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Sample records for cyathane diterpenoid natural

  1. Three new cyathane diterpenoids from the medicinal fungus Cyathus africanus.

    PubMed

    Han, Jun-Jie; Zhang, Lei; Xu, Jie-Kun; Bao, Li; Zhao, Feng; Chen, Yu-Hui; Zhang, Wei-Ku; Liu, Hong-Wei

    2015-05-01

    Three new cyathane diterpenoids, cyathin W (1), cyathin V (2), and cyathin T (3), were isolated from the solid culture of Cyathus africanus. The structures and configurations of these new compounds were elucidated on the basis of comprehensive spectroscopic analysis including 1D NMR, 2D NMR (HSQC, HMBC, NOESY), and HR-ESI-MS experiments. Compounds 1 and 3 showed moderate inhibition against nitric oxide production in lipopolysaccaride-activated macrophages with IC50 value of 80.07 and 88.87 μM, respectively. In cytotoxicity assay, compound 1 showed weak cytotoxicity against K562 cell line with IC50 value of 12.1 μM.

  2. Molecular Diversity and Potential Anti-neuroinflammatory Activities of Cyathane Diterpenoids from the Basidiomycete Cyathus africanus.

    PubMed

    Wei, Jing; Cheng, Yuanyuan; Guo, Wan-Hui; Wang, Da-Cheng; Zhang, Qiang; Li, Ding; Rong, Jianhui; Gao, Jin-Ming

    2017-08-21

    Ten new polyoxygenated cyathane diterpenoids, named neocyathins A-J (1-10), together with four known diterpenes (11-14), were isolated from the liquid culture of the medicinal basidiomycete fungus Cyathus africanus. The structures and configurations of these new compounds were elucidated through comprehensive spectroscopic analyses including 1D NMR, 2D NMR (HSQC, HMBC, NOESY) and HRESIMS, and electronic circular dichroism (ECD) data. Neuroinflammation is implicated in the pathogenesis of various neurodegenerative diseases, such as Alzheimers' disease (AD). All isolated compounds were evaluated for the potential anti-neuroinflammatory activities in BV2 microglia cells. Several compounds showed differential effects on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated and Aβ1-42-treated mouse microglia cell line BV-2. Molecular docking revealed that bioactive compounds (e.g., 11) could interact with iNOS protein other than COX-2 protein. Collectively, our results suggested that this class of cyathane diterpenoids might serve as important lead compounds for drug discovery against neuroinflammation in AD.

  3. Anti-inflammatory and cytotoxic cyathane diterpenoids from the medicinal fungus Cyathus africanus.

    PubMed

    Han, Junjie; Chen, Yuhui; Bao, Li; Yang, Xiaoli; Liu, Dailin; Li, Shaojie; Zhao, Feng; Liu, Hongwei

    2013-01-01

    Five novel cyathane diterpenes, cyathins D-H (1-5), as well as three known diterpenes, neosarcodonin O (6), cyathatriol (7),and 11-O-acetylcyathatriol (8), were isolated from the solid culture of Cyathus africanus. The structures of the new compounds were elucidated by spectroscopic methods. The absolute configurations of compounds 2 and 8 were determined by single-crystal X-ray crystallographic analysis, whereas the absolute configuration of C-14 in 1 was determined via the circular dichroism data of the [Rh(2)(OCOCF(3))(4)] complex. Compounds 3, 5, 6, 8, and 9 showed potent inhibition against nitric oxide production in lipopolysaccaride-activated macrophages with an IC(50) value of 2.57, 1.45, 12.0, 10.73, and 9.45μM, respectively. Compounds 6 and 8 showed strong cytotoxicity against Hela and K562 cell lines with the IC(50) value less than 10μM. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Diterpenoid alkaloids.

    PubMed

    Wang, Feng-Peng; Chen, Qiao-Hong; Liu, Xiao-Yu

    2010-04-01

    The lasting attention that researchers have devoted to diterpenoid alkaloids is due to their various bioactivities and toxicities, structural complexity, and intriguing chemistry. From 1998 to the end of 2008, more than 300 new diterpenoid alkaloids were isolated from Nature. This review focuses on their structural relationships, and investigations into their chemical reactions, synthesis, and biological activities. A table that lists the names, plant sources, and structural types is given along with 363 references.

  5. Enmein-type diterpenoid analogs from natural kaurene-type oridonin: Synthesis and their antitumor biological evaluation.

    PubMed

    Li, Dahong; Xu, Shengtao; Cai, Hao; Pei, Lingling; Zhang, Hengyuan; Wang, Lei; Yao, Hequan; Wu, Xiaoming; Jiang, Jieyun; Sun, Yijun; Xu, Jinyi

    2013-06-01

    A series of enmein-type diterpenoid analogs (11-20) derived from natural kaurene-type diterpenoid oridonin were synthesized and biologically evaluated. All target compounds showed improved anti-proliferative activities against four human cancer cell lines compared with natural oridonin and parent compound 10. Some compounds were more potent than positive control Taxol. Furthermore, mechanistic investigation showed that the representative compound 17 affected cell cycle and induced apoptosis at low micro-molar level in human hepatoma Bel-7402 cells, via an oxidative stress triggered mitochondria-related caspase-dependent pathway.

  6. A natural diterpenoid kamebacetal A with anti-tumor activity: Theoretical and experimental study

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Tang, Fu-ming; Zhang, Yi-Heng; Chen, Zhong

    2010-06-01

    Kamebacetal A ( 1) is an ent-kaurane diterpenoid isolated from Isodon racemosa (Hemsl) Hara. This natural product exhibits significant cytotoxicity against human Bel-7402 and HO-8910 tumor cells. The geometrical conformation of 1 has been optimized at the B3LYP/6-311+G(d) level of theory. The results indicated that the calculated geometric parameters are close to the X-ray crystal structure. The theoretical 13C NMR chemical shifts of 1 were also calculated at the GIAO-B3LYP level of theory with different basis sets. The calculated NMR chemical shifts are in closer agreement with the experimental results. A molecular electrostatic potential (MEP) map was used in an attempt to identify key features of the kamebacetal A to account for its anti-tumor activity. MEP investigations reveal that compound 1, which shows anti-tumor activity, possesses electron-rich regions that extend over the hydroxyl and carbonyl groups of compound 1. The data generated in this study is valuable as it provides an insight into kamebacetal A molecular and structure-activity relationships.

  7. Biosynthetic potential-based strain prioritization for natural product discovery: a showcase for diterpenoid-producing actinomycetes.

    PubMed

    Xie, Pengfei; Ma, Ming; Rateb, Mostafa E; Shaaban, Khaled A; Yu, Zhiguo; Huang, Sheng-Xiong; Zhao, Li-Xing; Zhu, Xiangcheng; Yan, Yijun; Peterson, Ryan M; Lohman, Jeremy R; Yang, Dong; Yin, Min; Rudolf, Jeffrey D; Jiang, Yi; Duan, Yanwen; Shen, Ben

    2014-02-28

    Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for the natural product community is to discover novel natural products efficiently and cost effectively. Here we report the development of a practical method to survey biosynthetic potential in microorganisms, thereby identifying the most promising strains and prioritizing them for natural product discovery. Central to our approach is the innovative preparation, by a two-tiered PCR method, of a pool of pathway-specific probes, thereby allowing the survey of all variants of the biosynthetic machineries for the targeted class of natural products. The utility of the method was demonstrated by surveying 100 strains, randomly selected from our actinomycete collection, for their biosynthetic potential of four classes of natural products, aromatic polyketides, reduced polyketides, nonribosomal peptides, and diterpenoids, identifying 16 talented strains. One of the talented strains, Streptomyces griseus CB00830, was finally chosen to showcase the discovery of the targeted classes of natural products, resulting in the isolation of three diterpenoids, six nonribosomal peptides and related metabolites, and three polyketides. Variations of this method should be applicable to the discovery of other classes of natural products.

  8. Biosynthetic Potential-Based Strain Prioritization for Natural Product Discovery: A Showcase for Diterpenoid-Producing Actinomycetes

    PubMed Central

    2015-01-01

    Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for the natural product community is to discover novel natural products efficiently and cost effectively. Here we report the development of a practical method to survey biosynthetic potential in microorganisms, thereby identifying the most promising strains and prioritizing them for natural product discovery. Central to our approach is the innovative preparation, by a two-tiered PCR method, of a pool of pathway-specific probes, thereby allowing the survey of all variants of the biosynthetic machineries for the targeted class of natural products. The utility of the method was demonstrated by surveying 100 strains, randomly selected from our actinomycete collection, for their biosynthetic potential of four classes of natural products, aromatic polyketides, reduced polyketides, nonribosomal peptides, and diterpenoids, identifying 16 talented strains. One of the talented strains, Streptomyces griseus CB00830, was finally chosen to showcase the discovery of the targeted classes of natural products, resulting in the isolation of three diterpenoids, six nonribosomal peptides and related metabolites, and three polyketides. Variations of this method should be applicable to the discovery of other classes of natural products. PMID:24484381

  9. Diterpenoids from Salvia prionitis.

    PubMed

    Lin, L Z; Wang, X M; Huang, X L; Huang, Y; Yang, B J

    1988-10-01

    Seven diterpenoids, 3-ketosapriparaquinone ( 1), salvilenone, 3-hydroxysalvilenone ( 2), arucadiol, royleanone, sugiol, and ferruginol were isolated from the root of SALVIA PRIONITIS Hance (Labiatae); Compounds 1 and 2 are new natural products. The structure of 1 was established through the interpretation of spectral data.

  10. ent-Labdane Diterpenoids from Dodonaea viscosa.

    PubMed

    Olivier, Wesley J; Kilah, Nathan L; Horne, James; Bissember, Alex C; Smith, Jason A

    2016-12-23

    Seven new and two known ent-labdane diterpenoids have been isolated from a single plant specimen of Dodonaea viscosa ssp. spatulata, found in Tasmania, Australia. Prior to this study, only seven different labdane diterpenoids had been isolated from D. viscosa. The structures of the natural products were assigned via 1D and 2D NMR spectroscopy and other standard spectroscopic methods. The absolute configuration of three ent-labdane diterpenoids was determined by single-crystal X-ray crystallography of synthetic derivatives. Significantly, the results of this study suggest that the absolute configuration of some known labdane diterpenoids may have been misassigned.

  11. Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation

    PubMed Central

    Hoyle, Christine I.; Chen, Jing; Chang, Weiyuan; Williams, Ronald W.; Rando, Roy J.

    2010-01-01

    Inflammation is associated with various pulmonary diseases and contributes to the pathogenesis of acute lung injury. We previously identified a proinflammatory signaling pathway triggered by G protein-coupled receptors (GPCRs) in which stimulation of Gq-coupled GPCRs results in activation of the transcription factor NF-κB. Because damage to the lung causes the release of multiple mediators acting through Gq-coupled GPCRs, this signaling pathway is likely to contribute to inflammatory processes in the injured lung. In an effort to identify novel inhibitors of lung inflammation, the National Institutes of Health Clinical Collection, a library of 446 compounds, was screened for inhibitory activity toward production of IL-8 induced by stimulation of the Gq-coupled tachykinin 1 receptor with substance P in A549 cells. Twenty-eight compounds that significantly inhibited substance P-induced IL-8 production were identified. The most potent inhibitor was triptolide, a diterpenoid compound from Tripterygium wilfordii Hook F, a vine used in traditional Chinese medicine for the treatment of autoimmune diseases. Triptolide inhibited IL-8 production induced by substance P with an IC50 of 2.3 × 10−8 M and inhibited NF-κB activation in response to an agonist of the protease-activated receptor 2 with an IC50 of 1.4 × 10−8 M. Anti-inflammatory effects of triptolide were assessed in vivo using a chlorine gas lung injury model in mice. Triptolide inhibited neutrophilic inflammation and the production of KC (Cxcl1) in the lungs of chlorine-exposed mice. The results demonstrate that triptolide exhibits anti-inflammatory activity in cultured lung cells and in an in vivo model of acute lung injury. PMID:20348278

  12. Diterpenoids from Fagonia mollis.

    PubMed

    Sallam, Amal; Nugroho, Alfarius Eko; Hirasawa, Yusuke; Chin-Piow, Wong; Kaneda, Toshio; Shirota, Osamu; Gedara, Sahar R; Morita, Hiroshi

    2014-09-01

    A new acyclic diterpenoid (1) and a new erythroxan diterpenoid (2), together with 4 erythroxan diterpenoids and 3 triterpenoids, have been isolated from the aerial parts of Fagonia mollis. Their structures were elucidated on the basis of 1D and 2D NMR data. The cytotoxic activity of the isolated compounds was investigated against HL-60 cancer cells.

  13. New clerodane diterpenoids from Croton crassifolius.

    PubMed

    Qiu, Maosong; Cao, Di; Gao, Youheng; Li, Shuhua; Zhu, Jinping; Yang, Bao; Zhou, Lian; Zhou, Yuan; Jin, Jing; Zhao, Zhongxiang

    2016-01-01

    Two new clerodane diterpenoids (1-2), one new clerodane diterpenoid alkaloid (3), as well as thirteen known compounds were isolated from Croton crassifolius. The structures of new compounds were established by a combination of spectroscopic methods, including HRMS, (1)H NMR, (13)C NMR, (1)H (1)H COSY, HSQC, HMBC, NOESY and X-ray crystallographic analysis. Compound 3 is firstly reported as the clerodane-type diterpenoid alkaloid in natural products. All of the compounds were evaluated for in vitro cytotoxic activities against CT26.WT cell using the MTT method.

  14. Natural Diterpenoid Compound Elevates Expression of Bim Protein, Which Interacts with Antiapoptotic Protein Bcl-2, Converting It to Proapoptotic Bax-like Molecule*

    PubMed Central

    Zhao, Lixia; He, Feng; Liu, Haiyang; Zhu, Yushan; Tian, Weili; Gao, Ping; He, Hongping; Yue, Wen; Lei, Xiaobo; Ni, Biyun; Wang, Xiaohui; Jin, Haijing; Hao, Xiaojiang; Lin, Jialing; Chen, Quan

    2012-01-01

    Overwhelming evidence indicates that Bax and Bak are indispensable for mediating cytochrome c release from mitochondria during apoptosis. Here we report a Bax/Bak-independent mechanism of cytochrome c release and apoptosis. We identified a natural diterpenoid compound that induced apoptosis in bax/bak double knock-out murine embryonic fibroblasts and substantially reduced the tumor growth from these cells implanted in mice. Treatment with the compound significantly increased expression of Bim, which migrated to mitochondria, altering the conformation of and forming oligomers with resident Bcl-2 to induce cytochrome c release and caspase activation. Importantly, purified Bim and Bcl-2 proteins cooperated to permeabilize a model mitochondrial outer membrane; this was accompanied by oligomerization of these proteins and deep embedding of Bcl-2 in the membrane. Therefore, the diterpenoid compound induces a structural and functional conversion of Bcl-2 through Bim to permeabilize the mitochondrial outer membrane, thereby inducing apoptosis independently of Bax and Bak. Because Bcl-2 family proteins play important roles in cancer development and relapse, this novel cell death mechanism can be explored for developing more effective anticancer therapeutics. PMID:22065578

  15. Osteogenic activity of natural diterpenoids isolated from Cupressus sempervirens fruits in calvarial derived osteoblast cells via differentiation and mineralization.

    PubMed

    Khan, Mohammad Faheem; Dev, Kapil; Lahiri, Shibani; Dixit, Manisha; Trivedi, Ritu; Singh, Divya; Maurya, Rakesh

    2014-12-15

    The aim of the present study was to investigate the antiosteoporotic activity of four structurally related diterpenoids: sugiol (1), trans-communic acid (2), 15-acetoxy imbricatolic acid (3) and imbricatolic acid (4). Their osteogenic effect was evaluated by using validated models including alkaline phosphatase (ALP) assay, mineralization assay and expression of osteogenic genes-bone morphogenetic protein-2 (BMP-2) and osteoblast transcription factor (RUNX2) - in primary calvarial cultures harvested from neonatal mice. Among them, compound 1 at a dose of 1.0 mg/kg body weight exhibited significant osteoprotective effects and did not show uterine estrogenicity at the same dose. Additionally, compound 1 treatment led to improved biomechanical properties as exhibited by increased power, energy and stiffness in femoral bones compared to untreated Ovx animals. Since osteoporotic compression fracture correlates with the mechanical characteristics of trabecular bone, so that it could effectively reduce the risk of this type of fracture by improving trabecular micro architecture in postmenopausal women. Therefore, our findings proposed that diterpenoids may be useful new chemical agents in the treatment of diseases associated with bone loss. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2012-08-01

    This review covers the isolation and chemistry of the diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, gibberellins, cembranes and their cyclization products and taxanes. There are 161 references.

  17. Diterpenoids from Leaves of Rubus chingii.

    PubMed

    Shu, Jicheng; Huang, Yingzheng; Cui, Hangqing; Peng, Caiying; Liu, Jianqun; Huang, Huilian

    2016-03-01

    The leaves of Rubus chingii were examined for their phytochemical composition and anti-yeast activity. In the process, seven diterpenoids (compounds 1-7), including a new natural compound (14β, 16-epoxy-7-pimarene-3α, 15β-diol, 1), were isolated and elucidated. Compound 1 exhibited moderate anti-Candida activity.

  18. New cis-clerodane diterpenoids from Croton schiedeanus.

    PubMed

    Puebla, Pilar; Correa, Sofía Ximena; Guerrero, Mario; Carron, Rosalía; San Feliciano, Arturo

    2005-03-01

    The acid fraction of extracts from the aerial part of Croton schiedeanus afforded six cis-clerodane type diterpenoids. Two of them (1 and 4) are new natural compounds. Structural elucidation was achieved on the basis of their spectral data.

  19. NMR spectroscopic search module for Spektraris, an online resource for plant natural product identification--Taxane diterpenoids from Taxus × media cell suspension cultures as a case study.

    PubMed

    Fischedick, Justin T; Johnson, Sean R; Ketchum, Raymond E B; Croteau, Rodney B; Lange, B Markus

    2015-05-01

    Development and testing of Spektraris-NMR, an online spectral resource, is reported for the NMR-based structural identification of plant natural products (PNPs). Spektraris-NMR allows users to search with multiple spectra at once and returns a table with a list of hits arranged according to the goodness of fit between query data and database entries. For each hit, a link to a tabulated alignment of (1)H NMR and (13)C NMR spectroscopic peaks (query versus database entry) is provided. Furthermore, full spectroscopic records and experimental meta information about each database entry can be accessed online. To test the utility of Spektraris-NMR for PNP identification, the database was populated with NMR data (total of 466 spectra) for ∼ 250 taxanes, which are structurally complex diterpenoids (including the anticancer drug taxol) commonly found in the genus Taxus. NMR data generated with metabolites purified from Taxus cell suspension cultures were then used to search Spektraris-NMR, and enabled the identification of eight taxanes with high confidence. A ninth isolated metabolite could be assigned, based on spectral searches, to a taxane skeletal class, but no high confidence hit was produced. Using various spectroscopic methods, this metabolite was characterized as 2-deacetylbaccatin IV, a novel taxane. These results indicate that Spektraris-NMR is a valuable resource for rapid and reliable identification of known metabolites and has the potential to contribute to de-replication efforts in novel PNP discovery.

  20. Functional identification of rice syn-copalyl diphosphate synthase and its role in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural products.

    PubMed

    Xu, Meimei; Hillwig, Matthew L; Prisic, Sladjana; Coates, Robert M; Peters, Reuben J

    2004-08-01

    Rice produces a number of phytoalexins, and at least one allelopathic agent, from syn-copalyl diphosphate (CPP), representing the only known metabolic fate for this compound. Thus, the class II terpene synthase that converts the universal diterpenoid precursor geranylgeranyl diphosphate to syn-CPP catalyzes the committed step in biosynthesis of these natural products. Here the extensive sequence information available for rice was coupled to recombinant expression and functional analysis to identify syn-copalyl diphosphate synthase (OsCPSsyn). In addition, OsCPSsyn mRNA was found to be specifically induced in leaves by conditions that stimulate phytoalexin biosynthesis. Therefore, transcription of OsCPSsyn seems to be an important regulatory point for controlling the production of these defensive compounds. Finally, alignments carried out with OsCPSsyn revealed that class II terpene synthases exhibit a sequence conservation pattern substantially different from that of the prototypical class I enzymes. One particularly notable feature is the specific conservation of the functionally cryptic 'insertional' sequence element in class II terpene synthases, indicating that this region is important for the corresponding cyclization reaction.

  1. NMR spectroscopicsearch module for Spektraris, an online resource for plant natural product identification – taxane diterpenoids from Taxus × media cell suspension cultures as a case study

    PubMed Central

    Fischedick, Justin T.; Johnson, Sean R.; Ketchum, Raymond E.B.; Croteau, Rodney B.; Lange, B. Markus

    2014-01-01

    Development and testing of Spektraris-NMR an online spectral resource, is reported for the NMR-based structural identification of plant natural products (PNPs). Spektraris-NMRallows users to search with multiple spectra at once and returns a table with alist of hits arranged according to the goodness of fit between query data and database entries. For each hit, a link to a tabulated alignment of 1H-NMR and 13C-NMR spectroscopic peaks (query versus database entry) is provided. Furthermore, full spectroscopic records and experimental meta information about each database entry can be accessed online. To test the utility of Spektraris-NMR for PNP identification, the database was populated with NMR data (total of 466 spectra) for ∼250 taxanes, which are structurally complex diterpenoids (including the anticancer drug taxol) commonly found in the genus Taxus. NMR data generated used was then generated with metabolites purified from Taxus cell suspension cultures to search Spektraris-NMR, and were able to identify eight taxanes with high confidence. A ninth isolated metabolite could be assigned, based on spectral searches, to a taxane skeletal class, but no high confidence hit was produced. Using various spectroscopic methods, this metabolite was characterized as the taxane 2-deacetylbaccatin IV, a novel taxane. These results indicate that Spektraris-NMR is a valuable resource for rapid and reliable identification of known metabolites and has the potential to contribute to de-replication efforts in the search for novel PNPs. PMID:25534952

  2. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2013-10-11

    Covering January to December 2012. Previous review, Nat.Prod.Rep., 2012, 29, 890-898. This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 169 references.

  3. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2016-10-28

    Covering January to December 2015. Previous review; Nat. Prod. Rep., 2015, 32, 1654-1663.This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 214 references.

  4. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2017-09-06

    Covering: January to December, 2016 previous review Nat. Prod. Rep., 2016, 33, 1227-1238This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembrenes and their cyclization products. There are 205 references.

  5. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2015-12-19

    Covering January to December 2014. Previous review, Nat. Prod. Rep., 2015, 32, 76-87 This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes, labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 200 references.

  6. Diterpenoids of terrestrial origin.

    PubMed

    Hanson, James R

    2015-01-01

    Covering: January to December 2013. Previous review, Nat. Prod. Rep., 2013, 30, 1346-1356. This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 179 references.

  7. Eriocalyxin B, a natural diterpenoid, inhibited VEGF-induced angiogenesis and diminished angiogenesis-dependent breast tumor growth by suppressing VEGFR-2 signaling

    PubMed Central

    Zhou, Xunian; Yue, Grace Gar-Lee; Liu, Minghua; Zuo, Zhili; Lee, Julia Kin-Ming; Li, Mingyue; Tsui, Stephen Kwok-Wing; Fung, Kwok-Pui; Sun, Handong; Pu, Jianxin; Lau, Clara Bik-San

    2016-01-01

    Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 μM) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion. Furthermore, EriB also caused G1 phase cell cycle arrest which was correlated with the down-regulation of the cyclin D1 and CDK4 leading to the inhibition of phosphorylated retinoblastoma protein expression. Investigation of the signal transduction revealed that EriB inhibited VEGF-induced phosphorylation of VEGF receptor-2 via the interaction with the ATP-binding sites according to the molecular docking simulations. The suppression of VEGFR-2 downstream signal transduction cascades was also observed. EriB was showed to inhibit new blood vessel formation in Matrigel plug model and mouse 4T1 breast tumor model. EriB (5 mg/kg/day) treatment was able to decrease tumor vascularization and suppress tumor growth and angiogenesis. Taken together, our findings suggested that EriB is a novel inhibitor of angiogenesis through modulating VEGFR-2 signaling pathway, which could be developed as a promising anti-angiogenic agent for treatment of angiogenesis-related human diseases, such as cancer. PMID:27756875

  8. Evaluation of Aconitum diterpenoid alkaloids as antiproliferative agents.

    PubMed

    Wada, Koji; Ohkoshi, Emika; Zhao, Yu; Goto, Masuo; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2015-04-01

    Little information has been reported on the antitumor effects of the diterpenoid alkaloid constituents of Aconitum plants, used in the herbal drug 'bushi'. This study was aimed at determining the antitumor activities of Aconitum C19-and C20-diterpenoid alkaloids and synthetic derivatives against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines. Newly synthesized C20-diterpenoid alkaloid derivatives showed substantial suppressive effects against all human tumor cell lines tested. In contrast, natural and derivatized C19-diterpenoid alkaloids showed only a slight or no effect. Most of the active compounds were hetisine-type C20-diterpenoid alkaloids, specifically kobusine and pseudokobusine analogs with two different substitution patterns, C-11 and C-11,15. Notably, several C20-diterpenoid alkaloids were more potent against multidrug-resistant KB subline KB-VIN cells. Pseudokobusine 11-3'-trifluoromethylbenzoate (94) is a possible promising new lead meriting additional evaluation against multidrug-resistant tumors.

