite sclareol

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

PubMed

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

Molecular docking and inhibition kinetics of α-glucosidase activity by labdane diterpenes isolated from tora seeds (Alpinia nigra B.L. Burtt.).

PubMed

Ghosh, Sudipta; Rangan, Latha

2015-02-01

Current approach against type 2 diabetes involves α-glucosidase inhibitors like acarbose associated with many side effects. Therefore, as an alternative to the existing drug, many natural products mainly from plant sources have been investigated which inhibit α-glucosidase. Here, we have selected medicinally important Alpinia nigra to explore its α-glucosidase inhibitory activity. Organic extracts of seeds and two purified natural diterpenes I: (E)-labda-8(17), 12-diene-15, 16-dial and II: (E)-8β, 17-epoxylabd-12-ene-15, 16-dial from A. nigra were investigated towards inhibition of α-glucosidase activity. Dose-dependent inhibition pattern were observed for seed extracts and both the compounds. Further, inhibition kinetics studies of the diterpenes indicated a non-competitive type of inhibition against α-glucosidase. Docking studies were carried out which revealed that both the diterpenes interacted within the active site of N-terminal and C-terminal domain of human maltase-glucoamylase enzyme, respectively. This is the first report of α-glucosidase inhibitory activity of these isolated diterpenes and their higher inhibitory potential than any terpenoids studied till date against α-glucosidase.

Antimicrobial evaluation of diterpenes from Copaifera langsdorffii oleoresin against periodontal anaerobic bacteria.

PubMed

Souza, Ariana B; de Souza, Maria G M; Moreira, Maísa A; Moreira, Monique R; Furtado, Niege A J C; Martins, Carlos H G; Bastos, Jairo K; dos Santos, Raquel A; Heleno, Vladimir C G; Ambrosio, Sergio Ricardo; Veneziani, Rodrigo C S

2011-11-18

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.

Extracellular localization of the diterpene sclareol in clary sage (Salvia sclarea L., Lamiaceae).

PubMed

Caissard, Jean-Claude; Olivier, Thomas; Delbecque, Claire; Palle, Sabine; Garry, Pierre-Philippe; Audran, Arthur; Valot, Nadine; Moja, Sandrine; Nicolé, Florence; Magnard, Jean-Louis; Legrand, Sylvain; Baudino, Sylvie; Jullien, Frédéric

2012-01-01

Sclareol is a high-value natural product obtained by solid/liquid extraction of clary sage (Salvia sclarea L.) inflorescences. Because processes of excretion and accumulation of this labdane diterpene are unknown, the aim of this work was to gain knowledge on its sites of accumulation in planta. Samples were collected in natura or during different steps of the industrial process of extraction (steam distillation and solid/liquid extraction). Samples were then analysed with a combination of complementary analytical techniques (gas chromatography coupled to a mass spectrometer, polarized light microscopy, environmental scanning electron microscopy, two-photon fluorescence microscopy, second harmonic generation microscopy). According to the literature, it is hypothesized that sclareol is localized in oil pockets of secretory trichomes. This study demonstrates that this is not the case and that sclareol accumulates in a crystalline epicuticular form, mostly on calyces.

Extracellular Localization of the Diterpene Sclareol in Clary Sage (Salvia sclarea L., Lamiaceae)

PubMed Central

Caissard, Jean-Claude; Olivier, Thomas; Delbecque, Claire; Palle, Sabine; Garry, Pierre-Philippe; Audran, Arthur; Valot, Nadine; Moja, Sandrine; Nicolé, Florence; Magnard, Jean-Louis; Legrand, Sylvain; Baudino, Sylvie; Jullien, Frédéric

2012-01-01

Sclareol is a high-value natural product obtained by solid/liquid extraction of clary sage (Salvia sclarea L.) inflorescences. Because processes of excretion and accumulation of this labdane diterpene are unknown, the aim of this work was to gain knowledge on its sites of accumulation in planta. Samples were collected in natura or during different steps of the industrial process of extraction (steam distillation and solid/liquid extraction). Samples were then analysed with a combination of complementary analytical techniques (gas chromatography coupled to a mass spectrometer, polarized light microscopy, environmental scanning electron microscopy, two-photon fluorescence microscopy, second harmonic generation microscopy). According to the literature, it is hypothesized that sclareol is localized in oil pockets of secretory trichomes. This study demonstrates that this is not the case and that sclareol accumulates in a crystalline epicuticular form, mostly on calyces. PMID:23133579

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

PubMed

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.

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

PubMed Central

Pelot, Kyle A.; Hagelthorn, David M.; Addison, J. Bennett

2017-01-01

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. PMID:28445526

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

PubMed

Hansen, Nikolaj L; Heskes, Allison M; Hamberger, Britta; Olsen, Carl E; Hallström, Björn M; Andersen-Ranberg, Johan; Hamberger, Björn

2017-02-01

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-epoxide lactone triptolide was the first of many diterpenoids identified, attracting interest due to the spectrum of bioactivities. To probe the genetic underpinning of diterpenoid diversity, an expansion of the class II diterpene synthase (diTPS) family was recently identified in a leaf transcriptome. Following detection of triptolide and simple diterpene scaffolds in the root, we sequenced and mined the root transcriptome. This allowed identification of the root-specific complement of TPSs and an expansion in the class I diTPS family. Functional characterization of the class II diTPSs established their activities in the formation of four C-20 diphosphate intermediates, precursors of both generalized and specialized metabolism and a novel scaffold for Celastraceae. Functional pairs of the class I and II enzymes resulted in formation of three scaffolds, accounting for some of the terpenoid diversity found in T. wilfordii. The absence of activity-forming abietane-type diterpenes encouraged further testing of TPSs outside the canonical class I diTPS family. TwTPS27, close relative of mono-TPSs, was found to couple with TwTPS9, converting normal-copalyl diphosphate to miltiradiene. The phylogenetic distance to established diTPSs indicates neo-functionalization of TwTPS27 into a diTPS, a function not previously observed in the TPS-b subfamily. This example of evolutionary convergence expands the functionality of TPSs in the TPS-b family and may contribute miltiradiene to the diterpenoids of T. wilfordii. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

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

PubMed

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.

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

PubMed

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

Hypophyllins A-D, Labdane-Type Diterpenoids with Vasorelaxant Activity from Hypoestes phyllostachya "Rosea".

PubMed

Wu, Xing-De; Luo, Dan; Tu, Wen-Chao; Deng, Zhen-Tao; Chen, Xue-Jiao; Su, Jia; Ji, Xu; Zhao, Qin-Shi

2016-12-16

Three rearranged labdane-type diterpenoids, hypophyllins A-C (1-3), and a caged labdane diterpenoid possessing a 8,9-dioxatricyclic[4.2.1.1 3,7 ]decane moiety, hypophyllin D (4), as well as two new biogenetically related diterpernoids, hypophyllins E (5) and F (6), were isolated from the aerial parts of Hypoestes phyllostachya "Rosea". The absolute configurations of 1-4 were determined by X-ray diffraction analysis. The plausible biogenetic pathway for 1-4 was also proposed. Compounds 4 and 5 showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.

Diterpenes from the Brown Alga Dictyota crenulata.

PubMed

De-Paula, Joel Campos; Bueno, Ludmila Bomeny; Cavalcanti, Diana Negrão; Yoneshigue-Valentin, Yocie; Teixeira, Valéria Laneuville

2008-06-04

The crude extract of the Brazilian brown alga Dictyota crenulata was analyzed by NMR spectroscopy and HRGC-MS techniques. Seven diterpenes were identified: pachydictyol A, dictyodial, 4beta-hydroxydictyodial A, 4beta-acetoxydictyodial A, isopachydictyol A, dictyol C and dictyotadiol. Xeniane diterpenes have previously been found in D. crenulata from the Pacific Ocean. The results characterize D. crenulata as a species that provides prenylated guaiane (group I) and xeniane diterpenes (group III), thus making it a new source of potential antiviral products.

Antiparasitic, Nematicidal and Antifouling Constituents from Juniperus Berries

USDA-ARS?s Scientific Manuscript database

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...

Leishmanicidal and reversal multidrug resistance constituents from Aeonium lindleyi.

PubMed

Kennedy, María L; Cortés, Fernando; Piñero, José E; Castanys, Santiago; López-Arencibia, Atteneri; Gamarro, Francisco; Bazzocchi, Isabel L; Jiménez, Ignacio A

2011-01-01

A new bicyclic diterpene with a labdane skeleton, 7-oxo-labd-8-en-15-ol ( 1), along with two known diterpenes and ten flavonoids were isolated from the leaves of Aeonium lindleyi (Crassulaceae). Their structures were elucidated on the basis of spectroscopic data, including 1D and 2D NMR experiments, and comparison with spectroscopic data reported in the literature. Labdan-8 α,15-diol (2) and labd-8(17)-en-3 β,15-diol (3) showed leishmanicidal activity against Leishmania tropica (IC (50) = 77.0 µM) and Leishmania braziliensis (IC (50) = 68.0 µM) similar to ketoconazole used as positive control. 5,3'-Dihydroxy-3,7,4',5'-tetramethoxyflavone (8) and combretol (9) showed moderate activity (growth inhibition 87.3 and 73.0 %, respectively, at 50 µM) against a multidrug-resistant L. tropica line. © Georg Thieme Verlag KG Stuttgart · New York.

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

USDA-ARS?s Scientific Manuscript database

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...

Diterpenes from the Marine Algae of the Genus Dictyota.

PubMed

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.

Capitate glandular trichomes of Paragutzlaffia henryi harbor new phytotoxic labdane diterpenoids.

PubMed

Wang, Ying; Luo, Shi-Hong; Hua, Juan; Liu, Yan; Jing, Shu-Xi; Li, Xiao-Nian; Li, Sheng-Hong

2015-11-18

The morphology and chemical profile of the capitate glandular trichomes (CGTs) of Paragutzlaffia henryi (Acanthaceae) were investigated. Four new labdane diterpenoids named paraguhenryisins A-D (1-4), together with the known physacoztomatin (5), were localized to the CGTs using laser microdissection coupled with cryogenic (1)H NMR and HPLC analyses and were traced and isolated from the CGT extract of inflorescences. Their structures were determined by spectroscopic methods and single-crystal X-ray diffraction. Bioassays indicated significant inhibitory effect for these diterpenoids on Arabidopsis thaliana seed germination and seedling root elongation. The most potent inhibitor, paraguhenryisin C (3), was interestingly detected in both the rhizosphere soil and water rinsed inflorescences extract of P. henryi but not the roots, with average contents in the rhizosphere soil relevant to its phytotoxic EC50 values. These results suggested that phytotoxic labdane diterpenoids in the CGTs might be released into the environment as a defensive measure for P. henryi against other competitive plants.

Diterpenes and Their Derivatives as Potential Anticancer Agents.

PubMed

Islam, Muhammad Torequl

2017-05-01

As therapeutic tools, diterpenes and their derivatives have gained much attention of the medicinal scientists nowadays. It is due to their pledging and important biological activities. This review congregates the anticancer diterpenes. For this, a search was made with selected keywords in PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society and miscellaneous databases from January 2012 to January 2017 for the published articles. A total 28, 789 published articles were seen. Among them, 240 were included in this study. More than 250 important anticancer diterpenes and their derivatives were seen in the databases, acting in the different pathways. Some of them are already under clinical trials, while others are in the nonclinical and/or pre-clinical trials. In conclusion, diterpenes may be one of the lead molecules in the treatment of cancer. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Antimicrobial activity and chemical analysis of Microlicia hatschbachii Wurdack (Melastomataceae) extract.

PubMed

Cassiano, Dayse S A; Pacheco, Alessandra G M; da Costa, Mateus M; Almeida, Jackson R G S; Vieira, Ivo J C; Branco, Alexsandro

2014-01-01

Aerial parts of Microlicia hatschbachii were extracted with hexane, and the extract was evaluated for antimicrobial activity by a broth dilution method. After phytochemical procedures: GC-MS identified aliphatic alkanes, carboxylic acids and methyl esters of long-chain fatty acids; and two diterpenoids [labd-8(17)-en-15-oic acid and labd-8(17),13-dien-15-oic acid] were identified by (1)H and (13)C NMR. The antimicrobial activity of the hexane extract could be attributed to the presence of labdanes. This identification is the first reported occurrence of labdane diterpenes in the Melastomataceae family.

Manoyl oxide (13R), the biosynthetic precursor of forskolin, is synthesized in specialized root cork cells in Coleus forskohlii.

PubMed

Pateraki, Irini; Andersen-Ranberg, Johan; Hamberger, Britta; Heskes, Allison Maree; Martens, Helle Juel; Zerbe, Philipp; Bach, Søren Spanner; Møller, Birger Lindberg; Bohlmann, Jörg; Hamberger, Björn

2014-03-01

Forskolin, a complex labdane diterpenoid found in the root of Coleus forskohlii (Lamiaceae), has received attention for its broad range of pharmacological activities, yet the biosynthesis has not been elucidated. We detected forskolin in the root cork of C. forskohlii in a specialized cell type containing characteristic structures with histochemical properties consistent with oil bodies. Organelle purification and chemical analysis confirmed the localization of forskolin and of its simplest diterpene precursor backbone, (13R) manoyl oxide, to the oil bodies. The labdane diterpene backbone is typically synthesized by two successive reactions catalyzed by two distinct classes of diterpene synthases. We have recently described the identification of a small gene family of diterpene synthase candidates (CfTPSs) in C. forskohlii. Here, we report the functional characterization of four CfTPSs using in vitro and in planta assays. CfTPS2, which synthesizes the intermediate copal-8-ol diphosphate, in combination with CfTPS3 resulted in the stereospecific formation of (13R) manoyl oxide, while the combination of CfTPS1 and CfTPS3 or CfTPS4 led to formation of miltiradiene, precursor of abietane diterpenoids in C. forskohlii. Expression profiling and phylogenetic analysis of the CfTPS family further support the functional diversification and distinct roles of the individual diterpene synthases and the involvement of CfTPS1 to CfTPS4 in specialized metabolism and of CfTPS14 and CfTPS15 in general metabolism. Our findings pave the way toward the discovery of the remaining components of the pathway to forskolin, likely localized in this specialized cell type, and support a role of oil bodies as storage organelles for lipophilic bioactive metabolites.

Manoyl Oxide (13R), the Biosynthetic Precursor of Forskolin, Is Synthesized in Specialized Root Cork Cells in Coleus forskohlii1[W][OPEN

PubMed Central

Pateraki, Irini; Andersen-Ranberg, Johan; Hamberger, Britta; Heskes, Allison Maree; Martens, Helle Juel; Zerbe, Philipp; Bach, Søren Spanner; Møller, Birger Lindberg; Bohlmann, Jörg; Hamberger, Björn

2014-01-01

Forskolin, a complex labdane diterpenoid found in the root of Coleus forskohlii (Lamiaceae), has received attention for its broad range of pharmacological activities, yet the biosynthesis has not been elucidated. We detected forskolin in the root cork of C. forskohlii in a specialized cell type containing characteristic structures with histochemical properties consistent with oil bodies. Organelle purification and chemical analysis confirmed the localization of forskolin and of its simplest diterpene precursor backbone, (13R) manoyl oxide, to the oil bodies. The labdane diterpene backbone is typically synthesized by two successive reactions catalyzed by two distinct classes of diterpene synthases. We have recently described the identification of a small gene family of diterpene synthase candidates (CfTPSs) in C. forskohlii. Here, we report the functional characterization of four CfTPSs using in vitro and in planta assays. CfTPS2, which synthesizes the intermediate copal-8-ol diphosphate, in combination with CfTPS3 resulted in the stereospecific formation of (13R) manoyl oxide, while the combination of CfTPS1 and CfTPS3 or CfTPS4 led to formation of miltiradiene, precursor of abietane diterpenoids in C. forskohlii. Expression profiling and phylogenetic analysis of the CfTPS family further support the functional diversification and distinct roles of the individual diterpene synthases and the involvement of CfTPS1 to CfTPS4 in specialized metabolism and of CfTPS14 and CfTPS15 in general metabolism. Our findings pave the way toward the discovery of the remaining components of the pathway to forskolin, likely localized in this specialized cell type, and support a role of oil bodies as storage organelles for lipophilic bioactive metabolites. PMID:24481136

Diterpenes as lead molecules against neglected tropical diseases.

PubMed

Barros de Alencar, Marcus Vinícius Oliveira; de Castro E Sousa, João Marcelo; Rolim, Hercília Maria Lins; de Medeiros, Maria das Graças Freire; Cerqueira, Gilberto Santos; de Castro Almeida, Fernanda Regina; Citó, Antônia Maria das Graças Lopes; Ferreira, Paulo Michel Pinheiro; Lopes, José Arimatéia Dantas; de Carvalho Melo-Cavalcante, Ana Amélia; Islam, Md Torequl

2017-02-01

Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs. For this, databases were searched using specific search terms. Among the 2338 collected reports, a total of 181 articles were included in this review. Of them, 148 dealt with investigations using single organisms, and 33 used multiple organisms. No mechanisms of action were reported in the case of 164 reports. A total of 93.92% were related to nonclinical studies, and 4.42% and 1.66% dealt with preclinical and clinical studies, respectively. The review displays that many diterpenes are effective upon Chagas disease, chikungunya, echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates against NTDs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

HPLC quantitation of kaurane diterpenes in Xylopia species.

PubMed

de Melo, A C; Cota, B B; de Oliveira, A B; Braga, F C

2001-01-01

Xylopia frutescens is a tree native to the Brazilian Amazon whose seeds are rich in kaurenoic acid, a diterpene that showed in vitro activity against Trypanosoma cruzi. Aiming to find out alternative sources for kaurenoic acid, the content of some kaurane diterpenes was evaluated in X. aromatica and X. brasiliensis, species occurring in the Cerrado area of Minas Gerais, and also in X. frutescens. A reversed phase HPLC isocratic method was developed and validated to perform the assays. Kaurenoic acid was found to be the most abundant diterpene within the analyzed species, with a 3.16+/-0.97% content in the seeds of X. frutescens, which also presented the highest amount of xylopic acid (1.09+/-0.33%). The highest concentration of 16-alpha-hydroxykauranoic acid (1.96+/-1.58%) was found in the stems of X. aromatica.

A new antibacterial diterpene from the roots of Salvia caespitosa.

PubMed

Ulubelen, A; Oksüz, S; Topcu, G; Gören, A C; Bozok-Johansson, C; Celik, C; Kökdil, G; Voelter, W

2001-01-01

From the roots of Saliva caespitosa Montbret and Aucher ex. Bentham a new diterpene 6beta-hydroxyisopimaric acid (1) has been isolated together with four known diterpenes, one new triterpenoid, 3-acetylvergatic acid (2), as well as five known triterpenoids, two steroids and a flavone. The structures of the compounds were established by spectroscopic analyses. The isolated compounds were tested against standard bacterial strains. Only the new diterpene, 6beta-hydroxyisopimaric acid has strong activity (MIC 9 microg/ml) against S. aureus and (MIC 18 microg/ml) against S. epidermidis as well as against B. subtilis (MIC 9 microg/ml).

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

PubMed

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.

Phytotoxic clerodane diterpenes from Salvia miniata Fernald (Lamiaceae).

PubMed

Bisio, Angela; Damonte, Gianluca; Fraternale, Daniele; Giacomelli, Emanuela; Salis, Annalisa; Romussi, Giovanni; Cafaggi, Sergio; Ricci, Donata; De Tommasi, Nunziatina

2011-02-01

Our ongoing research to identify natural growth inhibitors with diterpene and triterpene skeletons exuding from the surface of the aerial parts of Salvia species led us to study Salvia miniata Fernald. Ten clerodane diterpenoids were found, along with three known diterpenes. Most of the isolated compounds from S. miniata inhibited the germination of Papaver rhoeas L. and Avena sativa L. in Petri dish experiments. Parallel results have been obtained in experiments carried out to evaluate the subsequent growth of the seedlings of the target species in the presence of the tested compounds. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Diterpene resin acids in conifers.

PubMed

Keeling, Christopher I; Bohlmann, Jörg

2006-11-01

Diterpene resin acids are a significant component of conifer oleoresin, which is a viscous mixture of terpenoids present constitutively or inducibly upon herbivore or pathogen attack and comprises one form of chemical resistance to such attacks. This review focuses on the recent discoveries in the chemistry, biosynthesis, molecular biology, regulation, and biology of these compounds in conifers.

QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity.

PubMed

Sousa, Inês J; Ferreira, Maria-José U; Molnár, Joseph; Fernandes, Miguel X

2013-02-14

Multidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatrophane-type diterpenes from Euphorbia species were found to be strong MDR reversing agents. In this study we applied quantitative structure-activity relationship (QSAR) methodology in order to identify the most relevant molecular features of macrocyclic diterpenes with P-gp inhibitory activity and to determine which structural modifications can be performed to improve their activity. Using experimental biological data at two concentrations (4 and 40 μg/ml), we developed a QSAR model for a set of 51 bioactive diterpenic compounds which includes lathyrane and jatrophane-type diterpenes and another model just for jatrophanes. The cross-validation correlation values for all diterpenes QSAR models developed for biological activities at compound concentrations of 4 and 40 μg/ml were 0.758 and 0.729, respectively. Regarding the prediction ability, we get R²(pred) values of 0.765 and 0.534 for biological activities at compound concentrations of 4 and 40 μg/ml, respectively. Applying the cross-validation test to jatrophanes QSAR models, we obtained 0.680 and 0.787 for biological activities at compound concentrations of 4 and 40 μg/ml concentrations, respectively. For the same concentrations, the obtained R²(pred) values for jatrophanes models were 0.541 and 0.534, respectively. The obtained models were statistically valid and showed high prediction ability. Copyright © 2012 Elsevier B.V. All rights reserved.

Prediction of anticancer activity of diterpenes isolated from the paraiban flora through a PLS model and molecular surfaces.

PubMed

Scotti, Luciana; Scotti, Marcus T; Ishiki, Hamilton; Junior, Francisco J B M; dos, Santos Paula F; Tavares, Josean F; da Silva, Marcelo S

2014-05-01

The aim of this work was to predict the anticancer potential of 3 atisane, and 3 trachylobane diterpene compounds extracted from the roots of Xylopia langsdorffiana. The prediction of anticancer activity as expressed against PC-3 tumor cells was made using a PLS model built with 26 diterpenes in the training set. Significant statistical measures were obtained. The six investigated diterpenes were applied to the model and their activities against PC-3 cells were calculated. All the diterpenes were active, with atisane diterpenes showing the higher pICso values. In human prostate carcinoma PC-3 cells, the apoptosis mechanism is related to an inhibition of IKK/NF-KB. Antioxidant potential implies a greater electronic molecular atmosphere (increased donor electron capacity), which can reduce radical reactivity, and facilitate post donation charge accommodation. Molecular surfaces indicated a much greater electronic cloud over atisane diterpenes.

Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review.

PubMed

Aminimoghadamfarouj, Noushin; Nematollahi, Alireza

2017-06-17

Propolis is one of the complex, but valuable, bio-sources for discovering therapeutic compounds. Diterpenes are organic compounds composed of four isoprene units and are known for their biological and pharmacological characteristics, such as antibacterial, anticancer, and anti-inflammatory activities. Recently, advancements have been made in the development of antibacterial and anticancer leads from propolis-isolated diterpenes, and scrutiny of these compounds is being pursued. Thus, this review covers the progress in this arena, with a focus on the chemistry and biological activities of propolis diterpenes. It is anticipated that important information, in a comprehensive and concise manner, will be delivered here for better understanding of natural product drug discovery research.

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

PubMed

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.

Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity.

PubMed

Petiwala, Sakina M; Johnson, Jeremy J

2015-10-28

Recently, rosemary extracts standardized to diterpenes (e.g. carnosic acid and carnosol) have been approved by the European Union (EU) and given a GRAS (Generally Recognized as Safe) status in the United States by the Food and Drug Administration (FDA). Incorporation of rosemary into our food system and through dietary selection (e.g. Mediterranean Diet) has increased the likelihood of exposure to diterpenes in rosemary. In consideration of this, a more thorough understanding of rosemary diterpenes is needed to understand its potential for a positive impact on human health. Three agents in particular have received the most attention that includes carnosic acid, carnosol, and rosmanol with promising results of anti-cancer activity. These studies have provided evidence of diterpenes to modulate deregulated signaling pathways in different solid and blood cancers. Rosemary extracts and the phytochemicals therein appear to be well tolerated in different animal models as evidenced by the extensive studies performed for approval by the EU and the FDA as an antioxidant food preservative. This mini-review reports on the pre-clinical studies performed with carnosic acid, carnosol, and rosmanol describing their mechanism of action in different cancers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clerodane diterpenes: sources, structures, and biological activities†

PubMed Central

Li, Rongtao; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

2016-01-01

The clerodane diterpenoids are a widespread class of secondary metabolites and have been found in several hundreds of plant species from various families and in organisms from other taxonomic groups. These substances have attracted interest in recent years due to their notable biological activities, particularly insect antifeedant properties. In addition, the major active clerodanes of Salvia divinorum can be used as novel opioid receptor probes, allowing greater insight into opioid receptor-mediated phenomena, as well as opening additional areas for chemical investigation. This article provides extensive coverage of naturally occurring clerodane diterpenes discovered from 1990 until 2015, and follows up on the 1992 review by Merritt and Ley in this same journal. The distribution, chemotaxonomic significance, chemical structures, and biological activities of clerodane diterpenes are summarized. In the cases where sufficient information is available, structure activity relationship (SAR) correlations and mode of action of active clerodanes have been presented. PMID:27433555

Theoretical research into anticancer activity of diterpenes isolated from the paraiban flora.

PubMed

Ishiki, Hamilton; Junior, Francisco J B Mendonça; Santos, Paula F; Tavares, Josean F; Tavares, Josean F; Silva, Marcelo S; Scotti, Marcus T

2014-07-01

Many studies of the scientific literature discuss the anticancer activity of diterpenes inhibiting the Akt/IKK/NF-kappaB pro-survival signaling cascade, mainly by the activation of serine/threonine phosphatase PP2A. The aim of this work was to evaluate and compare the anticancer potential of three atisane, three kaurane and three trachylobane diterpenes extracted from the roots of Xylopia langsdorffiana. Thus, we investigated the reactivity (H-L(GAP) parameter), HOMO atmosphere favorable to neutralize the radical reactivity, and the docking of compounds with PP2A. With all approaches, this theoretical study showed that atisane diterpenes have favorable characteristics for antitumor activity, like electron donating ability and greater hydrophilic interactions with the enzyme, by inhibition of Akt/IKK/NF-kappaB, and activation of PP2A.

Antifungal diterpenes from Hypoestes serpens (Acanthaceae).

PubMed

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.

Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review

PubMed Central

Aminimoghadamfarouj, Noushin; Nematollahi, Alireza

2017-01-01

Propolis is one of the complex, but valuable, bio-sources for discovering therapeutic compounds. Diterpenes are organic compounds composed of four isoprene units and are known for their biological and pharmacological characteristics, such as antibacterial, anticancer, and anti-inflammatory activities. Recently, advancements have been made in the development of antibacterial and anticancer leads from propolis-isolated diterpenes, and scrutiny of these compounds is being pursued. Thus, this review covers the progress in this arena, with a focus on the chemistry and biological activities of propolis diterpenes. It is anticipated that important information, in a comprehensive and concise manner, will be delivered here for better understanding of natural product drug discovery research. PMID:28629133

The first structure of a bacterial diterpene cyclase: CotB2.

PubMed

Janke, Ronja; Görner, Christian; Hirte, Max; Brück, Thomas; Loll, Bernhard

2014-06-01

Sesquiterpenes and diterpenes are a diverse class of secondary metabolites that are predominantly derived from plants and some prokaryotes. The properties of these natural products encompass antitumor, antibiotic and even insecticidal activities. Therefore, they are interesting commercial targets for the chemical and pharmaceutical industries. Owing to their structural complexity, these compounds are more efficiently accessed by metabolic engineering of microbial systems than by chemical synthesis. This work presents the first crystal structure of a bacterial diterpene cyclase, CotB2 from the soil bacterium Streptomyces melanosporofaciens, at 1.64 Å resolution. CotB2 is a diterpene cyclase that catalyzes the cyclization of the linear geranylgeranyl diphosphate to the tricyclic cyclooctat-9-en-7-ol. The subsequent oxidation of cyclooctat-9-en-7-ol by two cytochrome P450 monooxygenases leads to bioactive cyclooctatin. Plasticity residues that decorate the active site of CotB2 have been mutated, resulting in alternative monocyclic, dicyclic and tricyclic compounds that show bioactivity. These new compounds shed new light on diterpene cyclase reaction mechanisms. Furthermore, the product of mutant CotB2(W288G) produced the new antibiotic compound (1R,3E,7E,11S,12S)-3,7,18-dolabellatriene, which acts specifically against multidrug-resistant Staphylococcus aureus. This opens a sustainable route for the industrial-scale production of this bioactive compound.

Phytoconstituents from Vitex agnus-castus fruits

PubMed Central

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.

2011-01-01

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 method (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. PMID:21163339

Clerodane and Ent-kaurane Diterpene Glycosyl and Glycoside Derivatives from the Leaves of Casearia sylvestris

USDA-ARS?s Scientific Manuscript database

Five new clerodane diterpene glycosides caseariasides A-E (1-4) and three new ent-kaurane diterpene glucosides sylvestrisides C-E (6-8) were isolated from the leaves of Casearia sylvestris. Their structures were determined on the basis of chemical and spectroscopic analyses....

Production of Putative Diterpene Carboxylic Acid Intermediates of Triptolide in Yeast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forman, Victor; Callari, Roberta; Folly, Christophe

The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production route of triptolide through engineered Saccharomyces cerevisiae (yeast) could provide a sustainable source of triptolide. A potential intermediate in the unknown biosynthetic route to triptolide is the diterpene dehydroabietic acid. Here, we report a biosynthetic route to dehydroabietic acid by transient expression of enzymes from T. wilfordii and Sitka spruce (Picea sitchensis) in Nicotiana benthamiana. The combinationmore » of diterpene synthases TwTPS9, TwTPS27, and cytochromes P450 PsCYP720B4 yielded dehydroabietic acid and a novel analog, tentatively identified as ‘miltiradienic acid’. This biosynthetic pathway was reassembled in a yeast strain engineered for increased yields of the pathway intermediates, the diterpene olefins miltiradiene and dehydroabietadiene. Introduction in that strain of PsCYP720B4 in combination with two alternative NADPH-dependent cytochrome P450 reductases resulted in scalable in vivo production of dehydroabietic acid and its analog from glucose. Approaching future elucidation of the remaining biosynthetic steps to triptolide, our findings may provide an independent platform for testing of additional recombinant candidate genes, and ultimately pave the way to biotechnological production of the high value diterpenoid therapeutic.« less

Production of Putative Diterpene Carboxylic Acid Intermediates of Triptolide in Yeast

DOE PAGES

Forman, Victor; Callari, Roberta; Folly, Christophe; ...

2017-06-13

The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production route of triptolide through engineered Saccharomyces cerevisiae (yeast) could provide a sustainable source of triptolide. A potential intermediate in the unknown biosynthetic route to triptolide is the diterpene dehydroabietic acid. Here, we report a biosynthetic route to dehydroabietic acid by transient expression of enzymes from T. wilfordii and Sitka spruce (Picea sitchensis) in Nicotiana benthamiana. The combinationmore » of diterpene synthases TwTPS9, TwTPS27, and cytochromes P450 PsCYP720B4 yielded dehydroabietic acid and a novel analog, tentatively identified as ‘miltiradienic acid’. This biosynthetic pathway was reassembled in a yeast strain engineered for increased yields of the pathway intermediates, the diterpene olefins miltiradiene and dehydroabietadiene. Introduction in that strain of PsCYP720B4 in combination with two alternative NADPH-dependent cytochrome P450 reductases resulted in scalable in vivo production of dehydroabietic acid and its analog from glucose. Approaching future elucidation of the remaining biosynthetic steps to triptolide, our findings may provide an independent platform for testing of additional recombinant candidate genes, and ultimately pave the way to biotechnological production of the high value diterpenoid therapeutic.« less

Microtropiosides A-F: ent-Labdane diterpenoid glucosides from the leaves of Microtropis japonica (Celastraceae).

PubMed

Koyama, Yuka; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Takeda, Yoshio

2010-04-01

From a 1-BuOH-soluble fraction of a MeOH extract of the leaves of Microtropis japonica, collected in the Okinawa islands, six ent-labdane glucosides, named microtropiosides A-F, were isolated together with one known acyclic sesquiterpene glucoside. Their structures were elucidated by a combination of spectroscopic analyses, and their absolute configurations determined by application of the beta-D-glucopyranosylation-induced shift-trend rule in (13)C NMR spectroscopy and the modified Mosher's method. Copyright 2010 Elsevier Ltd. All rights reserved.

Antimicrobial activity of the diterpenes flexibilide and sinulariolide derived from Sinularia flexibilis Quoy and Gaimard 1833 (Coelenterata: Alcyonacea, Octocorallia).

PubMed

Aceret, T L; Coll, J C; Uchio, Y; Sammarco, P W

1998-07-01

The soft coral Sinularia flexibilis is rarely overgrown by bacteria and algae. Various studies have shown that it contains diterpenes that protect it from competitors and predators. However, of the many diterpenoids isolated from S. flexibilis, only sinulariolide has been studied for antibiotic properties. Samples of soft corals were collected from Orpheus Island and freeze-dried for chemical extraction and isolation of pure diterpenes. Antimicrobial activity of the diterpenes was determined using the disc assay method with antibiotics as controls and the minimum inhibitory concentrations of the diterpenes were determined using the Tube Dilution Technique. Two out of the five diterpenes tested (sinulariolide and flexibilide), showed marked antimicrobial activity and inhibited growth of Gram-positive bacteria. Flexibilide was effective even at concentrations as low as 5 ppm, whereas sinulariolide was effective at concentrations of 10 ppm. These compounds show potential as antibiotics.

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

PubMed Central

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

2017-01-01

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. PMID:28146121

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

PubMed

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.

Phytoconstituents from Vitex agnus-castus fruits.

PubMed

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.

Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

NASA Astrophysics Data System (ADS)

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.

New approaches on the analyses of thermolabile coffee diterpenes by gas chromatography and its relationship with cup quality.

PubMed

Novaes, Fábio Junior Moreira; Oigman, Silvia Siag; de Souza, Rodrigo Octavio Mendonça Alves; Rezende, Claudia Moraes; de Aquino Neto, Francisco Radler

2015-07-01

A new gas chromatography method using pulsed split injector (PS-GC) was validated to quantify thermolabile diterpenes cafestol, kahweol and isokahweol in methanolysed Arabica coffee oils. Linearity was 0.99 from 8 to 69mgmL(-1), recovery ranged from 99% to 101% and precision of less than 4% was obtained. Besides, Soxhlet extraction time was evaluated and Tukey׳s test indicated that the mass of diterpenes obtained in 4h is equivalent to a 16h period, which represents a space-time yield four times higher. The microwave assisted methanolysis proved to be efficient to quantitatively convert the natural diterpene esters in their respective alcohols and fatty acid methyl esters, accompanied by PS-GC. Also, the intact diterpene esters were analyzed by GC for the first time by the comparison between cold on-column (COC) and PS injection techniques. In all these stages, the molecular integrity of the thermolabile furokaurane diterpenes was maintained. The methanolysed oils from 13 samples of green Brazilian Arabica coffees were analyzed by PS-GC and the diterpenes composition varied from 8 to 12% w/w in oil and 0.7-1% in coffee beans. The ratio between cafestol and kahweol was successfully used to predict the quality of coffee even before the roasting and brewing processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Furanolabdane diterpenes from Hypoestes purpurea.

PubMed

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.

New Labdane-Type Diterpenoids and Anti-Inflammatory Constituents from Hedychium coronarium

PubMed Central

Chen, Jih-Jung; Ting, Chia-Wei; Wu, Yi-Chin; Hwang, Tsong-Long; Cheng, Ming-Jen; Sung, Ping-Jyun; Wang, Tai-Chi; Chen, Jinn-Fen

2013-01-01

Four new labdane-type diterpenoids: hedychicoronarin (1), peroxycoronarin D (2), 7β-hydroxycalcaratarin A (3), and (E)-7β-hydroxy-6-oxo-labda-8(17),12-diene-15,16-dial (4), have been isolated from the rhizomes of Hedychium coronarium, together with 13 known compounds (5–17). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 3, 5, 6, and 10 exhibited inhibition (IC50 values ≤4.52 μg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3–6, 10, and 11 inhibited fMLP/CB-induced elastase release with IC50 values ≤6.17 μg/mL. PMID:23799360

New cassane diterpenes from Caesalpinia echinata.

PubMed

Cota, Betania Barros; de Oliveira, Djalma Menezes; de Siqueira, Ezequias Pessoa; Souza-Fagundes, Elaine Maria; Pimenta, Adriano M C; Santos, Daniel M; Rabello, Ana; Zani, Carlos Leomar

2011-10-01

An investigation of the ethanolic extract from stems of Caesalpinia echinata Lam (Leguminosae-Caesalpinioideae) led to the isolation of five new cassane diterpenes along with known lambertianic acid. Their structures were determined based on spectroscopic methods. A preliminary study on leishmanicidal activity demonstrated that compounds 1, 2 and 6 were found to inhibit the growth of amastigote-like forms of Leishmania amazonensis without affecting mononuclear cells obtained from human peripheral blood. Copyright © 2011 Elsevier B.V. All rights reserved.

Differential metabolism of diastereoisomeric diterpenes by Preussia minima, found as endophytic fungus in Cupressus lusitanica.

PubMed

Ud Din, Zia; de Medeiros, L S; Abreu, L M; Pfenning, Ludwig H; Lopes Jymeni, D B; Rodrigues-Filho, E

2018-08-01

The plant diastereoisomeric diterpenes ent-pimara-8(14)-15-dien-19-oic acid, obtained from Viguiera arenaria, and isopimara-8(14)-15-dien-18-oic acid, isolated from Cupressus lusitanica, were distinctly functionalized by the enzymes produced in whole cell cultures of the fungus Preussia minima, isolated from surface sterilized stems of C. lusitanica. The ent-pimaradienoic acid was transformed into the known 7β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid, and into the novel diterpenes 7-oxo-8 β-hydroxy-ent-pimara-8(14)-15-dien-19-oic and 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acids. Isopimara-8(14)-15-dien-18-oic acid was converted into novel diterpenes 11α-hydroxyisopimara-8(14)-15-dien-18-oic acid, 7β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, and 1β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, along with the known 7β-hydroxyisopimara-8(14)-15-dien-18-oic acid. All compounds were isolated and fully characterized by 1D and 2D NMR, especially 13 C NMR. The diterpene bioproduct 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid is an isomer of sphaeropsidin C, a phytotoxin that affects cypress trees produced by Shaeropsis sapinea, one of the main phytopathogen of Cupressus. The differential metabolism of the diterpene isomers used as substrates for biotransformation was interpreted with the help of computational molecular docking calculations, considering as target enzymes those of cytochrome P450 group. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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.

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

PubMed

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.

Bacterial Diterpene Synthases: New Opportunities for Mechanistic Enzymology and Engineered Biosynthesis

PubMed Central

Smanski, Michael J.; Peterson, Ryan M.; Huang, Sheng-Xiong; Shen, Ben

2012-01-01

Diterpenoid biosynthesis has been extensively studied in plants and fungi, yet cloning and engineering diterpenoid pathways in these organisms remain challenging. Bacteria are emerging as prolific producers of diterpenoid natural products, and bacterial diterpene synthases are poised to make significant contributions to our understanding of terpenoid biosynthesis. Here we will first survey diterpenoid natural products of bacterial origin and briefly review their biosynthesis with emphasis on diterpene synthases (DTSs) that channel geranylgeranyl diphosphate to various diterpenoid scaffolds. We will then highlight differences of DTSs of bacterial and higher organism origins and discuss the challenges in discovering novel bacterial DTSs. We will conclude by discussing new opportunities for DTS mechanistic enzymology and applications of bacterial DTS in biocatalysis and metabolic pathway engineering. PMID:22445175

Analgesic activity of diterpene alkaloids from Aconitum baikalensis.

PubMed

Nesterova, Yu V; Povet'yeva, T N; Suslov, N I; Zyuz'kov, G N; Pushkarskii, S V; Aksinenko, S G; Schultz, E E; Kravtsova, S S; Krapivin, A V

2014-08-01

We compared analgesic activities of individual alkaloids extracted from Baikal aconite (Aconitum baikalensis): napelline, hypaconitine, songorine, mesaconitine, 12-epinapelline N-oxide. The detected analgesic activity was comparable to that of sodium metamizole. The mechanisms of analgesia were different in diterpene alkaloids of different structure. The antinociceptive effect of atisine alkaloids (12-epinapelline N-oxide, songorine) was naloxonedependent and realized via opioid receptor modulation.

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

PubMed

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.

Production of the forskolin precursor 11β-hydroxy-manoyl oxide in yeast using surrogate enzymatic activities.

PubMed

Ignea, Codruta; Ioannou, Efstathia; Georgantea, Panagiota; Trikka, Fotini A; Athanasakoglou, Anastasia; Loupassaki, Sofia; Roussis, Vassilios; Makris, Antonios M; Kampranis, Sotirios C

2016-02-26

Several plant diterpenes have important biological properties. Among them, forskolin is a complex labdane-type diterpene whose biological activity stems from its ability to activate adenylyl cyclase and to elevate intracellular cAMP levels. As such, it is used in the control of blood pressure, in the protection from congestive heart failure, and in weight-loss supplements. Chemical synthesis of forskolin is challenging, and production of forskolin in engineered microbes could provide a sustainable source. To this end, we set out to establish a platform for the production of forskolin and related epoxy-labdanes in yeast. Since the forskolin biosynthetic pathway has only been partially elucidated, and enzymes involved in terpene biosynthesis frequently exhibit relaxed substrate specificity, we explored the possibility of reconstructing missing steps of this pathway employing surrogate enzymes. Using CYP76AH24, a Salvia pomifera cytochrome P450 responsible for the oxidation of C-12 and C-11 of the abietane skeleton en route to carnosic acid, we were able to produce the forskolin precursor 11β-hydroxy-manoyl oxide in yeast. To improve 11β-hydroxy-manoyl oxide production, we undertook a chassis engineering effort involving the combination of three heterozygous yeast gene deletions (mct1/MCT1, whi2/WHI2, gdh1/GDH1) and obtained a 9.5-fold increase in 11β-hydroxy-manoyl oxide titers, reaching 21.2 mg L(-1). In this study, we identify a surrogate enzyme for the specific and efficient hydroxylation of manoyl oxide at position C-11β and establish a platform that will facilitate the synthesis of a broad range of tricyclic (8,13)-epoxy-labdanes in yeast. This platform forms a basis for the heterologous production of forskolin and will facilitate the elucidation of subsequent steps of forskolin biosynthesis. In addition, this study highlights the usefulness of using surrogate enzymes for the production of intermediates of complex biosynthetic pathways. The combination of

The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats

PubMed Central

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

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

Treesearch

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...

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

Treesearch

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...

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

PubMed

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.

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

PubMed

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.

The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats.

PubMed

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

Molecular Cloning and Functional Analysis of Gene Clusters for the Biosynthesis of Indole-Diterpenes in Penicillium crustosum and P. janthinellum

PubMed Central

Nicholson, Matthew J.; Eaton, Carla J.; Stärkel, Cornelia; Tapper, Brian A.; Cox, Murray P.; Scott, Barry

2015-01-01

The penitremane and janthitremane families of indole-diterpenes are abundant natural products synthesized by Penicillium crustosum and P. janthinellum. Using a combination of PCR, cosmid library screening, and Illumina sequencing we have identified gene clusters encoding enzymes for the synthesis of these compounds. Targeted deletion of penP in P. crustosum abolished the synthesis of penitrems A, B, D, E, and F, and led to accumulation of paspaline, a key intermediate for paxilline biosynthesis in P. paxilli. Similarly, deletion of janP and janD in P. janthinellum abolished the synthesis of prenyl-elaborated indole-diterpenes, and led to accumulation in the latter of 13-desoxypaxilline, a key intermediate for the synthesis of the structurally related aflatremanes synthesized by Aspergillus flavus. This study helps resolve the genetic basis for the complexity of indole-diterpene natural products found within the Penicillium and Aspergillus species. All indole-diterpene gene clusters identified to date have a core set of genes for the synthesis of paspaline and a suite of genes encoding multi-functional cytochrome P450 monooxygenases, FAD dependent monooxygenases, and prenyl transferases that catalyse various regio- and stereo- specific oxidations that give rise to the diversity of indole-diterpene products synthesized by this group of fungi. PMID:26213965

Cancer chemopreventive agents, labdane diterpenoids from the stem bark of Thuja standishii (Gord.) Carr.

PubMed

Tanaka, R; Ohtsu, H; Iwamoto, M; Minami, T; Tokuda, H; Nishino, H; Matsunaga, S; Yoshitake, A

2000-12-20

Seven labdane-type diterpenoids from the stem bark of Thuja standishii (Gord.) Carr. (Cupressaceae) and their analogues showed strong inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among these compounds, 15,16-bisnor-13-oxolabda-8(17), 11E-dien-19-oic acid was revealed to have the strongest inhibitory effect on the EBV-EA activation, being stronger than that of beta-carotene which has been intensively studied in cancer prevention using animal models. 15,16-bisnor-13-Oxolabda-8(17), 11E-dien-19-oic acid was also found to exhibit the excellent anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.

Synthesis of ent-kaurane diterpene monoglycosides.

PubMed

Chaturvedula, Venkata Sai Prakash; Klucik, Josef; Upreti, Mani; Prakash, Indra

2011-10-03

Synthesis of two ent-kaurane diterpene glycosides, steviol 19-O-β-D-glucopyranosiduronic acid (steviol glucuronide, 5), and 13-hydroxy ent-kaur-16-en-19-oic acid-β-D-glucopyranosyl ester (7) has been achieved from a common starting material, steviol, using phase transfer catalyst. Also, synthesis of an additional 17-nor-ent-kaurane glycoside, namely 13-methyl-16-oxo-17-nor-ent-kauran-19-oic acid-β-D-glucopyranosyl ester (10) was performed using the starting material isosteviol and similar synthetic methodology. Synthesis of all three steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR as well as mass spectral (MS) data.

Volatile diterpene emission by two Mediterranean Cistaceae shrubs.

PubMed

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.

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

PubMed

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.

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

PubMed

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.