  9. Evaluation of Aconitum diterpenoid alkaloids as antiproliferative agents

    PubMed Central

    Wada, Koji; Ohkoshi, Emika; Zhao, Yu; Goto, Masuo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2015-01-01

    Little information has been reported on the antitumor effects of the diterpenoid alkaloid constituents of Aconitum plants, used in the herbal drug “bushi”. This study was aimed at determining the antitumor activities of Aconitum C19-and C20-diterpenoid alkaloids and synthetic derivatives against lung (A549), prostate (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN) cancer cell lines. Newly synthesized C20-diterpenoid alkaloid derivatives showed substantial suppressive effects against all human tumor cell lines tested. In contrast, natural and derivatized C19-diterpenoid alkaloids showed only a slight or no effect. Most of the active compounds were hetisine-type C20-diterpenoid alkaloids, specifically kobusine and pseudokobusine analogs with two different substitution patterns, C-11 and C-11,15. Notably, several C20-diterpenoid alkaloids were more potent against multidrug-resistant KB subline KB-VIN cells. Pseudokobusine 11-3′-trifluoromethylbenzoate (94) is a possible promising new lead meriting additional evaluation against multidrug-resistant tumors. PMID:25770782

  10. New Bioactive Macrocyclic Diterpenoids from Euphorbia helioscopia.

    PubMed

    Hua, Juan; Luo, Shi-Hong; Liu, Yan; Liu, Yan-Chun; Tan, Yan-Yun; Feng, Ling; Xiao, Chao-Jiang; Zhang, Ke-Qin; Li, Sheng-Hong; Niu, Xue-Mei

    2017-08-03

    Three new macrocyclic diterpenoids, euphoscopoids A - C (1 - 3), including two new jatrophanes and a new lathyrane, were isolated from the whole plant of Euphorbia helioscopia. Their structures were elucidated by spectroscopic methods. Antifeedant and cytotoxic activities of these isolates were evaluated. All compounds showed significant antifeedant activity against a generalist plant-feeding insect, Helicoverpa armigera, with EC50 values ranging from 2.05 to 4.34 μg/cm(2) . In addition, compound 2 showed moderate cytotoxicity against tumor cell lines NCI-H1975, HepG2, and MCF-2, while compounds 1 and 3 were not active at 80 μm. The results suggested not only the defensive function of macrocyclic diterpenoids in E. helioscopia against insect herbivores, but also their potential applications as new natural insect antifeedants. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  11. Pharicin A, a novel natural ent-kaurene diterpenoid, induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function.

    PubMed

    Xu, Han-Zhang; Huang, Ying; Wu, Ying-Li; Zhao, Yong; Xiao, Wei-Lie; Lin, Qi-Shan; Sun, Han-Dong; Dai, Wei; Chen, Guo-Qiang

    2010-07-15

    In this study, we report the functional characterization of a new ent-kaurene diterpenoid termed pharicin A, which was originally isolated from Isodon, a perennial shrub frequently used in Chinese folk medicine for tumor treatment. Pharicin A induces mitotic arrest in leukemia and solid tumor-derived cells identified by their morphology, DNA content and mitotic marker analyses. Pharicin A-induced mitotic arrest is associated with unaligned chromosomes, aberrant BubR1 localization and deregulated spindle checkpoint activation. Pharicin A directly binds to BubR1 in vitro, which is correlated with premature sister chromatid separation in vivo. Pharicin A also induces mitotic arrest in paclitaxel-resistant Jurkat and U2OS cells. Combined, our study strongly suggests that pharicin A represents a novel class of small molecule compounds capable of perturbing mitotic progression and initiating mitotic catastrophe, which merits further preclinical and clinical investigations for cancer drug development.

  12. Abietane diterpenoids from Cephalotaxus lanceolata.

    PubMed

    Chen, Xiao-Jiao; Ni, Ling; Bao, Mei-Fen; Wang, Li; Cai, Xiang-Hai

    2017-04-12

    A new abietane diterpenoid, 12-O-methyl-20-deoxocarnosol-3-one (1), and eight known abietane diterpenoids including 13-abietadien-12-one (2), 5,6-dehydrosugiol (3), sugiol (4), torreyayunnin (5), taxusabietane A (6), hinokiol (7), 3-acetoxyabieta-8,11,13-trien-12-ol (8), and martiusane (9) were obtained from leaves and twigs of Cephalotaxus lanceolata. The structures of isolated compounds (1-9) were determined based on analysis of their spectroscopic data and comparison with those reported in the literature. Compounds 3, 8 and 9 were first isolated from the plants of Cephalotaxus genus.

  13. Diterpenoids with Immunosuppressive Activities from Cinnamomum cassia.

    PubMed

    Zeng, Junfen; Xue, Yongbo; Shu, Penghua; Qian, Huiqin; Sa, Rongjian; Xiang, Ming; Li, Xiao-Nian; Luo, Zengwei; Yao, Guangmin; Zhang, Yonghui

    2014-08-22

    Three new diterpenoids with unprecedented carbon skeletons, cinncassiols F (1) and G (2) and 16-O-β-D-glucopyranosyl-19-deoxycinncassiol G (3), a new isoryanodane diterpenoid, 18-hydroxyperseanol (4), six known isoryanodane diterpenoids, 5-10, and a known ryanodane diterpenoid, 11, were isolated from the stem bark of Cinnamomum cassia. Compound 1 possesses an 11,13:12,13-diepoxy-6,11-epoxy:12,13-disecoisoryanodane diterpenoid skeleton bearing ketal and hemiketal functionalities, whereas compounds 2 and 3 feature an 11,12-secoisoryanodane diterpenoid skeleton with an 11,6-lactone moiety. The structures of the four new diterpenoids, 1-4, and their absolute configurations were established using HRESIMS, NMR, ECD, single-crystal X-ray diffraction, and chemical methods. Compounds 2 and 11 significantly inhibited the proliferation of murine T cells induced by ConA.

  14. Bacteria-induced static batch fungal fermentation of the diterpenoid cyathin A(3), a small-molecule inducer of nerve growth factor.

    PubMed

    Dixon, Emma; Schweibenz, Tatiana; Hight, Alison; Kang, Brian; Dailey, Allyson; Kim, Sarah; Chen, Meng-Yang; Kim, Yura; Neale, Sarah; Groth, Ashley; Ike, Trish; Khan, Sarah; Schweibenz, Brandon; Lieu, David; Stone, David; Orellana, Tania; Couch, Robin D

    2011-05-01

    Cyathin A(3), produced by the fungus Cyathus helenae, is a member of the cyathane family of diterpene natural products. While many of the cyathanes display antibacterial/antimicrobial activity or have cytotoxic activity against human cancer cell lines, their most exciting therapeutic potential is derived from their ability to induce nerve growth factor (NGF) release from glial cells, making the cyathanes attractive lead molecules for the development of neuroprotective therapeutics to prevent/treat Alzheimer's disease. To investigate if cyathin A(3) has NGF-inducing activity, we set out to obtain it using published C. helenae bench-scale fungal fermentations. However, to overcome nonproducing fermentations, we developed an alternative, bacteria-induced static batch fermentation approach to the production of cyathin A(3), as described in this report. HPLC, UV absorption spectra, and mass spectrometry identify cyathin A(3) in fungal fermentations induced by the timely addition of Escherichia coli K12 or Bacillus megabacterium. Pre-filtration of the bacterial culture abolishes cyathin A(3) induction, suggesting that bacteria-associated media changes or physical interaction between the fungus and bacteria underlie the induction mechanism. Through alteration of incubation conditions, including agitation, the timing of induction, and media composition, we optimized the fermentation to yield nearly 1 mg cyathin A(3)/ml media, a sixfold increase over previously described yields. Additionally, by comparison of fermentation profiles, we reveal that cyathin A(3) biosynthesis is regulated by carbon catabolite repression. We have used an enzyme-linked immunosorbent assay to illustrate that cyathin A(3) induces NGF release from cultured glial cells, and therefore cyathin A(3) warrants further examination in the development of neuroprotective therapeutics.

  15. Crotofolane diterpenoids from Croton caracasanus.

    PubMed

    Chávez, Katiuska; Compagnoneb, Reinaldo S; Riina, Ricarda; Briceño, Alexander; González, Teresa; Squitieri, Emilio; Landaetab, Carlos; Soscrún, Humberto; Suáreza, Alírica I

    2013-12-01

    Four new crotofolane-type diterpenoids, crotocarasin (A-D) (1-4), together with the known crotofolin E, were isolated from a dichloromethane extract of the stems of Croton caracasanus Pittier. The structures of the new compounds were determined by spectroscopic methods, and the structure of 3 was further confirmed by single-crystal X-ray data analyses.

  16. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  17. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules.

  18. Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

    PubMed Central

    2015-01-01

    Summary This review describes strategies for the chemical synthesis of xenicane diterpenoids and structurally related metabolites. Selected members from the four different subclasses of the Xenia diterpenoid family, the xenicins, xeniolides, xeniaphyllanes and xeniaethers, are presented. The synthetic strategies are discussed with an emphasis on the individual key reactions for the construction of the uncommon nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated. PMID:26734099

  19. Labdane diterpenoids from Salvia reuterana.

    PubMed

    Farimani, Mahdi Moridi; Miran, Mansour

    2014-12-01

    Three labdane diterpenoids, 14α-hydroxy-15-chlorosclareol (1), 14α-hydroxy-15-acetoxysclareol (2), and 6β-hydroxy-14α-epoxysclareol (3), together with the known diterpenoids sclareol (4), 6β-hydroxysclareol (5), and 14α-epoxysclareol (6), as well as other common plant constituents were isolated from the n-hexane extract of aerial parts of Salvia reuterana. The structures of the new compounds were established by extensive 1D and 2D NMR spectroscopic techniques. Compound 1 is the first example of a halogenated terpenoid in the genus Salvia. Compounds 1-6 were also tested for their inhibitory activity toward HeLa and MCF-7 cell lines. Preliminary structure-activity relationship studies indicated that double bond moiety in sclareol is an essential feature for activity and modification of this moiety significantly decreased the cytotoxic activity of the resulting compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives.

    PubMed

    Timoshenko, Mariya A; Kharitonov, Yurii V; Shakirov, Makhmut M; Bagryanskaya, Irina Yu; Shults, Elvira E

    2016-02-01

    A selective synthesis of 7- or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β- and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products.

  1. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives†

    PubMed Central

    Timoshenko, Mariya A.; Kharitonov, Yurii V.; Shakirov, Makhmut M.; Bagryanskaya, Irina Yu.

    2015-01-01

    Abstract A selective synthesis of 7‐ or 14‐nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α‐hydroxy‐15,16‐dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3‐nitroaniline, 3‐(trifluoromethyl)aniline, and 4‐(trifluoromethyl)aniline yield the subsequent 7α‐, 7β‐ and 14αnitrogen‐containing diterpenoids. The reaction with 2‐nitroaniline, 4‐nitro‐2‐chloroaniline, 4‐methoxy‐2‐nitroaniline, phenylsulfamide, or tert‐butyl carbamate proceeds with the formation of 7α‐nitrogen‐substituted diterpenoids as the main products. PMID:27308214

  2. A Novel Norclerodane Diterpenoid from the Roots of Croton crassifolius.

    PubMed

    Zhang, Zhan-Xin; Li, Hui-Hong; Fan, Gai-Xia; Li, Zheng-Yu; Dong, Le-Le; Li, Hong-Yu; Fei, Dong-Qing

    2015-11-01

    A chemical investigation of Croton crassifolius afforded a novel norclerodane diterpenoid (1) with an unprecedented six-membered oxygen ring between C-1 and C-12, together with three known compounds. The structure of the new compound was elucidated based on spectroscopic (IR, 1D, and 2D NMR) and HR-ESI-MS techniques. This report describes the first example of a natural norclerodane with a 4H-chromene ring system.

  3. Briarane Diterpenoids Isolated from Octocorals between 2014 and 2016

    PubMed Central

    Su, Yin-Di; Su, Jui-Hsin; Hwang, Tsong-Long; Wen, Zhi-Hong; Sheu, Jyh-Horng; Wu, Yang-Chang; Sung, Ping-Jyun

    2017-01-01

    The structures, names, bioactivities, and references of 124 briarane-type natural products, including 66 new metabolites, isolated between 2014 and 2016 are summarized in this review article. All of the briarane diterpenoids mentioned in this review were isolated from octocorals, mainly from Briareum violacea, Dichotella gemmacea, Ellisella dollfusi, Junceella fragilis, Junceella gemmacea, and Pennatula aculeata. Some of these compounds exhibited potential biomedical activities, including anti-inflammatory activity, antibacterial activity, and cytotoxicity towards cancer cells. PMID:28218675

  4. Cytotoxic diterpenoids from Salvia yunnanensis.

    PubMed

    Wu, Chun-Yan; Liao, Yang; Yang, Zi-Gang; Yang, Xing-Wei; Shen, Xiao-Ling; Li, Rong-Tao; Xu, Gang

    2014-10-01

    Forty-six abietane type diterpenoids possessing nine different fused ring systems were characterized from the roots of Salvia yunnanensis, six of which (salyunnanins A-F, 1-6) had different nor-abietane, homo-abietane, seco-abietane, and normal abietane architectures. Their structures were elucidated by comprehensive NMR and MS spectroscopic analyses. The inhibitory activities of these isolates against six human tumor lines were tested in vitro. Several of the compounds exhibited substantial cytotoxicity with IC50 values of 0.86-10.1μM.

  5. Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum.

    PubMed

    Ahmad, Hanif; Ahmad, Shujaat; Shah, Syed Adnan Ali; Latif, Abdul; Ali, Mumtaz; Khan, Farman Ali; Tahir, Muhammad Nawaz; Shaheen, Farzana; Wadood, Abdul; Ahmad, Manzoor

    2017-07-01

    Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Asymmetric synthesis and absolute stereochemistry of a labdane-type diterpenoid isolated from the rhizomes of Isodan yuennanensis.

    PubMed

    Deng, Heping; Cao, Wei; Zhang, Zhijiang; Liu, Bo

    2016-07-14

    The first synthesis of a labdane-type diterpenoid isolated from Isodon yuennanensis was achieved in fourteen steps from commercially available starting material, (+)-sclareolide. The synthesis features the Barton nitrite ester reaction to introduce an oxime at the angular methyl group and the Jones oxidation to construct the lactone segment. By comparison of the optical rotation of our synthetic sample and the natural sample, the absolute stereochemistry of the natural diterpenoid has been determined.

  7. Bioactive diterpenoids from Croton laevigatus.

    PubMed

    Zhang, Jun-Sheng; Tang, Ya-Qi; Huang, Jia-Luo; Li, Wei; Zou, Yi-Hong; Tang, Gui-Hua; Liu, Bo; Yin, Sheng

    2017-09-18

    Eight previously undescribed diterpenoids, crolaevinoids A-H, including two halimanes, four clerodanes, and two laevinanes, along with six known analogues were isolated from the twigs of Croton laevigatus. The structures of the previously undescribed were elucidated by spectroscopic analysis, and their absolute configurations were determined by combination of a single crystal X-ray diffraction and CD analysis (exciton chirality and Rh2(OCOCF3)4-induced methods). Crolaevinoids A and B represent the first halimane diterpenoids with a unique lactone bridge between C-12 and C-17. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. Furocrotinsulolide A and 3,4,15,16-diepoxy-cleroda-13(16),14-diene-12,17-olide exhibited pronounced inhibition of NO production with IC50 values of 10.4 ± 0.8 and 6.0 ± 1.0 μM, respectively, being more potent than the positive control, quercetin (IC50 = 13.1 ± 1.9 μM). Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Diterpenoid derivatives of Kenyan Croton sylvaticus.

    PubMed

    Ndunda, Beth; Langat, Moses K; Midiwo, Jacob O; Omosa, Leonidah K

    2015-04-01

    Kenyan Croton sylvaticus Hochst. ex Krauss gave four clerodane diterpenoids, the new ent-3,13E-clerodadiene-15-formate (1), the known 15-acetoxy-ent-3,13E-clerodadiene (2), ent-3,13E-clerodadien-15-ol (3) and hardwickiic acid (4), two known halimane diterpenoids, penduliflaworosin (5) and crotohalimaneic acid (6) and one labdane diterpenoid, labda-13E-ene-8a,15-diol (7). The compounds, when tested for their anti-microbial activities against Bacillus subtilis, Xanthomonas campestris and Candida albicans, were found to be inactive.

  9. Anticancer Activities of C18-, C19-, C20-, and Bis-Diterpenoid Alkaloids Derived from Genus Aconitum.

    PubMed

    Ren, Meng-Yue; Yu, Qing-Tian; Shi, Chun-Yu; Luo, Jia-Bo

    2017-02-13

    Cancer is one of the most common lethal diseases, and natural products have been extensively studied as anticancer agents considering their availability, low toxicity, and economic affordability. Plants belonging to the genus Aconitum have been widely used medically in many Asian countries since ancient times. These plants have been proven effective for treating several types of cancer, such as lung, stomach, and liver cancers. The main effective components of Aconitum plants are diterpenoid alkaloids-which are divided into C18-, C19-, C20-, and bis-diterpenoid alkaloids-are reportedly some of the most promising, naturally abundant compounds for treating cancer. This review focuses on the progress of diterpenoid alkaloids with different structures derived from Aconitum plants and some of their derivatives with potential anticancer activities. We hope that this work can serve as a reference for further developing Aconitum diterpenoid alkaloids as anticancer agents.

  10. Antimicrobial Diterpenoids of Wedelia trilobata (L.) Hitchc.

    PubMed

    Li, Shi-Fei; Ding, Jia-Yin; Li, Ya-Ting; Hao, Xiao-Jiang; Li, Shun-Lin

    2016-04-07

    Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1-7. Their structures and relative configuration were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR experiments. The antimicrobial activities of all isolated diterpenoids were evaluated against a panel of bacteria and fungi.

  11. ent-Kaurene diterpenoids from Isodon oresbius.

    PubMed

    Xiang, Wei; Li, Rong-Tao; Wang, Zong-Yu; Li, Sheng-Hong; Zhao, Qin-Shi; Zhang, Hong-Jie; Sun, Han-Dong

    2004-04-01

    Three new ent-kaurene diterpenoids, oreskaurins A-C (1-3), together with ten known ent-kaurene diterpenoids, enmenin monoacetate (4), effusanin E (5), adenolin B (6), maoecrystal G (7), enmelol (8), trichokaurin (9), sodoponin (10), trichorabdal A (11), nodosin (12), enmein (13), and a flavonoid, vitexin (14), were isolated from Isodon oresbius. Their structures were determined by spectroscopic means. Compound 12 showed inhibitory activity toward K562 cells with IC(50)=1.43 microg/ml.

  12. Five New C19 -Diterpenoid Alkaloids from Delphinium tianshanicum W.T.Wang.

    PubMed

    Zhang, Ji-Fa; Shan, Lian-Hai; Gao, Feng; Huang, Shuai; Zhou, Xian-Li

    2017-04-01

    Five new diterpenoid alkaloids, tianshanitines A-E (1 - 5), along with ten known compounds (6 - 15), were isolated from the EtOH extracts of the whole plant of Delphinium tianshanicum W.T.Wang. Their structures were determined based on extensive spectroscopic analyses, including 1D- and 2D-NMR, HR-ESI-MS, and the structure of tianshanitine C (3) was confirmed by X-ray diffraction analysis. Tianshanitine A (1) is the first example of natural diterpenoid alkaloid containing a benzoyl group at C(1) position. Tianshanitine B (2) is a rare natural diterpenoid alkaloid bearing a OH group at C(16) position. Compounds 1 - 5, 6, 8, 10, 12 and 14 were evaluated for cytotoxicity against HCT116, MCF-7 and HepG2 human cancer cell lines. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  13. 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

  14. Synthesis and biological evaluation of novel exo-methylene cyclopentanone tetracyclic diterpenoids as antitumor agents.

    PubMed

    Li, Jing; Zhang, Dayong; Wu, Xiaoming

    2011-01-01

    The structure of exo-methylene cyclopentanone, which exists in nature tetracyclic diterpenoids products, has been proved to be an innate group for the treatment of cancer and inflammation. In this letter, four different scaffolds of tetracyclic diterpenoids including the structure exo-methylene cyclopentanone were synthesized from steviol and isosteviol and evaluated in vitro for their antitumor activity against three human cancer lines. Compounds 1a, 1b, 2b and 3b showed significant cytotoxicity, particularly, tetracyclic diterpenoids 2b, 3b were identified as the most potent and selective anticancer agents superior to adriamycin with IC(50) values of 0.9 μM and 1.5 μM, against Hep-G2 and MDA-MB-231 cell lines, respectively.

  15. New norclerodane diterpenoids from the tubers of Dioscorea bulbifera.

    PubMed

    Tang, Ying; Xue, Yong-bo; Zhou, Lei; Zhang, Jin-wen; Yao, Guang-min; Luo, Zeng-wei; Du, Guang; Zhang, Yong-hui

    2014-01-01

    Phytochemical investigations of the tubers of Dioscorea bulbifera L. resulted in the isolation of nine norclerodane diterpenoids, including two new compounds, diosbulbins N (1) and P (3), a new naturally occurring compound, diosbulbin O (2), and six known ones, diosbulbins A-D, F and G (4-9). Their structures were established by spectroscopic and chemical methods. The absolute stereochemistry of 1 was determined by a modified Mosher's method, and the absolute configuration of 2 was determined by a single-crystal X-ray diffraction analysis with CuKα irradiation. Compounds 1-3 were evaluated for in vitro cytotoxicity against five human cancer cell lines.

  16. Abietane diterpenoids from Isodon inflexus.

    PubMed

    Xie, Wei-Dong; Li, Xia; Zhao, Jiang-He; Liu, Yong-Heng; Row, Kyung Ho

    2012-09-01

    Four abietane diterpenoids, inflexanin C, inflexanin D, inflexuside A and inflexuside B, were isolated from the aerial parts of Isodon inflexus. Their respective structures were established by NMR, mass spectrometry and CD as (+)-(1S,4R,5S,7S,8S,10S,13S)-1,7,18-trihydroxy-abieta-9(11)-ene-12-one 1-monoacetate, (+)-(1S,4R,5S,10S,13S)-1,18-dihydroxy-abieta-7,9(11)-diene-12-one 1-monoacetate, (-)-(1S,5S,10S,11R,13R)-1,11,13-trihydroxy-abieta-8-ene-7-one 1-O-β-D-glucopyranoside and (-)-(1S,5S,10S,11R,13R)-1,11,13-trihydroxy-abieta-8-ene-7-one 1-O-(2-O-coumaroyl)-β-D-glucopyranoside. All compounds showed strong inhibitory activity against nitric oxide (NO) production in RAW264.7 lipopolysaccaride (LPS)-activated macrophages. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Diterpenoid alkaloids and flavonoids from Delphinium trichophorum.

    PubMed

    Lin, Chao-Zhan; Zhao, Zhong-Xiang; Xie, Si-Min; Mao, Ju-Hua; Zhu, Chen-Chen; Li, Xiao-Hui; Zeren-dawa, Bairi; Suolang-qimei, Kangsa; Zhu, Dun; Xiong, Tian-Qin; Wu, Ai-Zhi

    2014-01-01

    Five hetisane-type C20-diterpenoid alkaloids, trichodelphinines A-E, one delnudine-type C20-diterpenoid alkaloid, trichodelphinine F and three known flavonoids, quercetin, quercetin 3-O-β-D-glucopyranoside, and quercetin 3-O-β-D-glucopyranoside-7-O-α-L-arabinopyranoside, were isolated from whole plants of Delphinium trichophorum Franch. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, (1)H-(1)H COSY, NOESY and X-ray crystallographic analysis, and from chemical evidence. The cytotoxic activities of the diterpenoid alkaloids were evaluated using the MTT method, and the IC50 values of their cytotoxicity against A549 cancer cells ranged from 12.03 to 52.79 μM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Diterpenoid Biopolymers: New Directions for Renewable Materials Engineering

    PubMed Central

    Hillwig, Matthew L.; Mann, Francis M.; Peters, Reuben J.

    2010-01-01

    Most types of ambers are naturally occurring, relatively hard, durable resinite polymers derived from the exudates of trees. This resource has been coveted for thousands of years due to its numerous useful properties in industrial processes, beauty, and purported medicinal properties. Labdane diterpenoid based ambers represent the most abundant and important resinites on earth. These resinites are a dwindling, non-renewable natural resource, so a new source of such materials needs to be established. Recent advances in sequencing technologies and biochemical engineering are rapidly accelerating the rate of identifying and assigning function to genes involved in terpenoid biosynthesis, as well as producing industrial-scale quantities of desired small-molecules in bacteria and yeast. This has provided new tools for engineering metabolic pathways capable of producing diterpenoid monomers that will enable the production of custom-tailored resinite-like polymers. Furthermore, this biosynthetic toolbox is continuously expanding, providing new possibilities for renewing dwindling stocks of naturally occurring resinite materials and engineering new materials for future applications. PMID:20857504

  19. Diterpenoid biopolymers: new directions for renewable materials engineering.

    PubMed

    Hillwig, Matthew L; Mann, Francis M; Peters, Reuben J

    2011-02-01

    Most types of ambers are naturally occurring, relatively hard, durable resinite polymers derived from the exudates of trees. This resource has been coveted for thousands of years due to its numerous useful properties in industrial processes, beauty, and purported medicinal properties. Labdane diterpenoid-based ambers represent the most abundant and important resinites on earth. These resinites are a dwindling nonrenewable natural resource, so a new source of such materials needs to be established. Recent advances in sequencing technologies and biochemical engineering are rapidly accelerating the rate of identifying and assigning function to genes involved in terpenoid biosynthesis, as well as producing industrial-scale quantities of desired small-molecules in bacteria and yeast. This has provided new tools for engineering metabolic pathways capable of producing diterpenoid monomers that will enable the production of custom-tailored resinite-like polymers. Furthermore, this biosynthetic toolbox is continuously expanding, providing new possibilities for renewing dwindling stocks of naturally occurring resinite materials and engineering new materials for future applications. © 2010 Wiley Periodicals, Inc.

  20. Isolation of antibacterial diterpenoids from Cryptomeria japonica bark.

    PubMed

    Li, Wen-Hsin; Chang, Shang-Tzen; Chang, Shan-Chwen; Chang, Hui-Ting

    2008-01-01

    The aims of the present study were to determine the antibacterial activity of bark extract of Cryptomeria japonica D. Don and to isolate potential antibacterial constituents. The results showed that the ethanolic extract of C. japonica bark possessed a good antibacterial activity. Nine compounds including seven diterpenoids (ferruginol (I), isopimaric acid (II), iguestol (III), isopimarol (IV), phyllocladan-16alpha-ol (V), sandaracopimarinol (VI) and sugiol (VII)) and two steroids (beta-sitosterol (VIII) and beta-sitostenone (IX)) were isolated from active subfractions; beta-sitostenone was isolated for the first time from this plant. Among these compounds, ferruginol possessed the strongest antibacterial activity and had MIC values ranging from 6.3 to 12.5 microg mL(-1) against all bacteria tested. Isopimaric acid was also an antibacterial natural product. Cryptomeria japonica bark extract and its diterpenoids, ferruginol and isopimaric acid, have the ability to inhibit the bacterial growth and can be used as the source for natural bactericides.

  1. To Gibberellins and Beyond! Surveying the Evolution of (Di)terpenoid Metabolism

    PubMed Central

    Zi, Jiachen; Mafu, Sibongile; Peters, Reuben J.

    2014-01-01

    The diterpenoids are classically defined by their composition, four isoprenyl units (20 carbons), and are generally derived from [E,E,E]-geranylgeranyl diphosphate (GGPP). Such metabolism seems to be ancient and has been extensively diversified, with ~12,000 diterpenoid natural products known. Particularly notable are the gibberellin phytohormones, whose requisite biosynthesis has provided a genetic reservoir giving rise to not only a large super-family of ~7,000 diterpenoids, but to some degree all plant terpenoid natural products. This review focuses on the diterpenoids, particularly the defining biosynthetic characteristics of the major superfamilies defined by the cyclization and/or rearrangement of GGPP catalyzed by diterpene synthases/cyclases, although some discussion also is provided of the important subsequent elaboration in those few cases where molecular genetic information is available. In addition, the array of biological activity providing the selective pressure driving the observed gene family expansion and diversification, along with biosynthetic gene clustering, will be discussed as well. PMID:24471837

  2. Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound

    PubMed Central

    Li, Dahong; Han, Tong; Liao, Jie; Hu, Xu; Xu, Shengtao; Tian, Kangtao; Gu, Xiaoke; Cheng, Keguang; Li, Zhanlin; Hua, Huiming; Xu, Jinyi

    2016-01-01

    Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field. PMID:27563888

  3. New kaurene diterpenoid glycosides from fenugreek seeds.

    PubMed

    Pang, Xu; Kang, Li-Ping; Yu, He-Shui; Zhao, Yang; Xiong, Cheng-Qi; Zhang, Jie; Ma, Bai-Ping

    2013-01-01

    Two new kaurene diterpenoid glycosides, named Graecumoside A (1) and B (2), were isolated from fenugreek seeds, along with three known flavonoid-C-glycosides, isoorientin (3), isovitexin (4) and vitexin (5). By combined analyses of 1D- and 2D-NMR, and MS spectroscopy, the structures of two new compounds were elucidated as 3-O-β- D-glucopyranosyl kaur-5, 16-dien-3β, 6, 13β-trihydroxy-7-oxo-18-oic acid methyl ester and 3-O-β-neohesperidosyl kaur-5, 16-dien-3β, 6, 13β-trihydroxy-7-oxo-18-oic acid methyl ester, respectively. The kaurene diterpenoid glycosides were first isolated and identified from fenugreek seeds.

  4. Neo-clerodane diterpenoids from Croton schiedeanus.

    PubMed

    Puebla, Pilar; López, Jose L; Guerrero, Mario; Carrón, Rosalía; Martín, M Luisa; San Román, Luis; San Feliciano, Arturo

    2003-02-01

    Two new neo-clerodane type furano diterpenoids were isolated from the aerial part of Croton schiedeanus, besides the clerodane diterpenes cis- and trans-dehydrocrotonin, previously isolated from other species of Croton. Structural elucidation was achieved on basis of extensive NMR experiments, including X-ray diffraction analysis and molecular mechanics calculations. The previously known flavonoids ayanin and quercetin-3,7-dimethyl ether were also obtained from the extract of this plant.

  5. Isolation of three diterpenoid acids from sunflowers, as oviposition stimulants for the banded sunflower moth, Cochylis hospes.

    PubMed

    Morris, Bruce D; Charlet, Laurence D; Foster, Stephen P

    2009-01-01

    The banded sunflower moth (BSFM), Cochylis hospes Walshingham (Lepidoptera: Cochylidae) is a specialist insect, the larvae of which feed on sunflowers, Helianthus spp., and a few other species of Compositae. It is one of the most important pests of sunflower in the USA. Previous work on H. annuus, the cultivated sunflower, revealed two diterpenoids that function as oviposition stimulants for female BSFM, and that other, more polar compounds also stimulated oviposition. Using a bioassay-guided approach, we isolated three additional diterpenoids, grandifloric acid (1), 15beta-hydroxy-ent-trachyloban-19-oic acid (2), and 17-hydroxy-16alpha-ent-kauran-19-oic acid (3), from polar fractions of pre-bloom sunflower head extracts. In laboratory bioassays, purified natural samples of each of these compounds stimulated oviposition by female BSFM. Structure-activity relationships of the five diterpenoids known to stimulate oviposition by female BSFM are discussed.

  6. New marine diterpenoids from the Okinawan soft coral Clavularia koellikeri.

    PubMed

    Iwashima, Makoto; Matsumoto, Yuuki; Takenaka, Yosuke; Iguchi, Kazuo; Yamori, Takao

    2002-10-01

    Chemical investigation of the Okinawan soft coral Clavularia koellikeri resulted in the isolation of two new cembrane diterpenoids (1 and 2) and one new dollabelane diterpenoid, 3. Their structures were determined on the basis of the results of spectroscopic analysis. Compounds 1 and 3 were examined for in vitro growth-inhibition effects toward tumor cells.

  7. Identification of a diverse synthetic abietane diterpenoid library for anticancer activity.

    PubMed

    Xu, Hongtao; Liu, Lili; Fan, Xiaoting; Zhang, Guanjun; Li, Yuanchao; Jiang, Biao

    2017-02-01

    A diverse natural-product-like synthetic abietane diterpenoid library contains about 56 compounds were obtained, and evaluated for their potential in vitro cytotoxic or antitumor activity against A549, PC-3 and SKOV-3 tumor cell lines by SRB assay. Treatment of A549 cells with the most potent compound ketone 19 showed induction of apoptosis, as revealed by JC-1 mitochondrial membrane potential staining, TUNNEL assay, western blotting analysis and flow cytometry assay.

  8. New Cytotoxic Tigliane Diterpenoids from Croton caudatus.

    PubMed

    Chen, Ying-Ying; Yang, Kun-Xian; Yang, Xing-Wei; Khan, Afsar; Liu, Lu; Wang, Bei; Zhao, Yun-Li; Liu, Ya-Ping; Li, Yan; Luo, Xiao-Dong

    2016-05-01

    Three new tigliane-type diterpenoids were isolated from the methanolic extract of the twigs and leaves of Croton caudatus, trivially named crotusins A-C (1-3). The structures of compounds 1-3 were elucidated on the basis of extensive spectral methods. These new compounds were highly oxygenated and heavily substituted. Cytotoxic activity against five human tumor cell lines was assessed for compounds 1-3 of which compound 3 showed significant inhibitory activity with IC50 values ranging from 0.49 to 4.19 µM against these cells, while crotusins A and B exhibited moderate activity.

  9. Briarane Diterpenoids from the Gorgonian Dichotella gemmacea

    PubMed Central

    La, Ming-Ping; Li, Jiao; Li, Cui; Tang, Hua; Liu, Bao-Shu; Sun, Peng; Zhuang, Chun-Lin; Li, Tie-Jun; Zhang, Wen

    2014-01-01

    Seven new briarane diterpenoids, gemmacolides AS-AY (1–7), were isolated together with ten known analogues (8–17) from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by the detailed analysis of spectroscopic data and comparison with reported data. The absolute configuration of compounds was determined based on electronic circular dichroism (ECD) experiments and genetic correlations as well. Compounds 15 and 16 were reported for the first time for the gorgonian. In the preliminary in vitro bioassays, compound 5 showed potential growth inhibitory activity against MG63 cells. PMID:25528959

  10. Antioxidative action of diterpenoids from Podocarpus nagi.

    PubMed

    Haraguchi, H; Ishikawa, H; Kubo, I

    1997-06-01

    Diterpenoids, totarol (1), totaradiol (2), 19-hydroxytotarol (3), totaral (4), 4 beta-carboxy-19-nortotarol (5), sugiol (6), isolated from Podocarpus nagi, were evaluated as antioxidants. Microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH and mitochondrial lipid peroxidation induced by Fe(III)-ADP/ NADH were inhibited by these terpenoids. They inhibited linoleic acid autoxidation but not generation of superoxide anion. Totarol (1) protected mitochondrial respiratory enzyme activities against NADPH induced oxidative injury. Totarane diterpenes from P. nagi were shown to be effective to protect biological systems and function against various oxidative stresses.

  11. ent-Kaurene diterpenoids from Blepharispermum hirtum.

    PubMed

    Fatope, Majekodunmi O; Varma, Gouri B; Alzri, Nasser M; Marwah, Ruchi G; Nair, Rani S

    2010-07-01

    The twigs and leaves of Blepharispermum hirtum Oliver (Asteraceae) were investigated for their larvicidal and antimicrobial activity. Fractionation of the extracts of the twigs, directed by brine shrimp test and antibacterial activities, led to the isolation of compounds 1-4; two of which are new ent-kaurene diterpenoids, blepharispins A and B (1 and 2, resp.). The structures of compounds 1 and 2 were established from spectral data. The absolute configuration at C(15) in 1 was inferred from Mosher ester analysis and relative configurations were suggested by a NOESY experiment. Compound 4 was significantly larvicidal to newly hatched naupleii of Artemia salina L. (BST LC(50)=1.3 (3.7-0.0) microg/ml), but the blepharispins were not (BST LC(50) > 500 microg/ml). Nevertheless, compound 1 inhibited the growth of Staphylococcus aureus and Bacillus subtilis at a MIC value of 62.5 microg/ml. The significance of the bioactivity results and the presence of ent-kaurene diterpenoids in B. hirtum are discussed from biosynthetic and local utilization viewpoints.

  12. Optimization of recombinant expression enables discovery of novel cytochrome P450 activity in rice diterpenoid biosynthesis

    PubMed Central

    Kitaoka, Naoki; Wu, Yisheng; Xu, Meimei; Peters, Reuben J.

    2015-01-01

    The oxygenation reactions catalyzed by cytochromes P450 (CYPs) play critical roles in plant natural products biosynthesis. At the same time, CYPs are one of most challenging enzymes to functionally characterize due to the difficulty of recombinantly expressing these membrane-associated monooxygenases. In the course of investigating rice diterpenoid biosynthesis we have developed a synthetic biology approach for functional expression of relevant CYPs in Escherichia coli. In certain cases activity was observed for only one of two closely related paralogs although it seems clear that related reactions are required for production of the known diterpenoids. Here we report that optimization of the recombinant expression system enabled characterization of not only these previously recalcitrant CYPs, but also discovery of additional activity relevant to rice diterpenoid biosynthesis. Of particular interest, CYP701A8 was found to catalyze 3β-hydroxylation of syn-pimaradiene, which is presumably relevant to momilactone biosynthesis, while CYP71Z6 & 7 were found to catalyze multiple reactions, with CYP71Z6 catalyzing the production of 2α,3α-dihydroxy-ent-isokaurene via 2α-hydroxy- ent-isokaurene, and CYP71Z7 catalyzing the production of 3α-hydroxy-ent-cassadien-2- one via 2α-hydroxy-ent-cassadiene and ent-cassadien-2-one, which may be relevant to oryzadione and phytocassane biosynthesis, respectively. PMID:25758958

  13. Manoyl oxide diterpenoids from Grindelia scorzonerifolia.

    PubMed

    Ybarra, María Inés; Popich, Susana; Borkosky, Susana A; Asakawa, Yoshinori; Bardón, Alicia

    2005-04-01

    Two new norditerpenoids, 4beta-hydroxy-19-normanoyl oxide (1) and 4alpha-hydroxy-18-normanoyl oxide (2), the new 18-O-alpha-l-arabinopyranosylmanoyl oxide (3a), and the known diterpenoids jhanol (4) and 18-hydroxy-13-epi-manoyl oxide (5) were isolated, together with other common plant constituents from an Argentine collection of Grindelia scorzonerifolia. The structures of the new compounds were established by extensive 1D and 2D NMR techniques and chemical transformations. Structural features of compounds 2 and 4 were verified by X-ray crystallographic analyses. The insecticidal effect of compound 3a was evaluated against the polyphagous pest Spodoptera frugiperda. Pupal and adult malformations leading to death occurred when 3a was incorporated in a larval diet at a concentration of 100 ppm.

  14. BI- and tricyclic diterpenoids from Halimium viscosum.

    PubMed

    Rodilla, J M; De Mendonça, D I; Ismael, M I; Figueiredo, J A; Silva, M L; Lopes, E

    2001-01-01

    The study of the acid and neutral parts of the n-hexane extract of Halimium viscosum (S. João da Pesqueira, Portugal) has led to the isolation of various known diterpenoids with the ent-halimane skeleton. Five new compounds have now been isolated, one with the ent-halimane skeleton, and four with the valparane skeleton, two of them with the valparane skeleton degraded. The structures of these compounds, determined by spectroscopic methods using 2D experiments (1H-13C, HMQC and HMBC), were dimethyl 1(10)-halimen-15,18-dioate, dimethyl 3,19-dinor-15-valparen-2,4-dioate, methyl 16-nor-2,3-secovalpara-3,15-dioxo-2-oate, 1,3,5,1 5-valparatetraene and 3R-4alpha-methoxy-15-valparen-2-one.

  15. Antifilarial activity of diterpenoids from Taxodium distichum.

    PubMed

    Kushwaha, Vikas; Saxena, Kirti; Verma, Richa; Verma, Shiv K; Katoch, Deepali; Kumar, Neeraj; Lal, Brij; Murthy, P Kalpana; Singh, Bikram

    2016-05-31

    Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi and B. timori, is a debilitating disease with an adverse social and economic impact. The infection remains unabated in spite of treatment with existing antifilarial drugs diethylcarbamazine (DEC) and ivermectin which are chiefly microfilaricides. There is therefore, need for macrofilaricides, embryostatic agents and better microfilaricides. In the present study we explored the antifilarial potential of crude extract and its molecular fractions of the plant Taxodium distichum using in vitro assay systems and rodent models of B. malayi infection. Ethanolic extract (A001) of aerial parts of T. distichum was solvent fractionated and sub-fractionated. Four molecules, 3-Acetoxylabda-8(20), 13-diene-15-oic acid (K001), Beta-sitosterol (K002), labda-8(20),13-diene-15-oic acid (K003) and Metasequoic acid A (K004) were isolated from the fractions and their structure determined by spectroscopic analysis. The extract, subfractions and molecules were evaluated for antifilarial activity against B. malayi by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) reduction and motility assays in vitro and in two animal models, Meriones unguiculatus and Mastomys coucha, harbouring B. malayi infection. A001 was effective in killing microfilariae (mf) and adult worms in vitro. The diterpenoid K003 produced 100 % reduction in motility of both mf and adult worms and > 80 % inhibition in MTT reduction potential of adult female worms. In B. malayi-M. unguiculatus model, A001 killed all the adult worms in > 80 % of infected animals. K003 was embryostatic (> 95 %) in this model. In the B. malayi-M. coucha model, K003 killed ~54 % of adult worms (macrofilaricidal activity) and rendered > 36 % female worms sterile; it also stopped any further rise in microfilaraemia after day 42 post-initiation of treatment. Ethanolic extract of aerial parts of the plant T. distichum possesses potent

  16. Bioactive Diterpenoid Containing a Reversible “Spring-Loaded” (E,Z)-dieneone Michael Acceptor

    PubMed Central

    Gupta, Prasoon; Sharma, Upasana; Schulz, Thomas C.; Sherrer, Eric S.; McLean, Amanda B.; Robins, Allan J.; West, Lyndon M.

    2012-01-01

    Three new briarane diterpenoids, briareolate esters L – N (1 – 3) have been isolated from a gorgonian Briareum asbestinum. Briareolate esters L (1) and M (2) are the first natural products possessing a 10-membered macrocyclic ring with a (E,Z)-dieneone and exhibit growth inhibition activity against both human embryonic stem cells (BG02) and a pancreatic cancer cell line (BxPC-3). Briareolate ester L (1), was found to contain a “spring-loaded” (E,Z)-dieneone Michael acceptor group that can form a reversible covalent bond to model sulfur-based nucleophiles. PMID:21749084

  17. Diterpenoid glycosyl esters from Phlomis younghusbandii and P. medicinalis roots.

    PubMed

    Katagiri, M; Ohtani, K; Kasai, R; Yamasaki, K; Yang, C R; Tanaka, O

    1994-01-01

    From the roots of Phlomis younghusbandii collected in Tibet, new furanolabdane-type diterpenoid glycosides named phlomisosides III and IV were isolated together with a known sweet furanolabdane-type diterpenoid glycoside, phlomisoside I. The structure of the common aglycone of phlomisosides III and IV, which we have named phlomisoic acid, was established as 15,16-epoxy-8,13(16),14-labdatrien-19-oic acid by MS and NMR spectroscopy. Phlomisosides III and IV are tasteless and the structures of these were determined to be the beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranosyl and the alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester of phlomisoic acid by chemical and spectroscopic methods, respectively. The diterpenoid glycoside constituents of the roots of P. medicinalis collected in Tibet were also elucidated, and baiyunoside and phlomisosides II and III were isolated and identified.

  18. Hepatoprotective diterpenoids from the roots of Salvia grandifolia.

    PubMed

    Kang, Jie; Zhang, Ting; Li, Li; Sun, Hua; Wang, Ding-Ding; Chen, Ruo-Yun

    2016-05-01

    One new diterpenoid, grandifolia G (1), together with a known diterpenoid (6,7,8,8a-tetrahydro-6,6-dimethyl-2-oxonaphtho[1,8-bc]furan-3-yl)-4-methylfuran-3-carboxylic acid (2), was isolated from 70% EtOH extract of root of Salvia grandifolia. Their structures were determined by UV, IR, HRESIMS, NMR spectra. Compounds 1 and 2 (10 μM) exhibited hepatoprotective activities (61 and 55%) against DL-galactosamine-induced cell damage in HL-7702 cells.

  19. Fimbriatols A–J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional Chinese Plant Flickingeria fimbriata (B1.) Hawkes

    PubMed Central

    Ding, Gang; Fei, Jiaodong; Wang, Jing; Xie, Yong; Li, Rongtao; Gong, Ningbo; Lv, Yang; Yu, Changyuan; Zou, Zhongmei

    2016-01-01

    Fimbriatols A–J (1–10), ten new ent-kaurane diterpenoids possessing differently highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes. The structures of these new compounds were determined by HRESI-MS, NMR, CD spectra and X-ray diffraction analysis. Compound 1 displayed moderately inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at the concentration of 0.022 μg/mL. Compounds 7–10 possess 3, 4-seco-ent-kaurane skeleton containing a disaccharide moiety with an unusual linkage at C-2′ to C-1′′ instead of the common linkage at C-6′ to C-1′′, and this is the first report in 600 more ent-kauranes found in nature, which might be originated from ent-kaurane diterpenoids through post-modified reactions of Baeyer-Villiger oxygenation and glycosylation. PMID:27484744

  20. Excisanin H, a novel cytotoxic 14,20-epoxy-ent-kaurene diterpenoid, and three new ent-kaurene diterpenoids from Rabdosia excisa.

    PubMed

    Gui, Ming-Yu; Aoyagi, Yutaka; Jin, Yong-Ri; Li, Xu-Wen; Hasuda, Tomoyo; Takeya, Koichi

    2004-03-01

    A novel 14,20-epoxy-ent-kaurene diterpenoid, excisanin H (1), and three new ent-kaurene diterpenoids, 2-4, were isolated from aerial parts of Rabdosia excisa along with eight known ent-kaurene diterpenoids, 5-12. The structural elucidations were made using spectral (HREIMS, IR, (1)H, (13)C, and 2D NMR) methods. The absolute configuration of 1 was determined by demonstrating that oxidation of kamebakaurin (8) produced excisanin H (1). These ent-kaurene diterpenoids all showed significant cytotoxic activity against P388 murine leukemia cells.

  1. Suppression of inflammatory responses by labdane-type diterpenoids.

    PubMed

    Girón, Natalia; Través, Paqui G; Rodríguez, Benjamín; López-Fontal, Raquel; Boscá, Lisardo; Hortelano, Sonsoles; de las Heras, Beatriz

    2008-04-15

    A series of 11 labdane-type diterpenoids (1-11) with various patterns of substitution were tested for potential anti-inflammatory activity. Of these compounds, 4 and 11 were selected to evaluate their influence on targets relevant to the regulation of the inflammatory response. These diterpenoids reduced the production of nitric oxide (NO), prostaglandin E2, and tumor necrosis factor-alpha in LPS-activated RAW 264.7 macrophages, with IC50 in the range 1-10 microM. Inhibition of these inflammatory mediators was related to inhibition of the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) at the transcriptional level, as determined by western-blot and RT-PCR. Examination of the effects of these diterpenoids on nuclear factor kappaB signaling showed that both compounds inhibit the phosphorylation of IkappaBalpha and IkappaBbeta, preventing their degradation and the nuclear translocation of the NF-kappaB p65 subunit. Inhibition of IKK activity was also observed. These derivatives displayed significant anti-inflammatory activity in vivo, suppressing mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibiting myeloperoxidase activity, an index of neutrophil infiltration. The anti-inflammatory effects of these labdane diterpenoids, together with their low cell toxicity, suggest potential therapeutic applications in the regulation of the inflammatory response.

  2. Supression of inflammatory responses by labdane-type diterpenoids

    SciTech Connect

    Giron, Natalia; Rodriguez, Benjamin; Lopez-Fontal, Raquel; Bosca, Lisardo; Hortelano, Sonsoles Heras, Beatriz de las

    2008-04-15

    A series of 11 labdane-type diterpenoids (1-11) with various patterns of substitution were tested for potential anti-inflammatory activity. Of these compounds, 4 and 11 were selected to evaluate their influence on targets relevant to the regulation of the inflammatory response. These diterpenoids reduced the production of nitric oxide (NO), prostaglandin E2, and tumor necrosis factor-{alpha} in LPS-activated RAW 264.7 macrophages, with IC50 in the range 1-10 {mu}M. Inhibition of these inflammatory mediators was related to inhibition of the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) at the transcriptional level, as determined by western-blot and RT-PCR. Examination of the effects of these diterpenoids on nuclear factor {kappa}B signaling showed that both compounds inhibit the phosphorylation of I{kappa}B{alpha} and I{kappa}B{beta}, preventing their degradation and the nuclear translocation of the NF-{kappa}B p65 subunit. Inhibition of IKK activity was also observed. These derivatives displayed significant anti-inflammatory activity in vivo, suppressing mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibiting myeloperoxidase activity, an index of neutrophil infiltration. The anti-inflammatory effects of these labdane diterpenoids, together with their low cell toxicity, suggest potential therapeutic applications in the regulation of the inflammatory response.

  3. Antimicrobial activity of clerodane diterpenoids from Polyalthia longifolia seeds.

    PubMed

    Marthanda Murthy, M; Subramanyam, M; Hima Bindu, M; Annapurna, J

    2005-06-01

    The diterpenoids 16alpha-hydroxy-cleroda-3,13 (14)-Z-diene-15,16-olide (1) and 16-oxo-cleroda-3, 13(14)-E-diene-15-oic acid (2), isolated from the hexane extract of the seeds of Polyalthia longifolia, demonstrated significant antibacterial and antifungal activities.

  4. Sabiperones A-F, new diterpenoids from Juniperus sabina.

    PubMed

    Janar, Jenis; Nugroho, Alfarius Eko; Wong, Chin Piow; Hirasawa, Yusuke; Kaneda, Toshio; Shirota, Osamu; Morita, Hiroshi

    2012-01-01

    Six new diterpenoids, sabiperones A-F (1-6) have been isolated from the aerial part of Juniperus sabina. Their structures were elucidated by spectroscopic methods including 2D NMR techniques. Sabiperone F showed moderate cell growth inhibitory activities against five human cancer cell lines.

  5. A new diterpenoid from the aerial parts of Andrographis paniculata.

    PubMed

    Wang, Chun-Hua; Li, Wen; Qiu, Rui-Xia; Jiang, Miao-Miao; Li, Guo-Qiang

    2014-01-01

    One new and seven known diterpenoids were isolated from the aerial parts of Andrographis paniculata, and their structures elucidated on the basis of spectroscopic and spectrometric analysis, as well as chemical methods. The in vitro antiviral activities of these compounds against respiratory syncytial virus (RSV) were assayed.

  6. Antibacterial activity of ent-kaurene diterpenoids from Rabdosia rosthornii.

    PubMed

    Kubo, Isao; Xu, Yunlong; Shimizu, Kuniyoshi

    2004-02-01

    Biological activities of ent-kaurene diterpenoids, rosthornins A-D, isolated from the ether extract of the dried leaves of Rabdosia rosthornii (Diels) Hara (Labiatae) were tested. They exhibited antibacterial activity specifically against Gram-positive bacteria, among which Propionibacterium acnes was noted to be the most susceptible.