Hypofolins A - L, ent-Labdane Diterpenoids from the Roots of Hypoestes phyllostachya 'Pink Splash'.

PubMed

Cheng, Bin; Ding, Lin-Fen; Yan, Tong; Xie, Zhang-Qiao; Zhang, Zhi-Jun; Song, Liu-Dong; Wu, Xing-De; Zhao, Qin-Shi

2018-06-01

Twelve new ent-labdane diterpenoids, hypofolins A - F (1 - 6) and hypofolins G - L (7a/7b, 8a/8b, and 9a/9b), were isolated from the roots of Hypoestes phyllostachya 'Pink Splash'. Their structures were elucidated by extensive 1D- and 2D-NMR spectroscopic and HR-MS data. The absolute configurations of 1, 2, 5, and 7a/7b were determined by single crystal X-ray diffraction and ECD analysis, as well as chemical transformations. Compounds 7a/7b, 8a/8b, and 9a/9b were isolated as three pairs of interconverting mixture of two isomers between ketone and hemiketal types. Compound 1 showed weak cytotoxicity against SMMC-7721 cell line with IC 50 value of 31.40 μm. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

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

PubMed

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 (<93%), limit of detection (0.0130 mg/mL), and limit of quantification (0.0406 mg/mL). The space-time 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.

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

PubMed

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.

Identification of new diterpene esters from green Arabica coffee beans, and their platelet aggregation accelerating activities.

PubMed

Wang, Xia; Meng, QianQian; Peng, XingRong; Hu, GuiLin; Qiu, MingHua

2018-10-15

Eight new ent-kaurane diterpene fatty acid esters, namely caffarolides A-H (1-8), were isolated from green beans of Coffea arabica. Their chemical structures were confirmed by extensive spectroscopic analysis including 1D, 2D NMR (HSQC, HMBC, 1 H- 1 H COSY, and ROESY), HRMS, IR and CD spectra and by GC-FID analysis. Interestingly, the diterpene moiety of these new compounds first occurred in genus Coffea. All the isolates were evaluated for platelet aggregation activity in vitro. As the results, caffarolides C, D and F (3, 4 and 6) showed induction effect for platelet aggregation and the possible structure-activity relationships have been discussed briefly. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed Central

Becker, K.; Schwaiger, S.; Waltenberger, B.; Pezzei, C. K.; Schennach, H.

2018-01-01

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. PMID:29576845

New isopimarane diterpenes and nortriterpene with cytotoxic activity from Ephorbia alatavica Boiss.

PubMed

Rozimamat, Rushangul; Hu, Rui; Aisa, Haji Akber

2018-06-01

Three new isopimarane diterpenes and one new nor-triterpenes, along with five known diterpenes were isolated from the whole areal part of Ephorbia alatavica Boiss. The structures of the new compounds (1-4) were determined based on extensive spectroscopic analysis, including HR-ESIMS, 1D and 2D NMR data. A plausible biosynthetic pathway for new compounds (1-4) were hypothesized. All isolated compounds were screen for cytotoxicity activity against MCF-8, HeLa and A549 cell lines in vitro by MTT assay. New compound 1 and known 9 showed potential cytotoxic activities with IC 50 values of 15.327 μg/mL, 23.066 μg/mL against MCF-8 cell lines, compound1 showed noteworthy cytotoxic activity with IC 50 13.033 μg/mL against A549 cancer cell line. New compounds 2, 4 and 4 showed moderate cytotoxic activities three human cancer lines with IC 50 value around 50 μg/mL, which compared with positive control doxorubicin (DOX). Copyright © 2018 Elsevier B.V. All rights reserved.

Minor diterpene glycosides from the leaves of Stevia rebaudiana.

PubMed

Ibrahim, Mohamed A; Rodenburg, Douglas L; Alves, Kamilla; Fronczek, Frank R; McChesney, James D; Wu, Chongming; Nettles, Brian J; Venkataraman, Sylesh K; Jaksch, Frank

2014-05-23

Two new diterpene glycosides in addition to five known glycosides have been isolated from a commercial extract of the leaves of Stevia rebaudiana. Compound 1 (rebaudioside KA) was shown to be 13-[(O-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid 2-O-β-d-glucopyranosyl-β-d-glucopyranosyl ester and compound 2, 12-α-[(2-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester. Five additional known compounds were identified, rebaudioside E, rebaudioside M, rebaudioside N, rebaudioside O, and stevioside, respectively. Enzymatic hydrolysis of stevioside afforded the known ent-kaurane aglycone 13-hydroxy-ent-kaur-16-en-19-oic acid (steviol) (3). The isolated metabolite 1 possesses the ent-kaurane aglycone steviol (3), while compound 2 represents the first example of the isomeric diterpene 12-α-hydroxy-ent-kaur-16-en-19-oic acid existing as a glycoside in S. rebaudiana. The structures of the isolated metabolites 1 and 2 were determined based on comprehensive 1D- and 2D-NMR (COSY, HSQC, and HMBC) studies. A high-quality crystal of compound 3 has formed, which allowed the acquisition of X-ray diffraction data that confirmed its structure. The structural similarities between the new metabolites and the commercially available stevioside sweeteners suggest the newly isolated metabolites should be examined for their organoleptic properties. Accordingly rebaudiosides E, M, N, O, and KA have been isolated in greater than gram quantities.

Identification of indole diterpenes in Ipomoea asarifolia and Ipomoea muelleri, plants tremorgenic to livestock

USDA-ARS?s Scientific Manuscript database

Ipomoea asarifolia has been associated with a tremorgenic syndrome in livestock in Brazil and was recently reported to contain tremorgenic indole diterpenes. Ipomoea muelleri has been reported to cause a similar tremorgenic syndrome in livestock in Australia. Ipomoea asarifolia and I. muelleri were ...

Characterization and evolutionary analysis of ent-kaurene synthase like genes from the wild rice species Oryza rufipogon.

PubMed

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.

Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata.

PubMed

Shaikh, Rafik U; Dawane, Ashwini A; Pawar, Rajendra P; Gond, Dhananjay S; Meshram, Rohan J; Gacche, Rajesh N

2016-03-01

The present study was carried out to evaluate anti-Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50 , 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti-H. pylori agents possessing urease inhibition. Copyright © 2015 John Wiley & Sons, Ltd.

Diterpenes and other constituents from Croton draco (Euphorbiaceae).

PubMed

Murillo, R M; Jakupovic, J; Rivera, J; Castro, V H

2001-03-01

Croton draco (Euphorbiaceae) from Guadalupe, San José, Costa Rica was collected in July 1992 and phytochemically studied (leaves, seeds, wood, bark, sap and flowers separately). Commonly known compounds such as 1-hydroxyjunenol, p-hydroxybenzaldehyde, p-methoxybenzoic acid, 3,4,5-trimethoxycinnamyl alcohol, the coumarin scopoletin, the nor-terpenoids 9-dehydrovomifoliol and 2,3-dihydrovomifoliol were obtained. Taspine, two aporphinic alkaloids, the diterpenes 9(11)-dehydrokaurenic acid, hardwikiic acid, the corresponding new 12-oxo derivative as well as five clerodanes and a phorbol ester were also isolated. Three clerodanes were not previously described and their NMR spectroscopical data and MS fragmentation patterns are reported.

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

PubMed Central

Smyrniotopoulos, Vangelis; Merten, Christian; Kaiser, Marcel; Tasdemir, Deniz

2017-01-01

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. PMID:28767061

Biotransformation of labdane and halimane diterpenoids by two filamentous fungi strains

PubMed Central

Seidl, Cláudia; Severino, Vanessa G. P.; Cardoso, Carmen Lúcia; Castro-Gamboa, Ian

2017-01-01

Biotransformation of natural products by filamentous fungi is a powerful and effective approach to achieve derivatives with valuable new chemical and biological properties. Although diterpenoid substrates usually exhibit good susceptibility towards fungi enzymes, there have been no studies concerning the microbiological transformation of halimane-type diterpenoids up to now. In this work, we investigated the capability of Fusarium oxysporum (a fungus isolated from the rhizosphere of Senna spectabilis) and Myrothecium verrucaria (an endophyte) to transform halimane (1) and labdane (2) acids isolated from Hymenaea stigonocarpa (Fabaceae). Feeding experiments resulted in the production of six derivatives, including hydroxy, oxo, formyl and carboxy analogues. Incubation of 1 with F. oxysporum afforded 2-oxo-derivative (3), while bioconversion with M. verrucaria provided 18,19-dihydroxy (4), 18-formyl (5) and 18-carboxy (6) bioproducts. Transformation of substrate 2 mediated by F. oxysporum produced a 7α-hydroxy (7) derivative, while M. verrucaria yielded 7α- (7) and 3β-hydroxy (8) metabolites. Unlike F. oxysporum, which showed a preference to transform ring B, M. verrucaria exhibited the ability to hydroxylate both rings A and B from substrate 2. Additionally, compounds 1–8 were evaluated for inhibitory activity against Hr-AChE and Hu-BChE enzymes through ICER-IT-MS/MS assay. PMID:29291077

Biotransformation of labdane and halimane diterpenoids by two filamentous fungi strains.

PubMed

Monteiro, Afif F; Seidl, Cláudia; Severino, Vanessa G P; Cardoso, Carmen Lúcia; Castro-Gamboa, Ian

2017-11-01

Biotransformation of natural products by filamentous fungi is a powerful and effective approach to achieve derivatives with valuable new chemical and biological properties. Although diterpenoid substrates usually exhibit good susceptibility towards fungi enzymes, there have been no studies concerning the microbiological transformation of halimane-type diterpenoids up to now. In this work, we investigated the capability of Fusarium oxysporum (a fungus isolated from the rhizosphere of Senna spectabilis ) and Myrothecium verrucaria (an endophyte) to transform halimane ( 1 ) and labdane ( 2 ) acids isolated from Hymenaea stigonocarpa (Fabaceae). Feeding experiments resulted in the production of six derivatives, including hydroxy, oxo, formyl and carboxy analogues. Incubation of 1 with F. oxysporum afforded 2-oxo-derivative ( 3 ), while bioconversion with M. verrucaria provided 18,19-dihydroxy ( 4 ), 18-formyl ( 5 ) and 18-carboxy ( 6 ) bioproducts. Transformation of substrate 2 mediated by F. oxysporum produced a 7 α -hydroxy ( 7 ) derivative, while M. verrucaria yielded 7 α - ( 7 ) and 3 β -hydroxy ( 8 ) metabolites. Unlike F. oxysporum , which showed a preference to transform ring B, M. verrucaria exhibited the ability to hydroxylate both rings A and B from substrate 2 . Additionally, compounds 1 - 8 were evaluated for inhibitory activity against Hr-AChE and Hu-BChE enzymes through ICER-IT-MS/MS assay.

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

PubMed

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

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

NASA Astrophysics Data System (ADS)

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

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

PubMed

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).

Enhanced Antibacterial Activity of Ent-Labdane Derivatives of Salvic Acid (7α-Hydroxy-8(17)-ent-Labden-15-Oic Acid): Effect of Lipophilicity and the Hydrogen Bonding Role in Bacterial Membrane Interaction.

PubMed

Echeverría, Javier; Urzúa, Alejandro; Sanhueza, Loreto; Wilkens, Marcela

2017-06-23

In the present study, the antibacterial activity of several ent -labdane derivatives of salvic acid (7α-hydroxy-8(17)- ent -labden-15-oic acid) was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus . For all of the compounds, the antibacterial activity was expressed as the minimum inhibitory concentration (MIC) in liquid media and minimum inhibitory amount (MIA) in solid media. Structure activity relationships (SAR) were employed to correlate the effect of the calculated lipophilicity parameters (logP ow ) on the inhibitory activity. Employing a phospholipidic bilayer (POPG) as a bacterial membrane model, ent -labdane-membrane interactions were simulated utilizing docking studies. The results indicate that (i) the presence of a carboxylic acid in the C-15 position, which acted as a hydrogen-bond donor (HBD), was essential for the antibacterial activity of the ent -labdanes; (ii) an increase in the length of the acylated chain at the C-7 position improved the antibacterial activity until an optimum length of five carbon atoms was reached; (iii) an increase in the length of the acylated chain by more than five carbon atoms resulted in a dramatic decrease in activity, which completely disappeared in acyl chains of more than nine carbon atoms; and (iv) the structural factors described above, including one HBD at C-15 and a hexanoyloxi moiety at C-7, had a good fit to a specific lipophilic range and antibacterial activity. The lipophilicity parameter has a predictive characteristic feature on the antibacterial activity of this class of compounds, to be considered in the design of new biologically active molecules.

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

PubMed

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.

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

PubMed

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.

Microtropins Q-W, ent-Labdane Glucosides: Microtropiosides G-I, Ursane-Type Triterpene Diglucoside and Flavonol Glycoside from the Leaves of Microtropis japonica.

PubMed

Terazawa, Saori; Uemura, Yuka; Koyama, Yuka; Kawakami, Susumu; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Kawahata, Masatoshi; Yamaguchi, Kentaro

2017-01-01

Microtropins Q-W, (2S,3R)-2-ethyl-2,3-dihydroxybutyrate of various glucosides and glucose, as well as three ent-labdane diterpenoid glucosides, named microtropiosides G, H and I, an ursane-type triterpene diglucoside and a flavonoid glycoside were isolated from the MeOH extract of the leaves of Microtropis japonica. The structure of microtropioside A, also isolated from the branches of M. japonica, was elucidated spectroscopically in a previous experiment and was found to possess a rare seven-membered oxyrane ring. Its structure was confirmed by X-ray crystallographic analysis of its pentaacetate.

Five New Guanacastane-Type Diterpenes from Cultures of the Fungus Psathyrella candolleana.

PubMed

Yin, Xia; Feng, Tao; Li, Zheng-Hui; Leng, Ying; Liu, Ji-Kai

2014-06-01

Five new guanacastane-type diterpenes, named guanacastepenes P-T (1-5), were isolated from cultures of the fungus Psathyrella candolleana. Their structures were elucidated on the basis of extensive spectroscopic methods. All of the compounds were tested for their 11β-hydroxysteroid dehydrogenase (11β-HSD1) inhibitory activity. Compound 3 exhibited inhibitory activity against both human and mouse isozymes of 11β-HSD1 with IC50 values of 6.2 and 13.9 μM, respectively.

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

PubMed Central

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

A new rearranged abietane diterpene and other constituents from Clerodendrum philipinum.

PubMed

Van Oanh, Ha; Sinh, Pham Xuan; An, Nguyen Thai; Hung, Ta Manh; Huong, Tran Thi Lan; Que, Do Thi Nguyet; Thao, Nguyen Phuong; Cuong, Nguyen Xuan; Dat, Nguyen Tien; Minh, Chau Van; Kiem, Phan Van

2009-03-01

From the methanolic extract of the roots of Clerodendrum philipinum, a new rearranged abietane diterpene (1) and eight known compounds were isolated by various chromatography methods. Their structures were identified by means of spectroscopic methods, including 1D- and 2D-NMR, as 17(15-->16),18(4-->3)-bisabeo-11,12,14,16-tetrahydroxy-3,5,8,11,13,15-abietahexaen-7-one (1), binankadsurin A, clerodenoside A, martynoside, acteoside, isoacteoside, astragalin, p3-sitosterol, and daucosterol. Binankadsurin A was found for the first time from a Clerodendrum species.

Lolitrem B and Indole Diterpene Alkaloids Produced by Endophytic Fungi of the Genus Epichloë and Their Toxic Effects in Livestock.

PubMed

Philippe, Guerre

2016-02-15

Different group of alkaloids are produced during the symbiotic development of fungal endophytes of the genus Epichloë in grass. The structure and toxicity of the compounds vary considerably in mammalian herbivores and in crop pests. Alkaloids of the indole-diterpene group, of which lolitrem B is the most toxic, were first characterized in endophyte-infected perennial ryegrass, and are responsible for "ryegrass staggers." Ergot alkaloids, of which ergovaline is the most abundant ergopeptide alkaloid produced, are also found in ryegrass, but generally at a lower rate than lolitrem B. Other alkaloids such as lolines and peramine are toxic for crop pests but have weak toxicological properties in mammals. The purpose of this review is to present indole-diterpene alkaloids produced in endophyte infected ryegrass from the first characterization of ryegrass staggers to the determination of the toxicokinetics of lolitrem B and of their mechanism of action in mammals, focusing on the different factors that could explain the worldwide distribution of the disease. Other indole diterpene alkaloids than lolitrem B that can be found in Epichloë infected ryegrass, and their tremorgenic properties, are presented in the last section of this review.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuadrado, Irene; Cidre, Florencia; Herranz, Sandra

Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showedmore » that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).« less

A Pimarane Diterpene and Cytotoxic Angucyclines from a Marine-Derived Micromonospora sp. in Vietnam's East Sea.

PubMed

Mullowney, Michael W; Ó hAinmhire, Eoghainín; Tanouye, Urszula; Burdette, Joanna E; Pham, Van Cuong; Murphy, Brian T

2015-09-15

A screening of our actinomycete fraction library against the NCI-60 SKOV3 human tumor cell line led to the isolation of isopimara-2-one-3-ol-8,15-diene (1), lagumycin B (2), dehydrorabelomycin (3), phenanthroviridone (4), and WS-5995 A (5). These secondary metabolites were produced by a Micromonospora sp. isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam. Compound 1 is a novel Δ(8,9)-pimarane diterpene, representing one of approximately 20 actinomycete-produced diterpenes reported to date, while compound 2 is an angucycline antibiotic that has yet to receive formal characterization. The structures of 1 and 2 were elucidated by combined NMR and MS analysis and the absolute configuration of 1 was assigned by analysis of NOESY NMR and CD spectroscopic data. Compounds 2-5 exhibited varying degrees of cytotoxicity against a panel of cancerous and non-cancerous cell lines. Overall, this study highlights our collaborative efforts to discover novel biologically active molecules from the large, underexplored, and biodiversity-rich waters of Vietnam's East Sea.

Blocking the L-type Ca2+ channel (Cav 1.2) is the key mechanism for the vascular relaxing effect of Pterodon spp. and its isolated diterpene methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate.

PubMed

de Fátima Reis, Carolina; de Andrade, Daniela Medeiros Lobo; Junior Neves, Bruno; de Almeida Ribeiro Oliveira, Leandra; Pinho, José Felippe; da Silva, Leidiane Pinha; Dos Santos Cruz, Jader; Bara, Maria Teresa Freitas; Andrade, Carolina Horta; Rocha, Matheus Lavorenti

2015-10-01

Pterodon spp. Vogel (Fabaceae), popularly known as "sucupira", has ethnopharmacological application which is described as having antispasmodic and relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could induce smooth muscle relaxation. So, this study investigated the mechanisms involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate). Vascular reactivity experiments were performed using rat aortic rings (n=5-8) with (E+) or without endothelium (E-) in an isolated bath organ. The SOR (0-56 μg/mL) relaxed phenylephrine (E+: 86.7±7.1%; E-: 92.3±4.7%) and KCl contracted rings (E-: 97.1±2.8%). In the same way, diterpene (0-48 μg/mL) also relaxed phenylephrine (E+: 94.5±3.6%; E-: 92.2±3.4%) and KCl contracted rings (E-: 99.7±0.2%). The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca2+-ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene-induced vasorelaxation. SOR and diterpene significantly reduced CaCl2-induced contraction stimulated by Bay K8644 (1 μM), phenylephrine (0.1 μM) or KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Cav 1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Cav 1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca2+ channel (Cav 1.2). Copyright © 2015 Elsevier Ltd. All rights reserved.

In vivo antimalarial activity of a labdane diterpenoid from the leaves of Otostegia integrifolia Benth.

PubMed

Endale, Abyot; Bisrat, Daniel; Animut, Abebe; Bucar, Franz; Asres, Kaleab

2013-12-01

In Ethiopian traditional medicine, the leaves of Otostegia integrifolia Benth. are used for the treatment of several diseases including malaria. In an ongoing search for effective, safe and cheap antimalarial agents from plants, the 80% methanol leaf extract O. integrifolia was tested for its in vivo antimalarial activity, in a 4-day suppressive assay against Plasmodium berghei. Activity-guided fractionation of this extract which showed potent antiplasmodial activity resulted in the isolation of a labdane diterpenoid identified as otostegindiol. Otostegindiol displayed a significant (P < 0.001) antimalarial activity at doses of 25, 50 and 100 mg/kg with chemosuppression values of 50.13, 65.58 and 73.16%, respectively. Acute toxicity studies revealed that the crude extract possesses no toxicity in mice up to a maximum dose of 5000 mg/kg suggesting the relative safety of the plant when administered orally. The results of the present study indicate that otostegindiol is among the antimalarial principles in this medicinal plant, and further support claims for the traditional medicinal use of the plant for the treatment of malaria. Copyright © 2013 John Wiley & Sons, Ltd.

Labdane diterpenoids from Curcuma amada rhizomes collected in Myanmar and their antiproliferative activities.

PubMed

Win, Nwet Nwet; Ito, Takuya; Ngwe, Hla; Win, Yi Yi; Prema; Okamoto, Yasuko; Tanaka, Masami; Asakawa, Yoshinori; Abe, Ikuro; Morita, Hiroyuki

2017-10-01

Four new labdane diterpenoids, 12β-hydroxy-15-norlabda-8(17),13(14)-dien-16-oic acid (1), (E)-15-ethoxy-15-methoxylabda-8(17),12-dien-16-al (2), (E)-15α-ethoxy-14α-hydroxylabda-8(17),12-dien-16-olide (3), and 15-ethoxy-12β-hydroxylabda-8(17),13(14)-dien-16,15-olide (4) were isolated from the methanol extract of Curcuma amada rhizomes collected in Myanmar, together with 13 known analogs. Their structures were elucidated by extensive spectroscopic techniques. All of the isolates were evaluated for their antiproliferative activities against a small panel of five different human cancer cell lines (A549, human lung cancer; HeLa, human cervical cancer; MCF7, human breast cancer; PANC-1 and PSN-1, human pancreatic cancer). Among the isolates, compounds 2-4, 7, 8, 12, and 17 showed mild antiproliferative activities with IC 50 values ranging from 19.7 to 96.1μM. (E)-14-Hydroxy-15-norlabda-8(17),12-dien-16-al (11) exhibited strong antiproliferative activities selectively against HeLa, PANC-1, and PSN-1 cells, with IC 50 values of 5.88, 1.00, and 3.98μM, respectively. These potencies were comparable to those of the positive control, 5-fluorouracil. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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.

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

PubMed

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.

Divergent synthesis and chemical reactivity of bicyclic lactone fragments of complex rearranged spongian diterpenes.

PubMed

Schnermann, Martin J; Beaudry, Christopher M; Genung, Nathan E; Canham, Stephen M; Untiedt, Nicholas L; Karanikolas, Breanne D W; Sütterlin, Christine; Overman, Larry E

2011-11-02

The synthesis and direct comparison of the chemical reactivity of the two highly oxidized bicyclic lactone fragments found in rearranged spongian diterpenes (8-substituted 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3-one and 6-substituted 7-acetoxy-2,8-dioxabicyclo[3.3.0]octan-3-one) are reported. Details of the first synthesis of the 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3-one ring system, including an examination of several possibilities for the key bridging cyclization reaction, are described. In addition, the first synthesis of 7-acetoxy-2,8-dioxabicyclo[3.3.0]octanones containing quaternary carbon substituents at C6 is disclosed. Aspects of the chemical reactivity and Golgi-modifying properties of these bicyclic lactone analogs of rearranged spongian diterpenes are also reported. Under both acidic and basic conditions, 8-substituted 2,7-dioxabicyclo[3.2.1]octanones are converted to 6-substituted-2,8-dioxabicyclo[3.3.0]octanones. Moreover, these dioxabicyclic lactones react with primary amines and lysine side chains of lysozyme to form substituted pyrroles, a conjugation that could be responsible for the unique biological properties of these compounds. These studies demonstrate that acetoxylation adjacent to the lactone carbonyl group, in either the bridged or fused series, is required to produce fragmented Golgi membranes in the pericentriolar region that is characteristic of macfarlandin E.

Two Bacterial Diterpene Synthases from Allokutzneria albata for Bonnadiene and for Phomopsene and Allokutznerene.

PubMed

Lauterbach, Lukas; Rinkel, Jan; Dickschat, Jeroen Sidney

2018-05-14

Two diterpene synthases from Allokutzneria albata were studied for their products, resulting in the identification of the new compound bonnadiene from the first enzyme. Although phylogenetically unrelated to fungal phomopsene synthase, the second enzyme produced a mixture of phomopsene and a biosynthetically linked new compound, allokutznerene, besides spiroviolene. Both enzymes were deeply studied for their mechanisms by isotopic labelling experiments, metal cofactor variation and site-directed mutagenesis. Oxidation products of phomopsene and allokutznerene are also discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai.

PubMed

Chu, Mei-Jun; Tang, Xu-Li; Qin, Guo-Fei; Sun, Yan-Ting; Li, Lei; de Voogd, Nicole J; Li, Ping-Lin; Li, Guo-Qiang

2017-07-01

Two pairs of new non-brominated racematic pyrrole derivatives, (±)-nakamurine D (1) and (±)-nakamurine E (2), two new diterpene alkaloids, isoagelasine C (16) and isoagelasidine B (21), together with 13 known pyrrole derivatives ((±)-3 - 15), five known diterpene alkaloids (17 - 20, 22) were isolated from the South China Sea sponge Agelas nakamurai. The racemic mixtures, compounds 1 - 4, were resolved into four pairs of enantiomers, (+)-1 and (-)-1, (+)-2 and (-)-2, (+)-3 and (-)-3, and (+)-4 and (-)-4, by chiral HPLC. The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non-brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL-60, K562, and HCT-116 cell lines with IC 50 values of 12.4, 16.0, and 19.8 μm, respectively. Compounds 16 - 19, 21, and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 μg/ml. Compounds 16 - 19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 μg/ml). © 2017 Wiley-VHCA AG, Zurich, Switzerland.

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

PubMed Central

Pereira, Rebeca Cristina Costa; Lourenço, André Luiz; Terra, Luciana; Abreu, Paula Alvarez; Laneuville Teixeira, Valéria; Castro, Helena Carla

2017-01-01

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. PMID:28335516

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

PubMed

Pereira, Rebeca Cristina Costa; Lourenço, André Luiz; Terra, Luciana; Abreu, Paula Alvarez; Laneuville Teixeira, Valéria; Castro, Helena Carla

2017-03-20

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.

Structure of kaurane-type diterpenes from Parinari sprucei and their potential anticancer activity.

PubMed

Braca, Alessandra; Armenise, Annahil; Morelli, Ivano; Mendez, Jeannette; Mi, Qiuwen; Chai, Hee-Byung; Swanson, Steven M; Kinghorn, A Douglas; De Tommasi, Nunziatina

2004-06-01

Twenty-three kaurane-type diterpenes 1 - 23, including twenty new natural products 1 - 20, have been isolated from the leaves of Parinari sprucei and their structures elucidated by spectroscopic and chemical analysis. The isolated compounds were tested for their cytotoxic activity towards a panel of cancer cell lines. Compounds 9 and 10 showed activity against all cell lines with ED (50) values in the range of 10 - 20 microg/mL. The previously known 13-hydroxy-15-oxozoapatlin 21 was evaluated in an in vivo hollow fiber test, and found to be active with KB and LNCaP cells at the concentrations used.

Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca²⁺-ATPase PfATP6.

PubMed

Guimarães, Daniel Silqueira Martins; Fonseca, Amanda Luisa da; Batista, Ronan; Comar Junior, Moacyr; Oliveira, Alaíde Braga de; Taranto, Alex Gutterres; Varotti, Fernando de Pilla

2015-04-01

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.

Relaxant effect of Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana A. St-Hil. & Tul., on tracheal smooth muscle.

PubMed

Martins, Italo R R; Dos Santos, Rosimeire F; de C Correia, Ana C; de Oliveira, Gislaine A; Macêdo, Cibério L; de S Monteiro, Fabio; Dos Santos, Paula F; de A Cavalcante, Fabiana; Tavares, Josean F; da Silva, Bagnólia A

2013-01-01

Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca(2+)-calmodulin complex was eliminated as chlorpromazine (10(-6) M), a calmodulin inhibitor, did not significantly alter the diterpene-induced relaxation (pD2 = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD2 = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K(+) channels. This was confirmed, as in the presence of 10 mM TEA(+) (a non-selective K(+) channel blocker), diterpene relaxation potency was significantly reduced (pD2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K(+) channel subtypes KATP, KV, SKCa and BKCa seem to be modulated positively by trachylobane-318 (pD2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the Kir subtype channel (pD2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10(-5) M trachylobane-318 (pD2 = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K(+) channels, particularly the KATP, KV, SKCa and BKCa subtypes.

Helikaurolides A-D with a Diterpene-Sesquiterpene Skeleton from Supercritical Fluid Extracts of Helianthus annuus L. var. Arianna.

PubMed

Torres, Ascensión; Molinillo, José M G; Varela, Rosa M; Casas, Lourdes; Mantell, Casimiro; Martínez de la Ossa, Enrique J; Macías, Francisco A

2015-10-02

Four novel compounds (1-4) with an unprecedented skeleton that combines a sesquiterpene lactone and a kaurane diterpene acid were isolated from Helianthus annuus L. var. Arianna extract, which was obtained under supercritical conditions. The structures of 1-4 were elucidated by NMR and MS analyses. The biosynthetic routes involve sesquiterpene lactones and kauranic acid, both of which were previously isolated from this species.

Relaxant effect of Ent‑7α‑hydroxytrachyloban‑18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana A. St-Hil. & Tul., on tracheal smooth muscle

PubMed Central

Martins, Italo R. R.; dos Santos, Rosimeire F.; Correia, Ana C. de C.; de Oliveira, Gislaine A.; Macêdo, Cibério L.; Monteiro, Fabio de S.; dos Santos, Paula F.; Cavalcante, Fabiana de A.; Tavares, Josean F.; da Silva, Bagnólia A.

2013-01-01

Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca2+-calmodulin complex was eliminated as chlorpromazine (10-6 M), a calmodulin inhibitor, did not significantly alter the diterpene-induced relaxation (pD2 = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD2 = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K+ channels. This was confirmed, as in the presence of 10 mM TEA+ (a non-selective K+ channel blocker), diterpene relaxation potency was significantly reduced (pD2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K+ channel subtypes KATP, KV, SKCa and BKCa seem to be modulated positively by trachylobane-318 (pD2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the Kir subtype channel (pD2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10-5 M trachylobane-318 (pD2 = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K+ channels, particularly the KATP, KV, SKCa and BKCa subtypes. PMID:23832615

Assessment of in vitro cardiotoxicity of extract fractions and diterpene alkaloids from Aconitum leucostomum Worosch: A short communication.

PubMed

Nie, Jihong; Wang, Fang; Ji, Tengfei; Zhao, Jun; Zhao, Feicui

2017-04-15

Aconitum leucostomum Worosch is a traditional Chinese medicine (TCM) and has a broad spectrum of health effects, but with a narrow therapeutic window. It is important to identify both the therapeutic ingredients and the toxic components to better utilize this TCM. The present study investigated the cardiotoxicity of the selected compounds in Aconitum leucostomum Worosch. The effects of extract of A. leucostomum Worosch and the isolated compounds on cardiocardiomyocytes were evaluated in vitro. Five known compounds in this TCM, including three C 18 -diterpene alkaloids, lappaconitine (2), N-deacetyllappaconitine (3), and ranaconitine (5), and two C 19 -diterpene alkaloids, delvestidine (1) and anthranoyllycoctonine (4), were isolated from A. leucostomum Worosch. The cardiotoxicity of these components and extract fractions, as measured by lactate dehydrogenase release and apoptosis, was ranked as follows, in descending order: delvestidine>anthranoyllycoctonine>pH 4 fraction>pH 8 fraction>aconitine>N-deacetyllappaconitine>ranaconitine>lappaconitine. The cytotoxicity of these compounds was shown to be dose-dependent, with delvestidine (1) and anthranoyllycoctonine (4) being the two most toxic compounds to cardiomyocytes in our assays. These results provide a basis for future rational use of this TCM, reducing side effects while retaining therapeutic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: a review.

PubMed

Chan, Eric Wei Chiang; Wong, Siu Kuin

2015-11-01

In this review, the phytochemistry and pharmacology of two ornamental gingers, Hedychium coronarium (butterfly ginger) and Alpinia purpurata (red ginger), are updated, and their botany and uses are described. Flowers of H. coronarium are large, showy, white, yellow or white with a yellow centre and highly fragrant. Inflorescences of A. purpurata are erect spikes with attractive red or pink bracts. Phytochemical investigations on the rhizomes of H. coronarium generated research interest globally. This resulted in the isolation of 53 labdane-type diterpenes, with little work done on the leaves and flowers. Pharmacological properties of H. coronarium included antioxidant, antibacterial, antifungal, cytotoxic, chemopreventive, anti-allergic, larvicidal, anthelminthic, analgesic, anti-inflammatory, anti-urolithiatic, anti-angiogenic, neuro-pharmacological, fibrinogenolytic, coagulant and hepatoprotective activities. On the contrary, little is known on the phytochemistry of A. purpurata with pharmacological properties of antioxidant, antibacterial, larvicidal, cytotoxic and vasodilator activities reported in the leaves and rhizomes. There is much disparity in terms of research effort within and between these two ornamental gingers.

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

PubMed

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.

Traditional preparation of Phaleria nisidai, a Palauan tea, reduces exposure to toxic daphnane-type diterpene esters while maintaining immunomodulatory activity.

PubMed

Kulakowski, Daniel; Kitalong, Christopher; Negrin, Adam; Tadao, Van-Ray; Balick, Michael J; Kennelly, Edward J

2015-09-15

The leaves of Phaleria nisidai Kaneh. (Thymelaeaceae) are brewed into a tea commonly used as a tonic, strengthening beverage and immune enhancer in Palau, Micronesia. Recently, the leaves of P. nisidai have been shown to contain toxic daphnane diterpene esters which may pose a public health threat to Palauans. This project documents the use frequency, preparation and side effects of P. nisidai. The content of daphnane diterpene esters in aqueous and methanol extracts and infusions prepared by healers in Palau is compared to assess the risk of daphnane ingestion associated with traditional consumption. Quantitative results are correlated with an in vitro assessment of the immunomodulating activity of the extracts. Research participants, comprising traditional healers and laypeople, were interviewed concerning use patterns and side effects of P. nisidai. Several traditional healers prepared and provided boiled tea samples for chemical analysis. Leaves were collected and methanolic and aqueous extractions were prepared in the laboratory. Peripheral blood mononuclear cells (PBMCs) were cultured with various concentrations of methanol and aqueous leaf extracts and their output of IFNγ was measured using ELISA. Cell proliferation was also assessed using the MTT assay. The concentration of selected daphnane diterpene esters in healer-prepared infusions, lab methanol and lab aqueous extracts was quantified using ultraperformance liquid chromatography-mass spectrometry-triple quadrupole detection (UPLC-MS-TQD). Through structured interviews it was determined that P. nisidai tea was used frequently, with many participants drinking it daily. The reported side effects were mild, and with the exception of diarrhea (n=2), no side effect was mentioned more than once. Methanol extracts contained 4.0μg simplexin, 17.6μg acetoxyhuratoxin and 2.3μg huratoxin per g dry leaf material. In traditional water infusions provided by healers and in standardized lab-prepared aqueous

Two rare-class tricyclic diterpenes with antitubercular activity from the Caribbean sponge Svenzea flava. Application of vibrational circular dichroism spectroscopy for determining absolute configuration.

PubMed

Avilés, Edward; Rodríguez, Abimael D; Vicente, Jan

2013-11-15

Two new natural products, 3 and 4, and their predecessor 7-isocyanoisoneoamphilecta-1(14),15-diene (2), of the rare isoneoamphilectane class of marine diterpenes, along with the known amphilectane diterpenes 6-8, were isolated from the n-hexane extract of the marine sponge Svenzea flava collected at Great Inagua Island, Bahamas. The molecular structures of compounds 3 and 4 were established by spectroscopic (1D/2D NMR, IR, UV, HRMS) methods and confirmed by a series of chemical correlation studies. In a first ever case study of the assignment of the absolute configuration of a molecule based on the isoneoamphilectane carbon skeleton, the absolute configuration of compound 5 was established as 3S,4R,7S,8S,11R,12S,13R by application of vibrational circular dichroism (VCD). In vitro anti-TB screenings revealed that metabolites 2-4 and, in particular, semisynthetic analogue 5, are strong growth inhibitors of Mycobacterium tuberculosis H37Rv.

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

PubMed

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.

Diterpene composition of defense secretion of four west AfricanTrinervitermes soldiers.

PubMed

Braekman, J C; Daloze, D; Dupont, A; Pasteels, J M; Josens, G

1984-09-01

The diterpene composition of the defensive secretions of minor and major soldiers is described for four sympatricTrinervitermes from the Ivory Coast. The degree of intra- and interspecific similarity between the secretions is assessed and related to available information on soldier behavior. A significant chemical dimorphism is observed between minor and major soldiers ofT. geminatus andT. togoensis. Both species build extensive foraging trails in the open air. During these excursions, the workers are protected by numerous minor soldiers, but only a few major ones. Internest comparison inT. geminatus suggests that the differences between minor and major soldiers is as large within a nest as between different nests. By, contrast, inT. trinervius andT. oeconomus both types of soldiers produce very similar secretions. The foraging habits of those species are far more cryptic. The first species builds earthen tunnels, and the second one forages in close proximity to its nest under cover of vegetation.

Chemical proteomics reveals HSP70 1A as a target for the anticancer diterpene oridonin in Jurkat cells.

PubMed

Dal Piaz, Fabrizio; Cotugno, Roberta; Lepore, Laura; Vassallo, Antonio; Malafronte, Nicola; Lauro, Gianluigi; Bifulco, Giuseppe; Belisario, Maria Antonietta; De Tommasi, Nunziatina

2013-04-26

Oridonin, an ent-kaurane diterpene isolated from well known Chinese medicinal plant Isodon rubescens, has been shown to have multiple biological activities. Among them, the anticancer activity has been repeatedly reported by many research groups. The chemopreventive and antitumor effects of oridonin have been related to its ability to interfere with several pathways which are involved in cell proliferation, cell cycle arrest, apoptosis and/or autophagy. Despite the number of studies performed on this diterpene, the molecular mechanism underlying its cellular activity remains to be elucidated. Hence, we tried to mine target protein(s) of oridonin by employing a mass spectrometry-based chemical proteomics approach, providing evidences that oridonin is able to directly bind the multifunctional, stress-inducible heat shock protein 70 1A (HSP70 1A). Oridonin/HSP70 complex formation was confirmed in leukemia-derived Jurkat cells. The characterization of HSP70 inhibition by oridonin was performed using chemical and biological approaches. Moreover, the binding site of oridonin on the chaperone was identified by a mass-based approach combined with Molecular Dynamics simulations. Although natural products showed high efficiency and several of these agents have now entered in clinical trials, information concerning the mechanisms of action at a molecular level of many of them is very poor or completely missed. Nevertheless, the identification of the molecular target of a drug candidate has several advantages. The most significant is the ability to set up target-based assays and to allow structure-activity relationship studies to guide medicinal chemistry efforts towards lead optimization. The knowledge of drug targets can also facilitate the identification of potential toxicities or side effects, if there is any precedent of toxicities for the identified target. Achieving this in an effective, unbiased and efficient manner subsists as a significant challenge for the new era

Diterpenes biochemical profile and transcriptional analysis of cytochrome P450s genes in leaves, roots, flowers, and during Coffea arabica L. fruit development.

PubMed

Ivamoto, Suzana T; Sakuray, Leonardo M; Ferreira, Lucia P; Kitzberger, Cíntia S G; Scholz, Maria B S; Pot, David; Leroy, Thierry; Vieira, Luiz G E; Domingues, Douglas S; Pereira, Luiz F P

2017-02-01

Lipids are among the major chemical compounds present in coffee beans, and they affect the flavor and aroma of the coffee beverage. Coffee oil is rich in kaurene diterpene compounds, mainly cafestol (CAF) and kahweol (KAH), which are related to plant defense mechanisms and to nutraceutical and sensorial beverage characteristics. Despite their importance, the final steps of coffee diterpenes biosynthesis remain unknown. To understand the molecular basis of coffee diterpenes biosynthesis, we report the content dynamics of CAF and KAH in several Coffea arabica tissues and the transcriptional analysis of cytochrome P450 genes (P450). We measured CAF and KAH concentrations in leaves, roots, flower buds, flowers and fruit tissues at seven developmental stages (30-240 days after flowering - DAF) using HPLC. Higher CAF levels were detected in flower buds and flowers when compared to fruits. In contrast, KAH concentration increased along fruit development, peaking at 120 DAF. We did not detect CAF or KAH in leaves, and higher amounts of KAH than CAF were detected in roots. Using P450 candidate genes from a coffee EST database, we performed RT-qPCR transcriptional analysis of leaves, flowers and fruits at three developmental stages (90, 120 and 150 DAF). Three P450 genes (CaCYP76C4, CaCYP82C2 and CaCYP74A1) had transcriptional patterns similar to CAF concentration and two P450 genes (CaCYP71A25 and CaCYP701A3) have transcript accumulation similar to KAH concentration. These data warrant further investigation of these P450s as potential candidate genes involved in the final stages of the CAF and KAH biosynthetic pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

Treesearch

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...

Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction.

PubMed

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.

Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction

PubMed Central

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 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. PMID:23662135

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

PubMed

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.

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

PubMed

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®

Terpene and lignan glycosides from the twigs and leaves of an endangered conifer, Cathaya argyrophylla.

PubMed

He, Wen-Jun; Fu, Zhao-Hui; Zeng, Guang-Zhi; Zhang, Yu-Mei; Han, Hong-Jin; Yan, He; Ji, Chang-Jiu; Chu, Hong-Biao; Tan, Ning-Hua

2012-11-01

Labdane diterpene glycosides cathargyroside A and cathargyroside B, monoterpene glycosides vervenone-10-O-β-D-glucopyranoside and vervenone-10-O-β-D-apiofuranosyl-(1″→6')-β-D-glucopyranoside, as well as lignan glycosides cedrusinin-4-O-α-L-rhamnopyranoside and (+)-cyclo-olivil-9'-O-β-D-xylopyranoside, along with 39 known compounds, were obtained from the methanol extract of the twigs and leaves of Cathaya argyrophylla. These compounds were identified mainly by analyzing their NMR and MS data. Almost all of these compounds were hitherto unknown in this genus. The isolated compounds were screened against Candida albicans and Staphylococcus aureus for antimicrobial assay, and against K562, HT-29, BEL-7402, SGC-7901, B16, BGC-823, U251 and A549 cancer cell lines for cytotoxic activities. One compound showed antimicrobial activity against C. albicans, and four of them displayed cytotoxicity. Similarity analysis on the chemical constituents of the genera Cathaya, Picea and Pinus supported their close phylogenetic relationships. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biota: sediment partitioning of aluminium smelter related PAHs and pulp mill related diterpenes by intertidal clams at Kitimat, British Columbia.

PubMed

Yunker, Mark B; Lachmuth, Cara L; Cretney, Walter J; Fowler, Brian R; Dangerfield, Neil; White, Linda; Ross, Peter S

2011-09-01

The question of polycyclic aromatic hydrocarbon (PAH) bioavailability and its relationship to specific PAH sources with different PAH binding characteristics is an important one, because bioavailability drives PAH accumulation in biota and ultimately the biochemical responses to the PAH contaminants. The industrial harbour at Kitimat (British Columbia, Canada) provides an ideal location to study the bioavailability and bioaccumulation of sediment hydrocarbons to low trophic level biota. Samples of soft shell clams (Mya arenaria) and intertidal sediment collected from multiple sites over six years at various distances from an aluminium smelter and a pulp and paper mill were analysed for 106 PAHs, plant diterpenes and other aromatic fraction hydrocarbons. Interpretation using PAH source ratios and multivariate data analysis reveals six principal hydrocarbon sources: PAHs in coke, pitch and emissions from anode combustion from the aluminium smelter, vascular plant terpenes and aromatised terpenes from the pulp and paper mill, petroleum PAHs from shipping and other anthropogenic activities and PAHs from natural plant detritus. Harbour sediments predominantly contain either pitch or pyrogenic PAHs from the smelter, while clams predominantly contain plant derived PAHs and diterpenes from the adjacent pulp mill. PAHs from the smelter have low bioavailability to clams (Biota-Sediment Accumulation Factors; BSAFs <1 for pitch and coke; <10 for anode combustion, decreasing to ∼0.1 for the mass 300 and 302 PAHs), possibly due to binding to pitch or soot carbon matrices. Decreases in PAH isomer ratios between sediments and clams likely reflect a combination of variation in uptake kinetics of petroleum PAHs and compound specific metabolism, with the importance of petroleum PAHs decreasing with increasing molecular weight. Plant derived compounds exhibit little natural bioaccumulation at reference sites, but unsaturated and aromatised diterpenes released from resins by

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shuaiyu; Korea Food Research Institute, 516 Baekhyun-dong, Bundang-gu, Songnam, Kyungki-do 463-746; Yoon, Yeo Cho

2012-05-11

Highlights: Black-Right-Pointing-Pointer Cafestol inhibits tube formation and migration of VEGF-stimulated HUVEC. Black-Right-Pointing-Pointer Cafestol inhibits phosphorylation of FAK and Akt. Black-Right-Pointing-Pointer 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 themore » 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.« less

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.

PubMed

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 <1 cup/week versus 3.12 (2.99-3.26) for ≥3 cups/day; p trend 0.12]. Based on the low levels of diterpenes found in traditionally prepared

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

PubMed Central

2011-01-01

Background 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. Methods 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. Results and Discussion 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 <1 cup/week versus 3.12 (2.99-3.26) for ≥ 3 cups/day; p trend 0.12]. Conclusions Based on

Preferentially Cytotoxic Constituents of Andrographis paniculata and their Preferential Cytotoxicity against Human Pancreatic Cancer Cell Lines.

PubMed

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.

A terpenoid isolated from sarang semut (Myrmecodia pendans) bulb and its potential for the inhibition and eradication of Streptococcus mutans biofilm.