  7. Metabolic Engineering of Synechocystis sp. PCC 6803 for Production of the Plant Diterpenoid Manoyl Oxide

    PubMed Central

    2015-01-01

    Forskolin is a high value diterpenoid with a broad range of pharmaceutical applications, naturally found in root bark of the plant Coleus forskohlii. Because of its complex molecular structure, chemical synthesis of forskolin is not commercially attractive. Hence, the labor and resource intensive extraction and purification from C. forskohlii plants remains the current source of the compound. We have engineered the unicellular cyanobacterium Synechocystis sp. PCC 6803 to produce the forskolin precursor 13R-manoyl oxide (13R-MO), paving the way for light driven biotechnological production of this high value compound. In the course of this work, a new series of integrative vectors for use in Synechocystis was developed and used to create stable lines expressing chromosomally integrated CfTPS2 and CfTPS3, the enzymes responsible for the formation of 13R-MO in C. forskohlii. The engineered strains yielded production titers of up to 0.24 mg g–1 DCW 13R-MO. To increase the yield, 13R-MO producing strains were further engineered by introduction of selected enzymes from C. forskohlii, improving the titer to 0.45 mg g–1 DCW. This work forms a basis for further development of production of complex plant diterpenoids in cyanobacteria. PMID:26133196

  8. Generating skeletal diversity from the C19 -diterpenoid alkaloid deltaline: a ring-distortion approach.

    PubMed

    Chen, Qi-Feng; Wang, Feng-Peng; Liu, Xiao-Yu

    2015-06-08

    The development of new drugs calls for large collections of diverse molecules with considerable complexity. Ring distortion of natural products provides an efficient and facile approach to access new architectures with intriguing biological activities, by harnessing their inherent complexity. In this study, such a strategy has been explored on an abundant C19 -diterpenoid alkaloid, deltaline, enabling the synthesis of 32 new derivatives bearing a broad spectrum of unique scaffolds. Extensive spectroscopic studies including X-ray crystallographic analyses strongly supported the structures of the obtained novel skeletons, which present comparable opportunities with the great contributions made by nature for discovery of new lead compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Macrocyclic Diterpenoids from the Latex of Euphorbia helioscopia.

    PubMed

    Hua, Juan; Liu, Yan-Chun; Jing, Shu-Xi; Luo, Shi-Hong; Li, Sheng-Hong

    2015-12-01

    One new jatrophane diterpenoid, 7α,9β,15β-triacetoxy-3β-benzoyloxy-14β-hydroxyjatropha-5E,11E-diene (3), together with four known macrocyclic diterpenoids, euphoheliosnoid A (1), epieuphoscopin B (2), euphohelioscopin A (4) and euphoscopin C (5), were isolated from the stem latex of Euphorbia helioscopia. Their structures were established by spectroscopic analyses. In the anti-inflammatory assay, euphohelioscopin A (4) exhibited moderate inhibitory activity on the release of cytokine TNF-α (IC50 = 23.7 ± 1.7 μM), IL-6 (IC50 = 46.1 ± 1.1 μM) and chemokine MCP-1 (IC50 = 33.7 ± 3.8 μM) in lipopolysaccharide (LPS) induced RAW 264.7 macrophages without notable cytotoxicity (IC50 > 80 μM).

  10. Structurally Diverse Diterpenoids from Isodon scoparius and Their Bioactivity.

    PubMed

    Jiang, Hua-Yi; Wang, Wei-Guang; Tang, Jian-Wei; Liu, Miao; Li, Xing-Ren; Hu, Kun; Du, Xue; Li, Xiao-Nian; Zhang, Hong-Bin; Pu, Jian-Xin; Sun, Han-Dong

    2017-07-28

    Fourteen new diterpenoids (1-14) based on four skeletal types and two known analogues (15 and 16) were isolated from the aerial parts of Isodon scoparius. Compound 2 is the first ent-kaurane diterpenoid featuring a 1,11-ether bridge, and the structures of these new compounds were established mainly by NMR and MS methods. The absolute configurations of 1 and 5 and the relative configuration of 3 were determined using single-crystal X-ray diffraction. The absolute configuration of 14 was determined by comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 4, and 15 were active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and they also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 1.0, 3.1, and 1.8 μM, respectively.

  11. Cytotoxic, apoptotic, and sensitization properties of ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep on human liver cancer HepG2 and Hep3b cell lines.

    PubMed

    Pham, Minh Quan; Iscache, Anne Laure; Pham, Quoc Long; Gairin, Jean Edouard

    2016-04-01

    Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, the second most common cause of death from cancer worldwide. A very poor prognosis and a lack of effective treatments make liver cancer a major public health problem, notably in less developed regions, particularly in eastern Asia. This fully justifies the search of new molecules and therapeutic strategies against HCC. Ent-kaurane diterpenoids are natural compounds displaying a broad spectrum of potential therapeutic effects including anticancer activity. In this study, we analyzed the pharmacological properties of a family of ent-kaurane diterpenoids from Croton tonkinensis Gagnep in human HepG2 and Hep3b cell lines, used as cellular reference models for in vitro evaluation of new molecules active on HCC. A structure-related cytotoxicity was observed against both HCC cell lines, enlighting the role of the 16-en-15-one skeleton of ent-kaurane diterpenoids. Cytotoxicity was closely correlated to apoptosis, evidenced by concentration-dependent subG1 cell accumulation, and increased annexin V expression. In addition, subtoxic concentration of ent-kaurane diterpenoid dramatically enhanced the sensitivity of HCC cells to doxorubicin. All together, our data bring strong support to the potential interest of ent-kaurane diterpenoids, alone or in combination with a cytotoxic agent, in cancer and more precisely against HCC.

  12. Identity, regulation, and activity of inducible diterpenoid phytoalexins in maize.

    PubMed

    Schmelz, Eric A; Kaplan, Fatma; Huffaker, Alisa; Dafoe, Nicole J; Vaughan, Martha M; Ni, Xinzhi; Rocca, James R; Alborn, Hans T; Teal, Peter E

    2011-03-29

    Phytoalexins constitute a broad category of pathogen- and insect-inducible biochemicals that locally protect plant tissues. Because of their agronomic significance, maize and rice have been extensively investigated for their terpenoid-based defenses, which include insect-inducible monoterpene and sesquiterpene volatiles. Rice also produces a complex array of pathogen-inducible diterpenoid phytoalexins. Despite the demonstration of fungal-induced ent-kaur-15-ene production in maize over 30 y ago, the identity of functionally analogous maize diterpenoid phytoalexins has remained elusive. In response to stem attack by the European corn borer (Ostrinia nubilalis) and fungi, we observed the induced accumulation of six ent-kaurane-related diterpenoids, collectively termed kauralexins. Isolation and identification of the predominant Rhizopus microsporus-induced metabolites revealed ent-kaur-19-al-17-oic acid and the unique analog ent-kaur-15-en-19-al-17-oic acid, assigned as kauralexins A3 and B3, respectively. Encoding an ent-copalyl diphosphate synthase, fungal-induced An2 transcript accumulation precedes highly localized kauralexin production, which can eventually exceed 100 μg · g(-1) fresh weight. Pharmacological applications of jasmonic acid and ethylene also synergize the induced accumulation of kauralexins. Occurring at elevated levels in the scutella of all inbred lines examined, kauralexins appear ubiquitous in maize. At concentrations as low as 10 μg · mL(-1), kauralexin B3 significantly inhibited the growth of the opportunistic necrotroph R. microsporus and the causal agent of anthracnose stalk rot, Colletotrichum graminicola. Kauralexins also exhibited significant O. nubilalis antifeedant activity. Our work establishes the presence of diterpenoid defenses in maize and enables a more detailed analysis of their biosynthetic pathways, regulation, and crop defense function.

  13. Semisynthesis of the antiviral abietane diterpenoid jiadifenoic acid C from callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin.

    PubMed

    González, Miguel A; Zaragozá, Ramón J

    2014-09-26

    The semisynthesis of the antiviral abietane diterpenoid (+)-jiadifenoic acid C starting from the available methyl ester of callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin is reported. A protocol for the isolation of methyl callitrisate (methyl 4-epidehydroabietate) in gram quantities from sandarac resin is also described. Allylic C-17 oxygenation was introduced by regioselective dehydrogenation of the isopropyl group of methyl callitrisate with DDQ followed by selenium-catalyzed allylic oxidation. Ester hydrolysis afforded (+)-jiadifenoic acid C in 22% overall yield from methyl callitrisate. This semisynthetic route provides a convenient source of this anti-Coxsackie virus B natural product for further biological studies.

  14. New ent-kaurene-type diterpenoids possessing cytotoxicity from the New Zealand liverwort Jungermannia species.

    PubMed

    Nagashima, Fumihiro; Kasai, Wakana; Kondoh, Masuo; Fujii, Makiko; Watanabe, Yoshiteru; Braggins, John Edward; Asakawa, Yoshinori

    2003-10-01

    Two new ent-kaurene-type and a new rearranged ent-kaurene-type diterpenoids possessing cytotoxicity against a human leukemia cell line have been isolated from the New Zealand liverwort Jungermannia species, together with previously known ent-kaurene-type diterpenoids. Their structures were established based on extensive NMR techniques.

  15. A new irregular diterpenoid from Opopanax chironium.

    PubMed

    Muckensturm, Bernard; Boulanger, Anna; Ouahabi, Souad; Reduron, Jean-Pierre

    2005-12-01

    The ethereal extract of the roots of Opopanax chironium yielded peucelinenoxide acetate (1), a new natural product with an irregular diterpene skeleton, besides the known coumarins gaudichaudin, columbianadin, peucedanin and officinalin isobutyrate.

  16. Diterpenoids from Croton laui and their cytotoxic and antimicrobial activities.

    PubMed

    Liu, Cui-Ping; Xu, Jin-Biao; Zhao, Jin-Xin; Xu, Cheng-Hui; Dong, Lei; Ding, Jian; Yue, Jian-Min

    2014-04-25

    Fourteen new diterpenoids including clerodane (1-12), labdane (13), and norlabdane (14) types, as well as nine known analogues were isolated from the aerial parts of Croton laui. Their structures were established on the basis of spectroscopic analysis, and that of crotonolide H (11) was confirmed by single-crystal X-ray crystallography. Crotonolide A (1) exhibited moderate cytotoxicity against two tumor cell lines, HL-60 (human premyelocytic leukemia, IC50 9.42 μM) and P-388 (murine leukemia, IC50 7.45 μM), and crotonolide G (10) displayed significant antibacterial activity against a panel of Gram-positive bacteria.

  17. A new antitubercular mulinane diterpenoid from Azorella madreporica Clos.

    PubMed

    Wächter, G A; Franzblau, S G; Montenegro, G; Suarez, E; Fortunato, R H; Saavedra, E; Timmermann, B N

    1998-07-01

    Bioactivity-guided fractionation of the petroleum ether extract of Azorella madreporica Clos has led to the isolation of the novel, antitubercular mulinane diterpenoid 1. The structure has been elucidated on the basis of its 1D and 2D NMR spectra and by comparison with mulinolic acid 2 and a dehydration product 3 obtained from 1. The MIC of 1 for growth inhibition of the H37Rv strain of Mycobacterium tuberculosis was determined as 20 microg/mL. LC-MS and NMR have suggested the presence of this new compound in four other species of Azorella.

  18. Cytotoxic clerodane diterpenoids from the leaves of Premna tomentosa.

    PubMed

    Chin, Young-Won; Jones, William P; Mi, Qiuwen; Rachman, Ismail; Riswan, Soedarsono; Kardono, Leonardus B S; Chai, Hee-Byung; Farnsworth, Norman R; Cordell, Geoffrey A; Swanson, Steven M; Cassady, John M; Kinghorn, A Douglas

    2006-06-01

    Three clerodane diterpenoids, premnones A-C (1-3), were isolated from a chloroform-soluble fraction of Premna tomentosa along with four known flavonoids and three known triterpenoids. Among these isolates, premnones A-C exhibited cytotoxic activity when evaluated against a small panel of tumor cell lines. However, premnone A was found to be inactive when evaluated in a follow-up in vivo hollow fiber assay at the highest dose tested (50mg/kg), using LNCaP, Lu1, and MCF-7 cells.

  19. Cytotoxic ent-kaurene diterpenoids from Isodon phyllostachys.

    PubMed

    Li, Xian; Xiao, Weilie; Pu, Jianxin; Ban, Lili; Shen, Yunheng; Weng, Zhiying; Li, Shenghong; Sun, Handong

    2006-07-01

    ent-Kaurene diterpenoids, phyllostachysins D-H (1-5), together with nine known compounds, rabdoloxins A-B (6-7), rabdoinflexin B (8), amethystoidin A (9), rabdokunmin D (10), macrocalyxin E (11), 5,7-dihydroxy-4'-hydroxylflavone (12), oleanolic acid (13) and daucosterol (14), were isolated from aerial parts of Isodon phyllostachys. Structures were elucidated on the basis of spectroscopic methods, especially using 2D-NMR spectroscopic analyses. All ent-kaurenoids were tested for their cytotoxic effects against K562 cells. Compound 9 was the most potent with an IC50 value of 0.69 microg/ml.

  20. Diterpenoids including a novel dimeric conjugate from Salvia leriaefolia.

    PubMed

    Choudhary, Muhammad Iqbal; Hussain, Amjad; Ali, Zulfiqar; Adhikari, Achyut; Sattar, Samina A; Ayatollahi, Syed A; Al-Majid, Abdullah M

    2012-02-01

    Salvialeriafone (1), a novel diterpene-norditerpene conjugate, was isolated from Salvia leriaefolia. Additionally, two new abietane-type diterpenoids, salvialerial (2) and salvialerione (3), as well as four known compounds, sugiol (4), salvicanaric acid (5), dehydroroyleanone (6), and cariocal (7), were isolated and identified. Their structures were determined by spectroscopic data analyses. Known compounds were isolated from this plant for the first time. Compounds 1, 5, 6, and 7 exhibited IN VITRO antiproliferative activity against the human cervical cancer cell line (Hela), while 6 showed cytotoxicity against the human prostate cancer cell line (PC3). © Georg Thieme Verlag KG Stuttgart · New York.

  1. Antiviral potential of a diterpenoid compound sugiol from Metasequoia glyptostroboides.

    PubMed

    Bajpai, Vivek K; Kim, Na-Hyung; Kim, Kangmin; Kang, Sun Chul

    2016-05-01

    This research reports first time antiviral activity of sugiol, a diterpenoid isolated from Metasequoia glyptostroboides in terms of its ability to inhibit in vitro growth of H1N1 influenza virus. Antiviral potential of sugiol was evaluated through hcytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Sugiol (500 μg/ml) was found to exhibit considerable anti-cytopathic effect on MDCK cell line confirming its antiviral efficacy against H1N1 influenza virus. These findings strongly reinforce the suggestion that sugiol could be a candidate of choice in combinational regimen with potential antiviral efficacy.

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

    PubMed

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

    2002-02-01

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

  3. Diterpenoids from the twigs and leaves of Croton caudatus var. tomentosus.

    PubMed

    Song, Jin-Tong; Han, Yang; Wang, Xiao-Ling; Shen, Tao; Lou, Hong-Xiang; Wang, Xiao-Ning

    2015-12-01

    One new 9,10-seco-abietane derivative, crotontomentosin A (1), four new abietane-type diterpenoids, crotontomentosins B-E (2-5), one new ent-halimane-type diterpenoid, crotontomentosin F (6), along with five known diterpenoids (7-11) and one known sesquiterpenoid (12) were obtained from the twigs and leaves of Croton caudatus Geisel. var. tomentosus Hook. The structures of the compounds were established on the basis of extensive spectroscopic data. Compounds 1-4 and 11 exhibited moderate to weak inhibitory activity against the proliferation of the Hela, Hep G2, MDA-MB-231, or A549 cell lines selectively.

  4. Functional characterization of wheat ent-kaurene(-like) synthases indicates continuing evolution of labdane-related diterpenoid metabolism in the cereals

    PubMed Central

    Zhou, Ke; Xu, Meimei; Tiernan, Mollie; Xie, Qian; Toyomasu, Tomonobu; Sugawara, Chizu; Oku, Madoka; Usui, Masami; Mitsuhashi, Wataru; Chono, Makiko; Chandler, Peter M.; Peters, Reuben J.

    2012-01-01

    Wheat (Triticum aestivum) and rice (Oryza sativa) are two of the most agriculturally important cereal crop plants. Rice is known to produce numerous diterpenoid natural products that serve as phytoalexins and/or allelochemicals. Specifically, these are labdane-related diterpenoids, derived from a characteristic labdadienyl/copalyl diphosphate (CPP), whose biosynthetic relationship to gibberellin biosynthesis is evident from the relevant expanded and functionally diverse family of ent-kaurene synthase-like (KSL) genes found in rice (OsKSL). Here we report biochemical characterization of a similarly expansive family of KSL from wheat (the TaKSLs). In particular, beyond ent-kaurene synthases (KS), wheat also contains several biochemically diversified KSLs. These react either with the ent-CPP intermediate common to gibberellin biosynthesis or with the normal stereoisomer of CPP that also is found in wheat (as demonstrated by the accompanying description of wheat CPP synthases). Comparison with a barley (Hordeum vulgare) KS indicates conservation of monocot KS, with early and continued expansion and functional diversification of KSLs in at least the small grain cereals. In addition, some of the TaKSLs that utilize normal CPP also will react with syn-CPP, echoing previous findings with the OsKSL family, with such enzymatic promiscuity/plasticity providing insight into the continuing evolution of diterpenoid metabolism in the cereal crop plant family, as well as more generally, which is discussed here. PMID:23009879

  5. 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 IC50 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.

  6. Functional characterization of wheat ent-kaurene(-like) synthases indicates continuing evolution of labdane-related diterpenoid metabolism in the cereals.

    PubMed

    Zhou, Ke; Xu, Meimei; Tiernan, Mollie; Xie, Qian; Toyomasu, Tomonobu; Sugawara, Chizu; Oku, Madoka; Usui, Masami; Mitsuhashi, Wataru; Chono, Makiko; Chandler, Peter M; Peters, Reuben J

    2012-12-01

    Wheat (Triticum aestivum) and rice (Oryza sativa) are two of the most agriculturally important cereal crop plants. Rice is known to produce numerous diterpenoid natural products that serve as phytoalexins and/or allelochemicals. Specifically, these are labdane-related diterpenoids, derived from a characteristic labdadienyl/copalyl diphosphate (CPP), whose biosynthetic relationship to gibberellin biosynthesis is evident from the relevant expanded and functionally diverse family of ent-kaurene synthase-like (KSL) genes found in rice the (OsKSLs). Herein reported is the biochemical characterization of a similarly expansive family of KSL from wheat (the TaKSLs). In particular, beyond ent-kaurene synthases (KS), wheat also contains several biochemically diversified KSLs. These react either with the ent-CPP intermediate common to gibberellin biosynthesis or with the normal stereoisomer of CPP that also is found in wheat (as demonstrated by the accompanying paper describing the wheat CPP synthases). Comparison with a barley (Hordeum vulgare) KS indicates conservation of monocot KS, with early and continued expansion and functional diversification of KSLs in at least the small grain cereals. In addition, some of the TaKSLs that utilize normal CPP also will react with syn-CPP, echoing previous findings with the OsKSL family, with such enzymatic promiscuity/elasticity providing insight into the continuing evolution of diterpenoid metabolism in the cereal crop plant family, as well as more generally, which is discussed here.

  7. Diterpenoid compounds and other lipids in deep-sea sediments and their geochemical significance

    NASA Technical Reports Server (NTRS)

    Simoneit, B. R. T.

    1977-01-01

    Cyclic diterpenoid compounds have been found by various investigators in the geosphere (e.g., fossil resins, coals, soil, shale, and deep-sea sediments). These compounds occur in significant amounts only in higher plants and are therefore potential markers of terrigenous plant lipids. Diterpenoids with the abietane skeleton (mainly dehydroabietic acid) have been identified in the lipids of sediment samples from the northeast Pacific Ocean, Black Sea, and North Atlantic Ocean. The presence of these resin-derived compounds was correlated with the terrigenous clay components and with the presence of pollen. The presence of polycyclic diterpenoids was also correlated with the distribution patterns and inferred sources of other sediment lipid constituents. Potamic transport, followed by turbidite redistribution, is the probable input mechanism of these resin-derived compounds to the deep-sea sediments. These diterpenoids appear to be excellent biological markers of resinous higher plants.

  8. Multiple pro-apoptotic targets of abietane diterpenoids from Salvia species.

    PubMed

    Akaberi, M; Mehri, S; Iranshahi, M

    2015-01-01

    The genus Salvia contains a large number of biologically active diterpenoids with various skeletons including abietanes, labdanes, clerodanes, pimaranes and icetexanes. Diterpenes of Salvia species showed various biological activities, particularly cytotoxic and anti-proliferative properties. In recent years many studies have been focused on the molecular mechanisms of these diterpenes in cancer cells. It should be noted, however, that anticancer studies on diterpenoids from Salvia species were dominated by tanshinones (a class of abietanes) over the past decades. A large number of targets of diterpenes have been identified in cancer cells including NF-κB, STAT3, Bcl-xL, β-catenin, cytochrome C and caspases. These studies give us deeper insights into the mechanisms of actions and cell signaling pathways of anticancer diterpenoids from Salvia species. This paper reviews protein targets of diterpenoids from Salvia species and highlights the gaps in our knowledge deserving future research.

  9. Diterpenoid compounds and other lipids in deep-sea sediments and their geochemical significance

    NASA Technical Reports Server (NTRS)

    Simoneit, B. R. T.

    1977-01-01

    Cyclic diterpenoid compounds have been found by various investigators in the geosphere (e.g., fossil resins, coals, soil, shale, and deep-sea sediments). These compounds occur in significant amounts only in higher plants and are therefore potential markers of terrigenous plant lipids. Diterpenoids with the abietane skeleton (mainly dehydroabietic acid) have been identified in the lipids of sediment samples from the northeast Pacific Ocean, Black Sea, and North Atlantic Ocean. The presence of these resin-derived compounds was correlated with the terrigenous clay components and with the presence of pollen. The presence of polycyclic diterpenoids was also correlated with the distribution patterns and inferred sources of other sediment lipid constituents. Potamic transport, followed by turbidite redistribution, is the probable input mechanism of these resin-derived compounds to the deep-sea sediments. These diterpenoids appear to be excellent biological markers of resinous higher plants.

  10. Rapid separation and characterization of diterpenoid alkaloids in processed roots of Aconitum carmichaeli using ultra high performance liquid chromatography coupled with hybrid linear ion trap-Orbitrap tandem mass spectrometry.

    PubMed

    Xu, Wen; Zhang, Jing; Zhu, Dayuan; Huang, Juan; Huang, Zhihai; Bai, Junqi; Qiu, Xiaohui

    2014-10-01

    The lateral root of Aconitum carmichaeli, a popular traditional Chinese medicine, has been widely used to treat rheumatic diseases. For decades, diterpenoid alkaloids have dominated the phytochemical and biomedical research on this plant. In this study, a rapid and sensitive method based on ultra high performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was developed to characterize the diterpenoid alkaloids in Aconitum carmichaeli. Based on an optimized chromatographic condition, more than 120 diterpenoid alkaloids were separated with good resolution. Using a systematic strategy that combines high resolution separation, highly accurate mass measurements and a good understanding of the diagnostic fragment-based fragmentation patterns, these diterpenoid alkaloids were identified or tentatively identified. The identification of these chemicals provided essential data for further phytochemical studies and toxicity research of Aconitum carmichaeli. Moreover, the ultra high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry platform was an effective and accurate tool for rapid qualitative analysis of secondary metabolite productions from natural resources.

  11. Characterization of New Ent-kaurane Diterpenoids of Yunnan Arabica Coffee Beans.

    PubMed

    Chu, Rui; Wan, Luo-Sheng; Peng, Xing-Rong; Yu, Mu-Yuan; Zhang, Zhi-Run; Zhou, Lin; Li, Zhong-Rong; Qiu, Ming-Hua

    2016-08-01

    Five new ent-kaurane diterpenoids, named mascaroside III-V (1-3), and 20-nor-cofaryloside I-II (4-5), together with seven known diterpenoids, were isolated from methanol extracts of the green coffee beans of Yunnan Arabica Coffee. Their chemical structures were elucidated by extensive spectroscopic analyses. Meanwhile, cytotoxicity assay against HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines showed that they have not evident inhibition of cytotoxicity.

  12. Bioactive ent-kaurane diterpenoids from Isodon rubescens.

    PubMed

    Zhang, Yuan-Yuan; Jiang, Hua-Yi; Liu, Miao; Hu, Kun; Wang, Wei-Guang; Du, Xue; Li, Xiao-Nian; Pu, Jian-Xin; Sun, Han-Dong

    2017-09-01

    Seven previously undescribed 7,20-epoxy-ent-kaurane diterpenoids, isojiangrubesins A-G, along with seventeen known ones, were isolated from the aerial parts of Isodon rubescens. Their structures were characterized on the basis of spectroscopic methods and signal-crystal X-ray diffraction. All of these compounds were evaluated for their in vitro cytotoxicity against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480). Four isolates exhibited significant inhibitory ability against all cell lines, with IC50 values ranging from 0.5 to 6.5 μM; They also strongly inhibited NO production in LPS-stimulated RAW264.7 cells. Copyright © 2017. Published by Elsevier Ltd.