PubMed

Gartika, Meirina; Pramesti, Hening T; Kurnia, Dikdik; Satari, Mieke H

2018-05-09

Dental caries remains a serious problem due to its detrimental effects on individual health and quality of life. The bulbs of Myrmecodia pendans (Merr & Perry), native plants of Papua, have been used as natural remedies for tumours, gout, diarrhoea, and fever. In this study, one of the active compounds of M. pendans was isolated, and its biological activity against the formation of Streptococcus mutans ATCC 25175 biofilm was tested. M. pendans was extracted with ethyl acetate using a Soxhlet apparatus. The extract was then separated, and chromatographic purification provided the isolated compound. The structure of the active compound was then characterized using UV, IR, NMR, and MS spectrometry. The obtained compound was added to S. mutans biofilms to determine the MBIC and MBEC values. The compound isolated from M. pendans was determined to be a labdane diterpene derivative with the formula C 31 H 50 O 3 . The MBIC value of the terpenoid towards the S. mutans biofilms was 50 ppm, and the MBEC value for the 1 min induction time was 40%. The terpenoid extracted from M. pendans has the potential to be developed into an antibacterial agent particularly for preventing the formation of biofilms.

Three new diterpenoids from the fruit of Vitex agnus-castus.

PubMed

Ono, Masateru; Nagasawa, Yumiko; Ikeda, Tsuyoshi; Tsuchihashi, Ryota; Okawa, Masafumi; Kinjo, Junei; Yoshimitsu, Hitoshi; Nohara, Toshihiro

2009-10-01

Three new labdane-type diterpenoids, viteagnusins F, G, and H, were isolated from the hexane extract of fruit (chasteberry) of Vitex agnus-castus L. (Verbenaceae) along with seven known compounds including four labdane-type diterpenoids, one norlabdane-type diterpenoid, one aromadendrane-type sesquiterpenoid, and one flavonoid. The chemical structures of the three new labdane-type diterpenoids were determined on the basis of spectroscopic data as well as chemical evidence.

Antiproliferative Effect of Synadenium grantii Hook f. stems (Euphorbiaceae) and a Rare Phorbol Diterpene Ester.

PubMed

Campos, Adriana; Vendramini-Costa, Débora Barbosa; Longato, Giovanna Barbarini; Zermiani, Tailyn; Ruiz, Ana Lúcia Tasca Gois; de Carvalho, João Ernesto; Pandiella, Atanasio; Cechinel Filho, Valdir

2016-11-01

Synadenium grantii is frequently used for the treatment of various diseases such as allergies, gastric disorders, and especially cancer. The aim of this study was to evaluate the possible antiproliferative potential of the methanol extract, fractions, and pure compounds from the stems of S grantii Phytochemical analysis was carried out by conventional chromatographic techniques, and the antiproliferative activity was analyzed using the sulforhodamine B assay and an MTT-based assay. Nonpolar fraction and its subfractions from the stems of S grantii exhibited promising cytostatic effect against several human tumor cell lines (glioma, breast, kidney, and lung), with total grown inhibition values ranging from 0.37 to 2.9 μg/mL. One of the active principles of this plant was identified as a rare phorbol diterpene ester, denoted as 3,4,12,13-tetraacetylphorbol-20-phenylacetate. This compound demonstrated antiproliferative activity against glioma, kidney, lung, and triple-negative breast cancer cell lines. These results demonstrate that S grantii stems produce active principles with relevant antiproliferative potential. © The Author(s) 2016.

A new diterpenoid glucoside and two new diterpenoids from the fruit of Vitex agnus-castus.

PubMed

Ono, Masateru; Eguchi, Keisuke; Konoshita, Masatarou; Furusawa, Chisato; Sakamoto, Junich; Yasuda, Shin; Ikeda, Tsuyoshi; Okawa, Masafumi; Kinjo, Junei; Yoshimitsu, Hitoshi; Nohara, Toshihiro

2011-01-01

A new labdane-type diterpenoid glucoside and two new labdane-type diterpenoids were isolated from the fruit (chasteberry) of Vitex agnus-castus L. (Verbenaceae) along with 14 known compounds comprising seven labdane-type diterpenoids, one halimane-type diterpenoid, two oleanane-type triterpenoids, two ursane-type triterpenoids, one aromadendrane-type sesquiterpenoid, and one flavonoid. Their structures were characterized on the basis of spectroscopic data as well as chemical evidence. Furthermore, the antioxidative activities of the flavonoid were evaluated using five different analyses.

Review on liver inflammation and antiinflammatory activity of Andrographis paniculata for hepatoprotection.

PubMed

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.

Analysis of sweet diterpene glycosides from Stevia rebaudiana: improved HPLC method.

PubMed

Kolb, N; Herrera, J L; Ferreyra, D J; Uliana, R F

2001-10-01

An improved analytical method was developed which may be applied to quality control of stevioside and rebaudioside A contents in dried leaves of Stevia rebaudiana before processing; in a selective sampling program searching for plants of higher yield in diterpene glycosides content; or when a large number of samples are sent to the laboratory for analysis. The procedure developed involves two steps: solvent extraction followed by an isocratic HPLC analysis. The sample, 1 g of dried leaves of S. rebaudiana, is ground and solvent-extracted with EtOH 70% (w/w) in Erlenmeyer flasks by shaking for 30 min in a 70 degrees C water bath. After the extract was cooled, it was filtered and analyzed by HPLC using an NH(2) column (250 x 4.6 mm) and a mixture of acetonitrile/water (80:20, v/v) as mobile phase, pH 5 adjusted with acetic acid. The detection was in the UV range at 210 nm (0.04 AUFS). Quantitation was performed by means of an external standard calibration curve for each analyte which had been obtained from standard solutions of pure stevioside and rebaudioside A. Working under these conditions there were no observed interference effects. The method saves time in sample preparation, and reduces sample handling and chromatographic analysis time, while having little loss of precision [coefficient of variation (CV%) between 1.8% and 3.0%] and recovery [between 98.5% and 100.5%]. The method was applied to 30 samples of S. rebaudiana from Misiones (Northeastern Argentina), and the stevioside content found ranged between 3.78 and 9.75% (weight) whereas Rebaudioside A content ranged between 1.62 and 7.27% (weight).

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

PubMed

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.

Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides.

PubMed

Guzzo, Luciana S; Perez, Andrea C; Romero, Thiago Rl; Azevedo, Adolfo O; Duarte, Igor Dg

2012-05-01

The opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, including non-steroidal anti-inflammatory drugs and α(2) -adrenoceptor agonists. The aims of the present study were to investigate the possible peripheral antinociceptive effect of cafestol, a diterpene present in the oil derived from coffee beans, and to evaluate the involvement of opioid peptides in its effect. The rat paw pressure test was used to assess antinocipeptive effects. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (2 μg/paw). All drugs were locally administered into the hind-paws of male Wistar rats. Intraplantar injection of cafestol (20, 40 and 80 μg) induced peripheral antinociception. The antinociceptive effect of cafestol was due to a local action because the higher dose (80 μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (25, 50 and 100 μg/paw) prevented the action of cafestol (80 μg/paw), whereas the aminopeptidase inhibitor bestatin (400 μg/paw) potentiated the antinociceptive effect of cafestol (40 μg/paw). The results of the present study provide evidence that cafestol treatment has a peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

The coffee diterpene kahweol inhibits tumor necrosis factor-{alpha}-induced expression of cell adhesion molecules in human endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hyung Gyun; Kim, Ji Young; Hwang, Yong Pil

2006-12-15

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 TNF{alpha}-induced monocytes to endothelial cells and suppressed the TNF{alpha}-induced protein and mRNA expression of the cell adhesion molecules, VCAM-1 and ICAM-1. Furthermore, kahweol inhibited the TNF{alpha}-induced JAK2-PI3K/Akt-NF-{kappa}B activation pathway in these cells. Overall, kahweol hasmore » 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.« less

Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway

PubMed Central

Fischedick, Justin T; Standiford, Miranda; Johnson, Delinda A.; Johnson, Jeffrey A.

2013-01-01

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in-vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H2O2 induced cell death. PMID:23507152

Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom.

PubMed

Salama, R; Sattayasai, J; Gande, A K; Sattayasai, N; Davis, M; Lattmann, E

2012-02-01

The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydroandrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.

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

PubMed Central

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

Genome-wide association study reveals candidate genes influencing lipids and diterpenes contents in Coffea arabica L.

PubMed

Sant'Ana, Gustavo C; Pereira, Luiz F P; Pot, David; Ivamoto, Suzana T; Domingues, Douglas S; Ferreira, Rafaelle V; Pagiatto, Natalia F; da Silva, Bruna S R; Nogueira, Lívia M; Kitzberger, Cintia S G; Scholz, Maria B S; de Oliveira, Fernanda F; Sera, Gustavo H; Padilha, Lilian; Labouisse, Jean-Pierre; Guyot, Romain; Charmetant, Pierre; Leroy, Thierry

2018-01-11

Lipids, including the diterpenes cafestol and kahweol, are key compounds that contribute to the quality of coffee beverages. We determined total lipid content and cafestol and kahweol concentrations in green beans and genotyped 107 Coffea arabica accessions, including wild genotypes from the historical FAO collection from Ethiopia. A genome-wide association study was performed to identify genomic regions associated with lipid, cafestol and kahweol contents and cafestol/kahweol ratio. Using the diploid Coffea canephora genome as a reference, we identified 6,696 SNPs. Population structure analyses suggested the presence of two to three groups (K = 2 and K = 3) corresponding to the east and west sides of the Great Rift Valley and an additional group formed by wild accessions collected in western forests. We identified 5 SNPs associated with lipid content, 4 with cafestol, 3 with kahweol and 9 with cafestol/kahweol ratio. Most of these SNPs are located inside or near candidate genes related to metabolic pathways of these chemical compounds in coffee beans. In addition, three trait-associated SNPs showed evidence of directional selection among cultivated and wild coffee accessions. Our results also confirm a great allelic richness in wild accessions from Ethiopia, especially in accessions originating from forests in the west side of the Great Rift Valley.

New pseudopterosin and seco-pseudopterosin diterpene glycosides from two Colombian isolates of Pseudopterogorgia elisabethae and their diverse biological activities.

PubMed

Rodríguez, Ileana I; Shi, Yan-Ping; García, Oscar J; Rodríguez, Abimael D; Mayer, Alejandro M S; Sánchez, Juan A; Ortega-Barria, Eduardo; González, José

2004-10-01

As part of an ongoing program to explore the chemical constituents of Caribbean marine invertebrates, a family of 13 new diterpene glycosides, pseudopterosins P-Z (1-11) and seco-pseudopterosins H (12) and I (13), have been isolated from the organic extracts of two collections of the sea whip Pseudopterogorgia elisabethae procured near the Colombian Southwestern Caribbean Sea. The structures of compounds 1-13, including absolute stereochemistry, have been proposed on the basis of comprehensive spectral analyses, chemical transformations, specific rotation, and TLC chromatographic analyses. Pseudopterosin Q (2) inhibited thromboxane B2 (TXB2) (IC50 = 4.7 microM) and superoxide anion (O2-) (IC50 = 11.2 microM) generation from E. coli lipopolysaccharide (LPS) activated rat neonatal microglia in vitro. In contrast, pseudopterosins P (1), U (6), V (7), W (8), and X (9) as well as seco-pseudopterosins H (12) and I (13) demonstrated minimal effects on both TXB2 and O2- release. In addition, some of the new compounds displayed strong antituberculosis, antiviral, antimalarial, and anticancer activity.

Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents.

PubMed

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).

The hallucinogenic diterpene salvinorin A inhibits leukotriene synthesis in experimental models of inflammation.

PubMed

Rossi, Antonietta; Pace, Simona; Tedesco, Federica; Pagano, Ester; Guerra, Germano; Troisi, Fabiana; Werner, Markus; Roviezzo, Fiorentina; Zjawiony, Jordan K; Werz, Oliver; Izzo, Angelo A; Capasso, Raffaele

2016-04-01

Leukotrienes (LTs) are lipid mediators derived from arachidonic acid (AA) involved in a number of autoimmune/inflammatory disorders including asthma, allergic rhinitis and cardiovascular diseases. Salvinorin A (SA), a diterpene isolated from the hallucinogenic plant Salvia divinorum, is a well-established analgesic compound, but its anti-inflammatory properties are under-researched and its effects on LT production is unknown to date. Here, we studied the possible effect of SA on LT production and verified its actions on experimental models of inflammation in which LTs play a prominent role. Peritoneal macrophages (PM) stimulated by calcium ionophore A23187 were chosen as in vitro system to evaluate the effect of SA on LT production. Zymosan-induced peritonitis in mice and carrageenan-induced pleurisy in rats were selected as LT-related models to evaluate the effect of SA on inflammation as well as on LT biosynthesis. SA inhibited, in a concentration-dependent manner, A23187-induced LTB4 biosynthesis in isolated PM. In zymosan-induced peritonitis, SA inhibited cell infiltration, myeloperoxidase activity, vascular permeability and LTC4 production in the peritoneal cavity without decreasing the production of prostaglandin E2. In carrageenan-induced pleurisy in rats, a more sophisticated model of acute inflammation related to LTs, SA significantly inhibited LTB4 production in the inflammatory exudates, along with reducing the phlogistic process in the lung. In conclusion, SA inhibited LT production and it was effective in experimental models of inflammation in which LTs play a pivotal role. SA might be considered as a lead compound for the development of drugs useful in LTs-related diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring the Influence of Domain Architecture on the Catalytic Function of Diterpene Synthases.

PubMed

Pemberton, Travis A; Chen, Mengbin; Harris, Golda G; Chou, Wayne K W; Duan, Lian; Köksal, Mustafa; Genshaft, Alex S; Cane, David E; Christianson, David W

2017-04-11

Terpenoid synthases catalyze isoprenoid cyclization reactions underlying the generation of more than 80,000 natural products. Such dramatic chemodiversity belies the fact that these enzymes generally consist of only three domain folds designated as α, β, and γ. Catalysis by class I terpenoid synthases occurs exclusively in the α domain, which is found with α, αα, αβ, and αβγ domain architectures. Here, we explore the influence of domain architecture on catalysis by taxadiene synthase from Taxus brevifolia (TbTS, αβγ), fusicoccadiene synthase from Phomopsis amygdali (PaFS, (αα) 6 ), and ophiobolin F synthase from Aspergillus clavatus (AcOS, αα). We show that the cyclization fidelity and catalytic efficiency of the α domain of TbTS are severely compromised by deletion of the βγ domains; however, retention of the β domain preserves significant cyclization fidelity. In PaFS, we previously demonstrated that one α domain similarly influences catalysis by the other α domain [ Chen , M. , Chou , W. K. W. , Toyomasu , T. , Cane , D. E. , and Christianson , D. W. ( 2016 ) ACS Chem. Biol. 11 , 889 - 899 ]. Here, we show that the hexameric quaternary structure of PaFS enables cluster channeling. We also show that the α domains of PaFS and AcOS can be swapped so as to make functional chimeric αα synthases. Notably, both cyclization fidelity and catalytic efficiency are altered in all chimeric synthases. Twelve newly formed and uncharacterized C 20 diterpene products and three C 25 sesterterpene products are generated by these chimeras. Thus, engineered αβγ and αα terpenoid cyclases promise to generate chemodiversity in the greater family of terpenoid natural products.

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

PubMed

Valares Masa, Cristina; Sosa Díaz, Teresa; Alías Gallego, Juan Carlos; Chaves Lobón, Natividad

2016-02-27

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.

In vitro and in vivo antitumor effect of trachylobane-360, a diterpene from Xylopia langsdorffiana.

PubMed

Pita, João Carlos Lima Rodrigues; Xavier, Aline Lira; de Sousa, Tatyanna Kelvia Gomes; Mangueira, Vivianne Mendes; Tavares, Josean Fechine; de Oliveira Júnior, Robson José; Veras, Robson Cavalcante; Pessoa, Hilzeth de Luna Freire; da Silva, Marcelo Sobral; Morelli, Sandra; Ávila, Veridiana de Melo Rodrigues; da Silva, Teresinha Gonçalves; Diniz, Margareth de Fátima Formiga Melo; Castello-Branco, Marianna Vieira Sobral

2012-08-10

Trachylobane-360 (ent-7α-acetoxytrachyloban-18-oic acid) was isolated from Xylopia langsdorffiana. Studies have shown that it has weak cytotoxic activity against tumor and non-tumor cells. This study investigated the in vitro and in vivo antitumor effects of trachylobane-360, as well as its cytotoxicity in mouse erythrocytes. In order to evaluate the in vivo toxicological aspects related to trachylobane-360 administration, hematological, biochemical and histopathological analyses of the treated animals were performed. The compound exhibited a concentration-dependent effect in inducing hemolysis with HC₅₀ of 273.6 µM, and a moderate in vitro concentration-dependent inhibitory effect on the proliferation of sarcoma 180 cells with IC₅₀ values of 150.8 µM and 150.4 µM, evaluated by the trypan blue exclusion test and MTT reduction assay, respectively. The in vivo inhibition rates of sarcoma 180 tumor development were 45.60, 71.99 and 80.06% at doses of 12.5 and 25 mg/kg of trachylobane-360 and 25 mg/kg of 5-FU, respectively. Biochemical parameters were not altered. Leukopenia was observed after 5-FU treatment, but this effect was not seen with trachylobane-360 treatment. The histopathological analysis of liver and kidney showed that both organs were mildly affected by trachylobane-360 treatment. Trachylobane-360 showed no immunosuppressive effect. In conclusion, these data reinforce the anticancer potential of this natural diterpene.

Inactivation of the indole-diterpene biosynthetic gene cluster of Claviceps paspali by Agrobacterium-mediated gene replacement.

PubMed

Kozák, László; Szilágyi, Zoltán; Vágó, Barbara; Kakuk, Annamária; Tóth, László; Molnár, István; Pócsi, István

2018-04-01

The hypocrealean fungus Claviceps paspali is a parasite of wild grasses. This fungus is widely utilized in the pharmaceutical industry for the manufacture of ergot alkaloids, but also produces tremorgenic and neurotoxic indole-diterpene (IDT) secondary metabolites such as paspalitrems A and B. IDTs cause significant losses in agriculture and represent health hazards that threaten food security. Conversely, IDTs may also be utilized as lead compounds for pharmaceutical drug discovery. Current protoplast-mediated transformation protocols of C. paspali are inadequate as they suffer from inefficiencies in protoplast regeneration, a low frequency of DNA integration, and a low mitotic stability of the nascent transformants. We adapted and optimized Agrobacterium tumefaciens-mediated transformation (ATMT) for C. paspali and validated this method with the straightforward creation of a mutant strain of this fungus featuring a targeted replacement of key genes in the putative IDT biosynthetic gene cluster. Complete abrogation of IDT production in isolates of the mutant strain proved the predicted involvement of the target genes in the biosynthesis of IDTs. The mutant isolates continued to produce ergot alkaloids undisturbed, indicating that equivalent mutants generated in industrial ergot producers may have a better safety profile as they are devoid of IDT-type mycotoxins. Meanwhile, ATMT optimized for Claviceps spp. may open the door for the facile genetic engineering of these industrially and ecologically important organisms.

The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.

PubMed

Lozano, E; Strauss, M; Spina, R; Cifuente, D; Tonn, C; Rivarola, H W; Sosa, M A

2016-02-01

The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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.

Molecular cloning and functional expression of geranylgeranyl pyrophosphate synthase from Coleus forskohlii Briq

PubMed Central

Engprasert, Surang; Taura, Futoshi; Kawamukai, Makoto; Shoyama, Yukihiro

2004-01-01

Background Isopentenyl diphosphate (IPP), a common biosynthetic precursor to the labdane diterpene forskolin, has been biosynthesised via a non-mevalonate pathway. Geranylgeranyl diphosphate (GGPP) synthase is an important branch point enzyme in terpenoid biosynthesis. Therefore, GGPP synthase is thought to be a key enzyme in biosynthesis of forskolin. Herein we report the first confirmation of the GGPP synthase gene in Coleus forskohlii Briq. Results The open reading frame for full-length GGPP synthase encodes a protein of 359 amino acids, in which 1,077 nucleotides long with calculated molecular mass of 39.3 kDa. Alignments of C. forskohlii GGPP synthase amino acid sequences revealed high homologies with other plant GGPP synthases. Several highly conserved regions, including two aspartate-rich motifs were identified. Transient expression of the N-terminal region of C. forskohlii GGPP synthase-GFP fusion protein in tobacco cells demonstrated subcellular localization in the chloroplast. Carotenoid production was observed in Escherichia coli harboring pACCAR25ΔcrtE from Erwinia uredovora and plasmid carrying C. forskohlii GGPP synthase. These results suggested that cDNA encoded functional GGPP synthase. Furthermore, C. forskohlii GGPP synthase expression was strong in leaves, decreased in stems and very little expression was observed in roots. Conclusion This investigation proposed that forskolin was synthesised via a non-mevalonate pathway. GGPP synthase is thought to be involved in the biosynthesis of forskolin, which is primarily synthesised in the leaves and subsequently accumulates in the stems and roots. PMID:15550168

Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice.

PubMed

Serrano, Felipe G; Tapia-Rojas, Cheril; Carvajal, Francisco J; Hancke, Juan; Cerpa, Waldo; Inestrosa, Nibaldo C

2014-12-18

Alzheimer's disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aβ oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3β (GSK-3β). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AβPPswe/PS-1 Alzheimer's model. ANDRO reduces the Aβ levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aβ oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression.

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

PubMed

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.

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

PubMed Central

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

Composition and Bioactivity of Lipophilic Metabolites from Needles and Twigs of Korean and Siberian Pines (Pinus koraiensis Siebold & Zucc. and Pinus sibirica Du Tour).

PubMed

Shpatov, Alexander V; Popov, Sergey A; Salnikova, Olga I; Kukina, Tatyana P; Shmidt, Emma N; Um, Byung Hun

2017-02-01

Lipophilic extractive metabolites in different parts of the shoot system (needles and defoliated twigs) of Korean pine, Pinus koraiensis, and Siberian pine, Pinus sibirica, were studied by GC/MS. Korean pine needles comprised mainly bornyl p-coumarate, heterocyclic 15-O-functionalized labdane type acids (lambertianic acid), 10-nonacosanol, sterols and their esters. While Siberian pine needles contained less bornyl p-coumarate, lambertianic acid, sterols and their esters, but were richer in other 15-O-functionalized labdane type acids. The major components of the twig extract of P. koraiensis were lambertianic acid, abietane and isopimarane type acids, cembrane type alcohols, 8-O-functionalized labdanoids, sterols, sterol esters, and acylglycerols. The same extract of P. sibirica differed in larger amounts of other 15-O-functionalized labdane type acids and pinolenic acid glycerides, but in less quantities of cembranoids and 8-O-functionalized labdanoids. The labdane type pinusolic acid was detected for the first time in Korean pine. P. koraiensis was found to be unique in the genus for an ability to synthesize phyllocladane diterpenoids. The content of bound Δ 5 -unsaturated polymethylene-interrupted fatty acids in the twig extracts of the both pines was similar or superior to that in their seed oil. Among the pines' metabolites tested isocembrol was strongest in inhibition of both α-glucosidase (IC 50 2.9 μg/ml) and NO production in activated macrophages (IC 50 3.6 μg/ml). © 2017 Wiley-VHCA AG, Zurich, Switzerland.

The clerodane diterpene casearin J induces apoptosis of T-ALL cells through SERCA inhibition, oxidative stress, and interference with Notch1 signaling

PubMed Central

De Ford, C; Heidersdorf, B; Haun, F; Murillo, R; Friedrich, T; Borner, C; Merfort, I

2016-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that preferentially affects children and adolescents. Over 50% of human T-ALLs possess activating mutations of Notch1. The clerodane diterpene casearin J (CJ) is a natural product that inhibits the sarcoendoplasmatic reticulum calcium ATPase (SERCA) pump and induces cell death in leukemia cells, but the molecular mechanism of cytotoxicity remains poorly understood. Here we show that owing to SERCA pump inhibition, CJ induces depletion of the endoplasmic reticulum calcium pools, oxidative stress, and apoptosis via the intrinsic signaling pathway. Moreover, Notch1 signaling is reduced in T-ALL cells with auto-activating mutations in the HD-domain of Notch1, but not in cells that do not depend on Notch1 signaling. CJ also provoked a slight activation of NF-κB, and consistent with this notion a combined treatment of CJ and the NF-κB inhibitor parthenolide (Pt) led to a remarkable synergistic cell death in T-ALL cells. Altogether, our data support the concept that inhibition of the SERCA pump may be a novel strategy for the treatment of T-ALL with HD-domain-mutant Notch1 receptors and that additional treatment with the NF-κB inhibitor parthenolide may have further therapeutic benefits. PMID:26821066

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

PubMed

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.

A Pseudopterane Diterpene Isolated From the Octocoral Pseudopterogorgia acerosa Inhibits the Inflammatory Response Mediated by TLR-Ligands and TNF-Alpha in Macrophages

PubMed Central

González, Yisett; Doens, Deborah; Santamaría, Ricardo; Ramos, Marla; Restrepo, Carlos M.; Barros de Arruda, Luciana; Lleonart, Ricardo; Gutiérrez, Marcelino; Fernández, Patricia L.

2013-01-01

Several diterpenoids isolated from terrestrial and marine environments have been identified as important anti-inflammatory agents. Although considerable progress has been made in the area of anti-inflammatory treatment, the search for more effective and safer compounds is a very active field of research. In this study we investigated the anti-inflammatory effects of a known pseudopterane diterpene (referred here as compound 1) isolated from the octocoral Pseudopterogorgia acerosa on the tumor necrosis factor- alpha (TNF-α) and TLRs- induced response in macrophages. Compound 1 inhibited the expression and secretion of the inflammatory mediators TNF-α, interleukin (IL)-6, IL-1β, nitric oxide (NO), interferon gamma-induced protein 10 (IP-10), ciclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1) induced by LPS in primary murine macrophages. This effect was associated with the inhibition of IκBα degradation and subsequent activation of NFκB. Compound 1 also inhibited the expression of the co-stimulatory molecules CD80 and CD86, which is a hallmark of macrophage activation and consequent initiation of an adaptive immune response. The anti-inflammatory effect was not exclusive to LPS because compound 1 also inhibited the response of macrophages to TNF-α and TLR2 and TLR3 ligands. Taken together, these results indicate that compound 1 is an anti-inflammatory molecule, which modulates a variety of processes occurring in macrophage activation. PMID:24358331

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

PubMed Central

2016-01-01

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 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. PMID:27490479

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

PubMed

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.

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

PubMed Central

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

2017-01-01

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. PMID:28266568

Cytotoxic Effects of Sarcophyton sp. Soft Corals—Is There a Correlation to Their NMR Fingerprints?

PubMed Central

Farag, Mohamed A.; Fekry, Mostafa I.; Al-Hammady, Montasser A.; Khalil, Mohamed N.; El-Seedi, Hesham R.; Meyer, Achim; Westphal, Hildegard; Wessjohann, Ludger A.

2017-01-01

Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton, with (ent)sarcophines as major components (17–100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC50 values ranging from 10–60 µg/mL. No obvious correlation between the extracts’ IC50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels. PMID:28677625

Cytotoxic Effects of Sarcophyton sp. Soft Corals-Is There a Correlation to Their NMR Fingerprints?

PubMed

Farag, Mohamed A; Fekry, Mostafa I; Al-Hammady, Montasser A; Khalil, Mohamed N; El-Seedi, Hesham R; Meyer, Achim; Porzel, Andrea; Westphal, Hildegard; Wessjohann, Ludger A

2017-07-04

Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton , with (ent)sarcophines as major components (17-100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC 50 values ranging from 10-60 µg/mL. No obvious correlation between the extracts' IC 50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels.

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudolf, Jeffrey D.; Dong, Liao-Bin; Cao, Hongnan

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 bacterialmore » 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.« less

Antiproliferative activity of Greek propolis.

PubMed

Pratsinis, Harris; Kletsas, Dimitris; Melliou, Eleni; Chinou, Ioanna

2010-04-01

The butanolic extract and the isolated chemical constituents, mainly diterpenes and flavonoids, from Greek propolis have been tested for their cytostatic activities against human malignant and normal cell strains. The extract and the diterpenes were found to be the most active against HT-29 human colon adenocarcinoma cells, without affecting normal human cells. Manool, a diterpene isolated for the first time from Greek propolis, was the most active compound, arresting the cancer cells at the G(2)/M phase of the cell cycle.

Andrographolide recovers cognitive impairment in a natural model of Alzheimer's disease (Octodon degus).

PubMed

Rivera, Daniela S; Lindsay, Carolina; Codocedo, Juan Francisco; Morel, Isidora; Pinto, Claudio; Cisternas, Pedro; Bozinovic, Francisco; Inestrosa, Nibaldo C

2016-10-01

The social species Octodon degus (degu) is the only wild-type South American rodent that develops Alzheimer's-like pathology with age. Here, we evaluated the ability of a natural product (Andrographolide, ANDRO), a diterpene of the labdane family obtained from the Asian plant Andrographis paniculata, to recover the cognitive decline in this long-lived animal model. We administered ANDRO to aged degus (56-month old) for 3 months. In addition, in 2 control groups (young degus: 12-month old and aged degus: 56-month old), we administrated saline solution as a vehicle. We evaluated cognitive performance through several behavioral tests. We also performed a series of physiological and biochemical analyses (e.g., electrophysiological and immunoblotting assessment) to identify possible mechanisms underlying cognitive performance associated with age. Our results suggest that there is an effect of aging on the loss of cognitive function, and this decrease in cognitive function was also related to a decrease in the synaptic functions and an increase in the main hallmarks of Alzheimer's disease (AD). More importantly, ANDRO treatments showed the following beneficial effects: (1) recovery of spatial memory and learning performance; (2) recovery of synaptic basal transmission; (3) partial or complete protection of certain synaptic proteins; and (4) a specific neuroprotective effect, including the reduction of phosphorylated tau protein and amyloid beta aggregate maturation in aged degus. Taken together, our results suggest that ANDRO could be used as a potential therapy for AD and support the use of O. degus as a natural model in which to study both neural damage associated with aging processes and the behavioral and neuropathological hallmarks of aging-related diseases such as AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats.

PubMed

Yen, Ting-Lin; Chen, Ray-Jade; Jayakumar, Thanasekaran; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsu, Ming-Jen; Yang, Chih-Hao; Chang, Chao-Chien; Lin, Yen-Kuang; Lin, Kuan-Hung; Sheu, Joen-Rong

2016-04-01

Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years because of its various pharmacologic activities. We determined that andrographolide modulates the mitogen-activated protein kinase (MAPK)-Nrf2-HO-1 signaling cascade in primary cerebral endothelial cells (CECs) to provide positive protection against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in rats. In the present study, andrographolide (10 μM) increased HO-1 protein and messenger RNA expressions, Nrf2 phosphorylation, and nuclear translocation in CECs, and these activities were disrupted by a p38 MAPK inhibitor, SB203580, but not by the extracellular signal-regulated kinase inhibitor PD98059 or c-Jun amino-terminal kinase inhibitor SP600125. Similar results were observed in confocal microscopy analysis. Moreover, andrographolide-induced Nrf2 and HO-1 protein expressions were significantly inhibited by Nrf2 small interfering RNA. Moreover, HO-1 knockdown attenuated the protective effect of andrographolide against oxygen-glucose deprivation-induced CEC death. Andrographolide (0.1 mg/kg) significantly suppressed free radical formation, blood-brain barrier disruption, and brain infarction in MCAO-insulted rats, and these effects were reversed by the HO-1 inhibitor zinc protoporphyrin IX. The mechanism is attributable to HO-1 activation, as directly evidenced by andrographolide-induced pronounced HO-1 expression in brain tissues, which was highly localized in the cerebral capillary. In conclusion, andrographolide increased Nrf2-HO-1 expression through p38 MAPK regulation, confirming that it provides protection against MCAO-induced brain injury. These findings provide strong evidence that andrographolide could

Mumic acids A-E: new diterpenoids from mumiyo.

PubMed

Kiren, Yuko; Nugroho, Alfarius Eko; Hirasawa, Yusuke; Shirota, Osamu; Bekenova, Myrzaim; Narbekovich, Narbekov Omorbay; Shapilova, Marina; Maeno, Hiromichi; Morita, Hiroshi

2014-01-01

Five new diterpenoids belonging to labdane and isopimarane skeletons, mumic acids A-E (1-5), have been isolated from mumiyo. Their structures and absolute configurations were elucidated on the basis of spectroscopic data and chemical derivatization.

Fungal and herbivore elicitation of a newly identified maize sesquiterpenoid, zealexin A4, is constrained by abiotic stress

USDA-ARS?s Scientific Manuscript database

The existence of microbe- or abiotic stress-inducible antimicrobials, termed phytoalexins, has only recently been discovered in maize. Identification and structural elucidation of the labdane-related diterpenoid kauralexins and sesquiterpenoid zealexins has collectively resulted in 10 novel pathogen...

ELAC (3,12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCβ activation.

PubMed

Murillo-Carretero, Maribel; Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; García-Bernal, Francisco; Navarro-Quiroz, Elkin A; Carrasco, Manuel; Macías-Sánchez, Antonio J; Herrero-Foncubierta, Pilar; Delgado-Ariza, Antonio; Verástegui, Cristina; Domínguez-Riscart, Jesús; Daoubi, Mourad; Hernández-Galán, Rosario; Castro, Carmen

2017-07-01

Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation. We isolated four lathyranes from the latex of Euphorbia plants and tested their effect on postnatal NPC proliferation, using neurosphere cultures. The bioactive lathyrane ELAC (3,12-di-O-acetyl-8-O-tigloilingol) was also injected into the ventricles of adult mice to analyse its effect on adult NPC proliferation in vivo. The lathyrane ELAC activated PKC and significantly increased postnatal NPC proliferation in vitro, particularly in synergy with FGF2. In addition ELAC stimulated proliferation of NPC, specifically affecting undifferentiated transit amplifying cells. The proliferative effect of ELAC was reversed by either the classical/novel PKC inhibitor Gö6850 or the classical PKC inhibitor Gö6976, suggesting that NPC proliferation is promoted in response to activation of classical PKCs, particularly PKCß. ELAC slightly increased the proportion of NPC expressing Sox2. The effects of ELAC disappeared upon acetylation of its C7-hydroxyl group. We propose lathyranes like ELAC as new drug candidates to modulate adult neurogenesis through PKC activation. Functional and structural comparisons between ELAC and phorboids are included. © 2017 The British Pharmacological Society.

The cholesterol-raising factor from coffee beans.

PubMed Central

Urgert, R; Katan, M B

1996-01-01

Coffee beans and some types of coffee brew-not the regular types of coffee prepared with a paper filter or with soluble coffee granules-contain the diterpenes cafestol and kahweol. Cafestol and kahweol raise the serum concentration of cholesterol and triglycerides in humans, and they also appear mildly to affect the integrity of liver cells. Both effects are transient after withdrawal of the diterpenes, and it is as yet unsure whether these effects are associated. Patients at increased risk of heart disease who drink large amounts of coffee should be advised to select brews low in diterpenes. PMID:9135590

Constituents of the Vietnamese medicinal plant Orthosiphon stamineus.

PubMed

Tezuka, Y; Stampoulis, P; Banskota, A H; Awale, S; Tran, K Q; Saiki, I; Kadota, S

2000-11-01

From the MeOH extract of the aerial part of Vietnamese Orthosiphon stamineus, five new isopimarane-type diterpenes [orthosiphols F-J (1-5)] and two new diterpenes [staminols A (6) and B (7)] with a novel carbon-framework, to which we proposed the name "staminane", and three new highly-oxygenated staminane-type diterpenes [staminolactones A (8) and B (9) and norstaminol A (10)1 were isolated. Moreover, staminolactone A (8) is 8,14-secostaminane-type and staminolactone B (9) is 13,14-secostaminane-type, while norstaminol A (10) is 14-norstaminen-type. Together with these new diterpenes, sixteen known compounds were also isolated and identified to be: 7,3',4'-tri-O-methylluteolin (11), eupatorin (12), sinensetin (13), 5-hydroxy-6,7,3',4'-tetramethoxyflavone (14), salvigenin (15), ladanein (16), tetramethylscutellarein (17), 6-hydroxy-5,7,4'-trimethoxyflavone (18), vomifoliol (19), aurantiamide acetate (20), rosmarinic acid (21), caffeic acid (22), oleanolic acid (23), ursolic acid (24), betulinic acid (25), and beta-sitosterol (26). All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the new diterpenes, except for 4, and flavonoids (11, 12, 16, 18) showed cytotoxicity with an ED50 value between 10 and 90 microg/ml.

Diterpenoids from Casearia sylvestris

USDA-ARS?s Scientific Manuscript database

Two highly oxygenated clerodane diterpenes casearins U (1) and V (2) and two ent-kaurane diterpene glucosides sylvestrisides A (3) and B (4) were isolated from the leaves of Casearia sylvestris, together with 13 known compounds. Their structures were established on the basis of 1D and 2D NMR spectro...

The effect of western juniper on the estrous cycle in beef cattle

USDA-ARS?s Scientific Manuscript database

Numerous evergreen trees and shrubs contain labdane acids, including isocupressic acid, which can cause late-term abortions in cattle. Recent research has shown that the bark from western juniper trees can also cause late-term abortions in cattle. Additionally, ranchers have observed that cattle in ...

Changes in the rumen bacterial microbiome of cattle exposed to ponderosa pine needles

USDA-ARS?s Scientific Manuscript database

Consumption of ponderosa pine needles, as well as needles and bark from a number of other trees, can cause abortions in cattle. The abortifacient compounds in these trees are labdane resin acids, including isocupressic acid and agathic acid. Previous research has demonstrated that cattle conditioned...

Development and validation of an RP-HPLC method for quantification of cinnamic acid derivatives and kaurane-type diterpenes in Mikania laevigata and Mikania glomerata.

PubMed

Bertolucci, Suzan Kelly; Pereira, Ana Bárbara; Pinto, José Eduardo; de Aquino Ribeiro, José Antônio; de Oliveira, Alaíde Braga; Braga, Fernão Castro

2009-02-01

MIKANIA GLOMERATA and MIKANIA LAEVIGATA (Asteraceae) are medicinal plants popularly named 'guaco' in Brazil. The leaves of both species are used to treat respiratory diseases, with coumarin (CO) and kaurane-type diterpenes being regarded as the bioactive constituents. A new and simple RP-HPLC method was developed and validated for the simultaneous quantification of CO, O-coumaric (OC), benzoylgrandifloric (BA), cinnamoylgrandifloric (CA) and kaurenoic (KA) acids in the species. Optimal separation was achieved with an alternating gradient elution of methanol and acetonitrile and detection was carried out by DAD at three different wavelengths: 210 nm for CO, OC, KA; 230 nm for BA; and 270 nm for CA. The extracts showed good stability during 42 hours under normal laboratory conditions (temperature of 23 +/- 2 degrees C). The standard curves were linear over the range 0.5 - 5.0 microg (CO), 0.25 - 4.0 microg (OC), 1.0 - 8.0 microg (BA), 0.5 - 3.0 microg (CA) and 0.8 - 12.0 microg (KA), with R(2) > 0.999 for all compounds. The method showed good precision for intra-day (RSD < 4.6 %) and inter-day assays (RSD < 4.4 %). The recovery was between 99.9 and 105.3 %, except for CO and OC in M. glomerata (73.2 - 91.6 % and 86.3 - 117.4 %, respectively). The limits of quantification and detection were in the range of 0.025 - 0.800 microg and 0.007 - 0.240 microg. The method was tested for new and old columns, temperature variation (26 and 28 degrees C) and by different operators in the same laboratory. The method was successfully applied to samples of both species.

Silencing brassinosteroid receptor BRI1 impairs herbivory-elicited accumulation of jasmonic acid-isoleucine and diterpene glycosides, but not jasmonic acid and trypsin proteinase inhibitors in Nicotiana attenuata.

PubMed

Yang, Da-Hai; Baldwin, Ian T; Wu, Jianqiang

2013-06-01

The brassinosteroid (BR) receptor, BR insensitive 1 (BRI1), plays a critical role in plant development, but whether BRI1-mediated BR signaling is involved in plant defense responses to herbivores was largely unknown. Here, we examined the function of BRI1 in the resistance of Nicotiana attenuata (Solanaceae) to its specialist insect herbivore Manduca sexta. Jasmonic acid (JA) and JA-isoleucine conjugate (JA-Ile) are important hormones that mediate resistance to herbivores and we found that after wounding or simulated herbivory NaBRI1 had little effect on JA levels, but was important for the induction of JA-Ile. Further experiments revealed that decreased JAR (the enzyme for JA-Ile production) activity and availability of Ile in NaBRI1-silenced plants were likely responsible for the low JA-Ile levels. Consistently, M. sexta larvae gained more weight on NaBRI1-silenced plants than on the control plants. Quantification of insect feeding-induced secondary metabolites revealed that silencing NaBRI1 resulted in decreased levels of carbon-rich defensive secondary metabolites (hydroxygeranyllinalool diterpene glycosides, chlorogenic acid, and rutin), but had little effect on the nitrogen-rich ones (nicotine and trypsin proteinase inhibitors). Thus, NaBRI1-mediated BR signaling is likely involved in plant defense responses to M. sexta, including maintaining JA-Ile levels and the accumulation of several carbon-rich defensive secondary metabolites. © 2013 Institute of Botany, Chinese Academy of Sciences.

Gersemiols A-C and Eunicellol A, Diterpenoids from the Arctic Soft Coral Gersemia fruticosa.

PubMed

Angulo-Preckler, Carlos; Genta-Jouve, Grégory; Mahajan, Nipun; de la Cruz, Mercedes; de Pedro, Nuria; Reyes, Fernando; Iken, Katrin; Avila, Conxita; Thomas, Olivier P

2016-04-22

Three new diterpenes named gersemiols A-C (1-3) and a new eunicellane diterpene, eunicellol A (4), have been isolated together with the known sesquiterpene (+)-α-muurolene (5) from the Arctic soft coral Gersemia fruticosa. The name gersemiane was assigned to the rare and unnamed diterpene skeleton of compounds 1-3 corresponding to 4-isopropyl-1,5,8a-trimethyltetradecahydrophenanthrene. The chemical structures were elucidated on the basis of extensive spectroscopic analysis (HR-ESIMS, 1D and 2D NMR) as well as coupling constant calculations for the determination of the relative configurations. All compounds were tested for their antimicrobial activity against several bacteria and fungi and eunicellol A was found to exhibit moderate and selective antibacterial activity.

Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii.

PubMed

Pateraki, Irini; Andersen-Ranberg, Johan; Jensen, Niels Bjerg; Wubshet, Sileshi Gizachew; Heskes, Allison Maree; Forman, Victor; Hallström, Björn; Hamberger, Britta; Motawia, Mohammed Saddik; Olsen, Carl Erik; Staerk, Dan; Hansen, Jørgen; Møller, Birger Lindberg; Hamberger, Björn

2017-03-14

Forskolin is a unique structurally complex labdane-type diterpenoid used in the treatment of glaucoma and heart failure based on its activity as a cyclic AMP booster. Commercial production of forskolin relies exclusively on extraction from its only known natural source, the plant Coleus forskohlii , in which forskolin accumulates in the root cork. Here, we report the discovery of five cytochrome P450s and two acetyltransferases which catalyze a cascade of reactions converting the forskolin precursor 13 R -manoyl oxide into forskolin and a diverse array of additional labdane-type diterpenoids. A minimal set of three P450s in combination with a single acetyl transferase was identified that catalyzes the conversion of 13 R -manoyl oxide into forskolin as demonstrated by transient expression in Nicotiana benthamiana . The entire pathway for forskolin production from glucose encompassing expression of nine genes was stably integrated into Saccharomyces cerevisiae and afforded forskolin titers of 40 mg/L.

Acetylcholine esterase inhibitors and melanin synthesis inhibitors from Salvia officinalis.

PubMed

Sallam, Amal; Mira, Amira; Ashour, Ahmed; Shimizu, Kuniyoshi

2016-09-15

Salvia officinalis is a traditionally used herb with a wide range of medicinal applications. Many phytoconstituents have been isolated from S. officinalis, mainly phenolic diterpenes, which possess many biological activities. This study aimed to evaluate the ability of the phenolic diterpenes of S. officinalis to inhibit acetylcholine esterase (AChE) as well as their ability to inhibit melanin biosynthesis in B16 melanoma cells. The phenolic diterpenes isolated from the aerial parts of S. officinalis were tested for their effect on melanin biosynthesis in B16 melanoma cell lines. They were also tested for their ability to inhibit AChE using Ellman's method. Moreover, a molecular docking experiment was used to investigate the binding affinity of the isolated phenolic diterpenes to the amino acid residues at the active sites of AChE. Seven phenolic diterpenes-sageone, 12-methylcarnosol, carnosol, 7b-methoxyrosmanol, 7a-methoxyrosmanol, isorosmanol and epirosmanol-were isolated from the methanolic extract of the aerial parts of S. officinalis. Isorosmanol showed a melanin-inhibiting activity as potent as that of arbutin. Compounds 7a-methoxyrosmanol and isorosmanol inhibited AChE activity by 50% and 65%, respectively, at a concentration of 500 µM. The results suggest that isorosmanol is a promising natural compound for further studies on development of new medications which might be useful in ageing disorders such as the declining of cognitive functions and hyperpigmentation. Copyright © 2016 Elsevier GmbH. All rights reserved.

Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs.

PubMed

Wang, Shu-Yao; A, Ji-Ye; Fei, Fei; Geng, Jian-Liang; Peng, Ying; Ouyang, Bing-Chen; Wang, Pei; Jin, Xiao-Liang; Zhao, Yu-Qing; Wang, Jian-Kun; Geng, Ting; Li, Yan-Jing; Huang, Wen-Zhe; Wang, Zhen-Zhong; Xiao, Wei; Wang, Guang-Ji

2017-10-01

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg -1 ) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg -1 ). Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Five new diterpenoids, viteagnusins A--E, from the fruit of Vitex agnus-castus.

PubMed

Ono, Masateru; Yamasaki, Toru; Konoshita, Masatarou; Ikeda, Tsuyoshi; Okawa, Masafumi; Kinjo, Junei; Yoshimitsu, Hitoshi; Nohara, Toshihiro

2008-11-01

Two new halimane-type diterpenoids, viteagnusins A and B, and three new labdane-type diterpenoids, viteagnusins C, D, and E, were isolated from the fruit of Vitex agnus-castus L. (Chasteberry, Verbenaceae) along with two known diterpenoids. Their chemical structures were determined on the basis of spectroscopic data.

Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production1

PubMed Central

Kim, Mi Jung; Jin, Jingjing; Zheng, Junshi

2015-01-01

Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides known as steviol glycosides (SGs), but also other labdane-type diterpenoids that may be spatially separated from SGs. However, their biosynthetic routes and spatial distribution in leaf tissues have not yet been elucidated. Here, we integrate metabolome and transcriptome analyses of Stevia to explore the biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific chemical analyses confirmed that SGs were accumulated in leaf cells but not in trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses from two different tissues of Stevia provided a comprehensive overview of dynamic metabolic activities in trichomes and leaf without trichomes. These metabolite-guided transcriptomics and phylogenetic and gene expression analyses clearly identified specific gene members encoding enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane-type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en-8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi-manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have evolved to use distinct metabolic pathways to avoid metabolic interferences in leaf tissues for efficient production of diverse secondary metabolites. PMID:26438788

Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production.

PubMed

Kim, Mi Jung; Jin, Jingjing; Zheng, Junshi; Wong, Limsoon; Chua, Nam-Hai; Jang, In-Cheol

2015-12-01

Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides known as steviol glycosides (SGs), but also other labdane-type diterpenoids that may be spatially separated from SGs. However, their biosynthetic routes and spatial distribution in leaf tissues have not yet been elucidated. Here, we integrate metabolome and transcriptome analyses of Stevia to explore the biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific chemical analyses confirmed that SGs were accumulated in leaf cells but not in trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses from two different tissues of Stevia provided a comprehensive overview of dynamic metabolic activities in trichomes and leaf without trichomes. These metabolite-guided transcriptomics and phylogenetic and gene expression analyses clearly identified specific gene members encoding enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane-type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en-8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi-manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have evolved to use distinct metabolic pathways to avoid metabolic interferences in leaf tissues for efficient production of diverse secondary metabolites. © 2015 American Society of Plant Biologists. All Rights Reserved.

Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii

PubMed Central

Pateraki, Irini; Andersen-Ranberg, Johan; Jensen, Niels Bjerg; Wubshet, Sileshi Gizachew; Heskes, Allison Maree; Forman, Victor; Hallström, Björn; Hamberger, Britta; Motawia, Mohammed Saddik; Olsen, Carl Erik; Staerk, Dan; Hansen, Jørgen; Møller, Birger Lindberg; Hamberger, Björn

2017-01-01

Forskolin is a unique structurally complex labdane-type diterpenoid used in the treatment of glaucoma and heart failure based on its activity as a cyclic AMP booster. Commercial production of forskolin relies exclusively on extraction from its only known natural source, the plant Coleus forskohlii, in which forskolin accumulates in the root cork. Here, we report the discovery of five cytochrome P450s and two acetyltransferases which catalyze a cascade of reactions converting the forskolin precursor 13R-manoyl oxide into forskolin and a diverse array of additional labdane-type diterpenoids. A minimal set of three P450s in combination with a single acetyl transferase was identified that catalyzes the conversion of 13R-manoyl oxide into forskolin as demonstrated by transient expression in Nicotiana benthamiana. The entire pathway for forskolin production from glucose encompassing expression of nine genes was stably integrated into Saccharomyces cerevisiae and afforded forskolin titers of 40 mg/L. DOI: http://dx.doi.org/10.7554/eLife.23001.001 PMID:28290983

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.

PubMed

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.

"Wild cannabis": A review of the traditional use and phytochemistry of Leonotis leonurus.

PubMed

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

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

PubMed

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.

Assessment of some diterpenoids in commercial distilled gin.

PubMed

Vichi, Stefania; Aumatell, Montserrat Riu; Buxaderas, Susana; López-Tamames, Elvira

2008-11-03

In the present study the qualitative and quantitative determination of diterpenoids in commercial distilled gin was carried out. This widely consumed juniper-based spirit is aromatized using Juniper (Juniperus communis) berries. Although juniper reportedly contains several diterpenic compounds, no studies have addressed the diterpenic composition of juniper-based spirits or beverages. With this objective, here we followed a multilevel factorial experimental design to optimize a direct immersion-solid phase microextraction (DI-SPME) method coupled to gas chromatography/mass spectrometry and analyzed eight commercial brands of gin. With total concentrations ranging from 10 to 190 microg L(-1), manool, manoyl oxide and trans-totarol were the most abundant diterpenoids of the 10 identified or tentatively identified at variable but not negligible concentrations in the distilled gin samples. The diterpenic composition allowed the brands to be differentiated. This indicates that these compounds contribute to the sensory characteristics of the distinct commercial brands, thus guaranteeing the authenticity and consequently the quality of the product.

The Full-Size ABCG Transporters Nb-ABCG1 and Nb-ABCG2 Function in Pre- and Postinvasion Defense against Phytophthora infestans in Nicotiana benthamiana

PubMed Central

Shibata, Yusuke; Ojika, Makoto; Sugiyama, Akifumi; Yazaki, Kazufumi; Jones, David A.; Kawakita, Kazuhito

2016-01-01

The sesquiterpenoid capsidiol is the major phytoalexin produced by Nicotiana and Capsicum species. Capsidiol is produced in plant tissues attacked by pathogens and plays a major role in postinvasion defense by inhibiting pathogen growth. Using virus-induced gene silencing-based screening, we identified two Nicotiana benthamiana (wild tobacco) genes encoding functionally redundant full-size ABCG (PDR-type) transporters, Nb-ABCG1/PDR1 and Nb-ABCG2/PDR2, which are essential for resistance to the potato late blight pathogen Phytophthora infestans. Silencing of Nb-ABCG1/2 compromised secretion of capsidiol, revealing Nb-ABCG1/2 as probable exporters of capsidiol. Accumulation of plasma membrane-localized Nb-ABCG1 and Nb-ABCG2 was observed at the site of pathogen penetration. Silencing of EAS (encoding 5-epi-aristolochene synthase), a gene for capsidiol biosynthesis, reduced resistance to P. infestans, but penetration by P. infestans was not affected. By contrast, Nb-ABCG1/2-silenced plants showed reduced penetration defense, indicating that Nb-ABCG1/2 are involved in preinvasion defense against P. infestans. Plastidic GGPPS1 (geranylgeranyl diphosphate synthase) was also found to be required for preinvasion defense, thereby suggesting that plastid-produced diterpene(s) are the antimicrobial compounds active in preinvasion defense. These findings suggest that N. benthamiana ABCG1/2 are involved in the export of both antimicrobial diterpene(s) for preinvasion defense and capsidiol for postinvasion defense against P. infestans. PMID:27102667

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, Larry G.; Cavin, Christophe; Itoh, Ken

2008-02-01

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,more » UGT1A6 and GCLC were lower in tissues from nrf2{sup -/-} mice than from nrf2{sup +/+} mice, but modest induction occurred in the mutant animals. Treatment of mouse embryonic fibroblasts (MEFs) from nrf2{sup +/+} mice with either coffee or the coffee-specific diterpenes cafestol and kahweol (C + K) increased NQO1 mRNA up to 9-fold. MEFs from nrf2{sup -/-} 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 {mu}mol/l furan, suggesting that this ring structure within C + K is insufficient for gene induction. Priming of nrf2{sup +/+} MEFs, but not nrf2{sup -/-} MEFs, with C + K conferred 2-fold resistance towards acrolein.« less

Effects of cafestol and kahweol from coffee grounds on serum lipids and serum liver enzymes in humans.

PubMed

Urgert, R; Schulz, A G; Katan, M B

1995-01-01

The diterpenes cafestol and kahweol are present in unfiltered coffee in oil droplets and floating fines. They elevate serum cholesterol and alanine aminotransferase (ALT). We measured fines in coffee brews, and examined diterpene availability from spent grounds in healthy volunteers. Turkish or Scandinavian boiled coffee contained 2-5 g fines/L and French press coffee contained 1.5 g fines/L. An intake of 8 g fine grounds/d for 3 wk increased cholesterol by 0.65 mmol/L (95% CI 0.41-0.89 mmol/L) and ALT by 18 U/L (95% CI 4-32 U/L) relative to control subjects (n = 7/group). In a crossover study (n = 15), mean serum cholesterol was 4.9 mmol/L after consumption of both fine and coarse grounds for 10 d (P = 0.43). Serum ALT activities were 29 U/L on fine and 21 U/L on coarse grounds (P = 0.02). Floating fines could contribute substantially to the hyperlipidemic and ALT-elevating effect of unfiltered coffee. Diterpene measurements in coffee brews should include the contribution of fines.

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

PubMed

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.

Impact of divalent metal ions on regulation of adenylyl cyclase isoforms by forskolin analogs.

PubMed

Erdorf, Miriam; Mou, Tung-Chung; Seifert, Roland

2011-12-01

Mammalian membranous adenylyl cyclases (mACs) play an important role in transmembrane signalling events in almost every cell and represent an interesting drug target. Forskolin (FS) is an invaluable research tool, activating AC isoforms 1-8. However, there is a paucity of AC isoform-selective FS analogs. Therefore, we examined the effects of FS and six FS derivatives on recombinant ACs 1, 2 and 5, representing members of different mAC families. Correlations of the pharmacological properties of the different AC isoforms revealed pronounced differences between ACs 1, 2 and 5. Additionally, potencies and efficacies of FS derivatives changed for any given AC isoform, depending on the metal ion, Mg(2+) or Mn(2+). The most striking effects of Mg(2+) and Mn(2+) on the diterpene profile were observed for AC2 where the large inhibitory effect of BODIPY-FS in the presence of Mg(2+) was considerably reduced in the presence of Mn(2+). Sequence alignment and docking experiments confirmed an exceptional position of AC2 compared to ACs 1 and 5 with respect to the structural environment of the catalytic core and cation-dependent diterpene effects. In conclusion, mAC isoforms 1, 2 and 5 exhibit a distinct pharmacological diterpene profile, depending on the divalent cation present. mAC crystal structures and modelling/docking studies provided an explanation for the pharmacological differences between the AC isoforms. Our study constitutes an important step towards the development of isoform-specific diterpenes exhibiting stimulatory or inhibitory effects. Copyright © 2011 Elsevier Inc. All rights reserved.

Establishment and analysis of in vitro biomass from Salvia corrugata Vahl. and evaluation of antimicrobial activity.

PubMed

Bisio, Angela; Fraternale, Daniele; Schito, Anna Maria; Parricchi, Anita; Dal Piaz, Fabrizio; Ricci, Donata; Giacomini, Mauro; Ruffoni, Barbara; De Tommasi, Nunziatina

2016-02-01

Demethylfruticuline A and fruticuline A, the most abundant compounds from the surface extract of Salvia corrugata Vahl., have shown antibacterial, antitumor and cytotoxic activities. In order to obtain these icetexane diterpenes from in vitro cultures of S. corrugata, protocols were developed for callus production, micropropagation and shoot regeneration. Analysis of the regenerated shoots showed the presence of both icetexanes, micropropagated plants contained only fruticuline A, while the callus contained trace amounts of both diterpenes. The yield of fruticuline A was higher in the methanolic extract of regenerated shoots than in those of fresh leaves and fresh shoot tips. In addition to these diterpenes, the regenerated shoot and micropropagated plant extracts afforded seven other diterpenes, one icetexane and six abietanes, identified by UV, IR, 1D- and 2D-NMR and HR-MS analysis. Five compounds (19-acetoxy-7α-hydroxyroyleanone, 7β,20-epoxy-11,12,19-trihydroxyabieta-8,11,13-triene, 7,20-dihydrofruticuline A, 7β-acetoxy-20-hydroxy-19,20-epoxyroyleanone, 7β-ethoxy-6β,20:19,20-diepoxyroyleanone) were previously undescribed. Although the crude plant surface extract did not possess any antibacterial activity, methanolic extracts of in vitro tissues and two compounds, namely 7β-acetoxy-20-hydroxy-19,20-epoxyroyleanone and 7β-ethoxy-6β,20:19,20-diepoxyroyleanone, isolated in suitable amounts, were active in varying degrees against multidrug resistant clinical strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Enterococcus faecium, displaying MIC values ranging from 32, 64 to 128μg/mL. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Activation and inhibition of adenylyl cyclase isoforms by forskolin analogs.

PubMed

Pinto, Cibele; Papa, Dan; Hübner, Melanie; Mou, Tung-Chung; Lushington, Gerald H; Seifert, Roland

2008-04-01

Adenylyl cyclase (AC) isoforms 1 to 9 are differentially expressed in tissues and constitute an interesting drug target. ACs 1 to 8 are activated by the diterpene, forskolin (FS). It is unfortunate that there is a paucity of AC isoform-selective activators. To develop such compounds, an understanding of the structure/activity relationships of diterpenes is necessary. Therefore, we examined the effects of FS and nine FS analogs on ACs 1, 2, and 5 expressed in Spodoptera frugiperda insect cells. Diterpenes showed the highest potencies at AC1 and the lowest potencies at AC2. We identified full agonists, partial agonists, antagonists, and inverse agonists, i.e., diterpenes that reduced basal AC activity. Each AC isoform exhibited a distinct pharmacological profile. AC2 showed the highest basal activity of all AC isoforms and highest sensitivity to inverse agonistic effects of 1-deoxy-forskolin, 7-deacetyl-1,9-dideoxy-forskolin, and, particularly, BODIPY-forskolin. In contrast, BODIPY-forskolin acted as partial agonist at the other ACs. 1-Deoxy-forskolin analogs were devoid of agonistic activity at ACs but antagonized the effects of FS in a mixed competitive/noncompetitive manner. At purified catalytic AC subunits, BODIPY-forskolin acted as weak partial agonist/strong partial antagonist. Molecular modeling revealed that the BODIPY group rotates promiscuously outside of the FS-binding site. Collectively, ACs are not uniformly activated and inhibited by FS and FS analogs, demonstrating the feasibility to design isoform-selective FS analogs. The two- and multiple-state models, originally developed to conceptualize ligand effects at G-protein-coupled receptors, can be applied to ACs to explain certain experimental data.

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

PubMed Central

Scott, Barry; Young, Carolyn A.; Saikia, Sanjay; McMillan, Lisa K.; Monahan, Brendon J.; Koulman, Albert; Astin, Jonathan; Eaton, Carla J.; Bryant, Andrea; Wrenn, Ruth E.; Finch, Sarah C.; Tapper, Brian A.; Parker, Emily J.; Jameson, Geoffrey B.

2013-01-01

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. PMID:23949005

Study of the Local Horizon. (Spanish Title: Estudio del Horizonte Local.) Estudo do Horizonte Local

NASA Astrophysics Data System (ADS)

Ros, Rosa M.

2009-12-01

The study of the horizon is fundamental to easy the first observations of the students at any education center. A simple model, to be developed in each center, allows to easy the study and comprehension of the rudiments of astronomy. The constructed model is presented in turn as a simple equatorial clock, other models (horizontal and vertical) may be constructed starting from it. El estudio del horizonte es fundamental para poder facilitar las primeras observaciones de los alumnos en un centro educativo. Un simple modelo, que debe realizarse para cada centro, nos permite facilitar el estudio y la comprensión de los primeros rudimentos astronómicos. El modelo construido se presenta a su vez como un sencillo modelo de reloj ecuatorial y a partir de él se pueden construir otros modelos (horizontal y vertical). O estudo do horizonte é fundamental para facilitar as primeiras observações dos alunos num centro educativo. Um modelo simples, que deve ser feito para cada centro, permite facilitar o estudo e a compreensão dos primeiros rudimentos astronômicos. O modelo construído apresenta-se, por sua vez, como um modelo simples de relógio equatorial e a partir dele pode-se construir outros modelos (horizontal e vertical)

Estudo espectral em raios-X duros de fontes do tipo Z com o HEXTE/RXTE

NASA Astrophysics Data System (ADS)

D'Amico, F.; Heindl, W. A.; Rothschild, R. E.

2003-08-01

Apresentam-se os resultados de um estudo espectral em raios-X de fontes do tipo Z. As fontes do tipo Z são binárias de raios-X de baixa massa (BXBM) com campo magnético intermediário (B~109G). Esta classe de fontes é composta por apenas 6 fontes Galácticas (a saber: ScoX-1, 9, 7, CygX-2, 5 e 0). A nossa análise se concentra na faixa de raios-X duros (E ~ 20keV), até cerca de 200keV, faixa ótima de operação do telescópio "High Energy X-ray Timing Experiment" (HEXTE), um dos três telescópios de raios-X à bordo do Rossi X-ray Timing Explorer (RXTE). Nossa motivação para tal estudo, uma busca de caudas em raios-X duros em fontes do tipo Z, foi o pouco conhecimento sobre a emissão nesta faixa de energia das referidas fontes quando comparadas, por exemplo, as fontes do tipo atoll (também BXBM). Apresentam-se a análise/redução de dados e explicita-se a maneira como o HEXTE mede o ru1do de fundo. Especial atenção é direcionada a este item devido a localização das fontes do tipo Z e também ao problema de contaminação por fontes próximas. Com exceção de ScoX-1, nenhuma cauda em raios-X duros foi encontrada para as outras fontes, a despeito de resultados de detecção dessas caudas em algumas fontes pelo satélite BeppoSAX. As interpretações deste resultado serão apresentadas. Do ponto de vista deste estudo, nós deduzimos que a produção de caudas de raios-X duros em fontes do tipo Z é um processo disparado quando, pelo menos, uma condição é satisfeita: o brilho da componente térmica do espectro precisa estar acima de um certo valor limiar de ~4´1036ergs-1.

Antiprotozoal Diterpenes from Perovskia abrotanoides.

PubMed

Tabefam, Marzieh; Farimani, Mahdi Moridi; Danton, Ombeline; Ramseyer, Justine; Kaiser, Marcel; Ebrahimi, Samad N; Salehi, Peyman; Batooli, Hossien; Potterat, Olivier; Hamburger, Matthias

2018-04-26

As part of a screening for new antiparasitic natural products from Iranian plants, n -hexane and ethyl acetate extracts from the aerial parts of Perovskia abrotanoides were found to exhibit strong inhibitory activity against Trypanosoma brucei rhodesiense and Leishmania donovani . The activity was tracked by high-performance liquid chromatography (HPLC)-based activity profiling. Preparative isolation by a combination of silica gel column chromatography and HPLC afforded 17 diterpenoids (1: -17: ), including 14 abietane-, two icetexane-, and one isopimarane-type derivatives. Among these, (5 R ,10 S )-11-hydroxy-12-methoxy-20-norabieta-8,11,13-triene (2: ), 12-hydroxy-norabieta-1(10),8,11,13-tetraene-1,11-furan (6: ), and 12-methoxybarbatusol (9: ) were new compounds, the structure of which was established by comprehensive spectroscopic data analysis (one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism). The antiprotozoal activity of the isolated compounds was evaluated against T. b. rhodesiense, Trypanosoma cruzi, L. donovani , and Plasmodium falciparum . Selectivity indexes (SI) were calculated in comparison to cytotoxicity on rat myoblast (L6) cells. Particularly active were 7 α -ethoxyrosmanol (4: ) with an IC 50 of 0.8 µM against T. b. rhodesiense (SI 14.9) and an IC 50 of 1.8 µM (SI 6.9) against L. donovani , ferruginol (8: ) with an IC 50 of 2.9 µM (SI 19.2) against P. falciparum , and miltiodiol (10: ) with an IC 50 of 0.5 µM (SI 10.5) against T. b. rhodesiense . None of the compounds exhibited selective toxicity against T. cruzi (SI ≤ 1.6). Georg Thieme Verlag KG Stuttgart · New York.

Annonaceae: Breaking the Wall of Inflammation

PubMed Central

Attiq, Ali; Jalil, Juriyati; Husain, Khairana

2017-01-01

Inventories of tropical forests have listed Annonaceae as one of the most diverse plant families. For centuries, it is employed in traditional medicines to cure various pathological conditions including snakebite, analgesic, astringent, diarrhea, dysentery, arthritis pain, rheumatism, neuralgia, and weight loss etc. Phytochemical analysis of Annonaceae family have reported the occurrence of alkaloids, flavonoids, triterpenes, diterpenes and diterpene flavone glycosides, sterols, lignans, and annonaceous acetogenin characteristically affiliated with Annonaceae sp. Numerous past studies have underlined the pleotropic pharmacological activities of the crude extracts and isolated compounds from Annonaceae species. This review is an effort to abridge the ethnobotany, morphology, phytochemistry, toxicity, and particularly focusing on the anti-inflammatory activity of the Annonaceae species. PMID:29104539

Studies on the biosynthesis of taxol: the taxane carbon skeleton is not of mevalonoid origin.

PubMed Central

Eisenreich, W; Menhard, B; Hylands, P J; Zenk, M H; Bacher, A

1996-01-01

A cell culture of Taxus chinensis was established to produce the diterpene 2alpha,5alpha,10beta,14beta-tetra-acetoxy4 ++ +(20),11-taxadiene (taxuyunnanine C) in 2.6% (dry weight) yield. The incorporation of [U-13C6]glucose, [1-13C]glucose, and [1,2-13C2]acetate into this diterpene was analyzed by NMR spectroscopy. Label from [1,2-13C2]acetate was diverted to the four acetyl groups of taxuyunnanine C, but not to the taxane ring system. Label from [1-13C]glucose and [U-13C6]glucose was efficiently incorporated into both the taxane ring system and the acetyl groups. The four isoprenoid moieties of the diterpene showed identical labeling patterns. The analysis of long-range 13C13C couplings in taxuyunnanine C obtained from an experiment with [U-13C6]glucose documents the involvement of an intramolecular rearrangement in the biosynthesis of the isoprenoid precursor. The labeling patterns are inconsistent with the mevalonate pathway. The taxoid data share important features with the alternative pathway of isoprenoid biosynthesis operating in certain eubacteria Rohmer, M., Knani, M., Simonin, P., Sutter, B. & Sahm, H. (1993) Biochem. J. 295, 517-524]. Images Fig. 1 Fig. 4 PMID:8692832

Molecular Diversity of Terpene Synthases in the Liverwort Marchantia polymorpha[OPEN

PubMed Central

Zhuang, Xun; Jiang, Zuodong; Jia, Qidong; Babbitt, Patricia C.

2016-01-01

Marchantia polymorpha is a basal terrestrial land plant, which like most liverworts accumulates structurally diverse terpenes believed to serve in deterring disease and herbivory. Previous studies have suggested that the mevalonate and methylerythritol phosphate pathways, present in evolutionarily diverged plants, are also operative in liverworts. However, the genes and enzymes responsible for the chemical diversity of terpenes have yet to be described. In this study, we resorted to a HMMER search tool to identify 17 putative terpene synthase genes from M. polymorpha transcriptomes. Functional characterization identified four diterpene synthase genes phylogenetically related to those found in diverged plants and nine rather unusual monoterpene and sesquiterpene synthase-like genes. The presence of separate monofunctional diterpene synthases for ent-copalyl diphosphate and ent-kaurene biosynthesis is similar to orthologs found in vascular plants, pushing the date of the underlying gene duplication and neofunctionalization of the ancestral diterpene synthase gene family to >400 million years ago. By contrast, the mono- and sesquiterpene synthases represent a distinct class of enzymes, not related to previously described plant terpene synthases and only distantly so to microbial-type terpene synthases. The absence of a Mg2+ binding, aspartate-rich, DDXXD motif places these enzymes in a noncanonical family of terpene synthases. PMID:27650333

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

PubMed Central

Fan, Dongsheng; Zhou, Shuangyan; Zheng, Zhiyuan; Zhu, Guo-Yuan; Yao, Xiaojun; Yang, Ming-Rong; Jiang, Zhi-Hong; Bai, Li-Ping

2017-01-01

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. PMID:28098763

Defense in the aeolidoidean genus Phyllodesmium (Gastropoda).

PubMed

Bogdanov, Alexander; Kehraus, Stefan; Bleidissel, Sabrina; Preisfeld, Gela; Schillo, Dorothee; Piel, Jörn; Brachmann, Alexander O; Wägele, Heike; König, Gabriele M

2014-09-01

The genus Phyllodesmium (Aeolidoidea, Gastropoda) comprises shell-less marine snails, whose defense strategies are not well investigated yet. Here we report results of the first chemical investigation of P. briareum, as well as a re-investigation of P. longicirrum and P. magnum. Briarane diterpenes were isolated from P. briareum, and their origin could be traced to its prey organism Briareum sp. (Octocorallia). Considerable enrichment of the soft coral secondary metabolites in the slug was shown. Re-investigation of P. magnum led to isolation of cembrane diterpenes, 2-phenylethylamide, and furano sesquiterpenes. Sequestration of chemicals seems to have influenced speciation and evolution of Phyllodesmium species. Structural similarity or dissimilarity of particular slug metabolites suggests a closer, or more distant relationship of the respective Phyllodesmium taxa.

ent-Rosane and abietane diterpenoids as cancer chemopreventive agents.

PubMed

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.

Estudo da região HII galática NGC 2579

NASA Astrophysics Data System (ADS)

Riffel, R.; Copetti, M. V. F.

2003-08-01

Desde a descoberta dos gradientes de abundância química em galáxias espirais, as regiões HII galáticas têm sido intensamente estudadas com o objetivo de determinar a forma do gradiente de abundância química na Via-Láctea. Entretanto, a forma do gradiente galático continua controversa e existem muitas regiões HII que continuam inexploradas. A região HII galática NGC 2579 é um objeto que aparece em imagens Ha, como uma pequena mancha brilhante de aproximadamente 2 segundos de arco de diâmetro a 20 segundos de arco ao leste de RCW 20, sendo NGC 2579 muitas vezes confundida com esta última. Apesar de seu alto brilho superficial, NGC 2579 é um objeto pouco estudado provavelmente por problemas de identificação deste objeto. Como parte de um projeto de reavaliação dos gradientes de abundância química das regiões HII na Via-Láctea, estamos realizando um estudo extensivo das propriedades físicas básicas como temperatura eletrônica, densidade eletrônica e composição química da região HII galática NGC 2579. Analisamos dados espectrofotométricos de fenda longa na faixa de 3700Å a 7750Å obtidos com o telescópio de 1.52 m do ESO, Chile, em 2002. Determinamos a temperatura eletrônica usando a razão entre as linhas do [OIII] (l4959+l5007/l4363) e a densidade eletrônica pela razão entre as linhas do [SII] (l6716/l6731). As abundâncias químicas do O, N, Cl, S, Ne e He foram determinadas. Realizamos um estudo de imagens fotométricas nas bandas UBVRI obtidas em 2000 no observatório astronômico San Pedro Mártir, México, para identificar e classificar as estrelas ionizantes de NGC 2579 e determinar a distância deste objeto.

Trans-β-Caryophyllene: An Effective Antileishmanial Compound Found in Commercial Copaiba Oil (Copaifera spp.)

PubMed Central

Soares, Deivid C.; Portella, Nathalya A.; Ramos, Mônica Freiman de S.; Siani, Antonio C.; Saraiva, Elvira M.

2013-01-01

This study investigated the leishmanicidal activity against Leishmania amazonensis of four commercial oils from Copaifera spp. named as C1, C2, C3, and C4, the sesquiterpene and diterpene pools obtained from distilling C4, and isolated β-caryophyllene (CAR). Copaiba oils chemical compositions were analyzed by gas chromatography and correlated with biological activities. Diterpenes-rich oils C2 and C3 showed antipromastigote activity. Sesquiterpenes-rich C1 and C4, and isolated CAR presented a dose-dependent activity against intracellular amastigotes, with IC50s of 2.9 µg/mL, 2.3 µg/mL, and 1.3 µg/mL (6.4 µM), respectively. Based on the highest antiamastigote activity and the low toxicity to the host cells, C4 was steamdistillated to separate pools of sesquiterpenes and diterpenes. Both pools were less active against L. amazonensis and more toxic for the macrophages than the whole C4 oil. The leishmanicidal activity of C3 and C4 oils, as well as C4 fractions and CAR, appears to be independent of nitric oxide production by macrophages. This study pointed out β-caryophyllene as an effective antileishmanial compound and also to its role as potential chemical marker in copaiba oils or fractions derived thereof, aiming further development of this rainforest raw material for leishmaniasis therapy. PMID:23864897

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

PubMed Central

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

Absolute Configuration of Andrographolide and Its Proliferation of Osteoblast Cell Lines

NASA Astrophysics Data System (ADS)

Chantrapromma, S.; Boonnak, N.; Pitakpornpreecha, T.; Yordthong, T.; Chidan Kumar, C. S.; Fun, H. K.

2018-05-01

Andrographolide, C20H30O5, is a labdane diterpenoid which was isolated from the leave of Andrographis paniculata. Its crystal structure is determined by single crystal X-ray diffraction: monoclinic, sp. gr. P21, Z = 2. Absolute configuration is determined by the refinement of the Flack parameter to 0.21(19). In the crystal, molecules are linked by O-H···O hydrogen bonds and C-H···O interactions into two dimensional network parallel to the (001) plane. Its proliferation of osteoblast cell lines is reported.

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

PubMed

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).

Baccharis pteronioides toxicity

USDA-ARS?s Scientific Manuscript database

Baccharis pteronioides DC. occasionally poisons livestock in the southwestern United States. Various toxins including diterpenic lactones, sesquiterpenes , flavonoids, saponins, tannins, phenolic compounds and essential oils have been isolated and described from several Baccharis species, but none...

ent-Copalic acid antibacterial and anti-biofilm properties against Actinomyces naeslundii and Peptostreptococcus anaerobius.

PubMed

Souza, Maria Gorete Mendes de; Leandro, Luís Fernando; Moraes, Thaís da Silva; Abrão, Fariza; Veneziani, Rodrigo Cassio Sola; Ambrosio, Sergio Ricardo; Martins, Carlos Henrique Gomes

2018-05-28

Diterpenes are an important class of plant metabolites that can be used in the search for new antibacterial agents. ent-Copalic acid (CA), the major diterpene in Copaifera species exudates, displays several pharmacological properties. This study evaluates the CA antibacterial potential against the anaerobic bacteria Peptostreptococcus anaerobius and Actinomyces naeslundii. Antimicrobial assays included time-kill and biofilm inhibition and eradication assays. Time-kill assays conducted for CA concentrations between 6.25 and 12.5 μg/mL evidenced bactericidal activity within 72 h. CA combined with chlorhexidine dihydrochloride (CHD) exhibited bactericidal action against P. anaerobius within 6 h of incubation. As for A. naeslundii, the same combination reduced the number of microorganisms by over 3 log10 at 24 h and exerted a bactericidal effect at 48 h of incubation. CA at 500 and 2000 μg/mL inhibited P. anaerobius and A. naeslundii biofilm formation by at least 50%, respectively. CA at 62.5 and 1.000 μg/mL eradicated 99.9% of pre-formed P. anaerobius and A. naeslundii biofilms, respectively. These results indicated that CA presents in vitro antibacterial activity and is a potential biofilm inhibitory agent. This diterpene may play an important role in the search for novel sources of agents that can act against anaerobic bacteria. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of underivatised low volatility compounds by comprehensive two-dimensional gas chromatography with a short primary column.

PubMed

Novaes, Fábio Junior Moreira; Kulsing, Chadin; Bizzo, Humberto Ribeiro; de Aquino Neto, Francisco Radler; Rezende, Claudia Moraes; Marriott, Philip John

2018-02-09

Comprehensive two-dimensional gas chromatography (GC×GC) approaches with cryogenic modulation were developed for the qualitative analysis of selected low volatility compounds in raw coffee bean extracts, without derivatisation. The approaches employed short first ( 1 D) and second ( 2 D) dimension columns, specifically a 1 D 65% phenyl methyl siloxane column (11m) and a 2 D 5% phenyl methyl siloxane column (1m), which allowed elution of high molar mass compounds (e.g.>600Da). Solutes included hydrocarbons, fatty acids, diterpenes, tocopherols, sterols, diterpene esters, and di- and triacylglycerides. An oven temperature program up to 370°C was employed. The effects of experimental conditions were investigated, revealing that the GC×GC results strongly depended on the cryogenic trap T, and oven T program. An appropriate condition was selected and further applied for group type analysis of low volatility compounds in green Arabica coffee beans. Retention indices were compiled for 1D GC analysis and were similar for the composite column data in GC×GC. The elution of some compounds was confirmed by use of authentic standards. The approach allowed direct analysis of coffee extract in ethyl acetate solution, with improved analyte peak capacity (approximately 200 compounds were detected) without prior fractionation or pre-treatment of the sample. This avoided potential hydrolysis of high molar mass conjugate esters as well as degradation of thermally labile compounds such as the derivatives of the diterpenes cafestol and kahweol. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroprotective Effects of Ferruginol, Jatrophone, and Junicedric Acid Against Amyloid-β Injury in Hippocampal Neurons.

PubMed

Zolezzi, Juan M; Lindsay, Carolina B; Serrano, Felipe G; Ureta, Roxana C; Theoduloz, Cristina; Schmeda-Hirschmann, Guillermo; Inestrosa, Nibaldo C

2018-01-01

Soluble amyloid-β (Aβ) oligomers have been recognized as early neurotoxic intermediates with a key role in the synaptic dysfunction observed in Alzheimer's disease (AD). Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Additionally, the presence of Aβ oligomers is associated with imbalanced intracellular calcium levels and apoptosis in neurons. In this context, we evaluated the effects of three diterpenes (ferruginol, jatrophone, and junicedric acid) that are found in medicinal plants and have several forms of biological activity. The intracellular calcium levels in hippocampal neurons increased in the presence of ferruginol, jatrophone, and junicedric acid, a result that was consistent with the observed increase in CA1 synaptic transmission in mouse hippocampal slices. Additionally, assays using Aβ peptide demonstrated that diterpenes, particularly ferruginol, restore LTP and reduce apoptosis. Recovery of the Aβ oligomer-induced loss of the synaptic proteins PSD-95, synapsin, VGlut, and NMDA receptor subunit 2A was observed in mouse hippocampal slices treated with junicedric acid. This cascade of events may be associated with the regulation of kinases, e.g., protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase II (CaMKII), in addition to the activation of the canonical Wnt signaling pathway and could thus provide protection against Aβ oligomers, which trigger synaptic dysfunction. Our results suggest a potential neuroprotective role for diterpenes against the Aβ oligomers-induced neurodegenerative alterations, which make them interesting molecules to be further studied in the context of AD.

Prolyl endopeptidase and thrombin inhibitory diterpenoids from the bark of Xylopia aethiopica.

PubMed

Diderot, Noungoue Tchamo; Silvere, Ngouela; Yasin, Amsha; Zareen, Seema; Fabien, Zelefack; Etienne, Tsamo; Choudhary, M Iqbal; Atta-Ur-Rahman

2005-09-01

The inhibitory effects of seven diterpenes, belonging to three different structural classes and isolated from the bark of Xylopia aethiopica, were investigated against the enzymes prolyl endopeptidase (PEP) and alpha-thrombin. Five compounds exhibited inhibitory activity against them.

Mass spectroscopic fingerprinting method for to differentiation between Scutellaria lateriflora and the Germander (Teucrium canadens and T. chamaedrys species

USDA-ARS?s Scientific Manuscript database

Scutellaria lateriflora, commonly known as skullcap, is used as an ingredient in numerous herbal products. However, it has been occasionally adulterated/contaminated with Teucrium canadense and Teucrium chamaedrys, commonly known as germander, which contain potentially hepatotoxic diterpenes. Due ...

Changes in the rumen bacterial microbiome of cattle exposed to ponderosa pine needles.

PubMed

Welch, K D; Stonecipher, C A; Gardner, D R; Cook, D; Pfister, J A

2017-05-01

Consumption of ponderosa pine needles, as well as needles and bark from a number of other trees, can cause abortions in cattle. The abortifacient compounds in these trees are labdane resin acids, including isocupressic acid and agathic acid. Previous research has demonstrated that cattle conditioned to pine needles metabolize the labdane resin acids more quickly than naïve cattle. The results from that study indicated that changes had occurred in the rumen of conditioned cattle. Therefore, in this study, the changes that occurred in the rumen bacterial microflora of cattle during exposure to ponderosa pine needles were evaluated. Cattle were dosed with ground pine needles twice daily for 7 d. Rumen samples were collected on d 0, 3, 7, and 14 (7 d after treatment stopped) and ruminal bacterial microbiome analyses were performed. There were 372 different genera of bacteria identified in the rumen samples. Principal coordinate analysis indicated that there was a significant difference in the rumen bacterial composition between the time points. There were 18 genera that increased in abundance from d 0 to d 7. Twenty three genera decreased in abundance from d 0 to d 7. The results from this study demonstrated that exposure of cattle to pine needles caused a clear shift in the rumen microbiome composition. In general, this shift lasted less than 1 wk post exposure, which indicates that any prophylactic treatment to manipulate the ruminal metabolism of the abortifacient compounds in pine needles would need to be continuously administered to maintain the necessary microbial composition in the rumen.

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

PubMed

Parveen, Iffat; Wang, Mei; Zhao, Jianping; Chittiboyina, Amar G; Tabanca, Nurhayat; Ali, Abbas; Baerson, Scott R; Techen, Natascha; Chappell, Joe; Khan, Ikhlas A; Pan, Zhiqiang

2015-11-01

Ginkgo biloba is one of the oldest living tree species and has been extensively investigated as a source of bioactive natural compounds, including bioactive flavonoids, diterpene lactones, terpenoids and polysaccharides which accumulate in foliar tissues. Despite this chemical diversity, relatively few enzymes associated with any biosynthetic pathway from ginkgo have been characterized to date. In the present work, predicted transcripts potentially encoding enzymes associated with the biosynthesis of diterpenoid and terpenoid compounds, including putative terpene synthases, were first identified by mining publicly-available G. biloba RNA-seq data sets. Recombinant enzyme studies with two of the TPS-like sequences led to the identification of GbTPS1 and GbTPS2, encoding farnesol and bisabolene synthases, respectively. Additionally, the phylogenetic analysis revealed the two terpene synthase genes as primitive genes that might have evolved from an ancestral diterpene synthase.

Structure elucidation of organic compounds from natural sources using 1D and 2D NMR techniques

NASA Astrophysics Data System (ADS)

Topcu, Gulacti; Ulubelen, Ayhan

2007-05-01

In our continuing studies on Lamiaceae family plants including Salvia, Teucrium, Ajuga, Sideritis, Nepeta and Lavandula growing in Anatolia, many terpenoids, consisting of over 50 distinct triterpenoids and steroids, and over 200 diterpenoids, several sesterterpenoids and sesquiterpenoids along with many flavonoids and other phenolic compounds have been isolated. For Salvia species abietanes, for Teucrium and Ajuga species neo-clerodanes for Sideritis species ent-kaurane diterpenes are characteristic while nepetalactones are specific for Nepeta species. In this review article, only some interesting and different type of skeleton having constituents, namely rearranged, nor- or rare diterpenes, isolated from these species will be presented. For structure elucidation of these natural diterpenoids intensive one- and two-dimensional NMR techniques ( 1H, 13C, APT, DEPT, NOE/NOESY, 1H- 1H COSY, HETCOR, COLOC, HMQC/HSQC, HMBC, SINEPT) were used besides mass and some other spectroscopic methods.

Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica.

PubMed

Somova, L I; Shode, F O; Moodley, K; Govender, Y

2001-10-01

The extractives, crude and pure, of Alepidea amatymbica (AA) and Xylopia aethiopica (XA) were subjected to bioassay-directed phytochemical examination for potential cardiovascular and diuretic activity. All extractives and derivatives (XA/O, AA/1, xylopic acid, AA/3, AA/4, AA/5, AA/6, XA/1, XA/2, XA/3) displayed low toxicity, with LC(50) 0.5-5.0 ng/ml. For the first time, diterpene kaurenoids were reported to have significant systemic hypotensive and coronary vasodilatory effect accompanied with bradycardia. These effects were attributed to calcium antagonistic mechanism. The diuretic and natriuretic effects found were similar to the effects of chlorothiazide, suggesting inhibition of Na+ and K+ reabsorption in the early portion of the distal tubule. Further experiments are needed to elaborate the exact mechanisms of the hypotensive and diuretic effects of diterpene kaurenoids.

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

USDA-ARS?s Scientific Manuscript database

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...

A synthetic approach to the fusicoccane A-B ring fragment based on a Pauson-Khand cycloaddition/Norrish type 1 fragmentation.

PubMed

Dake, Gregory R; Fenster, Erik E; Patrick, Brian O

2008-09-05

A synthetic approach to the A-B ring system within the fusicoccane family of diterpenes is presented. Key steps in this approach are a diastereoselective Pauson-Khand reaction, a Norrish 1 photofragmentation, a Charette cyclopropanation, and a ring-closing metathesis process.

Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Excavatolide B Isolated from the Culture-Type Formosan Gorgonian Briareum excavatum

PubMed Central

Lin, Yen-You; Lin, Sung-Chun; Feng, Chien-Wei; Chen, Pei-Chin; Su, Yin-Di; Li, Chi-Min; Yang, San-Nan; Jean, Yen-Hsuan; Sung, Ping-Jyun; Duh, Chang-Yih; Wen, Zhi-Hong

2015-01-01

In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum and investigated its anti-inflammatory activities. We found that excavatolide B significantly inhibited the mRNA expression of the proinflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-challenged murine macrophages (RAW 264.7). We also examined the anti-inflammatory and anti-nociceptive effects of excavatolide B on intraplantar carrageenan-induced inflammatory responses. Excavatolide B was found to significantly attenuate carrageenan-induced nociceptive behaviors, mechanical allodynia, thermal hyperalgesia, weight bearing deficits and paw edema. In addition, excavatolide B inhibited iNOS, as well as the infiltration of immune cells in carrageenan-induced inflammatory paw tissue. PMID:25923315

Antimicrobial activity of the ornamental species Salvia corrugata, a potential new crop for extractive purposes.

PubMed

Bisio, Angela; Romussi, Giovanni; Russo, Eleonora; Cafaggi, Sergio; Schito, Anna Maria; Repetto, Barbara; De Tommasi, Nunziatina

2008-11-26

As a part of our search for biologically active compounds from cultivated Salvia spp. we investigated Salvia corrugata Vahl. The activity of two isolated icetaxane diterpene quinones, fruticuline A and demethylfruticuline A, was assessed against 46 bacterial pathogens, mostly resistant to several primary antibiotics. The MIC for all the inhibited Gram-positive pathogens tested showed a very narrow distribution and ranged from 32 to 64 mg/L, regardless of their resistance patterns to other antibiotics. Demethylfruticuline A was shown to be highly bactericidal (>3 log(10) CFU decrease within 24 h) against Staphylococcus aureus and S. epidermidis and bacteriostatic against Enterococcus faecalis and E. faecium. Fruticuline A manifested bacteriostatic activity against all tested strains. S. corrugata can be viewed as an interesting source for these diterpenes, which, if well tolerated in vivo, may represent new medical agents useful for the treatment of serious infections caused by resistant Gram-positive pathogens.

Differences in ponderosa pine isocupressic acid concentrations across space and time

USDA-ARS?s Scientific Manuscript database

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...

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

PubMed

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.

Job strain and hypertension in women: Estudo Pro-Saúde (Pro-Health Study).

PubMed

Alves, Márcia Guimarães de Mello; Chor, Dóra; Faerstein, Eduardo; Werneck, Guilherme L; Lopes, Claudia S

2009-10-01

This study aimed to analyze the association between job strain and hypertension in the female population. A cross-sectional study was performed with 1,819 women who participated in the Estudo Pró-Saúde (Pro-Health Study), in the city of Rio de Janeiro, Southeastern Brazil, between 1999 and 2001. The Brazilian version of the short version of the Job Stress Scale (demand-control model) was used. Overall prevalence of measured hypertension (> or =140/90 mmHg and/or antihypertensive drug use) was 24%. Compared to participants with jobs classified as low strain, adjusted prevalence ratios for hypertension in women who performed passive and active high-strain jobs were, respectively, 0.93 (95% CI: 0.72;1.20), 1.06 (95% CI: 0.86;1.32) and 1.14 (95% CI: 0.88;1.47). Longitudinal analyses should be performed to clarify the role of these work environment psychosocial characteristics as a determinant of hypertension.

Um estudo espectrofotométrico da variável cataclísmica V3885 Sgr

NASA Astrophysics Data System (ADS)

Ribeiro, F. M. A.; Diaz, M. P.

2003-08-01

Variáveis Cataclísmicas são sistemas binários cerrados compostos de uma anã vermelha que transfere matéria para uma anã branca, em sistemas não magnéticos ocorre a formação de um disco de acresção em torno da anã branca. V3885 Sgr é uma variável cataclísmica classificada como sendo do tipo nova-like. É apresentado um estudo espectrofotométrico de V3885 Sgr de alta resolução temporal feito na região do visível. A região observada é centrada em Ha e abrange também a linha de HeI 6678. O primeiro resultado obtido neste estudo é a determinação do período orbital a partir de medidas da velocidade radial da linha de Ha como sendo 0,20716071(22) dias, resolvendo inconsistências quanto a esse valor na literatura e definindo uma efeméride a longo prazo para o sistema. Com este período e as medidas de velocidade radial do perfil de linha de Ha foi construído um diagrama de massas, através do qual restringimos as massas das componentes estelares do sistema e limitamos a inclinação orbital do sistema. Foram construídos diagramas de Greenstein para as linhas de Ha e HeI, onde os espectros médios em cada intervalo de fase são representados lado a lado em escala de cinza, indicando a existência de uma emissão intensa proveniente da parte posterior do disco. A partir da tomografia Doppler obtivemos perfis de emissividade radial para o disco tanto para a linha de Ha como para HeI. Os resultados obtidos são comparados com os de outros sistemas estudados com a mesma técnica. Serão apresentados também resultados da tomografia de flickering para o sistema.

Antimicrobial and antileishmanial activities of diterpenoids isolated from the roots of Salvia deserta

USDA-ARS?s Scientific Manuscript database

Four diterpenes with biological activity were isolated from Salvia deserta roots. Taxodione was considered leishmanicidal, with IC50 value of 0.46 µg/mL against Leishimania donovani and also exhibited antifungal and antimicrobial activities. Ferruginol displayed the greatest activity (24-h IC50 1.29...

Antisecretory actions of Baccharis trimera (Less.) DC aqueous extract and isolated compounds: analysis of underlying mechanisms.