  13. Structure and Absolute Configuration of Diterpenoids from Hymenaea stigonocarpa.

    PubMed

    Monteiro, Afif F; Batista, João M; Machado, Michelle A; Severino, Richele P; Blanch, Ewan W; Bolzani, Vanderlan S; Vieira, Paulo C; Severino, Vanessa G P

    2015-06-26

    Chemical investigations of the ethanolic extracts from the flowers and leaves of Hymenaea stigonocarpa Mart. ex Hayne afforded one new ent-halimane diterpenoid, 18-hydroxy-ent-halima-1(10),13-(E)-dien-15-oic acid (1), together with five known compounds (2-6). The structural elucidation was performed by means of NMR (COSY, HSQC, HMBC, and NOESY) and MS analyses. Complete (1)H and (13)C NMR data assignments are also reported for labd-13-en-8β-ol-15-oic (2) and labd-7,13-dien-15-oic (3) acids. The absolute configurations of 1 and 2 were established by comparison of experimental and calculated Raman optical activity spectra.

  14. Diterpenoids from Tetraclinis articulata that inhibit various human leukocyte functions.

    PubMed

    Barrero, Alejandro F; Quílez del Moral, José F; Lucas, Rut; Payá, Miguel; Akssira, Mohamed; Akaad, Said; Mellouki, Fouad

    2003-06-01

    Ten new compounds, eight of them pimarane derivatives (1-8), together with a menthane dimer (9) and a totarane diterpenoid (10), were isolated from the leaves and wood of Tetraclinis articulata. The structures of 1-10 were established by using spectroscopic techniques, including 2D NMR spectra. Pimaranes 1-5 were found to possess an unusual cis interannular union of the B and C rings, which, from a biogenetic perspective, could be derived from the hydration of a carbocation at C-8. Compounds 4-6 and a mixture of 7 and 11 modulated different human leukocyte functions at a concentration of 10 microM, mainly the degranulation process measured as myeloperoxidase release and, to a lesser extent, the superoxide production measured by chemiluminescence.

  15. Cytotoxic diterpenoid pseudodimers from the Korean sponge Phorbas gukhulensis.

    PubMed

    Jeon, Ju-eun; Liao, Lijuan; Kim, Heegyu; Sim, Chung J; Oh, Dong-Chan; Oh, Ki-Bong; Shin, Jongheon

    2013-09-27

    Four new cytotoxic diterpenoid pseudodimers (2-5), along with a previously reported one, gukulenin A (1), were isolated from the marine sponge Phorbas gukhulensis collected off the coast of Gagu-do, Korea. These novel compounds, designated gukulenins C-F (2-5), were determined by extensive spectroscopic analyses to be pseudodimers of the gagunins, like gukulenin A. The termini of the tropolone-containing side chains in gukulenins C-E (2-4) were found to have diverse modifications involving acetamides or taurine, whereas gukulenin F (5) was formed from 1 by the ring-opening of a cyclic hemiketal. The relative and absolute configurations were assigned by Murata's and modified Snatzke's methods using a HETLOC experiment and a CD measurement of a dimolybdenum complex, respectively. All of these compounds exhibited significant cytotoxicity against the K562 and A549 cell lines.

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

    PubMed

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

    2015-12-01

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

  17. Abietane diterpenoids from Salvia sclarea transformed roots as growth inhibitors of pathogenic Acanthamoeba spp.

    PubMed

    Kuźma, Łukasz; Derda, Monika; Hadaś, Edward; Wysokińska, Halina

    2015-01-01

    Amoebae from the genus Acanthamoeba are known agents leading to various diseases such as granulomatous amoebic encephalitis (GAE), a chronic progressive disease of the central nervous system, amoebic keratitis (AK), chronic eye infection, amoebic pneumitis (AP), chronic lung infection, and skin infections. It is known that various synthetic anti-Acanthamoeba substances are ineffective. Therefore, other substances, e.g., natural plant compounds, are the focus of biological investigations regarding anti-parasite activity. In this work, the ability of four abietane diterpenoids (ferruginol, salvipisone, aethiopinone, and 1-oxo-aethiopinone) to inhibit Acanthamoeba growth is reported. All investigated compounds were active against Acanthamoeba growing in vitro. Among them, ferruginol demonstrated the highest activity against Acanthamoeba. This compound inhibited Acanthamoeba growth by about 72% in a 3-day exposure period (IC50 17.45 μM), while aethiopinone and 1-oxo-aethiopinone demonstrated this activity at the level of 55-56%. Salvipisone reduced the growth of Acanthamoeba in vitro culture by 39%. For this compound, the value of IC50 was 701.94 μM after 72 h of exposure.

  18. 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.

  19. Antimicrobial and Antiparasitic Abietane Diterpenoids from the Roots of Clerodendrum eriophyllum

    PubMed Central

    Machumi, Francis; Samoylenko, Volodymyr; Yenesew, Abiy; Derese, Solomon; Midiwo, Jacob O.; Wiggers, Frank T.; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Walker, Larry A.

    2013-01-01

    Chromatographic separation of the roots of a Kenyan medicinal plant, Clerodendrum eriophyllum, led to the isolation of ten abietane diterpenoids (1-10), one of which (1) was isolated for the first time from a natural source. Using spectroscopic data, the structure of 1 was determined to be 12-hydroxy-8,12-abietadiene-3,11,14-trione. Circular dichroism (CD) spectra showed that the stereochemistry of compounds 1, 3, and 6-8 belongs to the normal series of abietane diterpenes, which confirmed the absolute stereochemistry of the isolated compounds. Compounds 2-10 were evaluated for their in vitro antiplasmodial, antileishmanial, antifungal and antibacterial activities. Compounds 3 and 7 exhibited potent antifungal activity (IC50/MIC 0.58/1.25 and 0.96/2.5 µg/mL, respectively) against C. neoformans, whereas 3, 6 and 7 showed strong antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with IC50/MIC values between 1.33–1.75/2.5–5 and 0.96–1.56/2.5 µg/mL, respectively. In addition, compounds 3 and 9 exhibited potent antileishmanial activity (IC50 0.08 and 0.20 µg/mL, respectively) against L. donovani, while 3 and 7 displayed weak antimalarial activity against Plasmodium falciparum, but 9 was inactive. PMID:20614808

  20. Anti-inflammatory tetraquinane diterpenoids from a Crinipellis species.

    PubMed

    Rohr, Markus; Oleinikov, Katharina; Jung, Mathias; Sandjo, Louis P; Opatz, Till; Erkel, Gerhard

    2017-01-15

    The small pro-inflammatory 10kDa chemokine CXCL10 (Interferon-inducible protein 10, IP-10) plays an important role in mediating immune responses through the activation and recruitment of leukocytes such as T cells, eosinophils, monocytes and NK cells to the sites of inflammation. Elevated levels of CXCL10 have been associated with chronic inflammatory and infectious diseases and therefore CXCL10 represents an attractive target for the development of new anti-inflammatory drugs. In a search for anti-inflammatory compounds from fungi inhibiting the inducible CXCL10 promoter activity, four new tetraquinane diterpenoids, crinipellin E (1), crinipellin F (2), crinipellin G (3) and crinipellin H (4) were isolated from fermentations of a Crinipellis species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds 1, 2, and 3 inhibited the LPS/IFN-γ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC50 values of 15μM, 1.5μM, and 3.15μM respectively, whereas compound 4 was devoid of any biological activity. Moreover, compounds 1, 2 and 3 reduced mRNA levels and synthesis of pro-inflammatory mediators such as cytokines and chemokines in LPS/IFN-γ stimulated MonoMac6 cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Clerodane-type diterpenoids from tuberous roots of Tinospora sagittata (Oliv.) Gagnep.

    PubMed

    Zhang, Geng; Ma, Haoran; Hu, Song; Xu, Hongfeng; Yang, Bo; Yang, Quanwei; Xue, Yongbo; Cheng, Lu; Jiang, Jie; Zhang, Jinwen; Wang, Fuqian; Zhang, Yonghui

    2016-04-01

    Three new clerodane type diterpenoids (2-4), together with one known analogues (1), were isolated from the tuberous roots of Tinospora sagittata (Oliv.) Gagnep. Compound 3 is an unusual clerodane diterpenoid with the carbonyl functionality at C-3, which represents the first example from this diterpenoid compounds class. The structures were established on the basis of spectroscopic data interpretation. The absolute configuration of 1 was determined for the first time by single-crystal X-ray diffraction analysis with CuKα irradiation. These isolates were evaluated for their cytotoxic activities against five human cancer cell lines and inhibitory activities on LPS-induced NO production in RAW264.7 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. 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.

  3. Four New Kaurane Diterpenoids from the Chinese Liverwort Jungermannia comata Nees.

    PubMed

    Li, Rui-Juan; Wang, Song; Li, Gang; Zhou, Jin-Chuan; Zhang, Jiao-Zhen; Zhang, You-Ming; Shi, Guo-Sheng; Lou, Hong-Xiang

    2016-12-01

    In our continuing program to find new bioactive compounds from the Chinese liverworts, four new kaurane-type diterpenoids, (6β)-kaur-16-ene-6,9-diol (1), (6β,12β)-kaur-16-ene-6,9,12-triol (2), (6β)-kaur-16-ene-5,6,9-triol (3), and kaur-16-ene-9,19-diol (4), have been isolated from the Chinese liverwort Jungermannia comata Nees. Five known kaurane-type diterpenoids (5 - 9) and four known trachylobane-type diterpenoids (10 - 13) were also obtained. The structures of the new compounds were established unequivocally on the basis of spectroscopic data. The absolute configuration of compound 1 was established by comparing experimental and calculated electronic circular dichroism spectra.

  4. Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors.

    PubMed

    Yan, Feng; Mosier, Philip D; Westkaemper, Richard B; Stewart, Jeremy; Zjawiony, Jordan K; Vortherms, Timothy A; Sheffler, Douglas J; Roth, Bryan L

    2005-06-21

    Salvinorin A is a naturally occurring hallucinogenic diterpenoid from the plant Salvia divinorumthat selectively and potently activates kappa-opioid receptors (KORs). Salvinorin A is unique in that it is the only known lipid-like molecule that selectively and potently activates a G-protein coupled receptor (GPCR), which has as its endogenous agonist a peptide; salvinorin A is also the only known non-nitrogenous opioid receptor agonist. In this paper, we identify key residues in KORs responsible for the high binding affinity and agonist efficacy of salvinorin A. Surprisingly, we discovered that salvinorin A was stabilized in the binding pocket by interactions with tyrosine residues in helix 7 (Tyr313 and Tyr320) and helix 2 (Tyr119). Intriguingly, activation of KORs by salvinorin A required interactions with the helix 7 tyrosines Tyr312, Tyr313, and Tyr320 and with Tyr139 in helix 3. In contrast, the prototypical nitrogenous KOR agonist U69593 and the endogenous peptidergic agonist dynorphin A (1-13) showed differential requirements for these three residues for binding and activation. We also employed a novel approach, whereby we examined the effects of cysteine-substitution mutagenesis on the binding of salvinorin A and an analogue with a free sulfhydryl group, 2-thiosalvinorin B. We discovered that residues predicted to be in close proximity, especially Tyr313, to the free thiol of 2-thiosalvinorin B when mutated to Cys showed enhanced affinity for 2-thiosalvinorin B. When these findings are taken together, they imply that the diterpenoid salvinorin A utilizes unique residues within a commonly shared binding pocket to selectively activate KORs.

  5. New clerodane diterpenoids from the twigs and leaves of Croton euryphyllus.

    PubMed

    Pan, Zhenghong; Ning, Desheng; Wu, Xingde; Huang, Sisi; Li, Dianpeng; Lv, Shihong

    2015-03-15

    Three new nor-clerodane diterpenoids, crotoeurins A-C (1-3), together with four known ones were isolated from the twigs and leaves of Croton euryphyllus. Among them, crotoeurin A (1) is a new nor-clerodane diterpenoid dimer with a unique cyclobutane ring via a [2+2] cycloaddition. Their structures were elucidated by spectroscopic analyses and the stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis. Compounds 1-3 exhibited neurite outgrowth-promoting activity on NGF-mediated PC12 cells at concentration of 10μM.

  6. Manoyl oxide alpha-arabinopyranoside and grindelic acid diterpenoids from Grindelia integrifolia.

    PubMed

    Ahmed, A A; Mahmoud, A A; Ahmed, U M; El-Bassuony, A A; Abd El-Razk, M H; Pare, P W; Karchesy, J

    2001-10-01

    Two new manoyl oxide-alpha-arabinopyranoside diterpenoids, 15-hydroxy-13-epi-manoyl oxide-14-O-alpha-L-arabinopyranoside (tarapacol-14-O-alpha-L-arabinopyranoside) (1) and 15-acetoxy-13-epi-manoyl oxide-14-O-alpha-L-arabinopyranoside (tarapacol-15-acetate-14-O-alpha-L-arabinopyranoside) (2), as well as a new grindelic acid derivative, 19-hydroxygrindelic acid (3), together with five known diterpenoids (tarapacol, tarapacanol A, grindelic acid, methyl grindeloate, 3beta-hydroxygrindelic acid, 4) were isolated from the aerial parts of Grindelia integrifolia. The structures of 1-3 were elucidated by spectral data analysis.

  7. A new rearranged tricyclic abietane diterpenoid from Salvia chloroleuca Rech. f. & Allen.

    PubMed

    Salimikia, Iraj; Moridi Farimani, Mahdi; Monsef-Esfahani, Hamid Reza; Gohari, Ahmad Reza

    2016-01-01

    Phytochemical investigation of the roots of Salvia chloroleuca led to the isolation and identification of a new rearranged abietane diterpenoid (1). Its structure was elucidated by interpretation of the 1D and 2D NMR spectra and completed by the analysis of the HR-ESI-MS data. Compound 1 is the secondly reported compound on a rearranged tricyclic abietane (4,5-seco-5,10-friedo-abietane) diterpenoid with a ketal functionality between C-2 and C-11. A plausible biosynthetic pathway of 1 was also proposed.

  8. Characterization of diterpenoids from Caesalpinia decapetala and their anti-TMV activities.

    PubMed

    Xu, Jing; Cao, Xiangrong; Liu, Feng; Ma, Jun; Liu, Xingyu; Tong, Ling; Su, Guochen; Ohizumi, Yasushi; Lee, Dongho; Wang, Lizhong; Guo, Yuanqiang

    2016-09-01

    Caesalpinia decapetala is a versatile medicinal plant belonging to the Fabaceae plant family. In our survey on plant secondary metabolites to obtain bioactive substances for the development of new agricultural anti-TMV agents, the chemical constituents of C. decapetala were investigated. This investigation led to the isolation of three new and ten known diterpenoids. Their structures including absolute configurations were elucidated based on the extensive NMR spectroscopic data analyses and the time-dependent density functional theory calculations. The following biological screenings revealed that most of these diterpenoids possessed anti-TMV activities. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Phytotoxic cis-clerodane diterpenoids from the Chinese liverwort Scapania stephanii.

    PubMed

    Li, Rui-Juan; Sun, Yi; Sun, Bin; Wang, Xiao-Ning; Liu, Shan-Shan; Zhou, Jin-Chuan; Ye, Jian-Ping; Zhao, Yu; Liu, Lei; Lee, Kuo-Hsiung; Lou, Hong-Xiang

    2014-09-01

    Five cis-clerodane diterpenoids, stephanialides A-E, along with seven known cis-clerodanes, scaparvins A-C, parvitexins B and C, 3-chloro-4-hydroxy-parvitexin A, and scapanialide B, were isolated from the Chinese liverwort Scapania stephanii. Their structures were established unequivocally on the basis of spectroscopic data. The absolute configuration of stephanialide A was determined by analysis of CD data using the octant rule. Phytotoxic activity evaluation showed that this type of diterpenoids can significantly inhibit root elongation of the seeds of Arabidopsis thaliana, Lepidium sativum and Brassica pekinensis.

  10. Functional characterization of wheat copalyl diphosphate synthases sheds light on the early evolution of labdane-related diterpenoid metabolism in the cereals

    PubMed Central

    Wu, Yisheng; Zhou, Ke; Toyomasu, Tomonobu; Sugawara, Chizu; Oku, Madoka; Abe, Shiho; Usui, Masami; Mitsuhashi, Wataru; Chono, Makiko; Chandler, Peter M.; Peters, Reuben J.

    2012-01-01

    Two of the most agriculturally important cereal crop plants are wheat (Triticum aestivum) and rice (Oryza sativa). Rice has been shown to produce a number of diterpenoid natural products as phytoalexins and/or allelochemicals – specifically, labdane-related diterpenoids, whose biosynthesis proceeds via formation of an eponymous labdadienyl/copalyl diphosphate (CPP) intermediate (e.g., the ent-CPP of gibberellin phytohormone biosynthesis). Similar to rice, wheat encodes a number of CPP synthases (CPS), and the three CPS characterized to date (TaCPS1,2,&3) all have been suggested to produce ent-CPP. However, several of the downstream diterpene synthases will only react with CPP intermediate of normal or syn, but not ent, stereochemistry, as described in the accompanying report. Investigation of additional CPS did not resolve this issue, as the only other functional synthase (TaCPS4) also produced ent-CPP. Chiral product characterization of all the TaCPS then revealed that TaCPS2 uniquely produces normal, rather than ent-, CPP; thus, providing a suitable substrate source for the downstream diterpene synthases. Notably, TaCPS2 is most homologous to the similarly stereochemically differentiated syn-CPP synthase from rice (OsCPS4), while the non-inducible TaCPS3 and TaCPS4 cluster with the rice OsCPS1 required for gibberellin phytohormone biosynthesis, as well as with a barley (Hordeum vulgare) CPS (HvCPS1) that also is characterized here as similarly producing ent-CPP. These results suggest that diversification of labdane-related diterpenoid metabolism beyond the ancestral gibberellins occurred early in cereal evolution, and included the type of stereochemical variation demonstrated here. PMID:23009878

  11. Crotofolane-Type Diterpenoids, Crotocascarins L-Q, and a Rearranged Crotofolane-Type Diterpenoid, Neocrotocascarin, from the Stems of Croton cascarilloides.

    PubMed

    Kawakami, Susumu; Inagaki, Masanori; Matsunami, Katsuyoshi; Otsuka, Hideaki; Kawahata, Masatoshi; Yamaguchi, Kentaro

    2016-01-01

    From the stems of Croton cascarilloides, further crotofolane-type diterpenoids, named crotocascarins L-Q (1-6), and a rearranged one (7), named neocrotocascarin were isolated. Their structures were elucidated from spectroscopic evidence. Also, the structures of crotocascarin O (4) and neocrotocascarin (7) were determined by X-ray crystallographic analyses. As a result, neocrotocascarin (7) was found to possess a new carbon framework. A plausible mechanism for the formation of neocrotocascarin (7) is also discussed.

  12. In vitro antituberculosis activity of diterpenoids from the Vietnamese medicinal plant Croton tonkinensis.

    PubMed

    Jang, Woong Sik; Jyoti, Md Anirban; Kim, Sukyung; Nam, Kung-Woo; Ha, Thi Kim Quy; Oh, Won Keun; Song, Ho-Yeon

    2016-01-01

    Diterpenoids from the Vietnamese medicinal plant Croton tonkinensis are rich in ent-kaurane, kaurane and the grayanane class and are valuable intermediate plant metabolites with different bioactivities. In this study, we report the antituberculosis activity of these diterpenoids against both susceptible and resistant strains of M. tuberculosis for the first time. All of the ent-kaurane, kaurane and grayanane diterpenoids showed high to moderate activity against Mycobacterium. The highest antituberculosis activity was observed for ent-1β,7α,14β-triacetoxykaur-16-en-15-one (cpp604), with MIC values of 0.78, 1.56 and 3.12-12.5 µg/ml against H37Ra, H37Rv and all other resistant strains of Mycobacterium tuberculosis examined. In addition, other ent-kaurane-type diterpenoids also showed very high activities against mycobacterium, including cpp609 (1.56 µg/ml), cpp610 (1.56 µg/ml), cpp601 (3.12-6.25 µg/ml), cpp602 (3.12-6.25 µg/ml), cpp607 (3.12-6.25 µg/ml) and cpp608 (3.12-6.25 µg/ml). From the structure-activity relationship, functional groups R3 and R5 of the ent-kaurane skeleton were found to modulate the antimycobacterial activity.

  13. Structure of salvioccidentalin, a diterpenoid with a rearranged neo-clerodane skeleton from Salvia occidentalis.

    PubMed

    Jaime-Vasconcelos, Miguel Ángel; Frontana-Uribe, Bernardo Antonio; Morales-Serna, José Antonio; Salmón, Manuel; Cárdenas, Jorge

    2011-10-31

    From the aerial parts of Salvia occidentalis (Labiatae) a new diterpenoid with a rearranged neo-clerodane skeleton was isolated. This new compound was named salvioccidentalin and its structure was established by spectroscopic means. A probable biogenetic relationship with salvigenolide from S. fulgens and salvileucalin A and spiroleucantholide from Salvia leucantha is proposed.

  14. Divinatorins A-C, new neoclerodane diterpenoids from the controlled sage Salvia divinorum.

    PubMed

    Bigham, Andrea K; Munro, Thomas A; Rizzacasa, Mark A; Robins-Browne, Roy M

    2003-09-01

    Three new neoclerodane diterpenoids, divinatorins A-C (7-9), have been isolated from the leaves of Salvia divinorum. The compounds were identified by spectroscopic methods as derivatives of the antibiotic (-)-hardwickiic acid (10), which was also isolated, along with four other known terpenoids. Neither the crude extract nor 7-9 displayed antimicrobial activity.

  15. Dysoxydensins A-G, seven new clerodane diterpenoids from Dysoxylum densiflorum.

    PubMed

    Gu, Ji; Cheng, Gui-Guang; Qian, Sheng-Yan; Li, Yan; Liu, Ya-Ping; Luo, Xiao-Dong

    2014-08-01

    Seven new clerodane diterpenoids, dysoxydensins A-G (1-7), together with six known clerodanes, were isolated from Dysoxylum densiflorum. The structures of all the compounds were elucidated by extensive spectroscopic analysis. These compounds were evaluated for their cytotoxic activities against five human cancer cell lines, and compounds 2, 3, and 5 showed moderate cytotoxic activities.

  16. Gaditanone, a Diterpenoid Based on an Unprecedented Carbon Skeleton Isolated from Euphorbia gaditana.

    PubMed

    Flores-Giubi, M Eugenia; Durán-Peña, María J; Botubol-Ares, José M; Escobar-Montaño, Felipe; Zorrilla, David; Macías-Sánchez, Antonio J; Hernández-Galán, Rosario

    2017-07-28

    A novel diterpenoid, gaditanone (2), which possesses an unprecedented 5/6/4/6-fused gaditanane tetracyclic ring skeleton, and a new jatrophane (1) were isolated from the aerial parts of Euphorbia gaditana. The chemical structures and absolute configurations were determined by extensive spectroscopic NMR studies and ECD data analysis. A proposed biosynthetic pathway is presented for compound 2.

  17. Cembrane-type diterpenoids from the Chinese liverworts Chandonanthus hirtellus and C. birmensis.

    PubMed

    Li, Rui-Juan; Lin, Zhao-Min; Kang, Ya-Qi; Guo, Yan-Xia; Lv, Xin; Zhou, Jin-Chuan; Wang, Song; Lou, Hong-Xiang

    2014-02-28

    Six new cembrane-type diterpenoids (1-6) were isolated from two species of Chandonanthus: Chandonanones A, B, and D-F (1, 2, and 4-6) were isolated from C. hirtellus, and chandonanones B, C, E, and F (2, 3, 5, and 6) from C. birmensis. Five known diterpenoids, (8E)-4α-acetoxy-12α,13α-epoxycembra-1(15),8-diene (7), isochandonanthone (8), chandonanthone (9), anadensin (10), and 2,10,14-triacetoxy-7,8,18,19-diepoxydolabell-3(E)-ene (11), were also obtained. The structures of the new metabolites were established by analyses of their spectroscopic data (1D NMR, 2D NMR, HRESIMS, and IR). The absolute configurations of compounds 1 and 2 were unequivocally confirmed using single-crystal X-ray diffraction analysis with Cu Kα radiation. Cytotoxicity tests of the isolated diterpenoids against seven cancer cell lines (DU145, PC3, A549, PC12, NCI-H292, NCI-H1299, and A172) revealed that some of the diterpenoids had weak activity.

  18. 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.

  19. 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

  20. A new mulinane diterpenoid from the cushion shrub Azorella compacta growing in Perú

    PubMed Central

    Salgado, Francisco; Areche, Carlos; Sepúlveda, Beatriz; Simirgiotis, Mario J.; Cáceres, Fátima; Quispe, Cristina; Quispe, Lina; Cano, Teresa

    2014-01-01

    Background: Azorella compacta is a rare yellow-green compact resinous cushion shrub growing from the high Andes of southern Perú to northwestern Argentina, and which is a producer of biologically active and unique diterpenoids. Objective: This study investigated the secondary metabolites present in a Peruvian sample of Azorella compacta and the evaluation of gastroprotective activity of the isolated compounds in a gastric- induced ulcer model in mice. Material and Methods: Six secondary metabolites (diterpenoids 1-6) present in the dichloromethane (DCM) extract of A. compacta growing in Perú were isolated by a combination of Sephadex LH-20 permeation and silica gel chromatography and their chemical structures were elucidated by spectroscopic methods (NMR) and molecular modeling. The gastroprotective activity of the new compound 1 was evaluated on the HCl/EtOH-induced gastric lesion model in mice and compared to the activity showed by the known compounds. Results: A new mulinane diterpene along with five known diterpenoids have been isolated from a Peruvian sample of A. compacta and the gastroprotective results show that compound 1 is less active than the other known mulinane diterpenoids isolated. Conclusions: A. compacta growing in Perú showed the presence of the new mulinane 1, which was poorly active in the HCl/EtOH-induced gastric lesion model in mice. Indeed, the activity was lower than other diterpenoids (2-6) showing an oxygenated function at C-16 or/and C-20, which confirm the role of an oxygenated group (OH or carboxylic acid) for the gastroprotective activity of mulinane compounds. PMID:25298672

  1. Jaridonin, a novel ent-kaurene diterpenoid from Isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells.

    PubMed

    Ma, Yong-Cheng; Ke, Yu; Zi, Xiaolin; Zhao, Wen; Shi, Xiao-Jing; Liu, Hong-Min

    2013-07-01

    Isodon rubescens, a Chinese herb, has been used as a folk, botanical medicine in China for inflammatory diseases and cancer treatment for many years. Recently, we isolated a new ent-kaurene diterpenoid, named Jaridonin, from Isodon rubescens. The chemical structure of Jaridonin was verified by infrared (IR), nuclear magnetic resonance (NMR), and mass spectrum (MS) data as well as X-ray spectra. Jaridonin potently reduced viabilities of several esophageal cancer cell lines, including EC109, EC9706 and EC1. Jaridonin treatment resulted in typical apoptotic morphological characteristics, increased the number of annexin V-positive staining cells, as well as caused a G2/M arrest in cell cycle progression. Furthermore, Jaridonin resulted in a significant loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, and then activation of Caspase-9 and -3, leading to activation of the mitochondria mediated apoptosis. Furthermore, these effects of Jaridonin were accompanied by marked reactive oxygen species (ROS) production and increased expression of p53, p21(waf1/Cip1) and Bax, whereas two ROS scavengers, N-acetyl-L-cysteine (LNAC) and Vitamin C, significantly attenuated the effects of Jaridonin on the mitochondrial membrane potential, DNA damage, expression of p53 and p21(waf1/Cip1) and reduction of cell viabilities. Taken together, our results suggest that a natural ent-kaurenoid diterpenoid, Jaridonin, is a novel apoptosis inducer and deserves further investigation as a new chemotherapeutic strategy for patients with esophageal cancer.

  2. Novel abietane diterpenoids and aromatic compounds from Cladonia rangiferina and their antimicrobial activity against antibiotics resistant bacteria.

    PubMed

    Yoshikawa, Kazuko; Kokudo, Naoki; Tanaka, Masami; Nakano, Tatsuro; Shibata, Hirofumi; Aragaki, Naokatsu; Higuchi, Tomihiko; Hashimoto, Toshihiro

    2008-01-01

    From Cladonia rangiferina were isolated two novel abietane diterpenoids, hanagokenols A (1) and B (2). Also in this investigation, four known abitetane diterpenoids (3-6), four known labdane diterpenoids (7-10), one known isopimarane diterpenoid (11), and six known aromatic compounds were isolated. These structures were elucidated primarily through extensive NMR experiments. Hanagokenol A (1) was a unique abietane diterpene having an ether linkage between C-6 and C-18 of sugiol. Hanagokenol B (2) is also a unique secoabietane diterpene, having gamma-lactone which occurred by cleavage and subsequently oxidation between C-6/C-7 of 12-hydroxydehydroabietinol. Furthermore, all the isolated compounds (1-17) were tested for the antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE).

  3. LC-MS- and (1)H NMR Spectroscopy-Guided Identification of Antifungal Diterpenoids from Sagittaria latifolia.

    PubMed

    Ravu, Ranga Rao; Jacob, Melissa R; Jeffries, Cynthia; Tu, Ying; Khan, Shabana I; Agarwal, Ameeta K; Guy, R Kiplin; Walker, Larry A; Clark, Alice M; Li, Xing-Cong

    2015-09-25

    Antifungal screening of small-molecule natural product libraries showed that a column fraction (CF) derived from the plant extract of Sagittaria latifolia was active against the fungal pathogen Cryptococcus neoformans. Dereplication analysis by liquid chromatography-mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy ((1)H NMR) indicated the presence of new compounds in this CF. Subsequent fractionation of the plant extract resulted in the identification of two new isopimaradiene-type diterpenoids, 1 and 2. The structures of 1 and 2 were determined by chemical methods and spectroscopic analysis as isopimara-7,15-dien-19-ol 19-O-α-l-arabinofuranoside and isopimara-7,15-dien-19-ol 19-O-α-l-(5'-acetoxy)arabinofuranoside, respectively. Compound 1 exhibited IC50 values of 3.7 and 1.8 μg/mL, respectively, against C. neoformans and C. gattii. Its aglycone, isopimara-7,15-dien-19-ol (3), resulting from acid hydrolysis of 1, was also active against the two fungal pathogens, with IC50 values of 9.2 and 6.8 μg/mL, respectively. This study demonstrates that utilization of the combined LC-MS and (1)H NMR analytical tools is an improved chemical screening approach for hit prioritization in natural product drug discovery.

  4. Isolation and bioactivity of diterpenoids from the roots of Salvia grandifolia.

    PubMed

    Kang, Jie; Li, Li; Wang, Dingding; Wang, Hongqing; Liu, Chao; Li, Baoming; Yan, Yu; Fang, Lianhua; Du, Guanhua; Chen, Ruoyun

    2015-08-01

    A phytochemical investigation of root extracts of Salvia grandifolia led to isolation of six previously unreported diterpenoids, grandifolias A-F, along with eight known compounds. The structures of grandifolias A-F were primarily established by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Their absolute configurations were assigned by their calculated and experimental electronic circular dichroism spectra or by X-ray diffraction analysis. All of the diterpenoids were evaluated for their vasorelaxant effects. Grandifolia B and isograndifoliol both exhibited dose-dependent vasorelaxant effects on rat aortic rings, preconstricted by KCl or norepinephrine, with EC50 values of 36.36-74.51μg/mL.

  5. Diterpenoids from the roots of Croton crassifolius and their anti-angiogenic activity.

    PubMed

    Wang, Jia-Jian; Chung, Hau Yin; Zhang, Yu-Bo; Li, Guo-Qiang; Li, Yao-Lan; Huang, Wei-Huan; Wang, Guo-Cai

    2016-02-01

    Six diterpenoids [crassifolin J, K, L, M, N and O] along with eleven known ones were isolated from the supercritical fluid extract (SFE) of the roots of Croton crassifolius (Euphorbiaceae). Their structures were elucidated using spectroscopic methods (IR, UV, HRESIMS, 1D and 2D NMR). The structure and stereochemistry of crassifolin J was confirmed by single-crystal X-ray diffraction analysis, and the absolute configurations of crassifolin K-M were determined by CD spectra. Twenty-three diterpenoids from this plant were screened for their anti-angiogenic activity using a wild-type zebrafish in vivo model. Four of the known compounds were active, of which penduliflaworosin possessed the best activity relative to the positive control (SU5416). Further study demonstrated that penduliflaworosin could inhibit vessel formation on Tg(fli1a:EGFP)y1-type zebrafish embryos.

  6. Antitumor activity and structure-activity relationship of diterpenoids with a dehydroabietyl skeleton.

    PubMed

    Rao, Xiaoping; Huang, Xiuzhi; He, Ling; Song, Jie; Song, Zhanqian; Shang, Shibin

    2012-12-01

    A series of novel diterpenoids including imines, amides and ureas with a dehydroabietyl skeleton were screened to hepatocellular carcinoma (SMMC-7721), lung cancer (A-549), glioma (C-6) and breast carcinoma (MCF-7) tumor cells by MTT method. Their antitumor activity and structure activity relationship were analyzed. Several of the title compounds such as I-2, I-10, I-6 and I-5, possess noticeable antitumor activity against SMMC-7721, A-549, C-6 and MCF-7 tumor cells, with lowest IC(50) values of 6.65, 0.75, 0.81 and 10.65μM, respectively. Based on the structure-activity relationship investigation, the three kinds of diterpenoids with a dehydroabietyl skeleton show high activity to SMMC-7721 cells. Imines derivatives exhibit broad spectrum and highly efficient activities to the selected four kinds of tumor cells.

  7. Library construction and biological evaluation of enmein-type diterpenoid analogues as potential anticancer agents.

    PubMed

    Li, Dahong; Xu, Shengtao; Cai, Hao; Pei, Lingling; Wang, Lei; Wu, Xiaoming; Yao, Hequan; Jiang, Jieyun; Sun, Yijun; Xu, Jinyi

    2013-05-01

    A library of promising enmein-type 14-O-diterpenoid derivatives was constructed from a commercially available kaurene-type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel-7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC-803 mice). These results warrant further preclinical investigations of these diterpenoid-based analogues as potential novel anticancer chemotherapeutics.

  8. Optimizing ultraperformance liquid chromatographic analysis of 10 diterpenoid compounds in Salvia miltiorrhiza using central composite design.

    PubMed

    Li, Peng; Xu, Gang; Li, Shao-Ping; Wang, Yi-Tao; Fan, Tai-Ping; Zhao, Qin-Shi; Zhang, Qing-Wen

    2008-02-27

    A rapid, sensitive, reproducible, and accurate ultraperformance liquid chromatographic (UPLC) method was developed for the simultaneous determination of 10 diterpenoid compounds (tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone I, 1,2-dihydrotanshinquinone, methylenetanshinquinone, miltirone, 5,6-dehydrosugiol, sugiol, and przewalskin) in Salvia miltiorrhiza for the first time. Central composite design was applied as a powerful tool to optimize the most dominant parameters that influence the resolution of UPLC, that is, gradient, flow rate, and column temperature. Under optimum conditions, all peaks except 1,2-dihydrotanshinquinone and methylenetanshinquinone could be baseline separated within 8 min. Furthermore, the contents of these compounds in S. miltiorrhiza samples collected from different provinces of China have also been compared. The results showed that UPLC is one of the most efficient methods for the analysis of diterpenoid compounds in S. miltiorrhiza and that it is a potential method for quality control of this valuable traditional Chinese medicine.

  9. Two Diterpenoids and a Cyclopenta[c]pyridine Derivative from Roots of Salvia digitaloids

    PubMed Central

    Wu, Shwu-Jen; Huang, Chieh-Hung; Chan, Yu-Yi; Liao, Yu-Ren; Hwang, Tsong-Long; Wu, Tian-Shung

    2014-01-01

    Two new glucosides, salviadigitoside A (1) and salviatalin A-19-O-β-glucoside (2), belonging to the salviatalin type diterpenoids, and a new cyclopenta[c]pyridine, salviadiginine A (3), were isolated from the roots of Salvia digitaloids. Structures of these compounds were determined on the basis of spectroscopic analysis. In addition, compounds 1–3 were evaluated for their anti-inflammatory activity, but the results showed a weak anti-inflammatory activity. PMID:24979137

  10. A Hexacyclic ent-Trachylobane Diterpenoid Possessing an Oxetane Ring from Mitrephora glabra

    PubMed Central

    Li, Chen; Lee, Dongho; Graf, Tyler N.; Phifer, Sharnelle S.; Nakanishi, Yuka; Burgess, Jason P.; Riswan, Soedarsono; Setyowati, Fransisca M.; Saribi, Achmad M.; Soejarto, Djaja D.; Farnsworth, Norman R.; Falkinham, Joseph O.; Kroll, David J.; Kinghorn, A. Douglas; Wani, Mansukh C.

    2008-01-01

    Three new ent-trachylobane diterpenoids (1–3) were isolated and structures elucidated from Mitrephora glabra Scheff. (Annonaceae). Mitrephorone A (1) possesses a hexacyclic ring system with adjacent ketone moieties and an oxetane ring, both of which are unprecedented among trachylobanes. All compounds were evaluated for cytotoxicity against a panel of cancer cells, where 1 displayed the most potent and broadest activity, and against a battery of antimicrobial assays, where all compounds were approximately equipotent. PMID:16321028

  11. Antimalarial diterpenoid dimers of a new carbon skeleton from Aphanamixis grandifolia.

    PubMed

    Zhang, Hua; Liu, Jia; Gan, Li-She; Dalal, Seema; Cassera, Maria B; Yue, Jian-Min

    2016-01-21

    Chemical investigation into the minor constituents of Aphanamixis grandifolia yielded three new diterpenoid dimers, aphadilactones E-G (1-3) featuring a new carbon skeleton. Their structures and absolute configurations were fully established by comprehensive spectroscopic data analysis and ECD calculation. Discovery of another two new dimers (4 and 5) suggested the structure of recently reported aphanamene A to be re-investigated. Compounds 1-5 showed moderate antimalarial activities with low micromolar IC50 values.

  12. Structure elucidation and complete NMR spectral assignments of four new diterpenoids from Smallantus sonchifolius.

    PubMed

    Dou, De-Qiang; Tian, Fang; Qiu, Ying-Kun; Kang, Ting-Guo; Dong, Feng

    2008-08-01

    Four new diterpenoids, named smaditerpenic acid A-D, together with five known compounds, were isolated from the H(2)O extract of the leaves of Smallantus sonchifolius (yacon) cultivated in Liaoning, China and their structures were elucidated on the basis of one- and two-dimensional NMR (including (1)H, (13)C-NMR, (1)H-(1)H COSY, HSQC, TOCSY, HMBC, and ROESY), electrospray ionization mass spectrometry (ESI-MS), and chemical methods.

  13. New marine cembrane-type diterpenoids from the Okinawan soft coral Clavularia koellikeri.

    PubMed

    Iwashima, M; Matsumoto, Y; Takahashi, H; Iguchi, K

    2000-12-01

    Seven new marine diterpenoids having a cembrane skeleton were isolated from the Okinawan soft coral Clavularia koellikeri. Their structures were determined based on the results of spectroscopic analysis and chemical conversions. Compound 1 showed cytotoxic activity against human colorectal adenocarcinoma cells (DLD-1, IC(50) 4.2 g/mL) and strong growth inhibition against human T lymphocytic leukemia cells (MOLT-4, IC(50) 0.9 g/mL).

  14. New marine sesquiterpenoids and diterpenoids from the Okinawan soft coral Clavularia koellikeri.

    PubMed

    Iguchi, Kazuo; Fukaya, Takashi; Yasumoto, Akiko; Watanabe, Kinzo

    2004-04-01

    Six new terpenoids (two maaliane-type sesquiterpenoids, 1 and 2, one aromadendrane-type sesquiterpenoid, 3, one noraromadendrane-type sesquiterpenoid, 4, and two neodolabellane-type diterpenoids, 5 and 6) were isolated from the Okinawan soft coral Clavularia koellikeri. The structures of these compounds were determined on the basis of the results of spectroscopic analysis, chemical conversion, and X-ray crystallographic analysis. Compound 6 exhibited modest growth-inhibition effect in vitro toward tumor cells.

  15. Simultaneous quantification of diterpenoids in Premna integrifolia using a validated HPTLC method.

    PubMed

    Yadav, Deepti; Tiwari, Neerja; Gupta, Madan M

    2011-02-01

    A sensitive, selective and robust densitometric high-performance thin layer chromatographic method was developed and validated for the determination of diterpenoids in the root bark of Premna integrifolia. Diterpenoids 1β,3α,8β-trihydroxy-pimara-15-ene (A), 6α,11,12,16-tetrahydroxy-7-oxo-abieta-8,11,13-triene (B) and 2α,19-dihydroxy-pimara-7,15-diene (C) were used as chemical markers for the standardization of P. integrifolia plant extracts. The separation was performed on silica gel 60F(254) high-performance thin layer chromatography plates using hexane/acetone/ethylacetate (60:20:20 v/v) as mobile phase. The quantitation of diterpenoids was carried out using densitometric reflection/absorption mode at 475 nm after post-chromatographic derivatization using vanillin-sulfuric acid reagent. A precise and accurate quantification can be performed for compounds A, B and C in the linear working concentration range of 1-10 μg/spot with good correlations (r(2) =0.9985, 0.9996 and 0.9992, respectively). The method was validated for peak purity, precision, robustness, limit of detection (LOD) and quantitation (LOQ) etc., as per the International Conference on Harmonization (ICH) guidelines. Specificity of quantitation was confirmed using retention factor (R(f)) and spectra correlation of markers in standard and sample tracks. The method reported here is simple and reproducible which may be applied for quantitative analysis of above diterpenoids in the root bark of P. integrifolia. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Licamichauxiioic-A and -B acids--two ent-kaurene diterpenoids from Licania michauxii.

    PubMed

    Chaudhuri, Swapan K; Badisa, Ramesh Babu; Pilarinou, Elsa; Walker, Evan H

    2002-02-01

    Bioassay-guided fractionation allowed the isolation of two new cytotoxic ent-kaurene diterpenoids, licamichauxiioic-A and -B acids (1 and 2) from the root extract of Licania michauxii Prance (Chrysobalanaceae). They were characterized as ent-15-oxo-9(11),16-kauradien-19-oic acid (1) and ent-15-oxo-13(14),16-kauradien-19-oic acid (2) by various spectroscopic methods, in particular, 1D and 2D NMR spectra, and chemical evidence.

  17. Fragmentation study of aminoalcohol-diterpenoid alkaloids by electrospray ionization time-of-flight mass spectrometry.

    PubMed

    Liu, Xiuxiu; Tang, Minghai; Wang, Lu; Chao, Ruobing

    2016-01-15

    Aminoalcohol-diterpenoid alkaloids were found to be a group of cardioactive substances in the lateral roots of Aconitum carmichaeli Debx. Studies on the fragmentation behaviors and features of these alkaloids in mass spectrometry would be important for their structural identification and in vivo metabolic research, which has not received much attention thus far. In this study, the fragmentation behaviors of 14 aminoalcohol-diterpenoid alkaloids were investigated by utilizing high-resolution time-of-flight tandem mass spectrometry. By analysis of the obtained MS(2) data, we summarized the fragmentation features of the corresponding alkaloids under different collision energy. The dissociation of functional groups from the skeleton was observed as the main fragmentation way in electrospray ionization (ESI) mode. The order of fragmentation sites was C1/C3 > C16 > C15 > C6 > N, with loss of one or more CH3OH, H2O, C2H4 (substituent on N atom) or CO (at C15 ) groups. The first systematic investigations on the fragmentation of aminoalcohol-diterpenoid alkaloids are described in this paper, setting the stage for an in-depth identification and study of the corresponding components in complex systems. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Enzymes for synthetic biology of ambroxide-related diterpenoid fragrance compounds.

    PubMed

    Zerbe, Philipp; Bohlmann, Jörg

    2015-01-01

    Ambrox and related ambroxides are highly priced in the fragrance industry, and valued for their delicate odor and fixative properties. Historically, ambrox was obtained from ambergris, a waxy excretion produced by sperm whales, now an endangered species. Synthetic ambroxides have replaced ambergris in perfume manufacture. Plant labdane diterpenoids can serve as starting material for ambroxide synthesis. Among these, the diterpene alcohol sclareol is the major industrial precursor obtained from cultivated clary sage (Salvia sclarea). In plants, a large family of diterpene synthase (diTPS) enzymes controls key reactions in diterpenoid biosynthesis. Advanced metabolite profiling and high-throughput sequencing of fragrant and medicinal plants have accelerated discovery of novel diTPS functions, providing a resource for combinatorial synthetic biology and metabolic engineering approaches. This chapter highlights recent progress on the discovery, characterization, and engineering of plant diTPSs with potential uses in ambroxide production. It features biosynthesis of sclareol, cis-abienol, and diterpene resin acids, as sources of genes and enzymes for diterpenoid bioproducts.

  19. Comparison of cytotoxicity and DNA damage potential induced by ent-kaurene diterpenoids from Isodon plant.

    PubMed

    Ding, Lan; Zhou, Qiyin; Wang, Li; Wang, Wei; Zhang, Shidong; Liu, Bo

    2011-09-01

    The cytotoxicity of six ent-kaurene diterpenoids isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara was evaluated against three human tumour HepG2, GLC-82 and HL-60 cell lines through SRB assay, and their DNA damage potential (against HepG2 cell line) was assessed by comet assay. Among the six ent-kaurene diterpenoids, Rabdosin B was most cytotoxic, followed by Oridonin, Epinodosin, Rabdosinate, Lasiokaurin and Epinodosinol. All of the six ent-kaurene diterpenoids induced significant DNA damage (p < 0.05) to HepG2 cells in a time- and dose-dependent manner except Lasiokaurin and Eponodosinol at 6 µmol L⁻¹ for 24 h. The structure-activity relationships (SARs) were discussed and it was found that exo-methylene cyclopentanone in the molecular structure was important for maintaining the cytotoxicity and DNA damage potential of the compounds.-OAc group at site C-1 in Lasiokaurin had a higher stereospecific blockade, which made the compound have less cytotoxicity and DNA damage potential than Oridonin (-OH at C-1).

  20. Large-scale profiling of diterpenoid glycosides from Stevia rebaudiana using ultrahigh performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Shafii, Behnaz; Vismeh, Ramin; Beaudry, Randy; Warner, Ryan; Jones, A Daniel

    2012-07-01

    The plant Stevia rebaudiana accumulates a suite of diterpenoid metabolites that are natural sweeteners finding increased use as sugar substitutes. To guide breeding of stevia plants that accumulate substances with desirable flavor in high yield, rapid and accurate methods are needed to profile these substances in plant populations. This report describes an 8-min ultrahigh performance liquid chromatography-tandem mass spectrometry method for separation and quantification of seven stevia glycosides including steviolbioside; stevioside; rebaudiosides A, B, and C; rubusoside; and dulcoside as well as aglycones steviol and isosteviol. This negative mode electrospray ionization/multiple reaction monitoring method yielded low limits of detection <1 ng/mL for steviol, 6 ng/mL for isosteviol, and <15 ng/mL for all stevia glycosides. Stevioside and Reb A, B, and C were quantified in more than 1,100 extracts from stevia leaves as part of a large-scale profiling exercise. Leaf tissue levels in this population spanned about two orders of magnitude for stevioside (2-125 mg/g dry weight), Reb A (2.5-164 mg/g), Reb B (0.5-50 mg/g), and Reb C (1.5-125 mg/g), but levels of individual metabolites exhibited independent variation. The wide spread of metabolite levels highlights the utility and importance of performing targeted metabolic profiling for large plant populations.

  1. Biochemical synthesis of uniformly (13)C-labeled diterpene hydrocarbons and their bioconversion to diterpenoid phytoalexins in planta.

    PubMed

    Ye, Zhongfeng; Nakagawa, Kazuya; Natsume, Masahiro; Nojiri, Hideaki; Kawaide, Hiroshi; Okada, Kazunori

    2017-06-01

    Phytocassanes and momilactones are the major diterpenoid phytoalexins inductively produced in rice as bioactive substances. Regardless of extensive studies on the biosynthetic pathways of these phytoalexins, bioconversion of diterpene hydrocarbons is not shown in planta. To elucidate the entire biosynthetic pathways of these phytoalexins, uniformly (13)C-labeled ent-cassadiene and syn-pimaradiene were enzymatically synthesized with structural verification by GC-MS and (13)C-NMR. Application of the (13)C-labeled substrates on rice leaves led to the detection of (13)C-labeled metabolites using LC-MS/MS. Further application of this method in the moss Hypnum plumaeforme and the nearest out-group of Oryza species Leersia perrieri, respectively, resulted in successful bioconversion of these labeled substrates into phytoalexins in these plants. These results demonstrate that genuine biosynthetic pathways from these diterpene hydrocarbons to the end product phytoalexins occur in these plants and that enzymatically synthesized [U-(13)C20] diterpene substrates are a powerful tool for chasing endogenous metabolites without dilution with naturally abundant unlabeled compounds.

  2. Studies on C20-Diterpenoid Alkaloids: Synthesis of the Hetidine Framework and Its Application to the Synthesis of Dihydronavirine and the Atisine Skeleton

    PubMed Central

    2015-01-01

    The full details of a synthesis of the hetidine framework of the C20-diterpenoid alkaloids and its conversion to the atisine core structure are reported. The application of the hetidine framework to the synthesis of dihydronavirine, which is the formal reduction product of the natural product navirine, is also described. Key to the success of these studies is the use of a Ga(III)-catalyzed cycloisomerization reaction of alkynylindenes to prepare a [6–7–6] framework that was advanced to the hetidine skeleton. Furthermore, a Michael/aldol sequence was developed for the construction of the bicyclo[2.2.2] framework that is characteristic of the hetidines and atisines. PMID:25004408

  3. Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium.

    PubMed

    Brockhoff, Anne; Behrens, Maik; Massarotti, Alberto; Appendino, Giovanni; Meyerhof, Wolfgang

    2007-07-25

    Sesquiterpene lactones are a major class of natural bitter compounds occurring in vegetables and culinary herbs as well as in aromatic and medicinal plants, where they often represent the main gustatory and pharmacologically active component. Investigations on sesquiterpene lactones have mainly focused on their bioactive potential rather than on their sensory properties. In the present study, we report about the stimulation of heterologously expressed human bitter taste receptors, hTAS2Rs, by the bitter sesquiterpene lactone herbolide D. A specific response to herbolide D was observed i.a. for hTAS2R46, a so far orphan bitter taste receptor without any known ligand. By further investigation of its agonist pattern, we characterized hTAS2R46 as a bitter receptor broadly tuned to sesquiterpene lactones and to clerodane and labdane diterpenoids as well as to the unrelated bitter substances strychnine and denatonium.

  4. Discovery and structure-activity relationships of ent-Kaurene diterpenoids as potent and selective 11β-HSD1 inhibitors: potential impact in diabetes.

    PubMed

    Deng, Xu; Shen, Yu; Yang, Jing; He, Juan; Zhao, Yu; Peng, Li-Yan; Leng, Ying; Zhao, Qin-Shi

    2013-07-01

    The biological screening of a collection of nature occurring diterpenoids against 11β-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11β-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC50 (human 11β-HSD1) = 9.4 nM and selectivity index (human 11β-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11β-HSD1 were generated using docking simulations. Based on the results, the structural-activity relationships (SARs) of compounds 1b and 2 were also discussed.

  5. Induction of apoptosis by new ent-kaurene-type diterpenoids isolated from the New Zealand liverwort Jungermannia species.