PubMed

Biondo, Thais Maíra A; Tanae, Mirtes M; Coletta, Eliana Della; Lima-Landman, Maria Teresa R; Lapa, Antonio J; Souccar, Caden

2011-06-22

Baccharis trimera (Less.) DC. (Asteraceae) is a species native to South America used in Brazilian folk medicine to treat gastrointestinal and liver diseases, kidney disorders and diabetes. Previous studies from this laboratory confirmed the antacid and antiulcer activities of the plant aqueous extract (AE) in rat and mouse models. To investigate the mechanisms involved in the antacid action of AE and isolated compounds from Baccharis trimera. AE was assayed in vivo in cold-restraint stress gastric ulcers and in pylorus-ligated mice. Nine fractions (F2-F10) previously isolated from AE were assayed in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands, and on gastric microsomal H(+), K(+)-ATPase preparations. Chlorogenic acids (F2, F3, F6, F7), flavonoids (F9), an ent-clerodane diterpene (F8) and a dilactonic neo-clerodane diterpene (F10) have been identified in these fractions. Intraduodenal injection of AE (1.0 and 2.0 g/kg) in 4h pylorus-ligated mice decreased the volume (20 and 50%) and total acidity (34 and 50%) of acid secretion compared to control values. Administered orally at the same doses AE protected against gastric mucosal lesions induced in mice by restraint at 4°C. Exposure of isolated rabbit gastric glands to fractions F8 (10-100 μM) and F9 (10-300 μg/ml) decreased the basal [(14)C]-AP uptake by 50 and 60% of control (Ratio=6.2±1.1), whereas the remaining fractions were inactive. In the presence of the secretagogues F2 and F4 (30-300 μg/ml) decreased the [(14)C]-AP uptake induced by histamine (His) with a 100-fold lower potency than that of ranitidine. F5 and F6 reduced the [(14)C]-AP uptake stimulated by carbachol (CCh), but they were 10 to 20-fold less potent than atropine. F8 (diterpene 2) and F9 (flavonoids) decreased both the His- and CCh-induced [(14)C]-AP uptake, whereas F10 (diterpene 1) was inactive against the [(14)C]-AP uptake stimulated by secretagogues. Diterpene 2 was the most

Two new diterpene phenols from Calocedrus decurrans.

PubMed

Veluthoor, Sheeba; Li, Shujun; Kelsey, Rick G; Dolan, Marc C; Panella, Nicholas A; Karchesy, Joe

2010-04-01

Two new p-cymene based diphenols (1-2) were isolated from the heartwood of Calocedrus decurrans. Structures were elucidated by 1D and 2D NMR techniques and HRMS. Libocedroquinone (3) was also isolated as a natural product for the first time. A new system of nomenclature is proposed for description of such oligomeric p-cymene derivatives.

Two new diterpene phenols from Calocedrus decurrans

Treesearch

Sheeba Veluthoor; Shujun Li; Rick G. Kelsey; Marc C. Dolan; Nicholas A. Panella; Joe Karchesy

2010-01-01

Two new p-cymene based diphenols (1-2) were isolated from the heartwood of Calocedrus decurrans. Structures were elucidated by 1D and 2D NMR techniques and HRMS. Libocedroquinone (3) was also isolated as a natural product for the first time. A new system of nomenclature is proposed for description of such oligomeric p...

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

Treesearch

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...

Qualitative and quantitative studies of chemical composition of sandarac resin by GC-MS.

PubMed

Kononenko, I; de Viguerie, L; Rochut, S; Walter, Ph

2017-01-01

The chemical composition of sandarac resin was investigated qualitatively and quantitatively by gas chromatography-mass spectrometry (GC-MS). Six compounds with labdane and pimarane skeletons were identified in the resin. The obtained mass spectra were interpreted and the mass spectrometric behaviour of these diterpenoids under EI conditions was described. Quantitative analysis by the method of internal standard revealed that identified diterpenoids represent only 10-30% of the analysed sample. The sandarac resin from different suppliers was analysed (from Kremer, Okhra, Color Rare, La Marchande de Couleurs, L'Atelier Montessori, Hevea). The analysis of different lumps of resins showed that the chemical composition differs from one lump to another, varying mainly in the relative distributions of the components.

A study of amber and copal samples using FT-Raman spectroscopy

NASA Astrophysics Data System (ADS)

Brody, Rachel H.; Edwards, Howell G. M.; Pollard, A. Mark

2001-05-01

FT-Raman spectra were collected from fossil resins originating from a variety of geographical locations. The spectral profiles of most of the fossil resins could be related to modern resins containing diterpenoid components with predominantly labdane skeletons. The spectra collected from the fossil resin sample from Borneo differed from other fossil resins and was found to contain triterpenoid components. The differences in the spectral profile of fossil resins containing diterpenoid components are shown to relate to differences in level of maturation rather than geographical origin. FT-Raman spectra of fossil resins cannot be used to distinguish source although the degree of maturation can be used as an indicator to narrow the range of possible geographical origins.

NO inhibitory constituents as potential anti-neuroinflammatory agents for AD from Blumea balsamifera.

PubMed

Ma, Jun; Ren, Quanhui; Dong, Bangjian; Shi, Zhaoyu; Zhang, Jie; Jin, Da-Qing; Xu, Jing; Ohizumi, Yasushi; Lee, Dongho; Guo, Yuanqiang

2018-02-01

Our continuous search for new nitric oxide (NO) inhibitory substances as anti-neuroinflammatory agents for AD resulted in the isolation of one new labdane diterpenoid and three new guaiane sesquiterpenoids, as well as ten known compounds from Blumea balsamifera. Their structures were elucidated by NMR spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The anti-neuroinflammatory effects were examined by inhibiting NO release in LPS-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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.

Rapid analysis of abietanes in conifers

Treesearch

P.J. Kersten; B.J. Kopper; K.F. Raffa; B.L. Illman

2006-01-01

Diterpene resin acids are major constituents of conifer oleoresin and play important roles in tree defense against insects and microbial pathogens. The tricyclic C-20 carboxylic acids are generally classified into two groups, the abietanes and the pimaranes. The abietanes have conjugated double bonds and exhibit characteristic UV spectra. Here, we report the analysis...

A screening method for cardiovascular active compounds in marine algae.

PubMed

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.

Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast

NASA Astrophysics Data System (ADS)

Scheler, Ulschan; Brandt, Wolfgang; Porzel, Andrea; Rothe, Kathleen; Manzano, David; Božić, Dragana; Papaefthimiou, Dimitra; Balcke, Gerd Ulrich; Henning, Anja; Lohse, Swanhild; Marillonnet, Sylvestre; Kanellis, Angelos K.; Ferrer, Albert; Tissier, Alain

2016-10-01

Rosemary extracts containing the phenolic diterpenes carnosic acid and its derivative carnosol are approved food additives used in an increasingly wide range of products to enhance shelf-life, thanks to their high anti-oxidant activity. We describe here the elucidation of the complete biosynthetic pathway of carnosic acid and its reconstitution in yeast cells. Cytochrome P450 oxygenases (CYP76AH22-24) from Rosmarinus officinalis and Salvia fruticosa already characterized as ferruginol synthases are also able to produce 11-hydroxyferruginol. Modelling-based mutagenesis of three amino acids in the related ferruginol synthase (CYP76AH1) from S. miltiorrhiza is sufficient to convert it to a 11-hydroxyferruginol synthase (HFS). The three sequential C20 oxidations for the conversion of 11-hydroxyferruginol to carnosic acid are catalysed by the related CYP76AK6-8. The availability of the genes for the biosynthesis of carnosic acid opens opportunities for the metabolic engineering of phenolic diterpenes, a class of compounds with potent anti-oxidant, anti-inflammatory and anti-tumour activities.

From labdanes to drimanes. Degradation of the side chain of dihydrozamoranic acid.

PubMed

Rodilla, Jesús M L; Díez, D; Urones, J G; Rocha, Pedro M

2004-04-30

A new route for the degradation of the saturated side chain of dihydrozamoranic acid has been devised, giving an advanced intermediate, compound 14, useful for the synthesis of insect antifeedants such as warburganal and polygodial.

A novel indole-diterpenoid, JBIR-03 with anti-MRSA activity from Dichotomomyces cejpii var. cejpii NBRC 103559.

PubMed

Ogata, Masahiro; Ueda, Jun-ya; Hoshi, Midori; Hashimoto, Junko; Nakashima, Takuji; Anzai, Kozue; Takagi, Motoki; Shin-ya, Kazuo

2007-10-01

A new indole-diterpene, JBIR-03 (1), was isolated from the fungus Dichotomomyces cejpii var. cejpii NBRC 103559 and its structure was determined based on the spectroscopic data. 1 exhibited anti-MRSA (methicillin-resistant Staphylococcus aureus) activity and antifungal activity against apple Valsa canker-causing fungus, Valsa ceratosperma, while it exhibited no toxicity towards human cancer cells.

Antimicrobial properties of some West African medicinal plants iv. Antimicrobial activity of xylopic acid and other constituente of the fruits of Xylopia aethiopica (Annonaceae).

PubMed

Boakye-Yiadom, K; Fiagbe, N I; Ayim, J S

1977-01-01

Xylopic acid and four other isolates from the fresh ripe fruits of Xylopia aethiopica a common ingredient in several Ghanaian folklore medicines and foods, have been examined for antimicrobial activity against five micro-organisms, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Xylopic acid and two other diterpene isolates were found to have antimicrobial properties.

Draft Genome Sequence of Grammothele lineata SDL-CO-2015-1, a Jute Endophyte with a Potential for Paclitaxel Biosynthesis.

PubMed

Das, Avizit; Ahmed, Oly; Baten, A K M Abdul; Bushra, Samira; Islam, M Tariqul; Ferdous, Ahlan Sabah; Islam, Mohammad Riazul; Khan, Haseena

2017-08-17

Grammothele lineata strain SDL-CO-2015-1, a basidiomycete fungus, was identified as an endophyte from a jute species, Corchorus olitorius var. 2015, and found to produce paclitaxel, a diterpenic polyoxygenated pseudoalkaloid with antitumor activity. Here, we report the draft genome sequence (42.8 Mb with 9,395 genes) of this strain. Copyright © 2017 Das et al.

Draft Genome Sequence of Grammothele lineata SDL-CO-2015-1, a Jute Endophyte with a Potential for Paclitaxel Biosynthesis

PubMed Central

Das, Avizit; Ahmed, Oly; Baten, A. K. M. Abdul; Bushra, Samira; Islam, M. Tariqul; Ferdous, Ahlan Sabah; Islam, Mohammad Riazul

2017-01-01

ABSTRACT Grammothele lineata strain SDL-CO-2015-1, a basidiomycete fungus, was identified as an endophyte from a jute species, Corchorus olitorius var. 2015, and found to produce paclitaxel, a diterpenic polyoxygenated pseudoalkaloid with antitumor activity. Here, we report the draft genome sequence (42.8 Mb with 9,395 genes) of this strain. PMID:28818909

Um Breve Balanço dos Estudos em Astronomia e Educação no Brasil no Período de 2010 a 2013

NASA Astrophysics Data System (ADS)

Goncalves, Erica de Oliveira; Kern, C.

2014-10-01

No Brasil, as pesquisas em ensino de astronomia para a Educação Básica vem ganhando destaque. Posto como importante área do conhecimento para estudantes e professores, os estudos em astronomia conquistam espaços nos documentos oficiais da educação e nos currículos escolares. Diante desse cenário, fez-se, neste trabalho, um mapeamento no banco de dados da Biblioteca Digital Brasileira de Teses e Dissertações , com base nas palavras-chave "astronomia" e "educação" no período de 2010 a 2013. Para compor o que aqui denominamos de balanço da área de estudo, foram selecionados trabalhos e analisados os títulos, os resumos, as considerações finais e as referências, bem como identificamos as fontes epistemológicas correntes nas pesquisas de pós-graduação no período supracitado. Identificou-se, na maior parte dos trabalhos pesquisados, referenciais teóricos relacionados & agrave; área de física, ciências e astronomia que envolvem discussões sobre currículo e práticas pedagógicas vinculados ao ensino de astronomia no ensino fundamental e médio da Educação Bãsica e nos cursos de formação de professores.

Analytical aspects of diterpene alkaloid poisoning with monkshood.

PubMed

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.

Profilaxia da trombose venosa profunda em cirurgia bariátrica: estudo comparativo com doses diferentes de heparina de baixo peso molecular

PubMed Central

Goslan, Carlos José; Baretta, Giórgio Alfredo Pedroso; de Souza, Hemuara Grasiela Pestana; Orsi, Bruna Zanin; Zanoni, Esdras Camargo A.; Lopes, Marco Antonio Gimenez; Engelhorn, Carlos Alberto

2018-01-01

Resumo Contexto A cirurgia bariátrica é considerada a melhor opção para o tratamento da obesidade, cujos pacientes são considerados de alto risco para fenômenos tromboembólicos. Objetivos Comparar o uso de doses diferentes de heparina de baixo peso molecular (HBPM) na profilaxia da trombose venosa profunda (TVP) em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, alteração na dosagem do fator anti-Xa e sangramento pré ou pós-operatório. Métodos Estudo comparativo transversal em pacientes submetidos à cirurgia bariátrica distribuídos em dois grupos, que receberam doses de HBPM de 40 mg (grupo controle, GC) e 80 mg (grupo de estudo, GE). Foram avaliados por ultrassonografia vascular e dosagem de KPTT, TAP, plaquetas e fator anti-Xa. Resultados Foram avaliados 60 pacientes, sendo 34 no GC e 26 no GE. Foi observada diferença significativa somente no peso (p = 0,003) e índice de massa corporal (p = 0,018) no GE em relação ao GC. Não houve diferença na dosagem de KPTT, TAP, plaquetas e fator anti-Xa entre os grupos. Não foram detectados TVP ou sangramentos significativos em ambos os grupos. Conclusões Não houve diferença estatisticamente significativa na utilização de doses maiores de HBPM na profilaxia da TVP em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, dosagem do fator anti-Xa e sangramento pré ou pós-operatório.

Improvements in the Methodology for Analyzing Receptor Subtypes and Neuronal Populations Affected by Anticholinesterase Exposure.

DTIC Science & Technology

1984-11-14

Slide-mounted tissue sections can be treated with [ H]forskolin (a diterpene plant derivative which is a potent activator of adenylate cyclase) to...protein activities are altered in response to the chronic presence of anticholinesterase agents. Significant progress and improvement has been made in...359 FILE COPY IMPROVEMENTS IN THE METHODOLOGY FOR ANALYZING RECEPTOR SUBTYPES AND NEURONAL POPULATIONS AFFECTED BY ANTICHOLINESTERASE EXPOSURE Annual

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

PubMed

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.

Synthesis, Antiviral and Cytotoxic Activity of Novel Terpenyl Hybrid Molecules Prepared by Click Chemistry.

PubMed

Pertino, Mariano Walter; Petrera, Erina; Alché, Laura Edith; Schmeda-Hirschmann, Guillermo

2018-06-03

Naturally occurring terpenes were combined by click reactions to generate sixteen hybrid molecules. The diterpene imbricatolic acid (IA) containing an azide group was used as starting compound for the synthesis of all the derivatives. The alkyne group in the terpenes cyperenoic acid, dehydroabietinol, carnosic acid γ-lactone, ferruginol, oleanolic acid and aleuritolic acid was obtained by esterification using appropriate alcohols or acids. The hybrid compounds were prepared by combining the IA azide function with the different terpene-alkynes under click chemistry conditions. The cytotoxic activity of the terpene hybrids 1 ⁻ 16 was assessed against Vero cells and tumour cell lines (HEP-2, C6 and Raw 264.7). Compounds 1 , 2 , 3 and 7 showed cytotoxic activity against the tested cell lines. The antiviral activity of the compounds was evaluated against HSV-1 KOS, Field and B2006 strain. For the pairs of hybrid compounds formed between IA-diterpene (compounds 3 ⁻ 8 , except for compound 7 ), a moderate activity was observed against the three HSV-1 strains with an interesting selectivity index (SI ≥10, SI = CC 50 /CE 50 ) for some compounds.

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

PubMed

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.

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

PubMed

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.

A Pauson-Khand and ring-expansion approach to the aquariane ring system.

PubMed

Thornton, Paul D; Burnell, D Jean

2006-07-20

[Structure: see text] The carbocyclic ring system of the aquariolide diterpenes has been synthesized by two routes involving a diastereoselective Pauson-Khand reaction and subsequent ring expansion. In one route, a tetracyclic enone was elaborated to generate the nine-membered ring by Grob fragmentation. In the second approach, a spirocyclic tricycle underwent a facile anionic oxy-Cope rearrangement to complete the synthesis of the desired ring system.

The enzymic preparation of (14)C-kaurene.

PubMed

Graebe, J E

1969-06-01

Endosperm from immature seeds of Cucurbita pepo L. converts 2-(14)C-DL-mevalonate to (14)C-(-)-kaurene with a yield of nearly 40% of the active isomer. Kaurene is the main product and the only diterpene hydrocarbon which is formed from mevalonate in the system and is therefore easily obtained radiochemically pure. The product was identified by thin-layer chromatography and recrystallization with authentic (-)-kaurene to constant specific radioactivity.

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

PubMed

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.

ent-Trachylobane diterpenoids from Xylopia langsdorffiana.

PubMed

Tavares, Josean Fechine; Queiroga, Karine F; Silva, Marianna Vieira B; Diniz, Margareth F F M; Filho, José M B; da-Cunha, Emidio V L; de Simone, Carlos Alberto; Júnior, João X de Araújo; Melo, Patrícia S; Haun, Marcela; da Silva, Marcelo Sobral

2006-06-01

Two new diterpenes of the ent-trachylobane type were isolated from the stems of Xylopia langsdorffiana, ent-7alpha-acetoxytrachyloban-18-oic acid (1) and ent-7alpha-hydroxytrachyloban-18-oic acid (2). The structures of these isolates were deduced by spectroscopic data interpretation. X-ray crystallography of 1 was used to confirm its structure. The cytotoxic activity of 1 against V79 fibroblasts and rat hepatocytes was investigated.

Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). II. Pathophysiological investigations in lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk-raised kids.

PubMed

Nawito, M; Ahmed, Y F; Zayed, S M; Hecker, E

1998-01-01

Lactating goats were fed on aerial parts of the herb Euphorbia peplus L. admixed with their usual green fodder. During the experimental feeding period they showed symptoms of general poisoning. In necropsy the main toxic effects were seen in the heart, lung and liver. Histopathological examinations revealed that the primary toxic effects originated from degenerative changes in parenchymal and endothelial cells. Adverse symptoms in the liver and kidney were also reflected in an alteration of the levels of certain serum enzymes and of blood urea nitrogen. The milk of the goats fed on E. peplus, consumed by their young kids, caused poisoning and even death, with signs similar to those observed in the adult dams. These observations support the hypothesis that the poisoning observed in both milk-raised kids and mother goats is caused by diterpene ester type toxins present in the aerial parts of the herb contaminating the dams fodder. Generally, such skin irritant and hyperplasiogenic toxins are known to be highly active tumour promoters of skin and other organ, e.g. in mice. Lactating goats--as an important source of milk around the world--in a setting similar to that described, may provide a valid experimental etiological model for investigation of food polluted by tumour-promoting diterpene ester toxins.

Immunomodulatory action of Copaifera spp oleoresins on cytokine production by human monocytes.

PubMed

Santiago, Karina Basso; Conti, Bruno José; Murbach Teles Andrade, Bruna Fernanda; Mangabeira da Silva, Jonas Joaquim; Rogez, Hervé Louis Ghislain; Crevelin, Eduardo José; Beraldo de Moraes, Luiz Alberto; Veneziani, Rodrigo; Ambrósio, Sérgio Ricardo; Bastos, Jairo Kenupp; Sforcin, José Maurício

2015-03-01

Copaifera spp oleoresins have been used in folk medicine for centuries; nevertheless, its immunomodulatory action has not been investigated. Thus, the goal of this study was to characterize different oleoresins and to verify their action on human monocytes regarding pro- and anti-inflammatory cytokine production (TNF-α and IL-10, respectively). The chemical composition of Brazilian Copaifera reticulata, Copaifera duckey and Copaifera multijuga oleoresins was analyzed by HPLC-MS. Cell viability was assessed by MTT method after incubation of cells with Copaifera spp. Noncytotoxic concentrations of oleoresins were incubated with human monocytes from healthy donors, and cytokine production was determined by ELISA. HPLC-MS analysis for terpenes allowed the identification of six diterpene acids and one sesquiterpene acid. Oleoresins exerted no cytotoxic effects on human monocytes. All oleoresins had a similar profile: LPS-induced TNF-α production was maintained by oleoresins, while a significant inhibitory action on IL-10 production was seen. Copaifera oleoresins seemed to exert an activator profile on human monocytes without affecting cell viability. Such effect may be due to the presence of either diterpene or sesquiterpene acids; however, further studies are necessary to determine the involvement of such compounds in Copaifera immunomodulatory effects. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

DOE PAGES

Luo, Dan; Callari, Roberta; Hamberger, Britta; ...

2016-08-09

The seed oil of Euphorbia lathyris L. contains a series of macrocyclic diterpenoids known as Euphorbia factors. They are the current industrial source of ingenol mebutate, which is approved for the treatment of actinic keratosis, a precancerous skin condition. Here, we report an alcohol dehydrogenase-mediated cyclization step in the biosynthetic pathway of Euphorbia factors, illustrating the origin of the intramolecular carbon–carbon bonds present in lathyrane and ingenane diterpenoids. This unconventional cyclization describes the ring closure of the macrocyclic diterpene casbene. Through transcriptomic analysis of E. lathyris L. mature seeds and in planta functional characterization, we identified three enzymes involved inmore » the cyclization route from casbene to jolkinol C, a lathyrane diterpene. These enzymes include two cytochromes P450 from the CYP71 clan and an alcohol dehydrogenase (ADH). CYP71D445 and CYP726A27 catalyze regio-specific 9-oxidation and 5-oxidation of casbene, respectively. When coupled with these P450-catalyzed monooxygenations, E. lathyris ADH1 catalyzes dehydrogenation of the hydroxyl groups, leading to the subsequent rearrangement and cyclization. The discovery of this nonconventional cyclization may provide the key link to complete elucidation of the biosynthetic pathways of ingenol mebutate and other bioactive macrocyclic diterpenoids.« less

Evaluation of morpho-anatomical and chemical differences between varieties of the medicinal plant Casearia sylvestris Swartz.

PubMed

Claudino, Josiane C; Sacramento, Luis V S do; Koch, Ingrid; Santos, Helen A; Cavalheiro, Alberto J; Tininis, Aristeu G; Santos, André G dos

2013-01-01

Casearia sylvestris Swartz (Salicaceae) has been used in traditional medicine and its leaf extracts have been exhibited important pharmacological activities. The species presents morphological, chemical and genetic variation. Two varieties are considered due external morphological differences: C. sylvestris var. sylvestris and var. lingua. There are difficulties in definition of these varieties. The objective of this work is to evaluate chemical and morpho-anatomical differences between C. sylvestris varieties that can be applied in their distinction for pharmaceutical or botanical purposes. Transverse and paradermic sections of leaves were prepared for morpho-anatomical, histochemical and quantitative microscopy (stomatal and palisade index) analyses. Diterpene profiles of the specimens were obtained by HPLC-DAD and TLC. Morpho-anatomical analyses demonstrated significant differences between the varieties only in paradermic sections: var. sylvestris--polygonal epidermic cell walls and hypostomatic; var. lingua--rounded epidermic cell walls and amphistomatic. No differences were observed for stomatal index; palisade index was found 2.8 for var. lingua and 3.9 for var. sylvestris. Chromatographic analyses confirmed previous results demonstrating that diterpene profile in varieties differs, with predominance of these metabolites in var. sylvestris. In conclusion, this work indicates that chromatographic analysis besides morpho-anatomical analysis can be applied in distinction of C. sylvestris varieties.

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

PubMed

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 (P<0.01) was observed at doses up to 200 mg/kg. At 100 mg/kg, the highest gastroprotective activity was provided by 15-hydroxyimbricatolal and 15-acetoxyimbricatolic acid, all of them being as active as the reference drug lansoprazole at 20 mg/kg. The cytotoxicity of the main diterpenes as well as lansoprazole was studied towards human lung fibroblasts (MRC-5) and determined by the MTT reduction assay. A concentration-dependent cell viability inhibition was found with IC50 values ranging from 125 up to 290 microM. Our results support the traditional use of the Araucaria araucana resin by the Mapuche culture.

Ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K(+) and Ca(2+) channels to reduce cytosolic calcium concentration on guinea pig ileum.

PubMed

Santos, Rosimeire F; Martins, Italo R R; Travassos, Rafael A; Tavares, Josean F; Silva, Marcelo S; Paredes-Gamero, Edgar J; Ferreira, Alice T; Nouailhetas, Viviane L A; Aboulafia, Jeannine; Rigoni, Vera L S; da Silva, Bagnólia A

2012-03-05

In this study we investigated the mechanism underlying the spasmolytic action of ent-7α-acetoxytrachyloban-18-oic acid (trachylobane-360) and ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318), diterpenes obtained from Xylopia langsdorfiana, on guinea pig ileum. Both compounds inhibited histamine-induced cumulative contractions (slope=3.5±0.9 and 4.4±0.7) that suggests a noncompetitive antagonism to histaminergic receptors. CaCl(2)-induced contractions were nonparallelly and concentration-dependently reduced by both diterpenes, indicating blockade of calcium influx through voltage-dependent calcium channels (Ca(v)). The Ca(v) participation was confirmed since both trachylobanes equipotently relaxed ileum pre-contracted with S-(-)-Bay K8644 (EC(50)=3.5±0.7×10-(5) and 1.1±0.2×10-(5)M) and KCl (EC(50)=5.5±0.3×10-(5) and 1.4±0.2×10-(5)M). K(+) channels participation was confirmed since diterpene-induced relaxation curves were significantly shifted to right in the presence of 5mM tetraethylammonium (TEA(+)) (EC(50)=0.5±0.04×10-(4) and 2.0±0.5×10-(5)M). ATP-sensitive K(+) channel (K(ATP)), voltage activated K(+) channels (K(V)), small conductance calcium-activated K(+) channels (SK(Ca)) or big conductance calcium-activated K(+) channels (BK(Ca)) did not seem to participate of trachylobane-360 spasmolytic action. However trachylobane-318 modulated positively K(ATP), K(V) and SK(Ca) (EC(50)=1.1±0.3×10-(5), 0.7±0.2×10-(5) and 0.7±0.2×10-(5)M), but not BK(Ca). A fluorescence analysis technique confirmed the decrease of cytosolic calcium concentration ([Ca(2+)](c)) induced by both trachylobanes in ileal myocytes. In conclusion, trachylobane-360 and trachylobane-318 induced spasmolytic activity by K(+) channel positive modulation and Ca(2+) channel blockade, which results in [Ca(2+)](c) reduction at cellular level leading to smooth muscle relaxation. Copyright © 2011. Published by Elsevier B.V.

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

PubMed

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

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

Biosynthesis of Diterpenoids in Tripterygium Adventitious Root Cultures1[OPEN

PubMed Central

Inabuy, Fainmarinat S.; Fischedick, Justin T.; Lange, Iris; Xu, Meimei

2017-01-01

Adventitious root cultures were developed from Tripterygium regelii, and growth conditions were optimized for the abundant production of diterpenoids, which can be collected directly from the medium. An analysis of publicly available transcriptome data sets collected with T. regelii roots and root cultures indicated the presence of a large gene family (with 20 members) for terpene synthases (TPSs). Nine candidate diterpene synthase genes were selected for follow-up functional evaluation, of which two belonged to the TPS-c, three to the TPS-e/f, and four to the TPS-b subfamilies. These genes were characterized by heterologous expression in a modular metabolic engineering system in Escherichia coli. Members of the TPS-c subfamily were characterized as copalyl diphosphate (diterpene) synthases, and those belonging to the TPS-e/f subfamily catalyzed the formation of precursors of kaurane diterpenoids. The TPS-b subfamily encompassed genes coding for enzymes involved in abietane diterpenoid biosynthesis and others with activities as monoterpene synthases. The structural characterization of diterpenoids accumulating in the medium of T. regelii adventitious root cultures, facilitated by searching the Spektraris online spectral database, enabled us to formulate a biosynthetic pathway for the biosynthesis of triptolide, a diterpenoid with pharmaceutical potential. Considering the significant enrichment of diterpenoids in the culture medium, fast-growing adventitious root cultures may hold promise as a sustainable resource for the large-scale production of triptolide. PMID:28751314

Soft Coral Sarcophyton (Cnidaria: Anthozoa: Octocorallia) Species Diversity and Chemotypes

PubMed Central

Aratake, Satoe; Tomura, Tomohiko; Saitoh, Seikoh; Yokokura, Ryouma; Kawanishi, Yuichi; Shinjo, Ryuichi; Reimer, James Davis; Tanaka, Junichi; Maekawa, Hideaki

2012-01-01

Research on the soft coral genus Sarcophyton extends over a wide range of fields, including marine natural products and the isolation of a number of cembranoid diterpenes. However, it is still unknown how soft corals produce this diverse array of metabolites, and the relationship between soft coral diversity and cembranoid diterpene production is not clear. In order to understand this relationship, we examined Sarcophyton specimens from Okinawa, Japan, by utilizing three methods: morphological examination of sclerites, chemotype identification, and phylogenetic examination of both Sarcophyton (utilizing mitochondrial protein-coding genes MutS homolog: msh1) and their endosymbiotic Symbiodinium spp. (utilizing nuclear internal transcribed spacer of ribosomal DNA: ITS- rDNA). Chemotypes, molecular phylogenetic clades, and sclerites of Sarcophyton trocheliophorum specimens formed a clear and distinct group, but the relationships between chemotypes, molecular phylogenetic clade types and sclerites of the most common species, Sarcophyton glaucum, was not clear. S. glaucum was divided into four clades. A characteristic chemotype was observed within one phylogenetic clade of S. glaucum. Identities of symbiotic algae Symbiodinium spp. had no apparent relation to chemotypes of Sarcophyton spp. This study demonstrates that the complex results observed for S. glaucum are due to the incomplete and complex taxonomy of this species group. Our novel method of identification should help contribute to classification and taxonomic reassessment of this diverse soft coral genus. PMID:22272344

Soft coral Sarcophyton (Cnidaria: Anthozoa: Octocorallia) species diversity and chemotypes.

PubMed

Aratake, Satoe; Tomura, Tomohiko; Saitoh, Seikoh; Yokokura, Ryouma; Kawanishi, Yuichi; Shinjo, Ryuichi; Reimer, James Davis; Tanaka, Junichi; Maekawa, Hideaki

2012-01-01

Research on the soft coral genus Sarcophyton extends over a wide range of fields, including marine natural products and the isolation of a number of cembranoid diterpenes. However, it is still unknown how soft corals produce this diverse array of metabolites, and the relationship between soft coral diversity and cembranoid diterpene production is not clear. In order to understand this relationship, we examined Sarcophyton specimens from Okinawa, Japan, by utilizing three methods: morphological examination of sclerites, chemotype identification, and phylogenetic examination of both Sarcophyton (utilizing mitochondrial protein-coding genes MutS homolog: msh1) and their endosymbiotic Symbiodinium spp. (utilizing nuclear internal transcribed spacer of ribosomal DNA: ITS- rDNA). Chemotypes, molecular phylogenetic clades, and sclerites of Sarcophyton trocheliophorum specimens formed a clear and distinct group, but the relationships between chemotypes, molecular phylogenetic clade types and sclerites of the most common species, Sarcophyton glaucum, was not clear. S. glaucum was divided into four clades. A characteristic chemotype was observed within one phylogenetic clade of S. glaucum. Identities of symbiotic algae Symbiodinium spp. had no apparent relation to chemotypes of Sarcophyton spp. This study demonstrates that the complex results observed for S. glaucum are due to the incomplete and complex taxonomy of this species group. Our novel method of identification should help contribute to classification and taxonomic reassessment of this diverse soft coral genus.

Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain.

PubMed

Ameyaw, Elvis O; Woode, Eric; Boakye-Gyasi, Eric; Abotsi, Wonder K M; Kyekyeku, James Oppong; Adosraku, Reimmel K

2014-04-01

Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including headache and neuralgia. An animal model of vincristine-induced sensory neuropathy was developed after repeated intraperitoneal injection in rats and used in the present work to study the effects of the ethanolic extract of X. aethiopica (XAE) and its diterpene xylopic acid (XA) in vincristine-induced neuropathic pain. Vincristine (0.1 mg kg(-1) day(-1)) was administered during two cycles of five consecutive days to induce chemotherapy-induced neuropathic pain. Static tactile anti-allodynic, anti-hyperalgesic, and cold anti-allodynic effects of XAE (30-300 mg kg(-1)) and XA (10-100 mg kg(-1)) were assessed using Von Frey filaments of bending forces of 4, 8, and 15 g, the Randall-Selitto paw pressure test, and cold water (4.5°C), respectively. Administration of vincristine caused the development of allodynia and hyperalgesia with no significant motor deficit, spontaneous pain, and foot deformity. XAE (30-300 mg kg(-1)) and XA (10-100 mg kg(-1)) exhibited anti-hyperalgesic, tactile, and cold anti-allodynic properties with XA exhibiting greater potency than XAE. Pregabalin (10-100 mg kg(-1)) used as control produced similar effect. These findings establish the anti-allodynic and anti-hyperalgesic effects of the ethanolic fruit XAE and its major diterpene XA in vincristine-induced neuropathtic pain.

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

PubMed

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.

The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1.

PubMed

Kim, Juewon; Kang, Young-Gyu; Lee, Jee-young; Choi, Dong-hwa; Cho, Young-uk; Shin, Jae-Min; Park, Jun Seong; Lee, John Hwan; Kim, Wan Gi; Seo, Dae Bang; Lee, Tae Ryong; Miyamoto, Yusei; No, Kyoung Tai

2015-09-05

Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid of confers, such as pinus species (P. densiflora, P. sylvestris) and grand fir (Abies grandis), and it induces various biological actions including antimicrobial, antiulcer, and cardiovascular activities. The cellular targets that mediate these actions are largely unknown yet. In this report, we suggest that DAA is an anti-aging reagent. DAA has lifespan extension effects in Caenorhabditis elegans, prevents lipofuscin accumulation, and prevents collagen secretion in human dermal fibroblasts. We found that these anti-aging effects are primarily mediated by SIRT1 activation. Lifespan extension effects by DAA were ameliorated in sir-2.1 mutants and SIRT1 protein expression was increased, resulting in the deacetylation of SIRT1 target protein PGC-1α. Moreover, DAA binds directly to the SIRT1 protein independent of the SIRT1 substrate NAD(+) levels. Through a molecular docking study, we also propose a binding model for DAA-SIRT1. Taken together, our results demonstrate that the anti-aging effects are the first identified biological property of DAA and that the direct activation of SIRT1 enzymatic activity suggests the potential use of this natural diterpene, or related compounds, in age-related diseases or as a preventive reagent against the aging process. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Links between Genetic Groups, Indole Alkaloid Profiles and Ecology within the Grass-Parasitic Claviceps purpurea Species Complex.

PubMed

Negård, Mariell; Uhlig, Silvio; Kauserud, Håvard; Andersen, Tom; Høiland, Klaus; Vrålstad, Trude

2015-04-28

The grass parasitic fungus Claviceps purpurea sensu lato produces sclerotia with toxic indole alkaloids. It constitutes several genetic groups with divergent habitat preferences that recently were delimited into separate proposed species. We aimed to 1) analyze genetic variation of C. purpurea sensu lato in Norway, 2) characterize the associated indole alkaloid profiles, and 3) explore relationships between genetics, alkaloid chemistry and ecology. Approximately 600 sclerotia from 14 different grass species were subjected to various analyses including DNA sequencing and HPLC-MS. Molecular results, supported by chemical and ecological data, revealed one new genetic group (G4) in addition to two of the three known; G1 (C. purpurea sensu stricto) and G2 (C. humidiphila). G3 (C. spartinae) was not found. G4, which was apparently con-specific with the recently described C. arundinis sp. nov, was predominantly found in very wet habitats on Molinia caerulea and infrequently in saline habitats on Leymus arenarius. Its indole-diterpene profile resembled G2, while its ergot alkaloid profile differed from G2 in high amounts of ergosedmam. In contrast to G1, indole-diterpenes were consistently present in G2 and G4. Our study supports and complements the newly proposed species delimitation of the C. purpurea complex, but challenges some species characteristics including host spectrum, habitat preferences and sclerotial floating ability.

Links between Genetic Groups, Indole Alkaloid Profiles and Ecology within the Grass-Parasitic Claviceps purpurea Species Complex

PubMed Central

Negård, Mariell; Uhlig, Silvio; Kauserud, Håvard; Andersen, Tom; Høiland, Klaus; Vrålstad, Trude

2015-01-01

The grass parasitic fungus Claviceps purpurea sensu lato produces sclerotia with toxic indole alkaloids. It constitutes several genetic groups with divergent habitat preferences that recently were delimited into separate proposed species. We aimed to 1) analyze genetic variation of C. purpurea sensu lato in Norway, 2) characterize the associated indole alkaloid profiles, and 3) explore relationships between genetics, alkaloid chemistry and ecology. Approximately 600 sclerotia from 14 different grass species were subjected to various analyses including DNA sequencing and HPLC-MS. Molecular results, supported by chemical and ecological data, revealed one new genetic group (G4) in addition to two of the three known; G1 (C. purpurea sensu stricto) and G2 (C. humidiphila). G3 (C. spartinae) was not found. G4, which was apparently con-specific with the recently described C. arundinis sp. nov, was predominantly found in very wet habitats on Molinia caerulea and infrequently in saline habitats on Leymus arenarius. Its indole-diterpene profile resembled G2, while its ergot alkaloid profile differed from G2 in high amounts of ergosedmam. In contrast to G1, indole-diterpenes were consistently present in G2 and G4. Our study supports and complements the newly proposed species delimitation of the C. purpurea complex, but challenges some species characteristics including host spectrum, habitat preferences and sclerotial floating ability. PMID:25928134

Analysis of Taiwan patents for the medicinal mushroom "Niu-Chang- Chih".

PubMed

Chen, Yu-Fen; Lu, Wen-Ling; Wu, Ming-Der; Yuan, Gwo-Fang

2013-04-01

"Niu-Chang-Chih" (Antrodia cinnanomea) is a medicinal mushroom that has only been collected from the aromatic tree, Cinnamomum kanehirai, which is native to Taiwan. A total of 105 Taiwan patent applications and patents for "Niu-Chang-Chih" were collected and analyzed. Patent applications and granted patents claiming newly identified functional components from "Niu-Chang-Chih," biologically pure cultures of the mushroom strain, and cultivation of "Niu-Chang-Chih" were examined. Several applications and patents claim identified active compounds from "Niu-Chang- Chih," which provide better patent protection. These newly identified functional compounds include cyclohexanones, maleic and succinic acid derivatives, labdane diterpenoids, and benzenoids. Newly identified functional proteins include a glutathione-dependent formaldehyde dehydrogenase (GFD), a glycoprotein named ACA1, and a laccase. Newly identified functional polysaccharides include ACP1, ACP2, and ACP3. The number of patents for newly identified compounds and their uses are expected to continue growing.

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

PubMed

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.

Some structures of marine natural products

DOE Office of Scientific and Technical Information (OSTI.GOV)

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)

Biosynthesis and Regulation of Bioprotective Alkaloids in the Gramineae Endophytic Fungi with Implications for Herbivores Deterrents.

PubMed

Luo, Hongping; Xie, Longxiang; Zeng, Jie; Xie, Jianping

2015-12-01

Four kinds of bioprotective alkaloids-peramine, loline, ergot alkaloid, indole-diterpenes, produced by grass-fungal endophyte symbioses, are deterrents or toxic to vertebrate and invertebrate herbivores. Ergot alkaloids have pharmacological properties and widely are used clinically. The regulation of alkaloids biosynthesis is under intensive study to improve the yield for better agricultural and medicinal application. In this paper, we summarize the structure, related genes, regulation, and toxicity of alkaloids. We focus on the biosynthesis and the regulation network of alkaloids.

Anti-tumor abietane diterpenes from the cones of Sequoia sempervirens.

PubMed

Son, Kwang-Hee; Oh, Hyun-Mi; Choi, Sung-Kyu; Han, Dong Cho; Kwon, Byoung-Mog

2005-04-15

A new abietane, namely, 20-hydroxyferruginol (1), together with known ferruginol (2), 18-hydroxyferruginol (3), sugiol (4), and 6alpha-hydroxysugiol (5), were isolated from the cones of Sequoia sempervirens. Their structures were elucidated through spectral data. Compounds 1 and 5 strongly inhibited colon, lung, and breast human tumors and oncogene transformed cells with GI(50) 2-5 microg/mL.

A systematic review of pharmacokinetic studies on herbal drug Fuzi: Implications for Fuzi as personalized medicine.

PubMed

Wu, Jin-Jun; Guo, Zhen-Zhen; Zhu, Yuan-Feng; Huang, Zhi-Jian; Gong, Xia; Li, Yu-Huan; Son, Wen-Jie; Li, Xiao-Yan; Lou, Yan-Mei; Zhu, Li-Jun; Lu, Lin-Lin; Liu, Zhong-Qiu; Liu, Liang

2018-03-01

Fuzi, which is the processed lateral roots of Aconitum carmichaeli Debx. (Ranunculaceae), is a traditional herbal medicine that is well known for its excellent pharmacological effects and acute toxicity. Aconitum alkaloids are responsible for its pharmacological activity and toxicity. Although a large number of studies on Fuzi have been reported, no comprehensive review on its pharmacokinetics has yet been published. This paper seeks to present a comprehensive review regarding the phytochemistry, pharmacokinetic features and toxicity of Fuzi. The regulation of drug-metabolizing enzymes (DMEs) and efflux transporters (ETs) by Fuzi is also concluded. Additionally, the use of Fuzi as a personalized medicine based on the bioavailability barrier (BB), which mainly comprises DMEs and ETs, is discussed. All available information on Fuzi was collected by searching for key words in PubMed, ScienceDirect, CNKI, Google Scholar, Baidu Scholar, and Web of Science. Aconitum alkaloids, which mainly include diester-diterpene alkaloids (DDAs), monoester-diterpene alkaloids (MDAs) and unesterified-diterpene alkaloids (UDAs), could be detected after Fuzi ingestion in vivo. The Aconitum alkaloids are rapidly absorbed in the intestine and extensively distributed in the body. DMEs, especially CYP3A4/5, are responsible for various types of metabolic reactions of the Aconitum alkaloids. ETs, including P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP), are involved in the efflux of the DDAs and MDAs. The kidney is the most important organ involved in the excretion of the Aconitum alkaloids. DDAs are the main toxic compounds present in Fuzi, and their acute toxicity is mainly due to their effects on the voltage-dependent sodium channels. Furthermore, Fuzi can substantially regulate DMEs and ETs. The toxicity of DDAs is acute. However, further investigations are necessary to determine the exact toxicological mechanisms. The

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

PubMed

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

2016-02-25

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, 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. Forty seven 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= 28.1g/100g; SD = 10.6) and (E)-β-caryophyllene (M = 19.0g/100g; 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 = 28.7g/100g; SD = 7.9), α-pinene (M = 12.3g/100g; SD = 3.6) and myrcene (M = 11.7g/100g; SD = 7.3). All these oil samples were isolated from pine needles harvested in Capo di Feno and Tre Padule. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

PubMed

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 < 0.05) cooking yield, Hunterlab a* values and sensory attributes without affecting proximate composition and shear force values relative to control. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis and scanning electron microscopy results revealed no significant changes in protein quality and 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.

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.

PubMed

Woode, Eric; Ameyaw, Elvis O; Boakye-Gyasi, Eric; Abotsi, Wonder K M

2012-10-01

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. 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. 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. These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain

PubMed Central

Ameyaw, Elvis O.; Woode, Eric; Boakye-Gyasi, Eric; Abotsi, Wonder K.M.; Kyekyeku, James Oppong; Adosraku, Reimmel K.

2014-01-01

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including headache and neuralgia. An animal model of vincristine-induced sensory neuropathy was developed after repeated intraperitoneal injection in rats and used in the present work to study the effects of the ethanolic extract of X. aethiopica (XAE) and its diterpene xylopic acid (XA) in vincristine-induced neuropathic pain. Materials and Methods: Vincristine (0.1 mg kg-1 day-1) was administered during two cycles of five consecutive days to induce chemotherapy-induced neuropathic pain. Static tactile anti-allodynic, anti-hyperalgesic, and cold anti-allodynic effects of XAE (30-300 mg kg-1) and XA (10-100 mg kg-1) were assessed using Von Frey filaments of bending forces of 4, 8, and 15 g, the Randall-Selitto paw pressure test, and cold water (4.5°C), respectively. Results: Administration of vincristine caused the development of allodynia and hyperalgesia with no significant motor deficit, spontaneous pain, and foot deformity. XAE (30-300 mg kg-1) and XA (10-100 mg kg-1) exhibited anti-hyperalgesic, tactile, and cold anti-allodynic properties with XA exhibiting greater potency than XAE. Pregabalin (10-100 mg kg-1) used as control produced similar effect. Conclusion: These findings establish the anti-allodynic and anti-hyperalgesic effects of the ethanolic fruit XAE and its major diterpene XA in vincristine-induced neuropathtic pain. PMID:24761123

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

PubMed Central

Woode, Eric; Ameyaw, Elvis O.; Boakye-Gyasi, Eric; Abotsi, Wonder K. M.

2012-01-01

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. PMID:23248562

Pterodon pubescens oil: characterisation, certification of origin and quality control via mass spectrometry fingerprinting analysis.

PubMed

Cabral, E C; Sevart, L; Spindola, H M; Coelho, M B; Sousa, I M O; Queiroz, N C A; Foglio, M A; Eberlin, M N; Riveros, J M

2013-02-01

The oil obtained from Pterodon pubescens (Leguminosae) seeds are known to display anti-cancer, anti-dermatogenic and anti-nociceptive activitiy. Phytochemical studies have demonstrated that its main constituents are diterpenoids with voucapan skeletons. Considering the potential biological activities of the oil, rapid and efficient methods for assessing its quality would facilitate certification and quality control. To develop a direct mass spectrometric fingerprinting method for the P. pubescens seed oil that would focus on the major diterpenoids constituents, enabling quality control, origin certification and recognition of marker species in commercially available products. Two techniques were used: (i) direct infusion electrospray ionisation (ESI) mass spectrometry after solvent extraction and dilution and (ii) ambient desorption/ionisation via easy ambient sonic-spray ionisation, EASI(+)-MS, performed directly on the seed surface or at a paper surface imprinted with the oil. From a combination of ESI-MS, HRESI-MS and ESI-MS/MS data, 12 diterpenes were characterised, and typical profiles were obtained for the oil extract or the crude oil via both ESI-MS and EASI-MS. These techniques require no or very simple sample preparation protocols and the whole analytical processes with spectra acquisition take just a few minutes. Both techniques, but particularly EASI-MS, provide simple, fast and efficient MS fingerprinting methodologies to characterise the P. pubescens oil with typical (di)terpene profiles being applicable to quality control and certification of authenticity and origin. Copyright © 2012 John Wiley & Sons, Ltd.

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

PubMed

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.

Isolation and Identification of Secondary Metabolites from the Aerial Parts of Stachys lavandulifolia Vahl.

PubMed

Sajjadi, Seyed Ebrahim; Ghanadian, Seyed Mustafa; Rabbani, Mohammad; Tahmasbi, Fateme

2017-01-01

Stachys lavandulifolia Vahl is an herbaceous wild plant native to Iran which is traditionally used in Iranian folk medicine as a mild sedative tea for reducing anxiety and for treatment of gastrointestinal disorders. Our previous study on ethyl acetate extract of S. lavandulifolia proved anti-anxiolytic activity and so the present study was designed to determine chemical components of this biologically active fraction. The extract was prepared using maceration method. Column chromatography and medium pressure liquid chromatography (MPLC) was used respectively to separate the fractions. Finally, some evaluated fractions were used for high pressure liquid (HPLC) and peak shaving recycle technique to achieve more purification. Separated compounds were determined using NMR analysis and mass spectroscopy. Six compounds have been isolated from ethylacetate extract of aerial parts of S. lavandulifolia including four flavonoids (apigenin, kumatakenin, penduletin and 4', 7-dihyroxy- 3, 5, 6-trimethoxy flavon), a labdan diterpenoid (labda-13-en-8, 15-diol), and an iridoid.

The effect of western juniper on the estrous cycle in beef cattle.

PubMed

Welch, Kevin D; Stonecipher, Clint A; Gardner, Dale R; Panter, Kip E; Parsons, Cory; Deboodt, Tim; Johnson, Bryan

2015-02-01

Numerous evergreen trees and shrubs contain labdane acids, including isocupressic acid, which can cause late-term abortions in cattle. Recent research has shown that the bark from western juniper trees can also cause late-term abortions in cattle. Additionally, ranchers have observed that cattle in western juniper-infested rangelands tend to have decreased conception rates. The objective of this study was to determine if western juniper alters the estrous cycle of cattle. Fourteen heifers (10 treated and 4 control) were monitored for 74 days for signs of normal estrous behavior, with a 21 day feeding trial with western juniper bark from days 28-48, after which the cattle were bred naturally with a bull. The cattle were checked for pregnancy 30 days after all cattle had been bred. The data from this study indicate that exposure to western juniper bark does not affect normal estrus, estrous cycle or conception rates of cattle. Published by Elsevier Ltd.

Estudo comparativo entre estrelas centrais de nebulosas planetárias deficientes em hidrogênio

NASA Astrophysics Data System (ADS)

Marcolino, W. L. F.; de Araújo, F. X.

2003-08-01

Apresentamos neste trabalho o resultado de um estudo das principais características espectrais das estrelas centrais de nebulosas planetárias (ECNP) deficientes em hidrogênio. A origem e a evolução dessas estrelas ainda constitui um problema em aberto na evolução estelar. Geralmente esses objetos são divididos em [WCE], [WCL] e [WELS]. Os tipos [WCE] e [WCL] apresentam um espectro típico de uma estrela Wolf-Rayet carbonada de população I e as [WELS] apresentam linhas fracas de carbono e oxigênio em emissão. Existem evidências que apontam a seguinte sequência evolutiva : [WCL] = > [WCE] = > [WELS] = > PG 1159 (pré anã-branca). No entanto, tal cenário apresenta falhas como por exemplo a falta de ECNP entre os tipos [WCL] e [WCE]. Baseados em uma amostra de 24 objetos obtida no telescópio de 1.52m em La Silla, Chile (acordo ESO/ON), ao longo do ano 2000, apresentamos os resultados da comparação das larguras equivalentes de diversas linhas relevantes entre os tipos [WCL], [WCE] e [WELS]. Verificamos que nossos dados estão de acordo com a sequência evolutiva. Baseado nas linhas de C IV, conseguimos dividir pela primeira vez as [WELS] em dois grupos principais. Além disso, os dados reforçam a afirmação de que as [WCE] são as estrelas que possuem a maior temperatura entre as ECNP deficientes em hidrogênio. Discutimos ainda, a escassez de dados disponíveis na literatura e a necessidade da obtenção de parametros físicos para estes objetos.

11-Step Total Synthesis of (−)-Maoecrystal V

PubMed Central

2016-01-01

An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (−)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product. PMID:27457680

[Educational status and patterns of weight gain in adulthood in Brazil: Estudo Pró-Saúde].

PubMed

Fonseca, Maria de Jesus Mendes da; França, Rosana de Figueiredo; Faerstein, Eduardo; Werneck, Guilherme Loureiro; Chor, Dóra

2012-11-01

The aim of the present study was to investigate the association between participant and parental educational status (considered as an indicator of socioeconomic status) and participant pattern of weight gain in adulthood. We analyzed data from 2 582 baseline participants (1999) of Estudo Pró-Saúde (Pro-Health Study), a longitudinal investigation of civil servants from a public university in Rio de Janeiro, Brazil. Self-administered questionnaires were used to identify patterns of weight gain in adulthood. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated for the association between parental and participant educational status and steady weight gain or weight cycling, with stable weight as a reference, using multinomial logistic regression models. For males, lower paternal educational level entailed a chance about 55% lower of weight cycling as compared to stable weight (OR = 0.45; IC95% = 0.26-0.78), whereas lower maternal schooling was related to increased risk of weight cycling, although without reaching statistical significance (OR = 1.68; IC95% = 0.94-3.00). The association between participant educational status and weight history was not statistically significant among men. In women, lower educational status entailed a chance 94% higher of self-reported weight cycling (OR = 1.94; 95% CI = 1.17-3.23), and there was no association between parental educational level and history of weight gain. In this study, changes in weight throughout life, both steady and cyclic, were associated with parental and participant educational status, with major differences between genders.

Cafestol, a diterpene molecule found in coffee, induces leukemia cell death.

PubMed

Lima, Cauê S; Spindola, Daniel G; Bechara, Alexandre; Garcia, Daniel M; Palmeira-Dos-Santos, Caroline; Peixoto-da-Silva, Janaina; Erustes, Adolfo G; Michelin, Luis F G; Pereira, Gustavo J S; Smaili, Soraya S; Paredes-Gamero, Edgar; Calgarotto, Andrana K; Oliveira, Carlos R; Bincoletto, Claudia

2017-08-01

To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit- granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Construção de um catálogo de aglomerados abertos para estudo da dinâmica da estrutura espiral da Galáxia

NASA Astrophysics Data System (ADS)

Carlos, I. M.; Lépine, J. R. D.

2003-08-01

Os aglomerados abertos são objetos de grande valor para o estudo da dinâmica da Galáxia devido esses objetos terem uma faixa de idade relativamente ampla. O trabalho visa estudar a dinâmica da estrutura espiral da Galáxia principalmente através do uso desses aglomerados, uma vez que o estudo da cinemática desses objetos é fundamental para esse objetivo. Nosso grupo trabalha no sentido de construir uma base de dados de aglomerados abertos contendo coordenadas, distância, idade, movimentos próprios e velocidades radiais e já disponibiliza uma nova versão do catálogo de aglomerados abertos o qual é uma compilação de edições anteriores, principalmente Lynga (1987), Mermilliod (1995) e ESO-B (Lauberts 1982). Nossa amostra possui cerca de 1630 aglomerados, mas nem todos os parâmetros acima citados foram determinados em sua totalidade. Para determinarmos esses parâmetros, derivamos as cores intrínsecas das estrelas membro de cada aglomerado a partir de seus tipos espectrais (busca feita no SIMBAD) obtendo assim o excesso de cor individual. A distribuição dos excessos de cor foi então utilizada para derivarmos o avermelhamento médio para cada aglomerado. De maneira similar, os tipos espectrais foram usados para estimar as magnitudes absolutas, e com as magnitudes absolutas e aparentes determinamos a respectiva distribuição do módulo de distância e finalmente a distância. Para determinar as idades foram confeccionados os diagramas cor-magnitude das estrelas de cada aglomerado onde foram superpostas a Seqüência Principal de Idade Zero (ZAMS). Superpomos a ZAMS de Schmidt-Kaler e isócronas de composição solar. Essas isócronas foram usadas para determinação das idades dos aglomerados. Uma vez que não temos ainda resultados finais, apresentamos então alguns diagramas cor-magnitude os quais foram usados para determinação, principalmente, da distância e idade dos aglomerados.

Manduca sexta recognition and resistance among allopolyploid Nicotiana host plants

PubMed Central

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

Organic matter characteristics in boreal forest soils under stands of silver birch, Norway spruce, and Norway spruce with a mixture of silver birch

NASA Astrophysics Data System (ADS)

Smolander, A.; Kitunen, V.

2012-04-01

The aim was to study how tree species and a tree species mixture affect microbial C and N transformations and two major plant secondary compound groups, terpenes and phenolic compounds in soil. The study site was a tree-species experiment in middle-eastern part of Finland containing plots of 43-year-old silver birch, Norway spruce and Norway spruce with a mixture of silver birch (22 and 37 % birch of the total stem number). Soil was podzol and humus type mor. Samples were taken from the organic layer. C and N in the microbial biomass, rates of C mineralization (CO2 evolution), net N mineralization and nitrification, and concentrations of total water-soluble phenolic compounds, condensed tannins and different kind of terpenes were measured. Amounts of C and N in the microbial biomass and the rates of C mineralization and net N mineralization were all lower under spruce than birch, and particularly net N mineralization was stimulated by birch mixture. Concentrations of total water-soluble phenolic compounds were on a similar level, irrespective of tree species. However, there were less low-molecular-weight phenolics and more high-molecular-weight phenolics under spruce than birch. Concentrations of condensed tannins and both sesqui- and diterpenes were all higher under spruce than birch but the concentrations of triterpenes were similar in all soils. The difference between tree species was greatest with monoterpenes which were measured from both organic layer and soil atmosphere: high concentrations under spruce and negligible under birch. Birch mixture tended to decrease the concentrations of condensed tannins and mono-, sesqui- and diterpenes.

Therapeutic Potential of Medicinal Plants and Their Constituents on Lung Inflammatory Disorders

PubMed Central

Kim, Hyun Pyo; Lim, Hyun; Kwon, Yong Soo

2017-01-01

Acute bronchitis and chronic obstructive pulmonary diseases (COPD) are essentially lung inflammatory disorders. Various plant extracts and their constituents showed therapeutic effects on several animal models of lung inflammation. These include coumarins, flavonoids, phenolics, iridoids, monoterpenes, diterpenes and triterpenoids. Some of them exerted inhibitory action mainly by inhibiting the mitogen-activated protein kinase pathway and nuclear transcription factor-κB activation. Especially, many flavonoid derivatives distinctly showed effectiveness on lung inflammation. In this review, the experimental data for plant extracts and their constituents showing therapeutic effectiveness on animal models of lung inflammation are summarized. PMID:27956716

Phytochemical, cytotoxic and chemotaxonomic study on Ajuga forrestii Diels (Labiatae).

PubMed

Chen, Tong; Diao, Qing-Yan; Yu, Hai-Zhou; Jiao, Chun-Li; Ruan, Jian

2018-04-01

A phytochemical investigation of Ajuga forrestii Diels led to the isolation of 14 compounds, including eight neo-clerodane diterpenes (1-8), two phytoecdysteroids (9, 11), one stigmastane sterol (10) and three iridoid glycosides (12-14). The structures of these compounds were identified by spectroscopic methods and a comparison of their data with those reported in the literature. This is the first report of compounds 1-14 from A. forrestii. The cytotoxic activities of the aqueous extract of A. forrestii and several compounds have been studied and the chemotaxonomic significance of isolated compounds has also been summarised.

Catalytic hydrogenation of the sweet principles of Stevia rebaudiana, Rebaudioside B, Rebaudioside C, and Rebaudioside D and sensory evaluation of their reduced derivatives.

PubMed

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

2012-11-16

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.

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

PubMed

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

2015-12-28

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.

The genus Caesalpinia L. (Caesalpiniaceae): phytochemical and pharmacological characteristics.

PubMed

Zanin, João L Baldim; de Carvalho, Bianca A; Martineli, Paloma Salles; dos Santos, Marcelo Henrique; Lago, João Henrique G; Sartorelli, Patrícia; Viegas, Cláudio; Soares, Marisi G

2012-06-29

The genus Caesalpinia (Caesalpiniaceae) has more than 500 species, many of which have not yet been investigated for potential pharmacological activity. Several classes of chemical compounds, such as flavonoids, diterpenes, and steroids, have been isolated from various species of the genus Caesalpinia. It has been reported in the literature that these species exhibit a wide range of pharmacological properties, including antiulcer, anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antirheumatic activities that have proven to be efficacious in ethnomedicinal practices. In this review we present chemical and pharmacological data from recent phytochemical studies on various plants of the genus Caesalpinia.

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

NASA Astrophysics Data System (ADS)

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.

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.

Rapid analysis of abietanes in conifers.

PubMed

Kersten, P J; Kopper, B J; Raffa, K F; Illman, B L

2006-12-01

Diterpene resin acids are major constituents of conifer oleoresin and play important roles in tree defense against insects and microbial pathogens. The tricyclic C-20 carboxylic acids are generally classified into two groups, the abietanes and the pimaranes. The abietanes have conjugated double bonds and exhibit characteristic UV spectra. Here, we report the analysis of abietanes by reversed-phase high-performance liquid chromatography using multiwavelength detection to optimize quantification of underivatized abietic, neoabietic, palustric, levopimaric, and dehydroabietic acids. The utility of the method is demonstrated with methanol extracts of white spruce (Picea glauca) phloem, and representative concentrations are reported.

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.

PubMed

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.

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

PubMed Central

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

Changes in the essential oil composition in the needles of Scots pine (Pinus sylvestris L.) under anthropogenic stress.

PubMed

Judzentiene, Asta; Stikliene, Aida; Kupcinskiene, Eugenija

2007-03-21

Unfavorable anthropogenic factors, such as air pollution, lead to biochemical responses in trees. Changes in the amounts of secondary metabolites may be early indicators of invisible injuries. The aim of this study was to evaluate composition of the essential oils in the needles of Scots pine (Pinus sylvestris L.) growing in the areas affected by pollutant emissions of main factories in Lithuania: a nitrogen fertilizer factory (NFF), a cement factory (CF), and an oil refinery (OR). Totally, 14 pine stands were examined along transects from the factories (July 2005). Volatile components of the needles were extracted and analyzed by GC and GC/MS. Over 70 components of the essential oils were identified in current-year and 1-year-old needles. Along the CF transect for current-year needles, the percentage of diterpenes was decreasing with the increasing pH of the pine bark (r = -0.582; p < 0.05) or with the increasing concentration of SO2 (r = -0.573; p < 0.05); for 1-year-old needles, the percentage of diterpenes was decreasing with the increasing pH of the bark (r = -0.534; p < 0.05). Along the OR transect, in both the current-year and 1-year-old needles, the percentage of diterpenes was decreasing with the increasing SO2 (respectively, r = -0.773; p < 0.01; r = -0.486; p < 0.05); an opposite relation was true for sesquiterpenes (respectively, r = -0.751; p < 0.01; r = 0.785; p < 0.01). The view was different along the NFF transect. For current-year needles, the percentage of monoterpenes was decreasing with the increasing NH3 (r = -0.669; p < 0.01); while the percentage of sesquiterpenes or oxysesquiterpenes was increasing with the increasing NH3 (respectively, r = 0.540; p < 0.05 and r = 0.688; p < 0.01). For each transect, cluster analysis of the percentages of components of essential oils in the needles allowed us to distinguish the most contrasting stands according to the concentration of air pollutants. Current-year needles were more effective as indicators of

Microbial Synthesis of the Forskolin Precursor Manoyl Oxide in an Enantiomerically Pure Form.

PubMed

Nielsen, Morten T; Ranberg, Johan Andersen; Christensen, Ulla; Christensen, Hanne Bjerre; Harrison, Scott J; Olsen, Carl Erik; Hamberger, Björn; Møller, Birger Lindberg; Nørholm, Morten H H

2014-12-01

Forskolin is a promising medicinal compound belonging to a plethora of specialized plant metabolites that constitute a rich source of bioactive high-value compounds. A major obstacle for exploitation of plant metabolites is that they often are produced in small amounts and in plants difficult to cultivate. This may result in insufficient and unreliable supply leading to fluctuating and high sales prices. Hence, substantial efforts and resources have been invested in developing sustainable and reliable supply routes based on microbial cell factories. Here, we report microbial synthesis of (13R)-manoyl oxide, a proposed intermediate in the biosynthesis of forskolin and other medically important labdane-type terpenoids. Process optimization enabled synthesis of enantiomerically pure (13R)-manoyl oxide as the sole metabolite, providing a pure compound in just two steps with a yield of 10 mg/liter. The work presented here demonstrates the value of a standardized bioengineering pipeline and the large potential of microbial cell factories as sources for sustainable synthesis of complex biochemicals. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides

NASA Astrophysics Data System (ADS)

Könst, Zef A.; Szklarski, Anne R.; Pellegrino, Simone; Michalak, Sharon E.; Meyer, Mélanie; Zanette, Camila; Cencic, Regina; Nam, Sangkil; Voora, Vamsee K.; Horne, David A.; Pelletier, Jerry; Mobley, David L.; Yusupova, Gulnara; Yusupov, Marat; Vanderwal, Christopher D.

2017-11-01

The lissoclimides are unusual succinimide-containing labdane diterpenoids that were reported to be potent cytotoxins. Our short semisynthesis and analogue-oriented synthesis approaches provide a series of lissoclimide natural products and analogues that expand the structure-activity relationships (SARs) in this family. The semisynthesis approach yielded significant quantities of chlorolissoclimide (CL) to permit an evaluation against the National Cancer Institute's 60-cell line panel and allowed us to obtain an X-ray co-crystal structure of the synthetic secondary metabolite with the eukaryotic 80S ribosome. Although it shares a binding site with other imide-based natural product translation inhibitors, CL engages in a particularly interesting and novel face-on halogen-π interaction between the ligand's alkyl chloride and a guanine residue. Our analogue-oriented synthesis provides many more lissoclimide compounds, which were tested against aggressive human cancer cell lines and for protein synthesis inhibitory activity. Finally, computational modelling was used to explain the SARs of certain key compounds and set the stage for the structure-guided design of better translation inhibitors.

Comparison of total phenolic content, scavenging activity and HPLC-ESI-MS/MS profiles of both young and mature leaves and stems of Andrographis paniculata.

PubMed

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.

Screening and Identification for Immunological Active Components from Andrographis Herba Using Macrophage Biospecific Extraction Coupled with UPLC/Q-TOF-MS.

PubMed

Wang, Yaqi; Jiao, Jiaojiao; Yang, Yuanzhen; Yang, Ming; Zheng, Qin

2018-04-30

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 IC 50 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.

Ecological Roles and Biological Activities of Specialized Metabolites from the Genus Nicotiana.

PubMed

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.

Soft Corals Biodiversity in the Egyptian Red Sea: A Comparative MS and NMR Metabolomics Approach of Wild and Aquarium Grown Species.

PubMed

Farag, Mohamed A; Porzel, Andrea; Al-Hammady, Montasser A; Hegazy, Mohamed-Elamir F; Meyer, Achim; Mohamed, Tarik A; Westphal, Hildegard; Wessjohann, Ludger A

2016-04-01

Marine life has developed unique metabolic and physiologic capabilities and advanced symbiotic relationships to survive in the varied and complex marine ecosystems. Herein, metabolite composition of the soft coral genus Sarcophyton was profiled with respect to its species and different habitats along the coastal Egyptian Red Sea via (1)H NMR and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) large-scale metabolomics analyses. The current study extends the application of comparative secondary metabolite profiling from plants to corals revealing for metabolite compositional differences among its species via a comparative MS and NMR approach. This was applied for the first time to investigate the metabolism of 16 Sarcophyton species in the context of their genetic diversity or growth habitat. Under optimized conditions, we were able to simultaneously identify 120 metabolites including 65 diterpenes, 8 sesquiterpenes, 18 sterols, and 15 oxylipids. Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS) were used to define both similarities and differences among samples. For a compound based classification of coral species, UPLC-MS was found to be more effective than NMR. The main differentiations emanate from cembranoids and oxylipids. The specific metabolites that contribute to discrimination between soft corals of S. ehrenbergi from the three different growing habitats also belonged to cembrane type diterpenes, with aquarium S. ehrenbergi corals being less enriched in cembranoids compared to sea corals. PCA using either NMR or UPLC-MS data sets was found equally effective in predicting the species origin of unknown Sarcophyton. Cyclopropane containing sterols observed in abundance in corals may act as cellular membrane protectant against the action of coral toxins, that is, cembranoids.

Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.

PubMed

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.

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

PubMed

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.

Regeneratory characteristics of complex extract and isolated diterpene alkaloids of Aconitum baikalense.

PubMed

Nesterova, Yu V; Povetieva, T N; Suslov, N I; Zhdanov, V V; Hrichkova, T Yu; Udut, E V; Chaykovskiy, A S; Gaydamovich, N N; Andreeva, T I; Dygai, A M

2012-02-01

The effects of complex extract from Aconitum baikalense on reparative regeneration of a plane dorsal skin wound were studied. Treatment with Aconitum baikalense tincture stimulated reparation and skin regeneration. The effects of the Aconitum baikalense alkaloids on functional activity of fibroblast precursors were studied in vitro by cultural methods. Mesaconitine, hypaconitine, songorine, napelline, and 12-epinapelline N-oxide significantly stimulated the growth of colonies from fibroblast precursors. This indicated direct stimulation of fibroblasts by aconite alkaloids, which could be a mechanism of reparative activity of the complex extract.

Isogermacrene A, a proposed intermediate in sesquiterpene biosynthesis.

PubMed

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.

Antifungal isopimaranes from Hypoestes serpens.

PubMed

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.

Discovery, Biosynthesis and Stress-Related Accumulation of Dolabradiene-Derived Defenses in Maize1[OPEN

PubMed Central

Mafu, Sibongile; Addison, J. Bennett; Wang, Qiang; Hughes, Chambers C.; Betsiashvili, Mariam

2018-01-01

Terpenoids are a major component of maize (Zea mays) chemical defenses that mediate responses to herbivores, pathogens, and other environmental challenges. Here, we describe the biosynthesis and elicited production of a class of maize diterpenoids, named dolabralexins. Dolabralexin biosynthesis involves the sequential activity of two diterpene synthases, ENT-COPALYL DIPHOSPHATE SYNTHASE (ZmAN2) and KAURENE SYNTHASE-LIKE4 (ZmKSL4). Together, ZmAN2 and ZmKSL4 form the diterpene hydrocarbon dolabradiene. In addition, we biochemically characterized a cytochrome P450 monooxygenase, ZmCYP71Z16, which catalyzes the oxygenation of dolabradiene to yield the epoxides 15,16-epoxydolabrene (epoxydolabrene) and 3β-hydroxy-15,16-epoxydolabrene (epoxydolabranol). The absence of dolabradiene and epoxydolabranol in Zman2 mutants under elicited conditions confirmed the in vivo biosynthetic requirement of ZmAN2. Combined mass spectrometry and NMR experiments demonstrated that much of the epoxydolabranol is further converted into 3β,15,16-trihydroxydolabrene (trihydroxydolabrene). Metabolite profiling of field-grown maize root tissues indicated that dolabralexin biosynthesis is widespread across common maize cultivars, with trihydroxydolabrene as the predominant diterpenoid. Oxidative stress induced dolabralexin accumulation and transcript expression of ZmAN2 and ZmKSL4 in root tissues, and metabolite and transcript accumulation were up-regulated in response to elicitation with the fungal pathogens Fusarium verticillioides and Fusarium graminearum. Consistently, epoxydolabranol significantly inhibited the growth of both pathogens in vitro at 10 µg mL−1, while trihydroxydolabrene-mediated inhibition was specific to F. verticillioides. These findings suggest that dolabralexins have defense-related roles in maize stress interactions and expand the known chemical space of diterpenoid defenses as genetic targets for understanding and ultimately improving maize resilience. PMID

The inhibitory effect of Mesembryanthemum edule (L.) bolus essential oil on some pathogenic fungal isolates

PubMed Central

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

Two distinct Epichloë species symbiotic with Achnatherum inebrians, drunken horse grass.

PubMed

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.

The inhibitory effect of Mesembryanthemum edule (L.) bolus essential oil on some pathogenic fungal isolates.

PubMed

Omoruyi, Beauty E; Afolayan, Anthony J; Bradley, Graeme

2014-05-23

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. 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. 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. 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.

Grayanotoxin poisoning: 'mad honey disease' and beyond.

PubMed

Jansen, Suze A; Kleerekooper, Iris; Hofman, Zonne L M; Kappen, Isabelle F P M; Stary-Weinzinger, Anna; van der Heyden, Marcel A G

2012-09-01

Many plants of the Ericaceae family, Rhododendron, Pieris, Agarista and Kalmia, contain diterpene grayanotoxins. Consumption of grayanotoxin containing leaves, flowers or secondary products as honey may result in intoxication specifically characterized by dizziness, hypotension and atrial-ventricular block. Symptoms are caused by an inability to inactivate neural sodium ion channels resulting in continuous increased vagal tone. Grayanotoxin containing products are currently sold online, which may pose an increasing risk. In humans, intoxication is rarely lethal, in contrast to cattle and pet poisoning cases. Scientific evidence for the medicinal properties of grayanotoxin containing preparations, such as honey or herbal preparation in use in folk medicine, is scarce, and such use may even be harmful.

Natural products with hypoglycemic, hypotensive, hypocholesterolemic, antiatherosclerotic and antithrombotic activities.

PubMed

Wang, H X; Ng, T B

1999-01-01

This article reviews compounds of botanical origin which are capable of lowering plasma levels of glucose and cholesterol and blood pressure, as well as compounds inhibiting atherosclerosis and thrombosis. Hypoglycemic natural products comprise flavonoids, xanthones, triterpenoids, alkaloids, glycosides, alkyldisulfides, aminobutyric acid derivatives, guanidine, polysaccharides and peptides. Hypotensive compounds include flavonoids, diterpenes, alkaloids, glycosides, polysaccharides and proteins. Among natural products with hypocholesterolemic activity are beta-carotene, lycopene, cycloartenol, beta-sitosterol, sitostanol, saponin, soybean protein, indoles, dietary fiber, propionate, mevinolin (beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor) and polysaccharides. Heparins, flavonoids, tocotrienols, beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors (statins), garlic compounds and fungal proteases exert antithrombotic action. Statins and garlic compounds also possess antiatherosclerotic activity.

NtPDR3, an iron-deficiency inducible ABC transporter in Nicotiana tabacum.

PubMed

Ducos, Eric; Fraysse, Staffan; Boutry, Marc

2005-12-19

In plants, the ABC transporter PDR (pleiotropic drug resistance) subfamily is composed of approximately 15 genes, few of which have been analyzed. We have identified NtPDR3, a Nicotiana tabacum PDR gene belonging to a cluster for which no functional data was previously available. NtPDR3 was found to be induced in suspension cells treated with methyl jasmonate, salicylic acid, 1-naphthalene acetic acid, or cembrene, a macrocyclic diterpene. In agreement with the identification of a putative iron deficiency element in the NtPDR3 transcription promoter region, we found that iron deficiency in the culture medium induced NtPDR3 expression, thus suggesting a new function of the PDR transporter family.

Two novel creatinine adducts of andrographolide in human urine.

PubMed

Qiu, Feng; Cui, Liang; Chen, Lixia; Sun, Jiawen; Yao, Xinsheng

2012-09-01

Andrographolide is a major labdane diterpenoid of the traditional Chinese and Ayurvedic medicine. Andrographis paniculate (Burm) Nees, is used in clinical situations in China mainly to treat fever, cold, and inflammation. In our previous study, fifteen metabolites of andrographolide were identified in human urine. However, there are still two other unknown metabolites. The aim of this study was to elucidate the structures of these two metabolites. 3. The two metabolites which are probably epimers were identified as creatinine adducts, and their structures were determined to be 14-deoxy-12-(creatinine-5-yl)-andrographolide-19-O-β-D-glucuronide A (Metabolite 1) and 14-deoxy-12-(creatinine-5-yl)-andrographolide-19-O-β-D-glucuronide B (Metabolite 2) by means of spectroscopic evidences. 4. It is for the first time that the formation of creatinine adducts as a novel metabolic pathway is reported. The mechanism was presumed that β-carbon (C-12) of α, β-unsaturated carbonyl was attacked by a 5-anion intermediate of creatinine formed through elimination of a proton, followed by the double bond migration from 12(13) to 13(14) and elimination of the hydroxyl group at C-14.

Andrographis paniculata (Burm. f.) Wall. ex Nees: A Review of Ethnobotany, Phytochemistry, and Pharmacology

PubMed Central

Sule, Abubakar; Rahman, K. M. Hafizur

2014-01-01

As aboriginal sources of medications, medicinal plants are used from the ancient times. Andrographis paniculata is one of the highly used potential medicinal plants in the world. This plant is traditionally used for the treatment of common cold, diarrhoea, fever due to several infective cause, jaundice, as a health tonic for the liver and cardiovascular health, and as an antioxidant. It is also used to improve sexual dysfunctions and serve as a contraceptive. All parts of this plant are used to extract the active phytochemicals, but the compositions of phytoconstituents widely differ from one part to another and with place, season, and time of harvest. Our extensive data mining of the phytoconstituents revealed more than 55 ent-labdane diterpenoids, 30 flavonoids, 8 quinic acids, 4 xanthones, and 5 rare noriridoids. In this review, we selected only those compounds that pharmacology has already reported. Finally we focused on around 46 compounds for further discussion. We also discussed ethnobotany of this plant briefly. Recommendations addressing extraction process, tissue culture, and adventitious rooting techniques and propagation under abiotic stress conditions for improvement of phytoconstituents are discussed concisely in this paper. Further study areas on pharmacology are also proposed where needed. PMID:25950015

Absolute Configurations and NO Inhibitory Activities of Terpenoids from Curcuma longa.

PubMed

Xu, Jing; Ji, Feifei; Kang, Jing; Wang, Hao; Li, Shen; Jin, Da-Qing; Zhang, Qiang; Sun, Hongwei; Guo, Yuanqiang

2015-06-24

Curcuma longa L., belonging to the Zingiberaceae family, is a perennial herb and has been used as a spice and a pigment in the food industry. In the ongoing search for inhibitory reagents of NO production and survey of the chemical composition of natural vegetable foods, the chemical constituents of C. longa used as spice were investigated. This investigation resulted in the isolation of 2 new terpenoids and 14 known analogues. Their structures were established on the basis of the extensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations of 1-4 were elucidated by comparison of the calculated and experimental ECD spectra. Among them, compound 1 is a rare norditerpene with an ent-labdane skeleton, and 2 is a skeletally novel sesquiterpene having an eight-membered ring. All of the compounds were found to possess NO inhibitory activities in murine microglial BV-2 cells. The discovery of two new compounds in this chemical investigation further disclosed the chemical composition of C. longa used a food spice, and the bioassay implied that the natural food spice C. longa, containing terpenoids with NO inhibitory activities, may be potentially promotive to human health.

An Unusual Diterpene-Enhygromic Acid and Deoxyenhygrolides from a Marine Myxobacterium, Enhygromyxa sp.

PubMed

Tomura, Tomohiko; Nagashima, Shiori; Yamazaki, Satoshi; Iizuka, Takashi; Fudou, Ryosuke; Ojika, Makoto

2017-04-06

Three new compounds, enhygromic acid ( 1 ) and deoxyenhygrolides A ( 2 ) and B ( 3 ), were isolated from a marine myxobacterium, Enhygromyxa sp. Compound 1 was found to be an acrylic acid derivative with a rare polycyclic carbon skeleton, decahydroacenaphthylene, by spectroscopic analyses. Compounds 2 and 3 were deoxy analogs of the known γ-alkylidenebutenolides, enhygrolides. Compound 1 exhibited cytotoxicity against B16 melanoma cells and anti-bacterial activity against Bacillus subtilis , and enhanced the NGF-induced neurite outgrowth of PC12 cells.

Copaifera of the Neotropics: A Review of the Phytochemistry and Pharmacology.

PubMed

da Trindade, Rafaela; da Silva, Joyce Kelly; Setzer, William N

2018-05-18

The oleoresin of Copaifera trees has been widely used as a traditional medicine in Neotropical regions for thousands of years and remains a popular treatment for a variety of ailments. The copaiba resins are generally composed of a volatile oil made up largely of sesquiterpene hydrocarbons, such as β-caryophyllene, α-copaene, β-elemene, α-humulene, and germacrene D. In addition, the oleoresin is also made up of several biologically active diterpene acids, including copalic acid, kaurenoic acid, alepterolic acid, and polyalthic acid. This review presents a summary of the ecology and distribution of Copaifera species, the traditional uses, the biological activities, and the phytochemistry of copaiba oleoresins. In addition, several biomolecular targets relevant to the bioactivities have been implicated by molecular docking methods.

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

PubMed

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.

An effective vacuum assisted extraction method for the optimization of labdane diterpenoids from Andrographis paniculata by response surface methodology.

PubMed

Wang, Ya-Qi; Wu, Zhen-Feng; Ke, Gang; Yang, Ming

2014-12-31

An effective vacuum assisted extraction (VAE) technique was proposed for the first time and applied to extract bioactive components from Andrographis paniculata. The process was carefully optimized by response surface methodology (RSM). Under the optimized experimental conditions, the best results were obtained using a boiling temperature of 65 °C, 50% ethanol concentration, 16 min of extraction time, one extraction cycles and a 12:1 liquid-solid ratio. Compared with conventional ultrasonic assisted extraction and heat reflux extraction, the VAE technique gave shorter extraction times and remarkable higher extraction efficiency, which indicated that a certain degree of vacuum gave the solvent a better penetration of the solvent into the pores and between the matrix particles, and enhanced the process of mass transfer. The present results demonstrated that VAE is an efficient, simple and fast method for extracting bioactive components from A. paniculata, which shows great potential for becoming an alternative technique for industrial scale-up applications.

A chemical proteomics approach reveals Hsp27 as a target for proapoptotic clerodane diterpenes.

PubMed

Faiella, Laura; Piaz, Fabrizio Dal; Bisio, Angela; Tosco, Alessandra; De Tommasi, Nunziatina

2012-10-01

Clerodane diterpenoids are a class of naturally occurring molecules widely distributed in the Lamiaceae family. Neo-clerodane diterpenoids from Salvia ssp were recently described as compounds inhibiting the proliferation of human cancer cell lines. To gain new insights into molecular mechanism(s) underlying the antitumor potential of this class of compounds, we used a chemical proteomics approach to analyse the cellular interactome of hardwickiic acid (HAA) selected as a representative molecule. HAA was linked to an opportune 1,1'-carbonyldiimidazole modified by 1,12-dodecanediamine and then immobilized on a matrix support. The modified beads were then used as bait for fishing the potential partners of HAA in a U937 cell lysate. We identified heat shock protein 27 (Hsp27), an ATP-independent antiapoptotic chaperone characterized for its tumorigenic and metastatic properties and now referenced as a major therapeutic target in many types of cancer, as a major HAA partner. Here, we also report the study of HAA-Hsp27 interaction by means of a panel of chemical and biological approaches, including surface plasmon resonance measurements limited proteolysis, and biochemical assays. Our data suggest that HAA could provide a potential tool to develop strategies for the discovery of Hsp27 chemical inhibitors.

Metabolic engineering and biotechnological approaches for production of bioactive diterpene tanshinones in Salvia miltiorrhiza.

PubMed

Kai, Guoyin; Hao, Xiaolong; Cui, Lijie; Ni, Xiaoling; Zekria, David; Wu, Jian-Yong

2014-10-11

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcriptional effect of an Aframomum angustifolium seed extract on human cutaneous cells using low-density DNA chips.

PubMed

Bonnet-Duquennoy, Mathilde; Dumas, Marc; Debacker, Adeline; Lazou, Kristell; Talbourdet, Sylvie; Franchi, Jocelyne; Heusèle, Catherine; André, Patrice; Schnebert, Sylvianne; Bonté, Frédéric; Kurfürst, Robin

2007-06-01

Studying photoexposed and photoprotected skin biopsies from young and aged women, it has been found that a specific zone, composed of the basal layers of the epidermis, the dermal epidermal junction, and the superficial dermis, is major target of aging and reactive oxygen species. We showed that this zone is characterized by significant variations at a transcriptional and/or protein levels. Using low-density DNA chip technology, we evaluated the effect of a natural mixture of Aframomum angustifolium seed extract containing labdane diterpenoids on these aging markers. Expression profiles of normal human fibroblasts (NHF) were studied using a customized cDNA macroarray system containing genes covering dermal structure, inflammatory responses, and oxidative stress defense mechanisms. For normal human keratinocyte (NHK) investigations, we chose OLISA technique, a sensitive and quantitative method developed by BioMérieux specifically designed to investigate cell death, proliferation, epidermal structure, differentiation, and oxidative stress defense response. We observed that this extract strongly modified gene expression profiles of treated NHK, but weakly for NHF. This extract regulated antioxidant defenses, dermal-epidermal junction components, and epidermal renewal-related genes. Using low-density DNA chip technology, we identified new potential actions of A. angustifolium seed extract on skin aging.

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

PubMed

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.

Bioactive Micronutrients in Coffee: Recent Analytical Approaches for Characterization and Quantification

PubMed Central

2014-01-01

Production of coffee beans is an important lifeline for the economy of several countries in Latin America, Africa, and Asia. The brew from this well sought for cash crop is readily consumed due to its good sensory qualities owing to the presence of many micronutrients. Some of these chemical compounds possess biological activities, including antiproliferative, antioxidant, and antimicrobial effects. Four representative groups of these micronutrients, namely, caffeine, chlorogenic acid, diterpenes, and trigonelline, play key roles in these bioactive effects of coffee. In order to guarantee the quality of coffee products and to protect consumer interest and safeguard their well-being, it is extremely important to employ sensitive and accurate analytical methods in the characterization and quantitative determination of these bioactive constituents. This review aims to present recent applications in this regard. PMID:24967266

Plant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications.

PubMed

Singh, Bharat; Sharma, Ram A

2015-04-01

The terpenoids constitute the largest class of natural products and many interesting products are extensively applied in the industrial sector as flavors, fragrances, spices and are also used in perfumery and cosmetics. Many terpenoids have biological activities and also used for medical purposes. In higher plants, the conventional acetate-mevalonic acid pathway operates mainly in the cytosol and mitochondria and synthesizes sterols, sesquiterpenes and ubiquinones mainly. In the plastid, the non-mevalonic acid pathway takes place and synthesizes hemi-, mono-, sesqui-, and diterpenes along with carotenoids and phytol tail of chlorophyll. In this review paper, recent developments in the biosynthesis of terpenoids, indepth description of terpene synthases and their phylogenetic analysis, regulation of terpene biosynthesis as well as updates of terpenes which have entered in the clinical studies are reviewed thoroughly.

Use of an injection port for thermochemolysis-gas chromatography/mass spectrometry: rapid profiling of biomaterials.

PubMed

Shadkami, Farzad; Helleur, Robert

2009-07-31

A simple and direct approach was developed for thermochemolytic analysis of a wide range of biomolecules present in plant materials using an injection port of a gas chromatograph/mass spectrometer (GC/MS) and a novel solids injector consisting of a coiled stainless steel wire placed inside a modified needle syringe. Optimum thermochemolysis (or Thermally Assisted Hydrolysis/Methylation) was achieved by using a suitable methanolic solution of trimethylsulfonium hydroxide (TMSH) or tetramethylammonium hydroxide (TMAH) with an injection port temperature of 350 degrees C. Intact, methylated flavonoids, saccharides, phenolic and fatty acids, lignin dimers and diterpene resin acids were identified. Samples include tea leaves, hemicelluloses, lignin isolates and herbal medicines. Unexpected chromatographic results using TMAH reagent revealed the presence of intact methylated trisaccharides (658 Da) and structurally informative dimer lignin markers.

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

PubMed

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.

The Iberian Peninsula in the Atlantic Community: Problems and Prospects.

DTIC Science & Technology

1983-05-09

Militares - Terceiro Encontro de Estudos Militares, 1979, pp. 23-24. 9. Horacio Rivero, "Spain: Free World Asset", Strategic Review, Spring 1976, p...34, Instituto de Altos Estudos Militares - Terceiro Encontro de Estudos Militares, 1979, pp. 66-68. 16. Thomas Carothers, "Spain, NATO and Democracy", The

Estudo de propriedades estruturais e opticas de multicamadas epitaxiais emissoras de luz baseadas em InGaN/GaN

NASA Astrophysics Data System (ADS)

Pereira, Sergio Manuel de Sousa

Esta tese apresenta os resultados de uma investigacao experimental em filmes epitaxiais emissores de luz baseados em InxGa1-xN. O InxGa1-xN e uma liga semicondutora ternaria do grupo III-N muito utilizada como camada activa numa gama de dispositivos optoelectronicos em desenvolvimento, incluindo diodos emissores de luz (LEDs) e diodos laser (LDs), para operacao na regiao do visivel e ultravioleta do espectro electromagnetico. Neste estudo, caracterizam-se as propriedade opticas e estruturais de camadas simples e pocos quânticos multiplos (Multiple Quantum Wells, MQWs) de InxGa1-xN/GaN, com enfase nas suas propriedades fisicas fundamentais. O objectivo central do trabalho prende-se com a compreensao mais profunda dos processos fisicos que estao por tras das suas propriedades opticas, preenchendo o fosso existente entre aplicacoes tecnologicas e o conhecimento cientifico. Nomeadamente, a tese aborda os problemas da medicao da fraccao de InN (x) em multicamadas ultrafinas sujeitas a tensoes, a influencia da composicao e das tensoes microscopicas nas propriedades opticas e estruturais. A questao relativa a segregacao de fases em multicamadas de InxGa1-xN/GaN e tambem discutida a luz dos resultados obtidos. A metodologia seguida assenta na integracao de resultados obtidos por tecnicas complementares atraves de uma analise sistematica e multidisciplinar. Esta abordagem passa pela combinacao de: 1) Crescimento de amostras por deposicao epitaxial em fase de vapor organometalico (MOVPE) com caracteristicas especificas de forma a tentar isolar parâmetros estruturais, tais como espessura e composicao; 2) Caracterizacao nanoestrutural por microscopia de forca atomica (AFM), microscopica electronica de varrimento (SEM), difraccao de raios-X e retro-dispersao de Rutherford (RBS); 3) Caracterizacao optica a escalas complementares por: espectroscopia de absorcao optica (OA), fotoluminescencia (PL), catodoluminescencia (CL) e microscopia confocal (CM) com analise espectral. Com

Arnica montana L. - a plant of healing: review.

PubMed

Kriplani, Priyanka; Guarve, Kumar; Baghael, Uttam S

2017-08-01

Arnica montana is a widely used therapeutic plant used traditionally to treat various ailments. The objective of this study was to evaluate the botany, phytochemistry and ethnopharmacology along with special emphasis given on pharmacological activity of plant A. montana. The plant extracts have been reported to possess antibacterial, antitumor, antioxidant, anti-inflammatory, antifungal and immunomodulatory activity. A wide range of chemical compounds including sesquiterpene lactones and their short-chain carbonic acid esters, flavonoids, carotenoids, essential oils, diterpenes, arnidiol, pyrrolizidine alkaloids, coumarins, phenolic acids, lignans and oligosaccharides, etc., are found in different parts of the plant. It has been scrutinized that extensive research has been carried out to explore the therapeutic potential of flowers of the plant. Therefore, investigations should be carried out to explore the therapeutic potential of other parts of the plant for better therapeutic utilization. © 2017 Royal Pharmaceutical Society.

Plant-derived isoprenoid sweeteners: recent progress in biosynthetic gene discovery and perspectives on microbial production.

PubMed

Seki, Hikaru; Tamura, Keita; Muranaka, Toshiya

2018-06-01

Increased public awareness of negative health effects associated with excess sugar consumption has triggered increasing interest in plant-derived natural sweeteners. Steviol glycosides are a group of highly sweet diterpene glycosides contained in the leaves of stevia (Stevia rebaudiana). Mogrosides, extracted from monk fruit (Siraitia grosvenorii), are a group of cucurbitane-type triterpenoid glycosides. Glycyrrhizin is an oleanane-type triterpenoid glycoside derived from the underground parts of Glycyrrhiza plants (licorice). This review focuses on the natural isoprenoid sweetening agents steviol glycosides, mogrosides, and glycyrrhizin, and describes recent progress in gene discovery and elucidation of the catalytic functions of their biosynthetic enzymes. Recently, remarkable progress has been made in engineering the production of various plant-specialized metabolites in microbial hosts such as Saccharomyces cerevisiae via the introduction of biosynthetic enzyme genes. Perspectives on the microbial production of plant-derived natural sweeteners are also discussed.

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

PubMed

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.

Volatile components of horsetail (Hippuris vulgaris L.) growing in central Italy.

PubMed

Cianfaglione, Kevin; Papa, Fabrizio; Maggi, Filippo

2017-10-01

Hippuris vulgaris, also known as horsetail or marestail, is a freshwater macrophyte occurring in lakes, rivers, ponds and marshes. According to 'The IUCN Red List of Threatened Species', H. vulgaris is at a high risk of extinction in Italy in the medium-term future. In the present study, we analysed for the first time the volatile composition of H. vulgaris growing in central Italy. For the purpose, the essential oil was obtained by hydrodistillation and analysed by GC-MS. The chemical composition was dominated by aliphatic compounds such as fatty acids (26.0%), ketones (18.7%) and alkanes (11.4%), whereas terpenoids were poorer and mostly represented by diterpenes (7.4%). n-Hexadecanoic acid (25.5%), hexahydrofarnesyl acetone (17.5%) and trans-phytol (7.4%) were the major volatile constituents. These compounds are here proposed as chemotaxonomic markers of the species.

Constituents of the root of Anemone tomentosa.