    PubMed

    Kondoh, Masuo; Nagashima, Fumihiro; Suzuki, Ikue; Harada, Motoki; Fujii, Makiko; Asakawa, Yoshinori; Watanabe, Yoshiteru

    2005-11-01

    Some diterpenoids show various biological activities, including anti-inflammatory, anti-HIV and anti-tumor activity. Previously, we have focused our research on the apoptosis-inducing properties of diterpenoids and found that some ent-kaurene-type diterpenoids induced apoptosis in human leukemia HL-60 cells. In this study, we have investigated the induction of apoptosis in HL-60 cells by the novel ent-kaurene-type diterpenoids, jungermannenones A (JA), B (JB), C (JC) and D (JD), isolated from the New Zealand liverwort Jungermannia species. Treatment of the cells with each compound for 12 h resulted in cytotoxicity (IC (50) values: A, 1.3; B, 5.3; C, 7.8; D, 2.7 microM) and caused DNA fragmentation and nuclear condensation, both biochemical markers of the induction of apoptosis. Treatment with the compounds resulted in activation of caspases, including caspase-3 and caspase-8. A broad-spectrum inhibitor of caspases, Z-Asp-CH (2)-DCB, attenuated the cytotoxicity induced by these compounds, suggesting that JA, JB, JC and JD induced apoptosis through a caspase-dependent pathway. JA and JD inhibited the activity of nuclear factor-kappaB, which is a transcriptional factor of anti-apoptotic factors. Thus, some of these new ent-kaurene-type diterpenoids may be promising candidates for anti-tumor agents.

  6. Studies on the minor constituents of the Caribbean gorgonian octocoral Briareum asbestinum Pallas. Isolation and structure determination of the eunicellin-based diterpenoids briarellins E--I.

    PubMed

    Rodríguez, A D; Cóbar, O M

    1995-11-01

    Five new eunicellin-type diterpenoids, briarellins E--I, along with several known diterpenoids of the asbestinane, briarane and eunicellane classes, were isolated from the Caribbean gorgonian octocoral Briareum asbestinum collected in Puerto Rico. The structures of these compounds were established on the basis of spectroscopic evidence.

  7. Hormonal diterpenoids derived from ent-kaurenoic acid are involved in the blue-light avoidance response of Physcomitrella patens.

    PubMed

    Miyazaki, Sho; Nakajima, Masatoshi; Kawaide, Hiroshi

    2015-01-01

    Gibberellins (GAs) are diterpenoid hormones that regulate growth and development in flowering plants. The moss Physcomitrella patens has part of the GA biosynthetic pathway from geranylgeranyl diphosphate to ent-kaurenoic acid via ent-kaurene, but it does not produce GA. Disruption of the ent-kaurene synthase gene in P. patens suppressed caulonemal differentiation. Application of ent-kaurene or ent-kaurenoic acid restored differentiation, suggesting that derivative(s) of ent-kaurenoic acid, but not GAs, are endogenous regulator(s) of caulonemal cell differentiation. The protonemal growth of P. patens shows an avoidance response under unilateral blue light. Physiological studies using gene mutants involved in ent-kaurene biosynthesis confirmed that diterpenoid(s) regulate the blue-light response. Here, we discuss the implications of these findings, and provide data for the ent-kaurene oxidase gene-disrupted mutant.

  8. New ent-Clerodane and Abietane Diterpenoids from the Roots of Kenyan Croton megalocarpoides Friis & M. G. Gilbert.

    PubMed

    Ndunda, Beth; Langat, Moses K; Mulholland, Dulcie A; Eastman, Harry; Jacob, Melissa R; Khan, Shabana I; Walker, Larry A; Muhammad, Ilias; Kerubo, Leonidah O; Midiwo, Jacob O

    2016-07-01

    The roots of the endangered medicinal plant Croton megalocarpoides collected in Kenya were investigated and twenty-two compounds isolated. Among them were twelve new ent-clerodane (1-12) and a new abietane (13) diterpenoids, alongside the known crotocorylifuran (4 a), two known abietane and four known ent-trachylobane diterpenoids, and the triterpenoids, lupeol and acetyl aleurotolic acid. The structures of the compounds were determined using NMR, HRMS and ECD. The isolated compounds were evaluated against a series of microorganisms (fungal and bacteria) and also against Plasmodium falciparum, however no activity was observed.

  9. Synthesis of ent-Kaurane and Beyerane Diterpenoids via Controlled Fragmentations of Overbred Intermediates**

    PubMed Central

    Cherney, Emily C.; Green, Jason C.

    2013-01-01

    In the first part of a two-phase pursuit of highly oxidized members of the ent-kaurane and beyerane diterpenoid families, steviol was identified as the ideal cyclase phase terminus. Accordingly, a synthesis of steviol has been developed. This synthesis features a polyene cyclization precursor designed to directly yield oxidation on the axial C19 methyl group. Construction of the necessary [3.2.1]bicyclic system found in the ent-kaurane skeleton was realized with two overbred intermediates. The resulting [3.2.1]bicyclic system undergoes Wagner–Meerwein rearrangement to yield the beyerane skeleton of isosteviol. PMID:23861294

  10. Four new C18-diterpenoid alkaloids with analgesic activity from Aconitum weixiense.

    PubMed

    Zhao, Da-Ke; Ai, Hong-Lian; Zi, Shu-Hui; Zhang, Li-Mei; Yang, Sheng-Chao; Guo, Hua-Chun; Shen, Yong; Chen, Yan-Ping; Chen, Ji-Jun

    2013-12-01

    Four new C18-diterpenoid alkaloids, weisaconitines A-D (1-4), were isolated from Aconitum weixiense. Based on extensive UV, IR, MS, 1D and 2D NMR analyses, their structures were elucidated as 8-O-ethyldolaconine (1), 4-demethylgenicunine B (2), 14-oxoaconosine (3), and 8-O-ethylaconosine (4). The analgesic activity of compound 4 was studied with CH3COOH-induced writhing model in mice. Compound 4 showed writhing inhibitions of 24% (50 mg/kg), 26% (100 mg/kg) and 34% (200 mg/kg), respectively, as compared to the reference drug aspirin (63%) at a dose of 200 mg/kg.

  11. Antispasmodic effects and structure-activity relationships of labdane diterpenoids from Marrubium globosum ssp. libanoticum.

    PubMed

    Rigano, Daniela; Aviello, Gabriella; Bruno, Maurizio; Formisano, Carmen; Rosselli, Sergio; Capasso, Raffaele; Senatore, Felice; Izzo, Angelo A; Borrelli, Francesca

    2009-08-01

    Marrubium globosum ssp. libanoticum is a medicinal plant used in Lebanon to reduce pain and smooth muscle spasms. A chloroform extract obtained from M. globosum aerial parts reduced acetylcholine-induced contractions in the isolated mouse ileum. The purification of this extract identified, among 12 isolated labdane diterpenoids, four new compounds, named 13-epicyllenin A (4), 13,15-diepicyllenin A (5), marrulibacetal (9), and marrulactone (11). Their structures were determined by spectroscopic methods. Compound 9, which exerted antispasmodic activity, is likely the active ingredient of the extract. Preliminary structure-activity relationships for this class of compounds are suggested.

  12. New cassane-type diterpenoids of Caesalpinia echinata (Leguminosae) exhibiting NF-κB inhibitory activities.

    PubMed

    Mitsui, Taichi; Ishihara, Risa; Hayashi, Ken-ichiro; Sunadome, Mitsuhisa; Matsuura, Nobuyasu; Nozaki, Hiroshi

    2014-01-01

    Seven new cassane-type diterpenoids, echinalides A-G (1-7), were isolated from the stem of Caesalpinia echinata LAM. (Leguminosae). The structures were established on the basis of their chemical properties and spectroscopic evidence, including two dimensional (2D)-NMR analysis. These compounds were assessed for inhibitory activity against nuclear factor κB (NF-κB). Echinalides C and D, in particular, significantly inhibited NF-κB-responsive reporter gene expression at 5.0 µM, an effect almost equivalent to that of parthenolide, a known potent inhibitor of NF-κB.

  13. Oscyp71Z2 involves diterpenoid phytoalexin biosynthesis that contributes to bacterial blight resistance in rice.

    PubMed

    Li, Wenqi; Shao, Min; Yang, Jie; Zhong, Weigong; Okada, Kazunori; Yamane, Hisakazu; Qian, Guoliang; Liu, Fengquan

    2013-06-01

    Bacterial blight is one of the most destructive rice diseases, which caused by Xoo, and results in yield losses, endangering worldwide food security. Diterpenoid phytoalexins, a type of antimicrobials produced in rice, are critical for resistance to fungal and bacterial pathogens. This article reports the characterization of the cytochrome P450 gene Oscyp71Z2, which belongs to the CYP71Z subfamily. Overexpression of Oscyp71Z2 in rice enhanced resistance to Xoo at the booting stage. The accumulation of phytoalexins was rapidly and strongly induced in Oscyp71Z2-overexpressing plants, and the transcript levels of genes related to the phytoalexin biosynthesis pathway were elevated. The H₂O₂ concentration in Oscyp71Z2-overexpressing plants was reduced in accordance with the increase in ROS-scavenging ability due to the induction of SOD as well as POD and CAT activation. We also showed that suppression of Oscyp71Z2 had no significantly effect on disease resistance to Xoo in rice. These results demonstrated that Oscyp71Z2 plays an important role in bacterial blight resistance by regulating the diterpenoid phytoalexin biosynthesis and H₂O₂ generation.

  14. An ent-kaurene-derived diterpenoid virulence factor from Xanthomonas oryzae pv. oryzicola.

    PubMed

    Lu, Xuan; Hershey, David M; Wang, Li; Bogdanove, Adam J; Peters, Reuben J

    2015-04-01

    Both plants and fungi produce ent-kaurene as a precursor to the gibberellin plant hormones. A number of rhizobia contain functionally conserved, sequentially acting ent-copalyl diphosphate and ent-kaurene synthases (CPS and KS, respectively), which are found within a well-conserved operon that may lead to the production of gibberellins. Intriguingly, the rice bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola (Xoc) contains a homologous operon. Here, we report biochemical characterization of the encoded CPS and KS, and the impact of insertional mutagenesis on virulence and the plant defense response for these genes, as well as that for one of the cytochromes P450 (CYP112) found in the operon. Activity of the CPS and KS found in this phytopathogen was verified - that is, Xoc is capable of producing ent-kaurene. Moreover, knocking out CPS, KS or CYP112 led to mutant Xoc that exhibited reduced virulence. Investigation of the effect on marker gene transcript levels suggests that the Xoc diterpenoid affects the plant defense response, most directly that mediated by jasmonic acid (JA). Xoc produces an ent-kaurene-derived diterpenoid as a virulence factor, potentially a gibberellin phytohormone, which is antagonistic to JA, consistent with the recent recognition of opposing effects for these phytohormones on the microbial defense response.

  15. Antiacetylcholinesterase and antioxidant ent-Kaurene diterpenoid, melissoidesin from Isodon wightii (Bentham) H. Hara.

    PubMed

    Thirugnanasampandan, R; Jayakumar, R; Narmatha Bai, V; Martin, Ebenezar; Rajendra Prasad, K J

    2008-05-20

    The ent kaurene diterpenoid, melissoidesin was isolated from the acetone extract of the leaves of Isodon wightii and the structure was designated as 3beta, 11beta, 15beta-trihydroxy-6alpha-acetoxy-ent-kaur-16-ene based on spectral data and previous reports. Melissoidesin isolated from the acetone extract of leaves showed potent antiacetylcholinesterase activity and the IC(50) value was observed as 215 microg mL(-1). DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity of melissoidesin was significant and the IC(50) value was 138 microg mL(-1). The significant reducing property of the melissoidesin was stronger in high concentration. IC(50) value of melissoidesin on hydroxyl radicals and metal chelation was observed as 99 and 143 microg mL(-1), respectively. The 50% inhibitory concentration of melissoidesin on lipid peroxidation was calculated as 133 microg mL(-1). These findings indicate that ent kaurene diterpenoid, melissoidesin was promising antiacetylcholinesterase and antioxidant which can be used as food and drug preparations.

  16. Diterpenoids with anti-inflammatory activity from the wood of Cunninghamia konishii.

    PubMed

    Chen, Yu-Chang; Li, Yen-Cheng; You, Bang-Jau; Chang, Wen-Te; Chao, Louis Kuoping; Lo, Lee-Chiang; Wang, Sheng-Yang; Huang, Guan-Jhong; Kuo, Yueh-Hsiung

    2013-01-04

    Two new diterpenoids, konishone (1) and 3b-hydroxy-5,6-dehydrosugiol (2), along with three known diterpenoids--hinokiol (3), sugiol (4), and 12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial (5)--were isolated from the wood of Cunninghamia konishii. Compound 1 is a novel skeleton of the 7,20-dinorabietane-type diterpene. In addition, when RAW264.7 macrophages were treated with different concentrations of compounds 1, 3, and 5 together with LPS, a significant concentration-dependent inhibition of NO production was detected. The IC₅₀ values for inhibition of nitrite production of compounds 1, 3, and 5 were about 9.8 ± 0.7, 7.9 ± 0.9, and 9.3 ± 1.3 μg/mL, respectively. This study presents the potential utilization of compounds 1, 3, and 5, as lead compounds for the development of anti-inflammatory drugs.

  17. Phytol a Natural Diterpenoid with Pharmacological Applications on Central Nervous System: A Review.

    PubMed

    Pereira Costa, Jessica; da Silva Oliveira, Johanssy; Mario Rezende Junior, Luis; de Freitas, Rivelilson Mendes

    2014-01-01

    Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol), a diterpene member of long and ramified chain of unsaturated acyclic alcohols. The objective of study was to conduct a systematic review of this diterpene and its pharmaceutical applications in Nervous System diseases in humans and/or rodents. Periodicals bases, such as ScienceDirect and PubMed, were used, as well as technological basis of European Patent Office, World Intellectual Property Organization, United States Patent and Trademark Office, Derwent Innovations Index(®), Latin American Bank of Patents and data base of Instituto Nacional de Propriedade Industrial (INPI-National Institute of Industrial Property). The software EndNote-X5 was utilized as reference with the keywords: phytol, anxiolytic, antidepressant and anticonvulsant and their correlations in English, Spanish and Portuguese from January 2003 to June 2014. There are many publications on phytol in international literature. However, there is a reduced number of articles related to pharmacological activities proposed here. In reference to technological bases, patents present a wide range of pharmacological and commercial applications as cosmetics, hypolipodemic, anxiolytic and antidepressant. Therefore, it is necessary to explore phytol molecules, which present high pharmacological potential from scientific and technological points of view, in search of transference of technologies to generate economical and industrial growth.

  18. [Identification of aminoalcohol-diterpenoid alkaloids in Aconiti Lateralis Radix Praeparata and study of their cardiac effects].

    PubMed

    Wang, Lu; Ding, Jia-Yu; Liu, Xiu-Xiu; Tang, Ming-Hai; Chao, Ruo-Bing; Wang, Feng-Peng

    2014-12-01

    In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.

  19. Salvinorins D-F, new neoclerodane diterpenoids from Salvia divinorum, and an improved method for the isolation of salvinorin A.

    PubMed

    Munro, Thomas A; Rizzacasa, Mark A

    2003-05-01

    Three new neoclerodane diterpenoids, salvinorins D-F (4-6), have been isolated from the leaves of Salvia divinorum. The structures were elucidated by chemical and spectroscopic methods, particularly 1D and 2D NMR. A simplified isolation method using chromatography on activated carbon also gave improved yields of the controlled substance salvinorin A (1) and of salvinorin C (3).

  20. Sesqui- and diterpenoids from three New Zealand liverworts: Bazzania novae-zelandiae, Gackstroemia sp. and Dendromastigophora sp.

    PubMed

    Nagashima, Fumihiro; Kuba, Yoshiaki; Ogata, Atsushi; Asakawa, Yoshinori

    2010-01-01

    Two new sesquiterpenoids, 1 and 2, were isolated from the unidentified liverwort Gackstroemia species, and three known sesquiterpenoids, 3-5, and a known sesqui- (6) and diterpenoid (7) were isolated from Bazzania novae-zelandiae and the unidentified Dendromastigophora species, respectively. Their structures were determined by spectroscopic analysis.

  1. Diterpenoids and aromatic compounds from the three New Zealand liverworts Jamesoniella kirkii, Balantiopsis rosea, and Radula species.

    PubMed

    Nagashima, Fumihiro; Kuba, Yoshiyuki; Asakawa, Yoshinori

    2006-06-01

    Three new aromatics were isolated from the New Zealand liverwort Balantiopsis rosea. A new bibenzyl was isolated from an unidentified Radula species, together with known bibenzyls. Jamesoniella kirkii yielded three known ent-isopimarane and two ent-kaurane diterpenoids. Their structures were confirmed by NMR techniques, chemical reaction, and X-ray crystallographic analysis.

  2. Abietane diterpenoids from the barks of Cryptomeria japonica.

    PubMed

    Yoshikawa, Kazuko; Suzuki, Kentaro; Umeyama, Akemi; Arihara, Shigenobu

    2006-04-01

    From the bark of Cryptomeria japonica were isolated sugikurojins I (1) and J (2), and an abietane derivative (3) was obtained for the first time as a natural product. These structures were elucidated primarily through extensive NMR experiments. Sugikurojin I (1) has a unique skeleton incorporating an abietane diterpene and a 1,10-secocadinane sesquiterpene. Sugikurojin J (2) is a peroxyester of hydroxyabietane diterpene and isopimarane acid diterpene. Compound 3 was p-quinone acid, which occurred by cleavage between C-7 and C-8 of sugiol; it was deduced to [4'-isopropyl-1(S),3,3-trimethyl-3',6'-dioxo-bicyclohexyl-1',4'-dien-2(R)-yl]-acetic acid. Also obtained in this investigation were three known diterpenes (4-6).

  3. An Investigation on the Quantitative Structure-Activity Relationships of the Anti-Inflammatory Activity of Diterpenoid Alkaloids.

    PubMed

    Li, Xiao; Li, Ning; Sui, Zhenyu; Bi, Kaishun; Li, Zuojing

    2017-02-27

    Diterpenoid alkaloids are extracted from plants. These compounds have broad biological activities, including effects on the cardiovascular system, anti-inflammatory and analgesic actions, and anti-tumor activity. The anti-inflammatory activity was determined by carrageenan-induced rat paw edema and experimental trauma in rats. The number of studies focused on the determination, quantitation and pharmacological properties of these alkaloids has increased dramatically during the past few years. In this work we built a dataset composed of 15 diterpenoid alkaloid compounds with diverse structures, of which 11 compounds were included in the training set and the remaining compounds were included in the test set. The quantitative chemistry parameters of the 15 diterpenoid alkaloids compound were calculated using the HyperChem software, and the quantitative structure-activity relationship (QSAR) of these diterpenoid alkaloid compounds were assessed in an anti-inflammation model based on half maximal effective concentration (EC50) measurements obtained from rat paw edema data. The QSAR prediction model is as follows: log ( E C 50 ) = - 0.0260 × SAA + 0.0086 × SAG + 0.0011 × VOL - 0.0641 × HE - 0.2628 × LogP - 0.5594 × REF - 0.2211 × POL - 0.1964 × MASS + 0.088 × BE + 0.1398 × HF (R² = 0.981, Q² = 0.92). The validated consensus EC50 for the QSAR model, developed from the rat paw edema anti-inflammation model used in this study, indicate that this model was capable of effective prediction and can be used as a reliable computational predictor of diterpenoid alkaloid activity.

  4. Jasmonoyl-l-isoleucine is required for the production of a flavonoid phytoalexin but not diterpenoid phytoalexins in ultraviolet-irradiated rice leaves.

    PubMed

    Miyamoto, Koji; Enda, Isami; Okada, Toshiki; Sato, Yumiko; Watanabe, Kohei; Sakazawa, Tomoko; Yumoto, Emi; Shibata, Kyomi; Asahina, Masashi; Iino, Moritoshi; Yokota, Takao; Okada, Kazunori; Yamane, Hisakazu

    2016-10-01

    Rice produces low-molecular-weight antimicrobial compounds known as phytoalexins, in response to not only pathogen attack but also abiotic stresses including ultraviolet (UV) irradiation. Rice phytoalexins are composed of diterpenoids and a flavonoid. Recent studies have indicated that endogenous jasmonyl-l-isoleucine (JA-Ile) is not necessarily required for the production of diterpenoid phytoalexins in blast-infected or CuCl2-treated rice leaves. However, JA-Ile is required for the accumulation of the flavonoid phytoalexin, sakuranetin. Here, we investigated the roles of JA-Ile in UV-induced phytoalexin production. We showed that UV-irradiation induces the biosynthesis of JA-Ile and its precursor jasmonic acid. We also showed that rice jasmonate biosynthesis mutants produced diterpenoid phytoalexins but not sakuranetin in response to UV, indicating that JA-Ile is required for the production of sakuranetin but not diterpenoid phytoalexins in UV-irradiated rice leaves.

  5. ent-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition As Detected in Situ by a Fluorescence Probe.

    PubMed

    Lin, Zhaomin; Guo, Yanxia; Gao, Yanhui; Wang, Shuqi; Wang, Xiaoning; Xie, Zhiyu; Niu, Huanmin; Chang, Wenqiang; Liu, Lei; Yuan, Huiqing; Lou, Hongxiang

    2015-05-14

    It is generally accepted that the origin of the cytotoxicity of ent-kaurane diterpenoids is due to the formation of reactive oxygen species (ROS) and that the α,β-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate the isolation of 32 new and 12 known ent-kaurane diterpenoids from two Chinese liverworts. These compounds and three semisynthesized derivatives were screened against human cancer cell lines. The results revealed that their anticancer activities are caused by ROS formation through Michael modification of the protein thiols and depletion of glutathione unselectively. We also found that N-acetylcysteine reverses the cytotoxicity of these diterpenoids by forming Michael adducts, not through a well-recognized ROS scavenging pathway as previously reported. In situ intracellular thiol detection helped us visualize the intracellular distribution of the diterpenoids and determine the potency of their cytotoxicity. An alkaline analogue was found to be more selective because of the altered subcellular distribution.

  6. Cytotoxic 3,4-seco-Atisane Diterpenoids from Croton barorum and Croton goudotii.

    PubMed

    Rakotonandrasana, Olga L; Raharinjato, Fanja H; Rajaonarivelo, Mialy; Dumontet, Vincent; Martin, Marie-Thérèse; Bignon, Jérôme; Rasoanaivo, Philippe

    2010-10-22

    In a screening program directed to the discovery of new anticancer agents from Madagascan plants, ethyl acetate extracts of Croton barorum and C. goudotii showed strong cytotoxic activity, with 100% inhibition at 10 μg/mL in a primary screen using the murine lymphocytic leukemia P388 cell line. Bioassay-guided fractionation led to the isolation of two new 3,4-seco-atisane diterpenoids, crotobarin (1) and crotogoudin (2). Their structures were elucidated by spectroscopic data interpretation. Compounds 1 and 2 produced a net progression in the number of cells arrested at the G2/M growth stage in the cell cycle of the K562 human leukemia cell line at 4 μM.

  7. 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

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

    PubMed

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

    2015-01-01

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

  9. Diterpenoids from the freshwater green algae Rhizoclonium hieroglyphicum with antibacterial activity.

    PubMed

    Perez Gutierrez, Rosa Martha; Garcia Baez, Efren

    2011-10-01

    Three new isopimarane diterpenes 7β-hydroxy-19α-methylmalonyloxy-isopimara-8(14),15-diene (1), 7β-hydroxy-14-oxo-isopimara-8(9),15-dien-19oic acid (2), and 7β-hydroxy-14-oxo-19α-methylmalonyloxy-isopimara-9(11),15-diene (3) in addition to the known compounds isopimaric acid (4), 7oxo-13-epi-pimara-14,15-dien-18oic acid (5), 7oxo-13-epi-pimara-8,15-dien-18oic acid (6), and 6β-hydroxyisopimaric acid (7) were isolated from the hexane extract of Rhizoclonium hieroglyphicum. The structures of compounds 1-7 were established by 1D and 2D NMR techniques. The isolated diterpenoids were screened for antimicrobial activity against gram-positive and gram-negative bacteria and yeast strains.

  10. Three New Abietane-Type Diterpenoids from Plectranthus africanus and Their Antibacterial Activities.

    PubMed

    Nzogong, Raïssa T; Nganou, Blaise K; Tedonkeu, Alex T; Awouafack, Maurice D; Tene, Mathieu; Ito, Takuya; Tane, Pierre; Morita, Hiroyuki

    2017-06-29

    Three new abietane-type diterpenoids, plectranthroyleanones A - C (1 - 3), together with five known compounds (4 - 8) were isolated from the methanol extract of the whole plant of Plectranthus africanus using column chromatography techniques. The structures of the new compounds were elucidated using a combination of 1D and 2D NMR and HRESIMS analyses. Compound 1 exhibited weak activities with minimal inhibitory concentration values of 75 µg/mL against gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus, and 150 µg/mL against two gram-negative bacteria, Pseudomonas aeruginosa and Klebsiella pneumoniae, respectively, while 2 and 3 had moderate antibacterial activity against K. pneumoniae with a minimal inhibitory concentration value of 37.5 µg/mL. Georg Thieme Verlag KG Stuttgart · New York.

  11. 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.

  12. Genetic Investigation of the Catabolic Pathway for Degradation of Abietane Diterpenoids by Pseudomonas abietaniphila BKME-9

    PubMed Central

    Martin, Vincent J. J.; Mohn, William W.