PubMed

Hu, Hao-Bin; Zheng, Xu-Dong; Jian, Yu-Feng; Liu, Jian-Xin; Zhu, Ji-Hua

2011-07-01

A new diterpene glycoside, tomentoside I (1), along with eleven known compounds, including the four coumarins, 4,5-dimethoxyl-7-methylcoumarin (2), 4,7-dimethoxyl-5-methylcoumarin (3), isofraxidin (4) and fraxidin (5) as well as the seven triterpenoids, oleanolic acid (6), oleanolic acid 3-O-α-L-arabinopyranoside (7), oleanolic acid 3-O-β-D-galactopyranosyl-(1→3)-β-D-glucopyranoside (8), hederagenin 3-O-α-L-arabinopyranoside (9), betulinic acid (10), 18-hydroxyursolic acid (11) and 2α,3β,23-trihydroxyurs-12-en-28-oic acid (12) were isolated from the ethanolic extract of the root of Anemone tomentosa and their chemical structures were elucidated by spectroscopic methods. The antimicrobial activities of compounds 1-12 were measured using the agar disc-diffusion method. Also, their antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) were evaluated.

Spasmolytic activity of trachylobanes ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid isolated from Xylopia langsdorfiana A. St-Hil. & Tul. (Annonaceae).

PubMed

Santos, Rosimeire F; Martins, Italo R R; Monteiro, Fabio de S; Travassos, Rafael de A; Janebro, Daniele I; Tavares, Josean F; Silva, Marcelo S; da Silva, Bagnólia A

2012-01-01

We aimed to investigate the possible spasmolytic activity of ent-7α-acetoxytrachyloban-18-oic acid (1) and ent-7α-hydroxytrachyloban-18-oic acid (2) on smooth muscle models. In male rat aorta and rat uterus, both diterpenes were unable to trigger spasmolytic action. However, 2 relaxed guinea-pig trachea: Compounds 1 and 2 antagonised, significantly and concentration-dependently, carbachol- and histamine-induced phasic contractions in guinea-pig ileum. Moreover, they induced a significant and concentration-dependent relaxation in pre-contracted (KCl, carbachol or histamine) guinea-pig ileum, with 2 being 15 times more potent than 1 in histamine-contracted ileum. These dissimilar results may be due to chemical differences between them. Thus, we demonstrated that 1 and 2 seem to be promising spasmolytic agents, although further studies are required to elucidate the spasmolytic action mechanism.

Stimulant Paste Preparation and Bark Streak Tapping Technique for Pine Oleoresin Extraction.

PubMed

Füller, Thanise Nogueira; de Lima, Júlio César; de Costa, Fernanda; Rodrigues-Corrêa, Kelly C S; Fett-Neto, Arthur G

2016-01-01

Tapping technique comprises the extraction of pine oleoresin, a non-wood forest product consisting of a complex mixture of mono, sesqui, and diterpenes biosynthesized and exuded as a defense response to wounding. Oleoresin is used to produce gum rosin, turpentine, and their multiple derivatives. Oleoresin yield and quality are objects of interest in pine tree biotechnology, both in terms of environmental and genetic control. Monitoring these parameters in individual trees grown in the field provides a means to examine the control of terpene production in resin canals, as well as the identification of genetic-based differences in resinosis. A typical method of tapping involves the removal of bark and application of a chemical stimulant on the wounded area. Here we describe the methods for preparing the resin-stimulant paste with different adjuvants, as well as the bark streaking process in adult pine trees.

Chemical composition profiling and antifungal activity of the essential oil and plant extracts of Mesembryanthemum edule (L.) bolus leaves.

PubMed

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

Coffee Consumption Increases the Antioxidant Capacity of Plasma and Has No Effect on the Lipid Profile or Vascular Function in Healthy Adults in a Randomized Controlled Trial.

PubMed

Agudelo-Ochoa, Gloria M; Pulgarín-Zapata, Isabel C; Velásquez-Rodriguez, Claudia M; Duque-Ramírez, Mauricio; Naranjo-Cano, Mauricio; Quintero-Ortiz, Mónica M; Lara-Guzmán, Oscar J; Muñoz-Durango, Katalina

2016-03-01

Coffee, a source of antioxidants, has controversial effects on cardiovascular health. We evaluated the bioavailability of chlorogenic acids (CGAs) in 2 coffees and the effects of their consumption on the plasma antioxidant capacity (AC), the serum lipid profile, and the vascular function in healthy adults. Thirty-eight men and 37 women with a mean ± SD age of 38.5 ± 9 y and body mass index of 24.1 ± 2.6 kg/m(2) were randomly assigned to 3 groups: a control group that did not consume coffee or a placebo and 2 groups that consumed 400 mL coffee/d for 8 wk containing a medium (MCCGA; 420 mg) or high (HCCGA; 780 mg) CGA content. Both were low in diterpenes (0.83 mg/d) and caffeine (193 mg/d). Plasma caffeic and ferulic acid concentrations were measured by GC, and the plasma AC was evaluated with use of the ferric-reducing antioxidant power method. The serum lipid profile, nitric oxide (NO) plasma metabolites, vascular endothelial function (flow-mediated dilation; FMD), and blood pressure (BP) were evaluated. After coffee consumption (1 h and 8 wk), caffeic and ferulic acid concentrations increased in the coffee-drinking groups, although the values of the 2 groups were significantly different (P < 0.001); caffeic and ferulic acid concentrations were undetectable in the control group. At 1 h after consumption, the plasma AC in the control group was significantly lower than the baseline value (-2%) and significantly increased in the MCCGA (6%) and HCCGA (5%) groups (P < 0.05). After 8 wk, no significant differences in the lipid, FMD, BP, or NO plasma metabolite values were observed between the groups. Both coffees, which contained CGAs and were low in diterpenes and caffeine, provided bioavailable CGAs and had a positive acute effect on the plasma AC in healthy adults and no effect on blood lipids or vascular function. The group that did not drink coffee showed no improvement in serum lipid profile, FMD, BP, or NO plasma metabolites. This trial was registered at

Matrix effect and optimization of LC-MSn determination of trachylobane-360 in mice blood.

PubMed

Pita, João Carlos Lima Rodrigues; Gomes, Isis Fernandes; Dos Santos, Socrates Golzio; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Diniz, Margareth de Fátima Formiga Melo; Sobral, Marianna Vieira

2014-11-01

Xylopia langsdorffiana A. St.-Hil. & Tul. (Annonaceae) is popularly known as "pimenteira-da-terra". Various constituents have been isolated from this species, including diterpenes, such as 8(17), 12E, 14-labdatrien-18-oic acid, ent-atisan-7α, 16α-diol (xylodiol), ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318) and ent-7α-acetoxytrachyloban-18-oic acid, a crystalline solid with a molecular weight of 360 and molecular formula of C22H32O4 (trachylobane-360). When administered intraperitoneally to mice, trachylobane-360 (T-360) significantly inhibits growth of the solid tumor sarcoma 180 transplanted in mice, without causing alterations in biochemical, hematological and histopathological parameters that are frequently associated with the clinical use of antineoplastic. Furthermore, this diterpene blocks voltage-dependent calcium channels (Cav), showing spasmolytic activity. The present study shows that variables such as extraction solvent (methanol, acetonitrile and chloroform), centrifugation force (1000, 7000 and 14,000×g), and centrifugation time (5, 15 and 25min), are important in the liquid-liquid extraction of T-360 from male Swiss mice blood in HPLC-MSn studies. The study confirms matrix influence on recovery and detection of T-360. The recovery for T-360 was 37.02% using chloroform as better extractor solvent, while centrifuged at 14,000×g for 15min demonstrated the importance of the parameters chosen for the extraction/recovery process of analyte. The effect of mice blood matrix for T-360 was -51.23%. This method was optimized by repeating the extraction procedure and acidification of samples. These conditions were essential in increasing recovery (49.47%) by decreasing the matrix effect (-37.60%). The efficiency of the process, after optimization with two extractions and acidification, increased by 14.19% when compared to the initial method, from 18.05% to 32.24%. According to Marchi et al. (2010), the matrix effect does not necessarily need to

Improved Properties and Microbiological Safety of Novel Cottage Cheese Containing Spices

PubMed Central

Knežević, Zvonimira Medverec; Frece, Jadranka; Markov, Ksenija; Kazazić, Snježana; Mrvčić, Jasna

2015-01-01

Summary The study focuses on developing novel cottage 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. PMID:27904380

Combined analysis by GC (RI), GC-MS and 13C NMR of the supercritical fluid extract of Abies alba twigs.

PubMed

Duquesnoy, Emilie; Marongiu, Bruno; Castola, Vincent; Piras, Alessandra; Porcedda, Silvia; Casanova, Joseph

2010-12-01

Two samples (leaves and twigs) of Abies alba Miller from Corsica were extracted using supercritical CO2 and their chemical compositions were compared with those of the essential oils obtained from the same batch of plant material. In total 45 components were identified using combined analysis by GC (RI), GC-MS and 13C NMR. It was observed that the contents of monoterpenes (mainly represented by limonene, alpha-pinene and camphene) were significantly lower in the supercritical fluid extract (SFE) than in the essential oil (EO). Conversely, the proportions of sesquiterpenes were much higher in CO2 extracts than in essential oils (around 30% vs 4%). Cis-abienol, a diterpene alcohol, was identified only in SFE, and the proportions of this constituent (7.5% and 17.3%) were determined using quantitative 13C NMR since it was under estimated using the standard conditions of GC.

Analgesic, anti-inflammatory, antipyretic and haematological effects of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives.

PubMed

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.

Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions

NASA Astrophysics Data System (ADS)

Newton, Christopher G.; Drew, Samuel L.; Lawrence, Andrew L.; Willis, Anthony C.; Paddon-Row, Michael N.; Sherburn, Michael S.

2015-01-01

The pseudopterosins are a family of diterpene marine natural products, which, by virtue of their interesting anti-inflammatory and analgesic properties, have attracted the attentions of many synthetic chemists. The most efficient syntheses reported to date are 14 and 20 steps in the longest linear sequence for chiral pool and enantioselective approaches, respectively, and all start with precursors that are easily mapped onto the natural product structure. Here, we describe an unconventional approach in which a chiral cross-conjugated hydrocarbon is used as the starting material for a series of three cycloadditions. Our approach has led to a significant reduction in the step count required to access these interesting natural products (10 steps chiral pool and 11 steps enantioselective). Furthermore it demonstrates that cross-conjugated hydrocarbons, erroneously considered by many to be too unstable and difficult to handle, are viable precursors for natural product synthesis.

Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as an L-type calcium channel blocker

PubMed Central

El Bardai, Sanae; Wibo, Maurice; Hamaide, Marie-Christine; Lyoussi, Badiaa; Quetin-Leclercq, Joëlle; Morel, Nicole

2003-01-01

The objective of the present study was to investigate the mechanism of the relaxant activity of marrubenol, a diterpenoid extracted from Marrubium vulgare. In rat aorta, marrubenol was a more potent inhibitor of the contraction evoked by 100 mM KCl (IC50: 11.8±0.3 μM, maximum relaxation: 93±0.6%) than of the contraction evoked by noradrenaline (maximum relaxation: 30±1.5%). In fura-2-loaded aorta, marrubenol simultaneously inhibited the Ca2+ signal and the contraction evoked by 100 mM KCl, and decreased the quenching rate of fura-2 fluorescence by Mn2+. Patch-clamp data obtained in aortic smooth muscle cells (A7r5) indicated that marrubenol inhibited Ba2+ inward current in a voltage-dependent manner (KD: 8±2 and 40±6 μM at holding potentials of −50 and −100 mV, respectively). These results showed that marrubenol inhibits smooth muscle contraction by blocking L-type calcium channels. PMID:14597602

Incorporating rosemary diterpenes in lamb diet to improve microbial quality of meat packed in different environments.

PubMed

Ortuño, Jordi; Serrano, Rafael; Bañón, Sancho

2017-09-01

The dietary use of phytochemicals may contribute to improving lamb meat preservation under different packing atmospheres. The objective was to test the preservative potential of a dietary rosemary extract (RE) containing carnosic acid and carnosol (at 1:1 w:w) in chilled lamb patties packed in air, vacuum and 70/30 O 2 /CO 2 modified atmosphere. Three experimental diets, (C) control, (RE) C plus 600 mg RE/kg feed and (E) C plus 600 mg vitamin E/kg, were given to fattening lambs. Unlike the C- and E-diets, the RE-diet had a double antimicrobial and antioxidant effect on the lamb patties packed in all the environments studied. The RE-diet inhibited total viable and lactic acid bacteria and Enterobacteriaceae, but not Brochothrix thermosphacta and Pseudomonas spp. and also improved oxidative stability (measured as CIE Lab color and thiobarbituric reagent substances), appearance and odor. The E-diet had a better antioxidant effect than the RE-diet but had no antimicrobial effects. Escherichia coli and Salmonella spp. were not detected. The dietary use of RE was most suitable for preserving vacuum-packed meat, which is more exposed to spoilage by anaerobic bacteria, while the use of dietary vitamin E allowed better control of oxidation in the meat packed in a bacteriostatic and oxidizing environment. © 2017 Japanese Society of Animal Science.

Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro.

PubMed

Zheng, Chun-Xia; Chen, Zhao-Hong; Zeng, Cai-Hong; Qin, Wei-Song; Li, Lei-Shi; Liu, Zhi-Hong

2008-09-01

Extracts of Tripterygium wilfordii Hook F have been used to treat glomerulonephritis for more than 30 years in China with dramatic antiproteinuric effects. Triptolide, a diterpene triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.

Screening of acetylcholinesterase inhibitors in marine organisms from the Caribbean Sea.

PubMed

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.

Chemical Composition of the Essential Oils from Different Morphological Parts of Pinus cembra L.

PubMed

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.

Composition and chemical variability of Corsican Pinus halepensis cone oil.

PubMed

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).

Authentication of the botanical origin of Western herbal products using Cimicifuga and Vitex products as examples.

PubMed

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.

Rosmarinus Officinalis Leaves as a Natural Source of Bioactive Compounds

PubMed Central

Borrás-Linares, Isabel; Stojanović, Zorica; Quirantes-Piné, Rosa; Arráez-Román, David; Švarc-Gajić, Jaroslava; Fernández-Gutiérrez, Alberto; Segura-Carretero, Antonio

2014-01-01

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). PMID:25391044

Pressurized hot water extraction (PHWE) for the green recovery of bioactive compounds and steviol glycosides from Stevia rebaudiana Bertoni leaves.

PubMed

Bursać Kovačević, Danijela; Barba, Francisco J; Granato, Daniel; Galanakis, Charis M; Herceg, Zoran; Dragović-Uzelac, Verica; Putnik, Predrag

2018-07-15

Stevia rebaudiana Bertoni leaves are a natural source of diterpenic glycosides, and various bioactive compounds. The objectives were to characterize antioxidants and steviol glycosides in the extracts obtained from Stevia after "green" pressurized hot water extraction (PHWE). PHWE extracts were obtained at different temperatures (100, 130, 160 °C); static extraction times (5 and 10 min), and cycle numbers (1, 2, 3) using a constant pressure of 10.34 MPa. Temperature was the most important parameter for extraction, where the highest recoveries of all bioactive compounds (except for carotenoids) were at 160 °C. Extracts obtained at longer static times had more steviol glycosides, condensed tannins, and chlorophyll A. Higher amounts of total phenols, condensed tannins, and steviol glycosides were obtained under higher cycle numbers. This study indicated that PHWE is useful for recovering polar and nonpolar antioxidants and steviol glycosides. PHWE may be a suitable technique for scale-up to industrial applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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.

[Salvia officinalis l. I. Botanic characteristics, composition, use and cultivation].

PubMed

Daniela, T

1993-06-01

Salvia officinalis L. is an essential oil containing plant, which does not wildly grow in the territories of the Czech and Slovak Republics but it can be successfully cultivated. It is a perennial half-shrub, from which non-flowering herbaceous sprouts or leaves are collected for pharmaceutical purposes. After drying at a temperature not exceeding 35 degrees C they are the plant drugs Herba salviae or Folium salviae. In PhBs, Herba salviae is official. The drug contains mainly ethereal oil (1-2%), diterpenes, triterpenes and tannin. The pharmacopoeial criterion of quality is the content of essential oil, which is produced in an increased amount in the plant in warm summer months. Herba salviae and the extracts prepared from it are used as an antiseptic agent, an antiphlogistic agent, in the inflammations of the oral cavity and gingivitis and also as a stomachic and an antihydrotic agent. Its utilization in cosmetics and food industry is also of importance.

The nature and fate of natural resins in the geosphere. XII. Investigation of C-ring aromatic diterpenoids in Raritan amber by pyrolysis-GC-matrix isolation FTIR-MS

PubMed Central

Anderson, Ken B

2006-01-01

Upper Cretaceous amber from the Raritan Formation (Sayerville, New Jersey) has been investigated by Pyrolysis-GC-MS and Pyrolysis-GC-matrix isolation FTIR-MS. Results establish the existence of two distinct forms of amber in this deposit. Both forms are Class Ib ambers, but they are unambiguously differentiated on the basis of their (intact) diterpenoid composition. The presence of callitrisate in both forms, and cupraene in samples designated form 1, strongly suggest that both derive from related-but-distinct species within the Cupressaceae. In addition to callitrisate, dehydroabietate and analogous 17-nor-, 16,17-dinor- and 15,16,17-trinor- analogues of these compounds are also observed. The distributions of these products in multiple samples suggest that they are the result of biological emplacement, rather than diagenetic modification of the parent compounds. This indicates that the distributions of diterpenes observed in these samples are representative of the original bioterpenoids and, hence, are useful for chemotaxonomic analyses. PMID:16759406

Chemotypes and Biomarkers of Seven Species of New Caledonian Liverworts from the Bazzanioideae Subfamily.

PubMed

Métoyer, Benjamin; Lebouvier, Nicolas; Hnawia, Edouard; Herbette, Gaëtan; Thouvenot, Louis; Asakawa, Yoshinori; Nour, Mohammed; Raharivelomanana, Phila

2018-06-05

Volatile components of seven species of the Bazzanioideae sub-family (Lepidoziaceae) native to New Caledonia, including three endemic species ( Bazzania marginata , Acromastigum caledonicum and A. tenax ), were analyzed by GC-FID-MS in order to index these plants to known or new chemotypes. Detected volatile constituents in studied species were constituted mainly by sesquiterpene, as well as diterpene compounds. All so-established compositions cannot successfully index some of them to known chemotypes but afforded the discovery of new chemotypes such as cuparane/fusicoccane. The major component of B. francana was isolated and characterized as a new zierane-type sesquiterpene called ziera-12(13),10(14)-dien-5-ol ( 23 ). In addition, qualitative intraspecies variations of chemical composition were very important particularly for B. francana which possessed three clearly defined different compositions. We report here also the first phytochemical investigation of Acromastigum species. Moreover, crude diethyl ether extract of B. vitatta afforded a new bis(bibenzyl) called vittatin ( 51 ), for which a putative biosynthesis was suggested.

Long-term exposure to enhanced UV-B radiation has no significant effects on growth or secondary compounds of outdoor-grown Scots pine and Norway spruce seedlings.

PubMed

Turtola, Satu; Sallas, Leena; Holopainen, Jarmo K; Julkunen-Tiitto, Riitta; Kainulainen, Pirjo

2006-11-01

The effects of long-term enhanced UV-B radiation on growth and secondary compounds of two conifer species were studied in an outdoor experiment. Scots pine (Pinus sylvestris) seedlings were exposed for two growing seasons and Norway spruce (Picea abies) seedlings for three growing seasons to supplemental UV-B radiation, corresponding to a 30% increase in ambient UV-B radiation. The experiment also included appropriate controls for ambient and increased UV-A radiation. Enhanced UV-B did not affect the growth of the conifer seedlings. In addition, neither the concentrations of terpenes and phenolics in the needles nor the concentrations of terpenes in the wood were affected. However, in the UV-A control treatment the concentrations of diterpenes in the wood of Scots pine decreased significantly compared to the ambient control. Apparently, a small increase in UV-B radiation has no significant effects on the secondary compounds and growth of Scots pine and Norway spruce seedlings.

Noncariogenic intense natural sweeteners.

PubMed

Kinghorn, A D; Kaneda, N; Baek, N I; Kennelly, E J; Soejarto, D D

1998-09-01

There is a definite relationship between the dietary consumption of sucrose and the incidence of dental caries. Noncaloric sucrose substitutes for use in the sweetening of foods, beverages, and medicines may be either synthetic compounds or natural products. In the United States, four potently sweet artificial sweeteners are approved, namely, saccharin, aspartame, acesulfame potassium, and sucralose. Highly sweet plant constituents are used in Japan and some other countries, including the diterpene glycoside stevioside and the protein thaumatin. Recent progress in a research project oriented towards the discovery and evaluation of novel potentially noncariogenic sweeteners from plants has focused on substances in the sesquiterpenoid, diterpenoid, triterpenoid, steroidal saponin, and proanthocyanidin structural classes. The feasibility of using Mongolian gerbil electrophysiological and behavioral assays to monitor the sweetness of plant extracts, chromatographic fractions, and pure isolates has been investigated. An in vivo cariogenicity study on the commercially available natural sweeteners stevioside and rebaudioside A has been carried out.

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

NASA Astrophysics Data System (ADS)

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.

Chemical composition of the essential oil of Stachys menthifolia Vis.

PubMed

Ćavar, Sanja; Maksimović, Milka; Vidic, Danijela; Šolić, Marija Edita

2010-02-01

Stachys menthifolia Vis. (Lamiaceae) is an endemic species from the Balkan Peninsula spread throughout Albania, Greece, Montenegro, and Croatia. This article presents the first investigation of the essential oil composition of this species from Croatia. Aerial parts of the plant were collected from three different natural habitats in the region of Biokovo Mountain. The studied populations showed similarity in qualitative, but not in quantitative, composition of their essential oils. Hydrodistilled volatile oil obtained from the plant material of S. menthifolia was subjected to gas chromatographic analysis coupled to mass spectrometry. More than 100 compounds were identified in the three samples, representing 86.8-90.8% of the total oil. The terpene profile of S. menthifolia is characterized by a high content of oxygenated sesquiterpenes (48.4-58.9%) and diterpene hydrocarbons (3.5-25.2%), with 8-alpha-acetoxyelemol (6.9-21.3%), abietatriene (3.5-21.1%), and 4'-methoxyacetophenone (4.5-17.0%) as the main constituents.

A review on phytochemistry and medicinal properties of the genus Achillea

PubMed Central

Saeidnia, S.; Gohari, AR.; Mokhber-Dezfuli, N.; Kiuchi, F.

2011-01-01

Achillea L. (Compositae or Asteraceae) is a widely distributed medicinal plant throughout the world and has been used since ancient time. Popular indications of the several species of this genus include treatment of wounds, bleedings, headache, inflammation, pains, spasmodic diseases, flatulence and dyspepsia. Phytochemical investigations of Achillea species have revealed that many components from this genus are highly bioactive. There are many reports on the mentioned folk and traditional effects. Although, the medicinal properties of Achillea plants are recognized worldwide, there are only one review article mainly about the structures of the phytochemical constituents of Achillea. The present paper reviews the medicinal properties of various species of Achillea, which have been examined on the basis of the scientific in vitro, in vivo or clinical evaluations. Various effects of these plants may be due to the presence of a broad range of secondary active metabolites such as flavonoids, phenolic acids, coumarins, terpenoids (monoterpenes, sesquiterpenes, diterpenes, triterpenes) and sterols which have been frequently reported from Achillea species. PMID:22615655

Synthesis of rebaudioside-A by enzymatic transglycosylation of stevioside present in the leaves of Stevia rebaudiana Bertoni.

PubMed

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.

Brown Algae Padina sanctae-crucis Børgesen: A Potential Nutraceutical

PubMed Central

Nogueira, Raquel B. S. S.; Tomaz, Anna Cláudia A.; Pessoa, Déborah R.; Xavier, Aline L.; Pita, João Carlos L. R.; Sobral, Marianna V.; Pontes, Marcela L. C.; Pessôa, Hilzeth L. F.; Diniz, Margareth F. F. M.; Miranda, George Emmanuel C.; Vieira, Maria Aparecida R.; Marques, Marcia O. M.; Souza, Maria de Fátima V.; Cunha, Emídio V. L.

2017-01-01

Padina sanctae-crucis Børgesen is distributed worldwide in tropical and subtropical seas; belongs to the Dictyotaceae family, and has proven to be an exceptional source of biologically active compounds. Four compounds were isolated and identified, namely: dolastane diterpene new for the genus Padina; phaeophytin and hidroxy-phaeophytin new for the family Dictyotaceae, and; mannitol first described in this species. Saturated fatty acids as compared to the percentages of unsaturated fatty acids were shown to be present in greater abundance. Palmitic and linolenic acid were the main saturated and unsaturated acids, respectively. Cytotoxic and antioxidant activities were evaluated using human erythrocytes. In vivo evaluations of acute toxicity and genotoxicity were performed in mice. Methanolic extract of P. sanctae-crucis presented antioxidant activity and did not induce cytotoxicity, genotoxicity or acute toxicity. Since Padina sanctae-crucis is already used as food, has essential fatty acids for the nutrition of mammals, does not present toxicity and has antioxidant activity, it can be considered as a potential nutraceutical. PMID:28954390

[Coffee as hepatoprotective factor].

PubMed

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.

Behavioral bioassays of termite trail pheromones : Recruitment and orientation effects of cembrene-A inNasutitermes costalis (Isoptera: Termitidae) and discussion of factors affecting termite response in experimental contexts.

PubMed

Hall, P; Traniello, J F

1985-11-01

The monocyclic 14-membered ring diterpene, cembrene-A, previously identified as a nasutitermitine trail pheromone, was tested for its effectiveness as a trail pheromone inNasutitermes costalis. Artificial trails prepared from serial dilutions of racemic cembrene-A over a concentration range of 10(-1)-10(-6) mg/ml were ineffective in recruiting termites. Serial dilutions of racemic cembrene-A ranging in concentration from 10(-1) to 10(-5) mg/ml produced an orientation effect. Chiral cembrene-A produced recruitment in soldiers at 10(-1) and 10(-3) mg/ml and was less ineffective in recruiting workers. Soldiers always showed a lower and more variable recruitment response to chiral cembrene-A than to sternal gland extracts. The behavioral response to both chiral and racemic cembrene-A was different in quantity and quality from that observed for sternal gland extract. Based on the results of these behavioral tests, cembrene-A appears to be a generalized nasute orientation pheromone which may show recruitment properties at unnaturally high concentrations.

Production of geranylgeraniol on overexpression of a prenyl diphosphate synthase fusion gene in Saccharomyces cerevisiae.

PubMed

Ohto, Chikara; Muramatsu, Masayoshi; Obata, Shusei; Sakuradani, Eiji; Shimizu, Sakayu

2010-07-01

An acyclic diterpene alcohol, (E,E,E)-geranylgeraniol (GGOH), is one of the important compounds used as perfume and pharmacological agents. A deficiency of squalene (SQ) synthase activity allows yeasts to accumulate an acyclic sesquiterpene alcohol, (E,E)-farnesol, in their cells. Since sterols are essential for the growth of yeasts, a deficiency of SQ synthase activity makes the addition of supplemental sterols to the culture media necessary. To develop a GGOH production method not requiring any supplemental sterols, we overexpressed HMG1 encoding hydroxymethylglutaryl-CoA reductase and the genes of two prenyl diphosphate synthases, ERG20 and BTS1, in Saccharomyces cerevisiae. A prototrophic diploid coexpressing HMG1 and the ERG20-BTS1 fusion accumulated GGOH with neither disruption of the SQ synthase gene nor the addition of any supplemental sterols. The GGOH content on the diploid cultivation in a 5-l jar fermenter reached 138.8 mg/l under optimal conditions.

Antibacterial and Hypoglycemic Diterpenoids from Salvia chamaedryoides.

PubMed

Bisio, Angela; De Mieri, Maria; Milella, Luigi; Schito, Anna M; Parricchi, Anita; Russo, Daniela; Alfei, Silvana; Lapillo, Margherita; Tuccinardi, Tiziano; Hamburger, Matthias; De Tommasi, Nunziatina

2017-02-24

A surface extract of the aerial parts of Salvia chamaedryoides afforded 13 diterpenes (1-13), with seven compounds (1, 3, 4, 7-9, 12) described for the first time. The structures of the new compounds were established using 1D and 2D NMR spectroscopic methods, HRESIMS, and ECD data. The potential hypoglycemic effects of the crude extract, fractions, and pure compounds from S. chamaedryoides were investigated by inhibition of α-glucosidase and α-amylase enzymes. The extract and its fractions showed a moderate dose-dependent inhibition; the pure compounds exhibited differential inhibitory activity against these two enzymes. Molecular modeling studies were also performed to suggest the interaction mode of compound 3 in the α-glucosidase enzyme active site. The antimicrobial activity of the purified compounds was investigated against 26 clinical pathogens. No activity was detected for the Gram-negative species tested nor on Candida albicans and C. glabrata, while variable susceptibilities were observed using Gram-positive staphylococcal and enterococcal species.

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

NASA Astrophysics Data System (ADS)

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.

Evolution of Volatile Emission in Rhus coriaria Organs During Different Stages of Growth and Evaluation of the Essential Oil Composition.

PubMed

Reidel, Rose Vanessa Bandeira; Cioni, Pier Luigi; Majo, Luigi; Pistelli, Luisa

2017-11-01

Rhus coriaria, also known as Sumac, has been traditionally used in many countries as spice, condiment, dying agent, and medicinal herb. The chemical composition of essential oils (EOs) and the volatile emissions from different organs of this species collected in Sicily (Italy) were analyzed by gas chromatography-flame ionization detection and gas chromatography/mass spectrometry. Monoterpene and sesquiterpene hydrocarbons were the most abundant class in the volatile emissions with β-caryophyllene and α-pinene were the main constituents in the majority of the examined samples. The EO composition was characterized by high amount of monoterpene and sesquiterpene hydrocarbons together with diterpenes. The main compounds in the EO obtained from the leaves and both stages of fruit maturation were cembrene and β-caryophyllene, while α-pinene and tridecanoic acid were the key compounds in the flower EO. All the data were submitted to multivariate statistical analysis showing many differences among the different plant parts and their ontogenetic stages. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Structure Elucidation, Antimicrobial and Cytotoxic Activities of a Halimane Isolated from Vellozia kolbekii Alves (Velloziaceae).

PubMed

Silva, Carmelita G; Santos Júnior, Helvécio M; Barbosa, Jussara P; Costa, Gisela L; Rodrigues, Felipe A R; Oliveira, Denilson F; Costa-Lotufo, Letícia V; Alves, Ruy J V; Eleutherio, Elis C A; Rezende, Claudia M

2015-12-01

A new halimane diterpene was isolated from Vellozia kolbekii Alves (Velloziaceae) and identified as (5R,8R,9S,13R)-halim-1,10-ene-15,16-diol (1). It showed cytotoxicity against three human cancer cell lines, SF-295 (glioblastoma), MDA-MB-435 (melanoma), and HCT-8 (colon adenocarcinoma). In the mechanism of cytotoxic action, halimane 1 interferes in two major phases of the cell cycle: in S phase, in which DNA synthesis occurs and where it is very sensitive to damage, and G2M phase which is the phase of preparation for mitosis and mitosis itself, showing apoptosis-inducing properties. Antimicrobial activity towards Gram-positive and Gram-negative bacteria was studied and, against Bacillus cereus, B. subtilis, Escherichia coli, and Pseudomonas aeruginosa, a MIC value of 0.025 μM was observed for halimane 1, which is more active than the positive control chloramphenicol. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

A comparison of the metabolism of the abortifacient compounds from Ponderosa pine needles in conditioned versus naive cattle.

PubMed

Welch, K D; Gardner, D R; Pfister, J A; Panter, K E; Zieglar, J; Hall, J O

2012-12-01

Isocupressic acid (ICA) is the abortifacient compound in ponderosa pine (Pinus ponderosa L.) needles, which can cause late-term abortions in cattle (Bos taurus). However, cattle rapidly metabolize ICA to agathic acid (AGA) and subsequent metabolites. When pine needles are dosed orally to cattle, no ICA is detected in their serum, whereas AGA is readily detected. Recent research has demonstrated that AGA is also an abortifacient compound in cattle. The observation has been made that when cattle are dosed with labdane acids for an extended time, the concentration of AGA in serum increases for 1 to 2 d but then decreases to baseline after 5 to 6 d even though they are still being dosed twice daily. Therefore, in this study we investigated whether cattle conditioned to pine needles metabolize ICA, and its metabolites, faster than naïve cattle. Agathic acid was readily detected in the serum of naïve cattle fed ponderosa pine needles, whereas very little AGA was detected in the serum of cattle conditioned to pine needles. We also compared the metabolism of ICA in vitro using rumen cultures from pine-needle-conditioned and naïve cattle. In the rumen cultures from conditioned cattle, AGA concentrations were dramatically less than rumen cultures from naïve cattle. Thus, an adaptation occurs to cattle conditioned to pine needles such that the metabolism AGA by the rumen microflora is altered.

Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors.

PubMed

de Araújo, Éverton José Ferreira; de Almeida, Antônia Amanda Cardoso; Silva, Oskar Almeida; da Costa, Iwyson Henrique Fernandes; Rezende-Júnior, Luis Mário; Lima, Francisco das Chagas Alves; Cavalheiro, Alberto José; Pessoa, Cláudia; de Moraes, Manoel Odorico; Ferreira, Paulo Michel Pinheiro

2017-02-23

Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors. Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed. The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D 1 complex is up to 1000-fold more favourable than the Cas X-GABA A complex. All ∆G° values obtained for Cas X-D 1 complexes were more negative than those seen with Cas X-GABA A complexes. Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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).

Sageone, a diterpene from Rosmarinus officinalis, synergizes with cisplatin cytotoxicity in SNU-1 human gastric cancer cells.

PubMed

Shrestha, Sabina; Song, Yeon Woo; Kim, Hyeonji; Lee, Dong Sun; Cho, Somi Kim

2016-12-01

Chemotherapy resistance is a major obstacle for the effective treatment of cancers. Although several studies have described the anticancer properties of rosemary extract and its components, the detailed mechanisms of action are poorly understood. Activity-guided fractionation and repeated chromatographic separation of the n-hexane fraction of the aqueous methanol extract over silica gel, RP C18, and Sephadex LH-20 led to the isolation of three compounds. The structures of the compounds were determined using 1 H, 13 C, and two-dimensional nuclear magnetic resonance spectroscopy, mass spectroscopy, and infrared spectroscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to evaluate the cytotoxicity of these compounds. Cell cycle, apoptotic cell populations, and mitochondrial membrane potential were analyzed by flow cytometry. Western blot analysis was conducted to detect apoptosis-related proteins. An abietane diterpenoid, sageone (1), an icetexane diterpenoid, (-)-barbatusol (2), and a monoterpene, (+)-verbenone (3), were identified. Of these compounds, sageone (1) showed cytotoxicity against SNU-1 cells with an IC 50 of 9.45 ± 1.33 µM. Sageone reduced the expression of Akt dramatically, as opposed to cisplatin, which increased phosphorylated Akt. Sageone combined with a subtoxic dose of cisplatin had synergistic effects on apoptosis induction in SNU-1 cells, as confirmed by calculating the combination index. Co-treatment was significantly more effective than monotherapy at reducing cell viability and inducing apoptosis, as determined by analyzing DNA fragmentation. The combined treatment of sageone and cisplatin markedly reduced Akt expression and phosphorylation, accompanied by increases in cleaved caspase-3, -9 and PARP. This is the first time compounds 1 and 2 have been isolated from R. officinalis. Sageone induced apoptosis in SNU-1 human gastric cancer cells and notably enhanced the cytotoxicity of cisplatin in SNU-1 cells, which are known to be resistant to cisplatin. These findings suggest that sageone represents a promising anticancer agent against gastric cancer that warrants further study. Copyright © 2016. Published by Elsevier GmbH.

Estudo em microondas do aprisionamento e precipitação de elétrons em explosões solares

NASA Astrophysics Data System (ADS)

Rosal, A. C.; Costa, J. E. R.

2003-08-01

Uma explosão solar é uma variação rápida e intensa do brilho que ocorre nas chamadas regiões ativas da atmosfera, constituídas por um plasma magnetizado com intensa indução magnética. Os modelos de explosões solares atuais, discutidos na literatura, apresentam características de aprisionamento e precipitação de elétrons em ambientes magnéticos simplificados. Neste trabalho, nos propusemos a separar a emissão dos elétrons aprisionados da emissão dos elétrons em precipitação apenas a partir da emissão em microondas, melhorando portanto o controle sobre o conjunto de parâmetros inferidos. A emissão em microondas da população em precipitação é bastante fraca e portanto da nossa base de dados de 130 explosões observadas pelo Rádio Polarímetro de Nobeyama, em sete freqüências, apenas para 32 foi possível separar as duas componentes de emissão com uma boa razão sinal/ruído. A partir de estudos das escalas de tempo das emissões devidas à variação gradual da emissão no aprisionamento e da variação rápida da emissão dos elétrons em precipitação foi possível obter a separação utilizando um filtro temporal nas emissões resultantes. Em nossa análise destas explosões estudamos os espectros girossincrotrônicos da emissão gradual, a qual associamos provir do topo dos arcos magnéticos e da emissão de variação rápida associada aos elétrons em precipitação. Estes espectros foram calculados e dos quais inferimos que a indução magnética efetiva do topo e dos pés foi em média, Btopo = 236 G e Bpés = 577 G, inferidas das freqüências de pico dos espectros em ntopo = 11,8 GHz e npés = 14,6 GHz com leve anisotropia (pequeno alargamento espectral). O índice espectral da distribuição não-térmica de elétrons d, inferido do índice espectral de fótons da emissão em regime opticamente fino, foi de dtopo = 3,3 e dpés = 3,9. Estes parâmetros são típicos da maioria das análises realizadas em ambiente único de

Determination of the molecular signature of fossil conifers by experimental palaeochemotaxonomy - Part 1: The Araucariaceae family

NASA Astrophysics Data System (ADS)

Lu, Y.; Hautevelle, Y.; Michels, R.

2012-08-01

Several extant species of the Araucariaceae family (one of the families of conifers) were invested for the experimental artificial maturation by confined pyrolysis, in order to realize the transformation of biomolecules to geomolecules in laboratory conditions. The experimental study of diagenetized molecular signatures of the Araucariaceae species (common, inter- and infra-generic characteristics) allow to complete our knowledge in botanical palaeochemotaxonomy. Such knowledge is relevant to the reconstitution of palaeoflora and palaeoclimatic reconstruction, archaeology and environmental studies. In this work, major carbon skeleton types of Araucariaceae are detected in the organic solvent extracts of fresh and pyrolyzed plants using gas chromatography-mass spectrometry. The results show that all species of Araucariaceae are firstly characterized by a predominance of saturated tetracyclic diterpenoids. Moreover, the Araucaria genus shows a high relative abundance of bicyclic sesquiterpenoids, particularly compounds of the cadalane-type compounds accompanied by those of eudesmane-type, bisabolane-type as well as chamazulene, pentamethyl-dihydroindenes. Diterpenoids are of the labdane-type, isopimarane, abietane-type (essentially derived from abietanoic acids) as well as isohexyl alkylaromatic hydrocarbons. Compared to the tetracyclic diterpenoids, these compounds show a relatively lower abundance, reaching trace levels in the case of saturated abietanes. Distribution of sesqui- and diterpenoids of Agathis shows some similarities to that of Araucaria, with the exception of one species, in which the tetracyclic compounds are absent and the abietane-type (essentially derived from abietanoic acids) predominant. High similarities between the Wollemia and Araucaria genera are observed. Both are characterized by some high relative abundance of tetracyclic compounds with no predominance of other specific diterpenoids.

Indoor terpene emissions from cooking with herbs and pepper and their secondary organic aerosol production potential

PubMed Central

Klein, Felix; Farren, Naomi J.; Bozzetti, Carlo; Daellenbach, Kaspar R.; Kilic, Dogushan; Kumar, Nivedita K.; Pieber, Simone M.; Slowik, Jay G.; Tuthill, Rosemary N.; Hamilton, Jacqueline F.; Baltensperger, Urs; Prévôt, André S. H.; El Haddad, Imad

2016-01-01

Cooking is widely recognized as an important source of indoor and outdoor particle and volatile organic compound emissions with potential deleterious effects on human health. Nevertheless, cooking emissions remain poorly characterized. Here the effect of herbs and pepper on cooking emissions was investigated for the first time to the best of our knowledge using state of the art mass spectrometric analysis of particle and gas-phase composition. Further, the secondary organic aerosol production potential of the gas-phase emissions was determined by smog chamber aging experiments. The emissions of frying meat with herbs and pepper include large amounts of mono-, sesqui- and diterpenes as well as various terpenoids and p-cymene. The average total terpene emission rate from the use of herbs and pepper during cooking is estimated to be 46 ± 5 gg-1Herbs min-1. These compounds are highly reactive in the atmosphere and lead to significant amounts of secondary organic aerosol upon aging. In summary we demonstrate that cooking with condiments can constitute an important yet overlooked source of terpenes in indoor air. PMID:27830718

Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

NASA Astrophysics Data System (ADS)

Maertens, Gaetan; L'homme, Chloe; Canesi, Sylvain

2014-12-01

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.

The essential oil qualitative and quantitative composition in the needles of Pinus sylvestris L. growing along industrial transects.

PubMed

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).

Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines of cassaine diterpenoids from the bark of Erythrophleum fordii.

PubMed

Ha, Manh Tuan; Tran, Manh Hung; Phuong, Thien Thuong; Kim, Jeong Ah; Woo, Mi Hee; Choi, Jae Sue; Lee, Suhyun; Lee, Jeong Hyung; Lee, Hyeong Kyu; Min, Byung Sun

2017-07-01

A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (3) from a natural source and that of the remaining eight known diterpenoids (4-5, 8-13) from E. fordii. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (1-13) was examined in vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (6-10, 12, 13) exhibited potent cytotoxic activity against all three cell lines with IC 50 values between 0.4μM and 5.9μM. Erythroformine B (7) significantly induced apoptosis in all three cancer cells in a concentration-dependent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

Kildgaard, Sara; Subko, Karolina; Phillips, Emma; Goidts, Violaine; de la Cruz, Mercedes; Díaz, Caridad; Gotfredsen, Charlotte H.; Frisvad, Jens C.; Nielsen, Kristian F.; Larsen, Thomas O.

2017-01-01

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 and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great 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 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, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated. PMID:28805711

Profiling of lipophilic and phenolic phytochemicals of four cultivars from cherimoya (Annona cherimola Mill.).

PubMed

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.

Elicitation of andrographolide in the suspension cultures of Andrographis paniculata.

PubMed

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.

Secondary metabolites from marine microorganisms.

PubMed

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.

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.

PubMed

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 < 0.05) in the 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 < 0.05) in rosmarinic acid, carnosic acid, and carnosol concentrations was detected. From this point of view, distillate rosemary leaves can be proposed as an ingredient in ruminant feed because they both alter neither the yield nor the quality of Murciano-Granadina goats' milk and allow for an increased concentration of polyphenolic components in the goats' milk and in the plasma of the suckling goat kid.

Methyl Jasmonate Induces Traumatic Resin Ducts, Terpenoid Resin Biosynthesis, and Terpenoid Accumulation in Developing Xylem of Norway Spruce Stems1

PubMed Central

Martin, Diane; Tholl, Dorothea; Gershenzon, Jonathan; Bohlmann, Jörg

2002-01-01

Norway spruce (Picea abies L. Karst) produces an oleoresin characterized by a diverse array of terpenoids, monoterpenoids, sesquiterpenoids, and diterpene resin acids that can protect conifers against potential herbivores and pathogens. Oleoresin accumulates constitutively in resin ducts in the cortex and phloem (bark) of Norway spruce stems. De novo formation of traumatic resin ducts (TDs) is observed in the developing secondary xylem (wood) after insect attack, fungal elicitation, and mechanical wounding. Here, we characterize the methyl jasmonate-induced formation of TDs in Norway spruce by microscopy, chemical analyses of resin composition, and assays of terpenoid biosynthetic enzymes. The response involves tissue-specific differentiation of TDs, terpenoid accumulation, and induction of enzyme activities of both prenyltransferases and terpene synthases in the developing xylem, a tissue that constitutively lacks axial resin ducts in spruce. The induction of a complex defense response in Norway spruce by methyl jasmonate application provides new avenues to evaluate the role of resin defenses for protection of conifers against destructive pests such as white pine weevils (Pissodes strobi), bark beetles (Coleoptera, Scolytidae), and insect-associated tree pathogens. PMID:12114556

Forskolin: genotoxicity assessment in Allium cepa.

PubMed

Mohammed, Khalid Pasha; Aarey, Archana; Tamkeen, Shayesta; Jahan, Parveen

2015-01-01

Forskolin, a diterpene, 7β-acetoxy-8,13-epoxy-1α,6β,9α-trihydroxy-labd-14-en-11-one (C22H34O7) isolated from Coleus forskohlii, exerts multiple physiological effects by stimulating the enzyme adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) concentrations. Forskolin is used in the treatment of hypertension, congestive heart failure, eczema, and other diseases. A cytogenetic assay was performed in Allium cepa to assess possible genotoxic effects of forskolin. Forskolin was tested at concentrations 5-100 μM for exposure periods of 24 or 48 h. Treated samples showed significant reductions in mitotic index (p < 0.05) and increases in the frequency of chromosome aberrations (p < 0.01) at both exposure times. The treated meristems showed chromosome aberrations including sticky metaphases, sticky anaphases, laggard, anaphase bridges, micronuclei, polyploidy, fragments, breaks, and C-mitosis. Forskolin may cause genotoxic effects and further toxicological evaluations should be conducted to ensure its safety. Copyright © 2014 Elsevier B.V. All rights reserved.

Tetracyclic diterpenoid hydrocarbons in some Australian coals, sediments and crude oils

NASA Astrophysics Data System (ADS)

Noble, Rohinton A.; Alexander, Robert; Kagi, Robert Ian; Knox, John

1985-10-01

Tetracyclic diterpenoid hydrocarbons (diterpanes) based on the ent-beyerane, phyllocladane and ent-kaurane skeletons have been identified in the hydrocarbon extracts of some Australian coals, sediments and crude oils. Structures were assigned to the geological diterpanes by comparison with synthetically prepared reference compounds. Studies of a sample suite consisting of low-rank coals and sediments indicate that the ratios of C-16 epimers of phyllocladane and ent-kaurane are maturity dependent, and that the relative proportion of the thermodynamically preferred 16β (H)-compounds increases with increasing thermal maturity. Thermodynamic equilibrium for the interconversion reactions is attained in sediments before the onset of crude oil generation. The most likely natural product precursors for the tetracyclic diterpanes are considered to be the tetracyclic diterpene hydrocarbons which occur widely in the leaf resins of conifers. Tetracyclic diterpanes have been identified in sediments and coals of Permian age or younger, suggesting that these compounds are markers for both modern and extinct families of conifers. In particular, phyllocladane is proposed as a marker for the Podocarpaceae family of conifers.

Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A†

PubMed Central

Lozama, Anthony; Cunningham, Christopher W.; Caspers, Michael J.; Douglas, Justin T.; Dersch, Christina M.; Rothman, Richard B.; Prisinzano, Thomas E.

2011-01-01

As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan containing natural products. PMID:21338114

Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A.

PubMed

Lozama, Anthony; Cunningham, Christopher W; Caspers, Michael J; Douglas, Justin T; Dersch, Christina M; Rothman, Richard B; Prisinzano, Thomas E

2011-04-25

As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan-containing natural products.

Essential oil from the leaves of Xylopia langsdorfiana (Annonaceae) as a possible spasmolytic agent.

PubMed

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.

Transdermal delivery of forskolin from emulsions differing in droplet size.

PubMed

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.

Indoor terpene emissions from cooking with herbs and pepper and their secondary organic aerosol production potential

NASA Astrophysics Data System (ADS)

Klein, Felix; Farren, Naomi J.; Bozzetti, Carlo; Daellenbach, Kaspar R.; Kilic, Dogushan; Kumar, Nivedita K.; Pieber, Simone M.; Slowik, Jay G.; Tuthill, Rosemary N.; Hamilton, Jacqueline F.; Baltensperger, Urs; Prévôt, André S. H.; El Haddad, Imad

2016-11-01

Cooking is widely recognized as an important source of indoor and outdoor particle and volatile organic compound emissions with potential deleterious effects on human health. Nevertheless, cooking emissions remain poorly characterized. Here the effect of herbs and pepper on cooking emissions was investigated for the first time to the best of our knowledge using state of the art mass spectrometric analysis of particle and gas-phase composition. Further, the secondary organic aerosol production potential of the gas-phase emissions was determined by smog chamber aging experiments. The emissions of frying meat with herbs and pepper include large amounts of mono-, sesqui- and diterpenes as well as various terpenoids and p-cymene. The average total terpene emission rate from the use of herbs and pepper during cooking is estimated to be 46 ± 5 gg-1Herbs min-1. These compounds are highly reactive in the atmosphere and lead to significant amounts of secondary organic aerosol upon aging. In summary we demonstrate that cooking with condiments can constitute an important yet overlooked source of terpenes in indoor air.

Glutathione metabolism as a determinant of therapeutic efficacy: a review.

PubMed

Arrick, B A; Nathan, C F

1984-10-01

Glutathione, as the chief nonprotein intracellular sulfhydryl, affects the efficacy and interactions of a variety of antineoplastic interventions, mainly through nucleophilic thioether formation or oxidation-reduction reactions. Thus, glutathione plays a role in the detoxification and repair of cellular injury by such diverse agents as mechlorethamine, melphalan, cyclophosphamide, nitrosoureas, 6-thiopurine, 4'-(9-acridinylamino)methanesulfon-m-anisidide, the quinone antibiotics (including Adriamycin, daunorubicin, and mitomycin C), the sesquiterpene lactones (such as vernolepin), and other sulfhydryl-reactive diterpenes (like jatrophone). Glutathione may play a similar role in host and tumor cell responses to radiation, hyperthermia, and the reactive reduction products of oxygen secreted by inflammatory cells. Further, glutathione participates in the formation of toxic metabolites of such chemotherapeutics as azathioprine and bleomycin and may affect the cellular uptake of other agents, such as methotrexate. It seems likely that alterations in glutathione metabolism of tumor or host as a result of one therapeutic intervention may affect the outcome of concurrent treatments. Knowledge of these interactions may be useful in designing combination therapy for neoplastic disease.

Effect-directed analysis via hyphenated high-performance thin-layer chromatography for bioanalytical profiling of sunflower leaves.

PubMed

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.

How coffee affects metabolic syndrome and its components.

PubMed

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.

Simultaneous structure-activity studies and arming of natural products by C-H amination reveal cellular targets of eupalmerin acetate.

PubMed

Li, Jing; Cisar, Justin S; Zhou, Cong-Ying; Vera, Brunilda; Williams, Howard; Rodríguez, Abimael D; Cravatt, Benjamin F; Romo, Daniel

2013-06-01

Natural products have a venerable history of, and enduring potential for the discovery of useful biological activity. To fully exploit this, the development of chemical methodology that can functionalize unique sites within these complex structures is highly desirable. Here, we describe the use of rhodium(II)-catalysed C-H amination reactions developed by Du Bois to carry out simultaneous structure-activity relationship studies and arming (alkynylation) of natural products at 'unfunctionalized' positions. Allylic and benzylic C-H bonds in the natural products undergo amination while olefins undergo aziridination, and tertiary amine-containing natural products are converted to amidines by a C-H amination-oxidation sequence or to hydrazine sulfamate zwitterions by an unusual N-amination. The alkynylated derivatives are ready for conversion into cellular probes that can be used for mechanism-of-action studies. Chemo- and site-selectivity was studied with a diverse library of natural products. For one of these-the marine-derived anticancer diterpene, eupalmerin acetate-quantitative proteome profiling led to the identification of several protein targets in HL-60 cells, suggesting a polypharmacological mode of action.

Indoor terpene emissions from cooking with herbs and pepper and their secondary organic aerosol production potential.

PubMed

Klein, Felix; Farren, Naomi J; Bozzetti, Carlo; Daellenbach, Kaspar R; Kilic, Dogushan; Kumar, Nivedita K; Pieber, Simone M; Slowik, Jay G; Tuthill, Rosemary N; Hamilton, Jacqueline F; Baltensperger, Urs; Prévôt, André S H; El Haddad, Imad

2016-11-10

Cooking is widely recognized as an important source of indoor and outdoor particle and volatile organic compound emissions with potential deleterious effects on human health. Nevertheless, cooking emissions remain poorly characterized. Here the effect of herbs and pepper on cooking emissions was investigated for the first time to the best of our knowledge using state of the art mass spectrometric analysis of particle and gas-phase composition. Further, the secondary organic aerosol production potential of the gas-phase emissions was determined by smog chamber aging experiments. The emissions of frying meat with herbs and pepper include large amounts of mono-, sesqui- and diterpenes as well as various terpenoids and p-cymene. The average total terpene emission rate from the use of herbs and pepper during cooking is estimated to be 46 ± 5 gg -1 Herbs min -1 . These compounds are highly reactive in the atmosphere and lead to significant amounts of secondary organic aerosol upon aging. In summary we demonstrate that cooking with condiments can constitute an important yet overlooked source of terpenes in indoor air.

Phytotoxic activity of Salvia x jamensis.

PubMed

Bisio, Angela; Fraternale, Daniele; Damonte, Gianluca; Millo, Enrico; Lanteri, Anna Paola; Russo, Eleonora; Romussi, Giovanni; Parodi, Brunella; Ricci, Donata; De Tommasi, Nunziatina

2009-12-01

A study has been carried out on the surface exudate of Salvia x jamensis, which showed a significant phytotoxic activity against Papaver rhoeas L. and Avena sativa L.. Bioguided separation of the exudate yielded active fractions from which 3 beta-hydroxy-isopimaric acid (1), hautriwaic acid (2), betulinic acid (3), 7,8 beta-dihydrosalviacoccin (4), isopimaric acid (5), 14 alpha-hydroxy-isopimaric acid (7), 15,16-epoxy-7 alpha, 10 beta-dihydroxy-clerod-3,13(16),14-trien-17,12;18,19-diolide (8), cirsiliol (5,3',4'-trihydroxy-6,7-dimethoxyflavone, 9) and two new neoclerodane diterpenes (6 and 10) were isolated. The structures of 6 and 10 were identified as 15,16-epoxy-10 beta-hydroxy-clerod-3,13(16),14-trien-17,12;18,19-diolide and 15,16-epoxy-7 alpha,10-dihydroxy-clerod-2,13(16),14-trien-17,12;18,19-diolide respectively on the basis of spectroscopic data analysis. All compounds, but 7, 8 and 10, were active in inhibiting the germination of the tested species.

Immunochemical Analysis of Paxilline and Ergot Alkaloid Mycotoxins in Grass Seeds and Plants.

PubMed

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.

Mining chemodiversity from biodiversity: pharmacophylogeny of medicinal plants of Ranunculaceae.

PubMed

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.

Simultaneous structure-activity studies and arming of natural products by C-H amination reveal cellular targets of eupalmerin acetate

NASA Astrophysics Data System (ADS)

Li, Jing; Cisar, Justin S.; Zhou, Cong-Ying; Vera, Brunilda; Williams, Howard; Rodríguez, Abimael D.; Cravatt, Benjamin F.; Romo, Daniel

2013-06-01

Natural products have a venerable history of, and enduring potential for the discovery of useful biological activity. To fully exploit this, the development of chemical methodology that can functionalize unique sites within these complex structures is highly desirable. Here, we describe the use of rhodium(II)-catalysed C-H amination reactions developed by Du Bois to carry out simultaneous structure-activity relationship studies and arming (alkynylation) of natural products at ‘unfunctionalized’ positions. Allylic and benzylic C-H bonds in the natural products undergo amination while olefins undergo aziridination, and tertiary amine-containing natural products are converted to amidines by a C-H amination-oxidation sequence or to hydrazine sulfamate zwitterions by an unusual N-amination. The alkynylated derivatives are ready for conversion into cellular probes that can be used for mechanism-of-action studies. Chemo- and site-selectivity was studied with a diverse library of natural products. For one of these—the marine-derived anticancer diterpene, eupalmerin acetate—quantitative proteome profiling led to the identification of several protein targets in HL-60 cells, suggesting a polypharmacological mode of action.

Lipase-catalysed esters synthesis of cafestol and kahweol.

PubMed

Novaes, Fábio Junior Moreira; Itabaiana Junior, Ivaldo; Sutili, Felipe Korbus; Marriott, Philip John; Bizzo, Humberto Ribeiro; Aquino Neto, Francisco Radler de; Souza, Rodrigo Octávio Mendonça Alves de; Rezende, Claudia Moraes

2018-09-01

Cafestol and kahweol (C&K), two coffee diterpene alcohols with structural similarity which exhibit anticarcinogenic effects, were isolated from green coffee Arabica beans, followed by their lipase-catalysed esterification and purification by preparative high-performance liquid chromatography (HPLC). The isolation and enzymatic synthesis parameters of C&K esters were studied, with the latter optimised by a Central Composite Design; both procedures were monitored by gas chromatography. Scale up and improved isolation conditions resulted in 1.29 g of C&K, with 98% purity from 300 g of green Arabica beans. The highest C&K ester yields were observed using an alcohol:fatty acid molar ratio of 1:5, 73.3 mg mL -1 of CAL-B enzyme, 70 °C and 240 rpm for 3 days in toluene, leading to 85-88% conversion among a variety of tested C&K esters, including n-C 14:0 -C 20:0 , C 18:1 , C 18:2 and C 18:3 . Copyright © 2018. Published by Elsevier Ltd.

Euclea undulata Thunb.: Review of its botany, ethnomedicinal uses, phytochemistry and biological activities.

PubMed

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.

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

PubMed Central

Prakash, Indra; Chaturvedula, Venkata Sai Prakash; Markosyan, Avetik

2014-01-01

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. PMID:24424316

Physiological Effects of Ergot Alkaloid and Indole-Diterpene Consumption on Sheep under Hot and Thermoneutral Ambient Temperature Conditions.

PubMed

Henry, Michelle L E; Kemp, Stuart; Dunshea, Frank R; Leury, Brian J

2016-06-02

A controlled feeding study was undertaken to determine the physiological and production effects of consuming perennial ryegrass alkaloids (fed via seed) under extreme heat in sheep. Twenty-four Merino ewe weaners (6 months; initial BW 30.8 ± 1.0 kg) were selected and the treatment period lasted 21 days following a 14 day acclimatisation period. Two levels of two factors were used. The first factor was alkaloid, fed at a nil (NilAlk) or moderate level (Alk; 80 μg/kg LW ergovaline and 20.5 μg/kg·LW lolitrem B). The second factor was ambient temperature applied at two levels; thermoneutral (TN; constant 21-22 °C) or heat (Heat; 9:00 AM-5:00 PM at 38 °C; 5:00 PM-9:00 AM at 21-22 °C), resulting in four treatments, NilAlk TN, NilAlk Heat, Alk TN and Alk Heat. Alkaloid consumption reduced dry matter intake ( p = 0.008), and tended to reduce liveweight ( p = 0.07). Rectal temperature and respiration rate were increased by both alkaloid and heat ( p < 0.05 for all). Respiration rate increased to severe levels when alkaloid and heat were combined, indicating the short term effects which may be occurring in perennial ryegrass toxicosis (PRGT) areas during severe weather conditions, a novel finding. When alkaloid ingestion and heat were administered separately, similar physiological responses occurred, indicating alkaloid ingestion causes a similar heat stress response to 38 °C heat.

Antibacterial Effect of Copaifera duckei Dwyer Oleoresin and Its Main Diterpenes against Oral Pathogens and Their Cytotoxic Effect

PubMed Central

Abrão, Fariza; Alves, Jessica A.; Andrade, Gessica; de Oliveira, Pollyanna F.; Ambrósio, Sérgio R.; Veneziani, Rodrigo C. S.; Tavares, Denise C.; Bastos, Jairo K.; Martins, Carlos H. G.

2018-01-01

This study evaluates the antibacterial activity of the Copaifera duckei Dwyer oleoresin and two isolated compounds [eperu-8(20)-15,18-dioic acid and polyalthic acid] against bacteria involved in primary endodontic infections and dental caries and assesses the cytotoxic effect of these substances against a normal cell line. MIC and MBC assays pointed out the most promising metabolites for further studies on bactericidal kinetics, antibiofilm activity, and synergistic antibacterial action. The oleoresin and polyalthic acid but not eperu-8(20)-15,18-dioic provided encouraging MIC and MBC results at concentrations lower than 100 μg mL−1. The oleoresin and polyalthic acid activities depended on the evaluated strain. A bactericidal effect on Lactobacillus casei (ATCC 11578 and clinical isolate) emerged before 8 h of incubation. For all the tested bacteria, the oleoresin and polyalthic acid inhibited biofilm formation by at least 50%. The oleoresin and polyalthic acid gave the best activity against Actinomyces naeslundii (ATCC 19039) and L. casei (ATCC 11578), respectively. The synergistic assays combining the oleoresin or polyalthic acid with chlorhexidine did not afford interesting results. We examined the cytotoxicity of C. duckei oleoresin, eperu-8(20)-15,18-dioic acid, and polyalthic acid against Chinese hamster lung fibroblasts. The oleoresin and polyalthic acid were cytotoxic at concentrations above 78.1 μg mL−1, whereas eperu-8(20)-15,18-dioic displayed cytotoxicity at concentrations above 312.5 μg mL−1. In conclusion, the oleoresin and polyalthic acid are potential sources of antibacterial agents against bacteria involved in primary endodontic infections and dental caries in both the sessile and the planktonic modes at concentrations that do not cause cytotoxicity. PMID:29515530

A Reappraising of Cosmography: the Interface Between Astronomical and Geographic Studies. (Breton Title: Releitura do Conceito de Cosmografia: a Interface Entre os Estudos Astronômicos e Geográficos.) Una Relectura del Concepto de Cosmografía: la Interfase Entre los Estudios Astronómicos y Geográficos

NASA Astrophysics Data System (ADS)

Azevedo Sobreira, Paulo Henrique

2012-12-01

The concept of "Cosmography" is in disuse since the 80s of the last century, but the astronomical themes previously discussed in the school subjects of Geography and Cosmography remain in current textbooks. The use of term "Cosmography" was rescued in this research, and the study of its re-signification prompted the appearance of the term Geographic Cosmography. The Geographic Cosmography is a field of studies of the Geography, whose set of knowledge and skills is predominantly scholar. It studies the interface between terrestrial and celestial knowledge, and assigns a geographic significance to them. It examines human and natural relationships with Sidereal Space and its consequences for society and nature. O conceito de "Cosmografia" está em desuso desde os anos 80 do século XX, mas os temas astronômicos anteriormente abordados nas disciplinas escolares de Cosmografia e de Geografia permanecem nos atuais livros didáticos. O uso do termo "Cosmografia" foi resgatado nesta pesquisa e o estudo de sua ressignificação proporcionou o surgimento do termo Cosmografia Geográfica. A Cosmografia Geográfica é um campo de estudos da Geografia, cujo conjunto de conhecimentos e habilidades é predominantemente escolar. Estuda a interface entre os conhecimentos terrestres e os celestes e lhes atribui significância geográfica. Analisa as relações humanas e naturais com o Espaço Sideral e suas consequências para a sociedade e a natureza.

Aunque el concepto de "Cosmografía" no se usa desde la década de los '80 del siglo pasado, los temas astronómicos que se enseñaban anteriormente en las asignaturas escolares de Cosmografía y de Geografía permanecen en los actuales libros didácticos. El uso del término "Cosmografía" fue rescatado en esta investigación y el estudio de su resignificación proporcionó el surgimiento del término Cosmografía Geográfica. La Cosmografía Geográfica es un campo de estudio de la Geografía, donde

UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small-molecule natural product libraries.

PubMed

Yang, Jin; Liang, Qian; Wang, Mei; Jeffries, Cynthia; Smithson, David; Tu, Ying; Boulos, Nidal; Jacob, Melissa R; Shelat, Anang A; Wu, Yunshan; Ravu, Ranga Rao; Gilbertson, Richard; Avery, Mitchell A; Khan, Ikhlas A; Walker, Larry A; Guy, R Kiplin; Li, Xing-Cong

2014-04-25

The generation of natural product libraries containing column fractions, each with only a few small molecules, using a high-throughput, automated fractionation system, has made it possible to implement an improved dereplication strategy for selection and prioritization of leads in a natural product discovery program. Analysis of databased UPLC-MS-ELSD-PDA information of three leads from a biological screen employing the ependymoma cell line EphB2-EPD generated details on the possible structures of active compounds present. The procedure allows the rapid identification of known compounds and guides the isolation of unknown compounds of interest. Three previously known flavanone-type compounds, homoeriodictyol (1), hesperetin (2), and sterubin (3), were identified in a selected fraction derived from the leaves of Eriodictyon angustifolium. The lignan compound deoxypodophyllotoxin (8) was confirmed to be an active constituent in two lead fractions derived from the bark and leaves of Thuja occidentalis. In addition, two new but inactive labdane-type diterpenoids with an uncommon triol side chain were also identified as coexisting with deoxypodophyllotoxin in a lead fraction from the bark of T. occidentalis. Both diterpenoids were isolated in acetylated form, and their structures were determined as 14S,15-diacetoxy-13R-hydroxylabd-8(17)-en-19-oic acid (9) and 14R,15-diacetoxy-13S-hydroxylabd-8(17)-en-19-oic acid (10), respectively, by spectroscopic data interpretation and X-ray crystallography. This work demonstrates that a UPLC-MS-ELSD-PDA database produced during fractionation may be used as a powerful dereplication tool to facilitate compound identification from chromatographically tractable small-molecule natural product libraries.

Synthesis and cholinesterase inhibition of cativic acid derivatives.

PubMed

Alza, Natalia P; Richmond, Victoria; Baier, Carlos J; Freire, Eleonora; Baggio, Ricardo; Murray, Ana Paula

2014-08-01

Alzheimer's disease (AD) is a neurodegenerative disorder associated with memory impairment and cognitive deficit. Most of the drugs currently available for the treatment of AD are acetylcholinesterase (AChE) inhibitors. In a preliminary study, significant AChE inhibition was observed for the ethanolic extract of Grindelia ventanensis (IC₅₀=0.79 mg/mL). This result prompted us to isolate the active constituent, a normal labdane diterpenoid identified as 17-hydroxycativic acid (1), through a bioassay guided fractionation. Taking into account that 1 showed moderate inhibition of AChE (IC₅₀=21.1 μM), selectivity over butyrylcholinesterase (BChE) (IC₅₀=171.1 μM) and that it was easily obtained from the plant extract in a very good yield (0.15% w/w), we decided to prepare semisynthetic derivatives of this natural diterpenoid through simple structural modifications. A set of twenty new cativic acid derivatives (3-6) was prepared from 1 through transformations on the carboxylic group at C-15, introducing a C2-C6 linker and a tertiary amine group. They were tested for their inhibitory activity against AChE and BChE and some structure-activity relationships were outlined. The most active derivative was compound 3c, with an IC₅₀ value of 3.2 μM for AChE. Enzyme kinetic studies and docking modeling revealed that this inhibitor targeted both the catalytic active site and the peripheral anionic site of this enzyme. Furthermore, 3c showed significant inhibition of AChE activity in SH-SY5Y human neuroblastoma cells, and was non-cytotoxic. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Mode of action of microbial anti-MRSA agents].

PubMed

Tomoda, Hiroshi

2012-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is known as a major nosocomial pathogen that has also developed resistance to many antibiotics. Moreover, MRSA resistance to a last-resort antibiotic, vancomycin, has been reported. Therefore, new anti-infectious agents to prevent and treat MRSA infection are needed. Based on this background, our group has focused on the discovery of new microbial agents active against MRSA infection. Viridicatumtoxin and spirohexaline, produced by Penicillium sp. FKI-3368, were isolated as inhibitors of undecaprenyl pyrophosphate (UPP) synthase of Staphylococcus aureus, which was involved in cell wall synthesis. Viridicatumtoxin and spirohexaline with a pentacyclic spiro skeleton inhibited UPP synthase activity with an IC(50) value of 4.0 and 9.0 µM, respectively. Actually, the growth of gram-positive bacteria including MRSA was strongly inhibited by the compounds. Our computational modeling experiments indicated that spirohexaline A was inserted into the substrate pocket of UPP synthase and interacted with Glu(88) via a carbamoyl group of the compound, with Ala(76), Met(54) and Asn(35) via three hydroxyl groups, and with certain hydrophobic amino acids via a spiro ring. Cyslabdan, produced by Streptomyces sp. K04-0144, was isolated as a potentiator of β-lactam imipenem activity against MRSA. The compound consisted of a labdan skeleton and an N-acetylcysteine. Cyslabdan potentiated imipenem activity by over 1000 fold, drastically reducing the MIC value of imipenem against MRSA from 16 to 0.03 µg/mL. The binding proteins of cyslabdan were investigated in the lysate of MRSA to identify FemA, which was involved in the formation of the pentaglycine interpeptide bridge in MRSA peptidoglycan.

O que bilíngues bimodais têm a nos dizer sobre desenvolvimento bilíngue?

PubMed Central

de Quadros, Ronice Müller; Lillo-Martin, Diane; Pichler, Deborah Chen

2013-01-01

O objetivo deste trabalho é apresentar o que as pesquisas que estamos desenvolvendo com crianças ouvintes, filhas de pais surdos, adquirindo Língua Brasileira de Sinais (Libras) e Português e Língua de Sinais Americana (ASL) e Inglês (Lillo-Martin et al. 2010) têm a nos dizer sobre desenvolvimento bilíngue. Os dados deste estudo fazem parte de um banco de dados de interações espontâneas coletadas longitudinalmente, alternando contextos de aquisição da Libras e do português como língua alvo, no Brasil e dados coletados longitudinalmente. nos mesmos contextos, de crianças adquirindo ASL e inglês1. Além disso, há também dados do estudo experimental com testes aplicados nos dois pares de línguas que se agregam ao presente estudo. Uma visão geral dos estudos desenvolvidos sobre a aquisição bilíngue bimodal por crianças ouvintes, filhas de pais surdos, será apresentada e, então, serão expostos alguns aspectos linguísticos deste tipo de aquisição, considerando as discussões sobre aquisição bilíngue a partir da pesquisa realizada. PMID:24431480

BdorCSP2 Is Important for Antifeed and Oviposition-Deterring Activities Induced by Rhodojaponin-III against Bactrocera dorsalis

PubMed Central

Dong, Xiaolin; Wang, Peidan; Hu, Meiying; Zhong, Guohua

2013-01-01

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. PMID:24155937

Geranylgeranyl diphosphate synthases from Scoparia dulcis and Croton sublyratus. cDNA cloning, functional expression, and conversion to a farnesyl diphosphate synthase.

PubMed

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.

Plants as natural antioxidants for meat products

NASA Astrophysics Data System (ADS)

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.

Transcriptional transitions in Alphonso mango (Mangifera indica L.) during fruit development and ripening explain its distinct aroma and shelf life characteristics.

PubMed

Deshpande, Ashish B; Anamika, Krishanpal; Jha, Vineet; Chidley, Hemangi G; Oak, Pranjali S; Kadoo, Narendra Y; Pujari, Keshav H; Giri, Ashok P; Gupta, Vidya S

2017-08-18

Alphonso is known as the "King of mangos" due to its unique flavor, attractive color, low fiber pulp and long shelf life. We analyzed the transcriptome of Alphonso mango through Illumina sequencing from seven stages of fruit development and ripening as well as flower. Total transcriptome data from these stages ranged between 65 and 143 Mb. Importantly, 20,755 unique transcripts were annotated and 4,611 were assigned enzyme commission numbers, which encoded 142 biological pathways. These included ethylene and flavor related secondary metabolite biosynthesis pathways, as well as those involved in metabolism of starch, sucrose, amino acids and fatty acids. Differential regulation (p-value ≤ 0.05) of thousands of transcripts was evident in various stages of fruit development and ripening. Novel transcripts for biosynthesis of mono-terpenes, sesqui-terpenes, di-terpenes, lactones and furanones involved in flavor formation were identified. Large number of transcripts encoding cell wall modifying enzymes was found to be steady in their expression, while few were differentially regulated through these stages. Novel 79 transcripts of inhibitors of cell wall modifying enzymes were simultaneously detected throughout Alphonso fruit development and ripening, suggesting controlled activity of these enzymes involved in fruit softening.

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

PubMed Central

Brinker, Anita M.; Ma, Jun; Lipsky, Peter E.; Raskin, Ilya

2013-01-01

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-α (TNF-α), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-γ). 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. PMID:17250858

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae).

PubMed

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.

Screening of herbal extracts for activation of the human peroxisome proliferator-activated receptor.

PubMed

Rau, O; Wurglics, M; Dingermann, Th; Abdel-Tawab, M; Schubert-Zsilavecz, M

2006-11-01

The peroxisome proliferator-activated receptors play a pivotal role in metazoan lipid and glucose homeostasis. Synthetic activators of PPARalpha (fibrates) and PPARgamma (glitazones) are therefore widely used for treatment of dislipidemia and diabetes, respectively. There is growing evidence for herbal compounds to influence nuclear receptor signalling e.g. the PPARs. We recently reported carnosic acid and carnosol, both being diterpenes found in the labiate herbs sage and rosemary, to be activators of PPARgamma. The subsequent screening of a variety of ethanolic extracts, obtained from traditionally used herbs, for PPAR activation, led to an exceptionally high hit rate. Among 52 extracts nearly the half significantly activated PPARgamma and 14 activated PPARalpha in addition, whereas three of them were pan-PPAR activators, which also activated PPARdelta. The most active extracts, for which a concentration dependent effect could be shown, were the extracts of Alisma plantago aquatica (ze xie/european waterplantain), Catharanthus roseus (madagascar periwinkle), Acorus calamus (sweet calamus), Euphorbia balsamifera (balsam spurge), Jatropha curcas (barbados nut), Origanum majorana (marjoram), Zea mays (corn silk), Capsicum frutescens (chilli) and Urtica dioica (stinging nettle). The results of the present study provide a possible rationale for the traditional use of many herbs as antidiabetics.

Chemistry and toxicology of molds isolated from water-damaged buildings.

PubMed

Jarvis, Bruce B

2002-01-01

There is increasing evidence of health risks associated with damp buildings and homes in which high levels of microbes are found. Although concerns have traditionally centered on microbial pathogens and allergenic effects, recent work has suggested that fungi pose the more serious risk. Evidence is accumulating that certain toxigenic molds are particularly a risk for human health through exposure, via inhalation, of fungal spores. Many of these fungi produce toxins (mycotoxins) some of which have been shown to cause animal and human intoxications, usually in an agricultural setting. The fungus, Stachybotrys chartarum (S. atra) is considered to be one of the more serious threats to people living and working in water-damaged buildings. This mold has a long history of being responsible for animal toxicoses, and in recent years, being associated with infant pulmonary hemosiderosis (bleeding in the lungs) of infants exposed to spores of this fungus in their homes. S. atra produces a variety of potent toxins and immunosuppressant agents, including a novel class of diterpenes (atranones) of unusual structure. More research is needed to determine the impact to health resulting from inhalation of toxigenic mold spores.

Protein Tyrosine Phosphatase 1B Inhibitors from the Stems of Akebia quinata.

PubMed

An, Jin-Pyo; Ha, Thi Kim Quy; Kim, Jinwoong; Cho, Tae Oh; Oh, Won Keun

2016-08-19

PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B inhibitors, one new diterpene glycoside (1) and 13 known compounds (2-14) were isolated from the methanol extract of the stems of Akebia quinata. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR and MS. Compounds 2, 3, 6, 8 and 11 showed significant inhibitory effects on the PTP1B enzyme, with IC50 values ranging from 4.08 ± 1.09 to 21.80 ± 4.74 μM. PTP1B inhibitors also had concentration-dependent cytotoxic effects on breast cancer cell lines, such as MCF7, MDA-MB-231 and tamoxifen-resistant MCF7 (MCF7/TAMR) (IC50 values ranging from 0.84 ± 0.04 to 7.91 ± 0.39 μM). These results indicate that compounds 6 and 8 from Akebia quinata may be lead compounds acting as anti-breast cancer agents.

Deoxypodophyllotoxin isolated from Juniperus communis induces apoptosis in breast cancer cells.

PubMed

Benzina, Sami; Harquail, Jason; Jean, Stephanie; Beauregard, Annie-Pier; Colquhoun, Caitlyn D; Carroll, Madison; Bos, Allyson; Gray, Christopher A; Robichaud, Gilles A

2015-01-01

The study of anticancer properties from natural products has regained popularity as natural molecules provide a high diversity of chemical structures with specific biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we screened and isolated compounds with anti-breast cancer properties from Juniperus communis (common Juniper). Using bioassay-guided fractionation of a crude plant extract, we identified the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin (DPT) as potent inducers of caspase-dependent programmed cell death (apoptosis) in malignant MB231 breast cancer cells. Further elucidation revealed that DPT, in contrast to isocupressic acid, also concomitantly inhibited cell survival pathways mediated by the MAPK/ERK and NFκB signaling pathways within hours of treatment. Our findings emphasize the potential and importance of natural product screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous peoples of North America can provide new candidate entities with desirable bioactivities to develop new cancer therapies.

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.

PubMed

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.

Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides.

PubMed

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.

Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides

PubMed Central

dos Santos, Cintia Miranda; Campos, Jaqueline Ferreira; dos Santos, Helder Freitas; Balestieri, José Benedito Perrella; Silva, Denise Brentan

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. PMID:29213354

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.

PubMed

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.

The Genome of the Generalist Plant Pathogen Fusarium avenaceum Is Enriched with Genes Involved in Redox, Signaling and Secondary Metabolism

PubMed Central

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

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

PubMed Central

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 eucalyptol (43.7%), phytol (11.5%), α-farnesene (9.6%), and pentacosane (7.6%). Cytotoxicity of essential oil of leaves of M. domestica was evaluated by sulforhodamine B (SRB) assays. The essential oil of leaves of M. domestica, tested against three cancer cell lines, namely, C-6 (glioma cells), A549 (human lung carcinoma), CHOK1 (Chinese hamster ovary cells), and THP-1 (human acute monocytic leukemia cell). The highest activity showed by essential oil on C-6 cell lines (98.2%) at concentration of 2000 μg/ml compared to control. It is the first paper in literature to exploit the chemical composition and cytotoxic activity of leaves essential oil of M. domestica. PMID:22619691

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems.

PubMed

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.

Converting environmental risks to benefits by using spent coffee grounds (SCG) as a valuable resource.

PubMed

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.

Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cárdenas, Casimiro; IBIMA; Research Support Central Services

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-negativemore » 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.« less

Chemical composition and antimicrobial activity of the essential oils from the gum of Turkish pistachio (Pistacia vera L.).

PubMed

Alma, Mehmet Hakki; Nitz, Siegfried; Kollmannsberger, Hubert; Digrak, Metin; Efe, Fatih Tuncay; Yilmaz, Necmettin

2004-06-16

The essential oil from the gum of Pistachio (Pistacia vera L. (Anacardiaceae)) grown in Turkey was obtained by the hydro-distillation method, and its chemical composition was analyzed by GC and GC-MS. Moreover, the antimicrobial activities of the oil against the growth of 13 bacteria and 3 pathogenic yeasts were evaluated using the agar-disk diffusion and minimum inhibitory concentration (MIC) methods. The results showed that the essential oil contained about 89.67% monoterpenes, 8.1% oxygenated monoterpenes and 1.2% diterpenes. alpha-Pinene (75.6%), beta-pinene (9.5%), trans-verbenol (3.0%), camphene (1.4%), trans-pinocarveol (about 1.20%), and limonene (1.0%) were the major components. The antimicrobial results showed that the oil inhibited nine bacteria and all the yeasts studied, and the activities were considerably dependent upon concentration and its bioactive compounds such as carvacrol, camphene, and limonene. Moreover, the essential oil of the gum was found to be more effective yeastcide than Nystatin, synthetic yeastcide. Furthermore, the antibacterial activities of the oil were lower than those of standard antibiotics, ampicillin sodium, and streptomycine sulfate under the conditions studied.

Platycladus orientalis leaves: a systemic review on botany, phytochemistry and pharmacology.

PubMed

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.

Differential Timing of Spider Mite-Induced Direct and Indirect Defenses in Tomato Plants1[w

PubMed Central

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

Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum

PubMed Central

Rupcic, Zeljka; Rascher, Monique; Kanaki, Sae; Wittstein, Kathrin

2018-01-01

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. PMID:29509661

Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum.

PubMed

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.

Wirelessly controlled micro- and nanostructures for bioapplications

NASA Astrophysics Data System (ADS)

Lindo, Andre Machado

Apresentar uma contribuicao para a caracterizacao e compreensao do comportamento hidrodinâmico da laguna Ria de Aveiro, baseada num estudo experimental e num estudo de modelacao numerica, e o objectivo deste trabalho. As caracteristicas hidrologicas da Ria de Aveiro foram investigadas atraves da realizacao de varias campanhas de amostragem, tendo sido efectuadas medicoes de altura de agua, salinidade, temperatura da agua e velocidade da corrente em varias estacoes distribuidas ao longo de quatro canais principais da laguna. None

Experiências internacionais da aplicação de sistemas de apoio à decisão clínica em gastroenterologia

PubMed Central

Tenório, Josceli Maria; Hummel, Anderson Diniz; Sdepanian, Vera Lucia; Pisa, Ivan Torres; de Fátima Marin, Heimar

2015-01-01

Objetivo Descrever as experiências recentes com a aplicação de sistemas de apoio à decisão clínica em gastroenterologia, de forma a estabelecer o nível de desenvolvimento, testes e vantagens conferidas à prática médica com a introdução desses softwares. Métodos Foi realizada busca nas bases de dados PubMed, LILACS e ISI Web of Knowledge, utilizando termos relacionados à sistemas de apoio à decisão e à gastroenterogia, incluindo artigos originais publicados no período entre 2005 e 2010. Foram recuperadas 104 publicações, na busca inicial e, após a aplicação dos critérios de inclusão e exclusão, foram eleitos nove estudos para leitura do texto completo. Resultados Os sistemas de apoio à decisão clínica apresentam grande multiplicidade de problemas clínicos e investigação de doenças. Em 89% dos casos, são descritos modelos experimentais para o desenvolvimento de sistemas de apoio à decisão clínica. A descrição dos resultados obtidos por técnicas de inteligência artificial em 78% das publicações. Em dois dos estudos foram realizadas comparações com o médico e em apenas uma publicação um estudo controlado foi descrito, mostrando evidências de melhorias na prática médica. Conclusão Os estudos mostram potenciais benefícios dos sistemas de apoio à decisão clínica à prática médica, porém, estudos controlados em ambiente real devem ser realizados para comprovar esta perspectiva. PMID:26491625

Physicochemical and antimicrobial properties of copaiba oil: implications on product quality control.

PubMed

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

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

PubMed Central

Das, Sonjit; Joardar, Swarnalata; Dua, Tarun K.; Bhattacharjee, Niloy; Khanra, Ritu; Kalita, Jatin; Saha, Achintya; Ray, Supratim

2018-01-01

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. PMID:29854073

Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain.

PubMed

Woode, Eric; Ameyaw, Elvis Ofori; Boakye-Gyasi, Eric; Abotsi, Wonder Kofi Mensah; Oppong Kyekyeku, James; Adosraku, Reimmel; Biney, Robert Peter

2016-12-01

Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders. The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models. Acute muscle pain was induced in gastrocnemius muscle of Sprague-Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30-300 mg/kg), XA (10-100 mg/kg) or morphine (1-10 mg/kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall-Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain. XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED 50 mg/kg: XAE = 22.9; XA = 6.2) and skeletal hyperalgesia (XAE = 39.9; XA = 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED 50 : XAE = 13.0; XA = 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED 50 : XAE = 79.1; XA = 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia. These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.

Cloning and expression of a CYP720B orthologue involved in the biosynthesis of diterpene resin acids in Pinus brutia.

PubMed

Semiz, Asli; Sen, Alaattin

2015-03-01

Cytochrome P450 monooxygenases mediate a broad range of oxidative reactions involved in the biosynthesis of both primary and secondary metabolites in plants. Until now, only two P450 genes, CYP720B1 from Pinus taeda and CYP720B4 from Picea sitchensis, have been functionally characterised and described in the literature. The purpose of this study was to describe the cloning and expression of CYP720B from Pinus brutia due to its suggested role in the synthesis of bioactive compounds used for chemical defence against insects. A PCR product of the P. brutia CYP720B gene was cloned into the pCR8/GW/TOPO cloning vector. After optimising the sequence for codon usage in yeast, it was transferred into the inducible expression vector pYES-DEST52 and transfected into the S. cerevisiae INVSc1 strain. Sequence analysis showed that the P. brutia CYP720B gene contains an open reading frame of 1,464 nucleotides, which encodes a 53,570 Da putative protein of 487 amino acid residues. The putative protein contains the classic heme-binding sequence motif that is conserved in all P450 enzymes. It shares 99 and 61% identity with the deduced amino acid sequences of CYP720B1 from Pinus taeda and CYP720B4 from Picea sitchensis, respectively. Recombinant CYP720B protein expression was confirmed using western blot analysis. Furthermore, recombinant CYP720B was functionally active, showing a Soret peak at approximately 448 nm in the reduced CO difference spectra. These data suggest that the cloned gene is an orthologue of CYP720B in P. brutia and might be involved in DRA biosynthesis.

Tendências De Teses e Dissertações Sobre Educação em Astronomia No Brasil

NASA Astrophysics Data System (ADS)

Bretones, Paulo Sergio; Megid Neto, Jorge

2005-07-01

Apresentam-se os resultados de uma pesquisa do tipo estado da arte sobre teses e dissertações defendidas no Brasil e relativas ao ensino de Astronomia, com objetivo de identificar essa produção e conhecer as principais tendências da pesquisa nesse campo. Foram localizadas 13 dissertações de mestrado e 3 teses de doutorado, as quais foram estudadas em função dos seguintes aspectos: isntituição, ano de defesa, nível escolar abrangido no estudo, foco temático do estudo e gênero de trabalho acadêmico. Pretende-se assim colaborar com a divulgação ampla da produção acadêmica na área. Ao mesmo tempo o estudo possibilita, a partir de investigações decorrentes, apontar as contribuições dessa produção para o ensino e sinalizar com necessidades a serem supridas por futuras pesquisas.

Equatorial Scintillation Predictions from C/NOFS Planar Langmuir Probe Electron Density Fluctuation Data

DTIC Science & Technology

2014-09-05

Brasil Tel: 55 21 3527 1682; Fax: 55 21 3527 1154 E-mail: epoc@cetuc.puc-rio.br FINAL PERFORMANCE REPORT Equatorial scintillation...Costa Centro de Estudos em Telecomunicações/CETUC Rua Marquês de São Vicente, 225 – Gávea 22451-900 Rio de Janeiro - RJ – Brasil Tel: 55 21 3527...Emanoel Costa Centro de Estudos em Telecomunicações/CETUC Rua Marquês de São Vicente, 225 – Gávea 22451-900 Rio de Janeiro - RJ – Brasil Tel: 55

Comparing the variation of needle and wood terpenoids in Scots pine provenances.

PubMed

Manninen, A M; Tarhanen, S; Vuorinen, M; Kainulaine, P

2002-01-01

We determined variation in both the concentration and composition of terpenoids in needles and wood within nine Scots pine (Pinus sylvestris) provenances. Seedlings of different provenances representing a 1200-km N-S transect from Estonia to northern Finland were cultivated in Suonenjoki nursery field, central Finland, for seven years. Growth of seedlings and the number of vertical resin ducts in wood were also determined. alpha-Pinene and 3-carene were the major monoterpenes both in the needles and wood. The total monoterpene concentration was about five times higher in the needles than in the wood. A strong positive correlation was found between proportional quantities of several terpenes of the needles and wood, particularly for 3-carene, sabinene, and terpinolene. The needles contained both labdane-type and tricyclic resin acids, whereas the wood contained only tricyclic ones. The wood had a four times higher tricyclic resin acid concentration than the needles. The highest total monoterpene concentration in the needles and in the wood occurred in the most northern Muonio provenance and in the most southern Saaremaa provenance plants, respectively. The amount of high 3-carene genotype trees decreased among the northern provenances. The wood of the most northern Muonio provenance showed the lowest total resin acid concentration, but provenance did not affect total tricyclic resin acids in the needles. Korpilahti provenance trees from central Finland had the best growth in height. In addition, Korpilahti and Ruokolahti provenance trees showed largest radial growth of stem and smallest number of vertical resin ducts. The results suggest that especially the proportional quantity of 3-carene in the needles could be used in estimating the amount of this compound in the wood and vice versa.

Geranylgeranyl diphosphate synthase from Scoparia dulcis and Croton sublyratus. Plastid localization and conversion to a farnesyl diphosphate synthase by mutagenesis.

PubMed

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.

Seasonal variation of the essential oil from two Brazilian native Aldama La Llave (Asteraceae) species.

PubMed

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.

The Chinese Herb Isolate Yuanhuacine (YHL-14) Induces G2/M Arrest in Human Cancer Cells by Up-regulating p21 Protein Expression through an p53 Protein-independent Cascade*

PubMed Central

Zhang, Ruowen; Wang, Yulei; Li, Jingxia; Jin, Honglei; Song, Shaojiang; Huang, Chuanshu

2014-01-01

Yuanhuacine (YHL-14), the major component of daphnane diterpene ester isolated from the flower buds of Daphne genkwa, has been reported to have activity against cell proliferation in various cancer cell lines. Nevertheless, the potential mechanism has not been explored yet. Here we demonstrate that YHL-14 inhibits bladder and colon cancer cell growth through up-regulation of p21 expression in an Sp1-dependent manner. We found that YHL-14 treatment resulted in up-regulation of p21 expression and a significant G2/M phase arrest in T24T and HCT116 cells without affecting p53 protein expression and activation. Further studies indicate that p21 induction by YHL-14 occurs at the transcriptional level via up-regulation of Sp1 protein expression. Moreover, our results show that p38 is essential for YHL-14-mediated Sp1 protein stabilization, G2/M growth arrest induction, and anchorage-independent growth inhibition of cancer cells. Taken together, our studies demonstrate a novel mechanism of YHL-14 against cancer cell growth in bladder and colon cancer cell lines, which provides valuable information for the design and synthesis of other new conformation-constrained derivatives on the basis of the structure of YHL-14 for cancer therapy. PMID:24451377

The identity of Romanian amber (rumanite) with Baltic amber (succinite).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stout, E. C.; Beck, C. W.; Anderson, K. B.

Romanian amber (rumanite) has been considered to be a separate species of fossil resin for more than a century. While earlier investigators held it to be very similar to succinite (Baltic amber), modern scholars have assigned it a distinctly different botanical origin. We have found that almost all of the constituents of the ether-soluble fractions of 13 specimens of authentic rumanite identified by gas chromatography-mass spectrometry have previously been reported in the soluble fraction of succinite, including succinic acid and its monoterpene esters. Additionally and significantly, the soluble fraction of rumanite contains a number defunctionalized compounds that do not preexistmore » in succinite, but that are produced by pyrolysis of whole succinite or of its insoluble polymeric fraction. Simultaneous methylation pyrolysis-gas chromatography-mass spectrometry of the polymeric fraction of seven of the rumanite specimens yielded further copious amounts of dimethyl succinate, a number of diterpene resin acid methyl esters, and additional defunctionalized compounds known to be pyrolysis products of succinite. The evidence shows conclusively that the botanical origin of rumanite is not distinct from that of succinite. Rather, rumanite is a succinite that has suffered partial thermal degradation in the course of the folding of the Oligocene Kliwa sandstone formation in which it is most commonly found.« less

Erythrolic acids A-E, Meroterpenoids from a Marine-Derived Erythrobacter sp

PubMed Central

Hu, Youcai; Legako, Aaron G.; Espindola, Ana Paula D.M.; MacMillan, John B.

2012-01-01

Erythrolic acids A-E (1–5) are five unusual meroterpenoids isolated from the bacterium Erythrobacter sp. derived from a marine sediment sample collected in Galveston, TX. The structures were elucidated by means of detailed spectroscopic analysis and chemical derivatization. The erythrolic acids contain a 4-hydroxybenzoic acid appended with a modified terpene side chain. The side chain modifications include oxidation of a terminal methyl substituent and in the case of 1–4 addition of a 2-carbon unit to give terpene side chains of unusual length; C22 for 1 and 2, C17 for 3 and C12 for 4. The relative and absolute configurations of the meroterpenoids were determined by coupling constant, NOE and Mosher’s analysis. In vitro cytotoxicity towards a number of non-small cell lung cancer (NSCLC) cell lines revealed only modest activity for erythrolic acid D (4) (2.5 μM against HCC44). The discovery of these unusual diterpenes, along with the previously reported erythrazoles, demonstrate the natural product potential of a previously unstudied group of bacteria for drug discovery. The unusual nature of the terpene side chain, we believe, involves an oxidation of a terminal methyl group to a carboxylic acid and subsequent Claisen condensation with acetyl-CoA. PMID:22384985