    2000-01-01

    We have cloned and sequenced the dit gene cluster encoding enzymes of the catabolic pathway for abietane diterpenoid degradation by Pseudomonas abietaniphila BKME-9. The dit gene cluster is located on a 16.7-kb DNA fragment containing 13 complete open reading frames (ORFs) and 1 partial ORF. The genes ditA1A2A3 encode the α and β subunits and the ferredoxin of the dioxygenase which hydroxylates 7-oxodehydroabietic acid to 7-oxo-11,12-dihydroxy-8,13-abietadien acid. The dioxygenase mutant strain BKME-941 (ditA1::Tn5) did not grow on nonaromatic abietanes, and transformed palustric and abietic acids to 7-oxodehydroabietic acid in cell suspension assays. Thus, nonaromatic abietanes are aromatized prior to further degradation. Catechol 2,3-dioxygenase activity of xylE transcriptional fusion strains showed induction of ditA1 and ditA3 by abietic, dehydroabietic, and 7-oxodehydroabietic acids, which support the growth of strain BKME-9, as well as by isopimaric and 12,14-dichlorodehydroabietic acids, which are diterpenoids that do not support the growth of strain BKME-9. In addition to the aromatic-ring-hydroxylating dioxygenase genes, the dit cluster includes ditC, encoding an extradiol ring cleavage dioxygenase, and ditR, encoding an IclR-type transcriptional regulator. Although ditR is not strictly required for the growth of strain BKME-9 on abietanes, a ditR::Kmr mutation in a ditA3::xylE reporter strain demonstrated that it encodes an inducer-dependent transcriptional activator of ditA3. An ORF with sequence similarity to genes encoding permeases (ditE) is linked with genes involved in abietane degradation. PMID:10850995

  13. Cespitulones A and B, Cytotoxic Diterpenoids of a New Structure Class from the Soft Coral Cespitularia taeniata

    PubMed Central

    Lin, Yu-Chi; Wang, Shih-Sheng; Chen, Chung-Hsiung; Kuo, Yao-Haur; Shen, Ya-Ching

    2014-01-01

    Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between C-20 and C-11. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against human medulloblastoma and colon adenocarcinoma cancer cells. PMID:24905485

  14. Mannolides A-C with an Intact Diterpenoid Skeleton Providing Insights on the Biosynthesis of Antitumor Cephalotaxus Troponoids.

    PubMed

    Ni, Gang; Zhang, Hua; Fan, Yao-Yue; Liu, Hong-Chun; Ding, Jian; Yue, Jian-Min

    2016-04-15

    Three new diterpenoids, mannolides A-C (1-3), and two new Cephalotaxus troponoids, 4 and 5, were isolated from Cephalotaxus mannii and structurally characterized by spectroscopic data and X-ray crystallography. The discovery of compounds 1-3 featuring a new intact carbon skeleton, proposed as cephalotane, sheds new light on the biogenesis of Cephalotaxus troponoids, a rare class of antitumor C19 norditerpenoids. Antitumor tests showed that the tropone motif is essential for the activity.

  15. An effective O-demethylation of some C19-diterpenoid alkaloids with HBr-glacial acetic acid.

    PubMed

    Zou, Chun-Lan; Ji, Hong; Xie, Guang-Bo; Chen, Dong-Lin; Wang, Feng-Peng

    2008-01-01

    The aconitine-type alkaloids talatisamine (1), 8,14-diacetyltalatisamine (11), and compound 3, the lycoctonine-type alkaloid deltaline (5), and the 7,17-seco C(19)-diterpenoid alkaloids 7 and 9 were treated with HBr-glacial acetic acid to give useful O-demethylated derivatives 2, 2, 4, 6, 8, and 10 respectively in good to high yields (49-90%).

  16. The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica

    PubMed Central

    Edwards, Jennifer; Brown, Martha; Peak, Emily; Bartholomew, Barbara; Nash, Robert J.; Hoffmann, Karl F.

    2015-01-01

    Background Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. Methodology/ Principle Findings Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and

  17. (4aS,10aS)-7-Hydr­oxy-8-isopropyl-1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octa­hydro­phenanthrene: a new diterpenoid compound

    PubMed Central

    Zeroual, Abdellah; Mazoir, Noureddine; Daran, Jean-Claude; Akssira, Mohamed; Benharref, Ahmed

    2008-01-01

    The new title diterpenoid compound, C20H30O, is a natural product isolated from Tetra­clinis articulata wood via chloro­form extraction. The asymmetric unit contains four mol­ecules with the same S,S configuration, deduced from the chemical synthesis. Indeed, an overlay analysis, calculated using structure-matching software, shows that the four mol­ecules can be superimposed. The central ring has a half-chair conformation, whereas the saturated ring displays a chair conformation. PMID:21201941

  18. Labdane Diterpenoids from Salvia leriifolia: Absolute Configuration, Antimicrobial and Cytotoxic Activities.

    PubMed

    Farimani, Mahdi Moridi; Taleghani, Akram; Aliabadi, Abbas; Aliahmadi, Atousa; Esmaeili, Mohammad Ali; Namazi Sarvestani, Nazanin; Khavasi, Hamid Reza; Smieško, Martin; Hamburger, Matthias; Nejad Ebrahimi, Samad

    2016-09-01

    Fractionation of an n-hexane extract of the aerial parts of Salvia leriifolia led to the isolation of two new (1, 2) and two known (3, 4) labdane diterpenoids, together with three other known compounds. The structures were established by a combination of 1D and 2D NMR, and HRESIMS. The structures of 1 and 3 were confirmed by single-crystal X-ray analysis. The absolute configuration of 1-4 was established by electronic circular dichroism spectroscopy. Compounds 1-4 were evaluated for their cytotoxic activities against MCF-7 human breast cancer cells. Labdanes 3 and 4 were additionally tested against MDA-MB231 human breast cancer and DU-145 human prostate cancer cell lines. Compound 4 showed IC50 values of 25, 50, and 50 µM against MCF-7, MDA-MB231, and DU-145 cells, respectively. Compounds 1-4 were tested for activity against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria. Compound 3 showed an MIC of 213 µM against methicillin-resistant S. aureus.

  19. 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.

  20. Nature

    NASA Astrophysics Data System (ADS)

    Heinhorst, Sabine; Cannon, Gordon

    1997-01-01

    The fact that two of the original articles by this year's Nobel laureates were published in Nature bears witness to the pivotal role of this journal in documenting pioneering discoveries in all areas of science. The prize for Physiology or Medicine was awarded to immunologists Peter C. Doherty (University of Tennessee) and Rolf M. Zinkernagel (University of Zurich, Switzerland), honoring work that, in the 1970s, laid the foundation for our current understanding of the way in which our immune system differentiates between healthy cells and virus-infected ones that are targeted for destruction (p 465 in the October 10 issue of vol. 383). Three researchers share the Chemistry award for their discovery of C60 buckminsterfullerenes. The work by Robert Curl, Richard Smalley (both at Rice University), and Harry Kroto (University of Sussex, UK) has led to a burst of new approaches to materials development and in carbon chemistry (p 561 of the October 17 issue of vol. 383). This year's Nobel prize in physics went to three U.S. researchers, Douglas Osheroff (Stanford University) and David M. Lee and Robert C. Richardson (Cornell University), who were honored for their work on superfluidity, a frictionless liquid state, of supercooled 3He (p 562 of the October 17 issue of vol. 383).

  1. Effects of radix curcumae-derived diterpenoid C on Helicobacter pylori-induced inflammation and nuclear factor kappa B signal pathways

    PubMed Central

    Huang, Xuan; Lv, Bin; Zhang, Shuo; Dai, Qun; Chen, Bing-Bing; Meng, Li-Na

    2013-01-01

    AIM: To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori (H. pylori)-infected inflammation, intestinal metaplasia, and nuclear factor kappa B (NF-κB) signaling pathway in vitro. METHODS: We used I-type H. pylori to infect human gastric epithelial gastric epithelium cell line (GES-1) cell lines, and then H. pylori-infected GES-1 cells were treated with radix curcumae (RC)-derived diterpenoid C of different concentrations (5, 10, 20 μg/mL) and amoxicillin. The expression of p65, IκB kinase (IKK) α and IKKγ proteins was detected with Western blotting, and the expression of interleukin (IL)-8, IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method. Data were analyzed using SPSS software ver18.0. For comparisons between groups of more than two unpaired values, one-way analysis of variance (ANOVA) was used. If an ANOVA F value was significant, post hoc comparisons were performed between groups. If results were not normally distributed, the Mann-Whitney U test was used to compare two groups of unpaired values, whereas for comparisons between groups of more than two unpaired values, the Kruskal-Wallis H test was used. Statistical significance was established at P < 0.05. RESULTS: The MTT assay results revealed the inhibited rate of GES-1, and indicated that the IC5 of RC-derived diterpenoid C and amoxicillin all were 5 μg/mL for gastric GES-1 cells. The expression of IL-8 was significantly increased, especially at 12 h time point; and the expression of IL-4 was decreased in H. pylori-infected GES-1 cells. After H. pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin, the expression of IL-8 was decreased at 12, 24, 48, 72 h points (P < 0.01), especially in high-concentration diterpenoid C (20 μg/mL) group; and the expression of IL-4 was increased, especially in moderate and high-concentration diterpenoid C (10 and 20 μg/mL) groups. RC

  2. CYP701A8: a rice ent-kaurene oxidase paralog diverted to more specialized diterpenoid metabolism.

    PubMed

    Wang, Qiang; Hillwig, Matthew L; Wu, Yisheng; Peters, Reuben J

    2012-03-01

    All higher plants contain an ent-kaurene oxidase (KO), as such a cytochrome P450 (CYP) 701 family member is required for gibberellin (GA) phytohormone biosynthesis. While gene expansion and functional diversification of GA-biosynthesis-derived diterpene synthases into more specialized metabolism has been demonstrated, no functionally divergent KO/CYP701 homologs have been previously identified. Rice (Oryza sativa) contains five CYP701A subfamily members in its genome, despite the fact that only one (OsKO2/CYP701A6) is required for GA biosynthesis. Here we demonstrate that one of the other rice CYP701A subfamily members, OsKOL4/CYP701A8, does not catalyze the prototypical conversion of the ent-kaurene C4α-methyl to a carboxylic acid, but instead carries out hydroxylation at the nearby C3α position in a number of related diterpenes. In particular, under conditions where OsKO2 catalyzes the expected conversion of ent-kaurene to ent-kaurenoic acid required for GA biosynthesis, OsKOL4 instead efficiently reacts with ent-sandaracopimaradiene and ent-cassadiene to produce the corresponding C3α-hydroxylated diterpenoids. These compounds are expected intermediates in biosynthesis of the oryzalexin and phytocassane families of rice antifungal phytoalexins, respectively, and can be detected in rice plants under the appropriate conditions. Thus, it appears that OsKOL4 plays a role in the more specialized diterpenoid metabolism of rice, and our results provide evidence for divergence of a KO/CYP701 family member from GA biosynthesis. This further expands the range of enzymes recruited from the ancestral GA primary pathway to the more complex and specialized labdane-related diterpenoid metabolic network found in rice.

  3. A novel isopimarane diterpenoid with acetylcholinesterase inhibitory activity from Nepeta sorgerae, an endemic species to the Nemrut Mountain.

    PubMed

    Yilmaz, Anil; Cağlar, Pinar; Dirmenci, Tuncay; Gören, Nezhun; Topçu, Gülaçti

    2012-06-01

    From the dichloromethane extract of Nepeta sorgerae, the isolation and structure elucidation are now reported of a new isopimarane diterpenoid, named sorgerolone, and two known triterpenoids, oleanolic acid and ursolic acid. Antioxidant activity of the extracts and the isolated terpenoids was determined by the DPPH free radical scavenging and lipid peroxidation inhibition (beta-carotene bleaching) methods. Anticholinesterase activity of the extracts and isolates was investigated by Ellman's method against AChE and BChE enzymes. Although the antioxidant activity results were low, the AChE enzyme inhibition of the extracts and terpenoids was very promising.

  4. Cytotoxic and anticarcinogenic activity of the ent-kaurene diterpenoid, melissoidesin, from Isodon wightii (Bentham) H. Hara.

    PubMed

    Thirugnanasampandan, R; Jayakumar, R

    2009-01-01

    Isodon wightii is a common plant found in the Western Ghats of South India. The ent-kaurene diterpenoid melissoidesin, isolated from the leaves of I. wightii, showed significant cytotoxicity against lung cancer and neuroblastoma cell lines with IC(50) values of 6 and 4.2 microg mL(-1), respectively. The prevention of deoxyribose degradation activity of melissoidesin was significant and the IC(50) value was calculated to be 163.1 microg mL(-1). The anticarcinogenic activity of melissoidesin by comet assay showed significant DNA damage protecting activity in a dose-dependent manner.

  5. The marine-derived pachycladin diterpenoids as novel inhibitors of wild-type and mutant EGFR.

    PubMed

    Mohyeldin, Mohamed M; Akl, Mohamed R; Siddique, Abu Bakar; Hassan, Hossam M; El Sayed, Khalid A

    2017-02-15

    Epidermal growth factor receptor (EGFR) is a key player in proliferation and metastasis of various cancers. Discovery of novel EGFR inhibitors is still an urgent clinical oncology unmet need. Pachycladins are eunicellin-based diterpenoids isolated from the soft coral Cladiella pachycladous species. This study evaluated the anticancer activity of pachycladins A-E against diverse breast and cervical cancer cells. Pachycladin A (1) potently inhibited the proliferation of multiple cancer cell lines, without being cytotoxic to non-cancerous cells. The antiproliferative activity of 1 is mediated through cytostatic mechanisms rather than inducing apoptosis, as evidenced by lack of TUNEL response. Additionally, 1 arrested cell cycle in either G1 or G2/M phase, according to the cancer type, which induced caspase-dependent and independent apoptosis only after prolonged treatment. Meanwhile, 1 potently decreased microvessel formation and endothelial cell migration, suggesting its potential antiangiogenic activity. Different kinase profiling platforms revealed the exquisite potency and selectivity of 1 towards EGFR, even compared to other members of the EGFR family. In cancer cells, the antiproliferative activity of 1 was associated with suppression of EGFR activation and its downstream effectors. Interestingly, 1 significantly inhibited the drug-resistant T790M EGFR mutant, which is believed to be an attractive feature of EGFR inhibitors. Docking studies characterized the structural determinants required for efficient wild and mutant EGFR inhibition. Overlay studies of 1 with known EGFR inhibitors provided future guidance to chemically improve its binding affinity. Together, the anticancer activity of 1 is mediated by direct effects on tumor growth and angiogenesis, selectively via deactivating EGFR signaling, providing an excellent scaffold to control EGF-dependent cancers.

  6. Distribution and carbon isotope patterns of diterpenoids and triterpenoids in modern temperate C3 trees and their geochemical significance

    NASA Astrophysics Data System (ADS)

    Diefendorf, Aaron F.; Freeman, Katherine H.; Wing, Scott L.

    2012-05-01

    Tricyclic diterpenoids and pentacyclic triterpenoids are nearly exclusively produced by gymnosperms and angiosperms, respectively. Even though both classes of terpenoids have long been recognized as plant biomarkers, their potential use as phylogenetically specific δ13C proxies remains largely unexplored. Little is known of how terpenoid abundance and carbon isotope composition vary either with plant phylogenetic position, functional group, or during synthesis. Here, we report terpenoid abundances and isotopic data for 44 tree species in 21 families, representing both angiosperms and gymnosperms, and both deciduous and evergreen leaf habits. Di- and triterpenoid abundances are significantly higher in evergreens compared to deciduous species, reflecting differences in growth strategies and increased chemical investment in longer-lived leaves. Carbon isotope abundances of terpenoid lipids are similar to leaf tissues, indicating biosynthetic isotope effects are small for both the MVA (-0.4‰) and MEP (-0.6‰) pathways. Leaf and molecular isotopic patterns for modern plants are consistent with observations of amber, resins and plant biomarkers in ancient sediments. The δ13C values of ancient diterpenoids are higher than triterpenoids by 2-5‰, consistent with observed isotopic differences between gymnosperms and angiosperms leaves, and support the relatively small lipid biosynthetic effects reported here. All other factors being equal, evergreen plants will dominate the abundance of terpenoids contributed to soils, sediments and ancient archives, with similar inputs estimated for angiosperm and gymnosperm trees when scaled by litter flux.

  7. Isolation and chemical modification of clerodane diterpenoids from Salvia species as potential agonists at the kappa-opioid receptor.

    PubMed

    Li, Yiqiang; Husbands, Stephen M; Mahon, Mary F; Traynor, John R; Rowan, Michael G

    2007-07-01

    The clerodane diterpenoid salvinorin A (1), the main active component of the psychotropic herb Salvia divinorum, has been reported to be a potent agonist at the kappa-opioid receptor. Computer modeling suggested that splendidin (2) from S. splendens, as well as related compounds, might possess similar activities. In the present study, this hypothesis was tested by determination of the binding properties of a series of structural congeners, compounds 2-8, at the mu-, delta-, and kappa-opioid receptors. However, none of these compounds showed significant binding to any of the opioid-receptor subtypes, thus disproving the above hypothesis. The novel compounds 7 and 8 were obtained semi-synthetically by selective modification of salvifarin (5), isolated from Salvia farinacea, upon epoxide-ring opening with AcOH in the presence of indium(III) triflate. Also, the X-ray crystal structure of salvifaricin (6; Fig.), obtained from S. farinacea, was determined for the first time and used, in combination with in-depth NMR experiments, to elucidate the absolute configurations of the new products. Our experiments demonstrate that the relatively well-accessible diterpenoid 6 could be used as starting material for future studies into the structure-activity relationship at the kappa-opioid receptor.

  8. Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells.

    PubMed

    Bao, Han; Zhang, Le-Le; Liu, Qian-Yu; Feng, Lu; Ye, Yang; Lu, Jin-Jian; Lin, Li-Gen

    2016-06-18

    The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R‒T (1-3) and caesalsappanins M and N (4 and 5), together with seven known compounds 6-12. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute configurations of compounds 1 and 4 were determined by the corresponding CD spectra. All the isolated compounds were tested for their cytotoxicity against ovarian cancer A2780 and HEY, gastric cancer AGS, and non-small cell lung cancer A549 cells. Compound 1 displayed significant toxicity against the four cell lines with the IC50 values of 9.9 ± 1.6 µM, 12.2 ± 6.5 µM, 5.3 ± 1.9 µM, and 12.3 ± 3.1 µM, respectively. Compound 1 induced G1 phase cell cycle arrest in A2780 cells. Furthermore, compound 1 dose-dependently induced A2780 cells apoptosis as evidenced by Hoechst 33342 staining, Annexin V positive cells, the up-regulated cleaved-PARP and the enhanced Bax/Bcl-2 ratio. What's more, compound 1 also promoted the expression of the tumor suppressor p53 protein. These findings indicate that cassane diterpenoids might have potential as anti-cancer agents, and further in vivo animal studies and structural modification investigation are needed.

  9. Serrulatane Diterpenoid from Eremophila neglecta Exhibits Bacterial Biofilm Dispersion and Inhibits Release of Pro-inflammatory Cytokines from Activated Macrophages.

    PubMed

    Mon, Htwe H; Christo, Susan N; Ndi, Chi P; Jasieniak, Marek; Rickard, Heather; Hayball, John D; Griesser, Hans J; Semple, Susan J

    2015-12-24

    The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management.

  10. Indole-diterpenoids with anti-H1N1 activity from the aciduric fungus Penicillium camemberti OUCMDZ-1492.

    PubMed

    Fan, Yaqin; Wang, Yi; Liu, Peipei; Fu, Peng; Zhu, Tonghan; Wang, Wei; Zhu, Weiming

    2013-07-26

    An aciduric fungal strain, Penicillium camemberti OUCMDZ-1492, was isolated from an acidic marine niche, mangrove soil and mud, around the roots of Rhizophora apiculata. Six new indole-diterpenoids (1-6), along with five known analogues, emindole SB (7), 21-isopentenylpaxilline (8), paspaline (9), paxilline (10), and dehydroxypaxilline (11), were isolated from the fermentation broth of P. camemberti OUCMDZ-1492 grown at pH 5.0. On the basis of spectroscopic analyses, CD spectra, quantum ECD calculations, and chemical methods, new structures 1-6 were established as 3-deoxo-4b-deoxypaxilline, 4a-demethylpaspaline-4a-carboxylic acid, 4a-demethylpaspaline-3,4,4a-triol, 2'-hydroxypaxilline, 9,10-diisopentenylpaxilline, and (6S,7R,10E,14E)-16-(1H-indol-3-yl)-2,6,10,14-tetramethylhexadeca-2,10,14-triene-6,7-diol, respectively. Compounds 1-3 and 5-10 exhibited significant activity against the H1N1 virus with IC50 values of 28.3, 38.9, 32.2, 73.3, 34.1, 26.2, 6.6, 77.9, and 17.7 μM, respectively. The results showed that 3-oxo, 4b-hydroxy, and 9-isopentenyl substitutions tend to increase the anti-H1N1 activity of hexacyclic indole-diterpenoids.

  11. Antioxidant, lipid peroxidation inhibition and free radical scavenging efficacy of a diterpenoid compound sugiol isolated from Metasequoia glyptostroboides.

    PubMed

    Bajpai, Vivek K; Sharma, Ajay; Kang, Sun Chul; Baek, Kwang-Hyun

    2014-01-01

    To investigate the antioxidant efficacy of a biologically active diterpenoid compound sugiol isolated from Metasequoia glyptostroboides (M. glyptostroboides) in various antioxidant models. An abietane type diterpenoid sugiol, isolated from ethyl acetate extract of M. glyptostroboides cones, was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl radicals. The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities. Consequently, the sugiol exerted lipid peroxidation inhibitory effect by 76.5% as compared to α-tocopherol (80.13%) and butylated hydroxyanisole (76.59%). In addition, the sugiol had significant scavenging activities of 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%, 72.42%, 72.99% and 85.04%, when compared to the standard compound ascorbic acid (81.69%, 74.62%, 73.00% and 73.79%) and α-tocopherol/butylated hydroxyanisole (84.09%, 78.61%, 74.45% and 70.02%), respectively. These findings justify the biological and traditional uses of M. glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  12. Isolation of diterpenoid alkaloids from herb and flowers of aconitum napellus ssp. vulgare and electrospray ion trap multiple MS study of these alkaloids

    PubMed

    Chen; Koelliker; Oehme; Katz

    1999-05-01

    Chemical investigation of herb and flowers of Aconitum napellus L. ssp. vulgare led to the isolation of 12 diterpenoid alkaloids. Their chemical structures were identified on the basis of NMR and MS and of their complete ion trap multiple fragmentation mass spectrometry study.

  13. Isolation of cytotoxic diterpenoids from the Chilean medicinal plant Azorella compacta Phil from the Atacama Desert by high-speed counter-current chromatography.

    PubMed

    Bórquez, Jorge; Bartolucci, Nandy López; Echiburú-Chau, Carlos; Winterhalter, Peter; Vallejos, Javier; Jerz, Gerold; Simirgiotis, Mario J

    2016-06-01

    Azorella compacta (Apiaceae) is a native Chilean cushion shrub which produces a resin containing mulinane and azorellane diterpenoids. This plant has been used since pre-Colombian times to treat inflammation and dental neuralgias. In this work the first preparative fractionation of diterpenoids present in this plant by means of high-speed counter-current chromatography (HSCCC) was applied, and cytotoxic effects of the isolated compounds were evaluated for the first time against a panel of MCF7 cells. The major compounds isolated were identified by means of spectroscopy as azorellanol, 13α, 14α-dihydroxymulin-11-en-20-oic acid, mulinolic acid, mulin-11,13-dien-20-oic acid, 17-acetoxy-mulin-11,13-dien-20 oic acid, and 17-acetoxy-mulinic acid (compounds 7, 9-11 and 13, respectively), and four minor diterpenoids [7-deacetyl-azorellanol (6), 13-epi-azorellanol, 7-acetoxy-mulin-9,12-diene, and 17-acetoxy-mulin-11,13-dien-20-oic acid (compounds 4, 8 and 12)], together with three new minor diterpenoids: 13β,14β-dihydroxymulin-11-en-20-oic acid (1), 13-epiazorellanone (2) and 13-epi-7-deacetyl-azorellanol (3) were identified. Besides, compounds 4, 6, 7, 8 and 11 displayed good cytotoxic activity (less than 50% cell viability at 100 µM). Among them, compound 7, an acetylated azorellane, was the most active. HSCCC allowed the isolation of 13 diterpenoids present in A. compacta. Three compounds are reported for the first time. Isolated azorellanes are more potent cytotoxic agents than are mulinanes. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  14. Recombination of diterpenoid structure units: synthesis of antitumor amides bearing functionalized bicyclo[3.2.1]octane ring.

    PubMed

    Mao, Zewei; Li, Yan; Chen, Jingbo; Wang, Yuanyuan; Zhang, Hongbin

    2010-07-15

    In this work, 23 new amides (14-36) bearing a representative diterpenoid structure unit, the functionalized bicyclo[3.2.1]octane ring, have been synthesized and its antitumor potential is studied. In vitro studies demonstrate that a number of amides with the bicyclo[3.2.1]oct-3-en-2-one subunit are active against HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 tumor cell lines. The hybrid derivative, compound 20, was found to be the most potent compound (IC(50)=1.05 microM against HL-60) and more active than cisplatin (DDP), the positive control. Additionally, compound 20 exhibited broad spectrum in vitro anticancer activity with IC(50) values of 1.1-4.3 microM against the five tested cancer cell lines.

  15. Cassane-type diterpenoids from Caesalpinia echinata (Leguminosae) and their NF-κB signaling inhibition activities.

    PubMed

    Mitsui, Taichi; Ishihara, Risa; Hayashi, Ken-ichiro; Matsuura, Nobuyasu; Akashi, Haruo; Nozaki, Hiroshi

    2015-08-01

    Fourteen cassane-type diterpenoids, echinalides H-U, were isolated from the stem of Caesalpinia echinata Lam. (Leguminosae). The structures of the echinalides were elucidated by spectroscopic investigation, including 2D NMR spectroscopic analysis. The structures of echinalide H and echinalide T were further confirmed by single-crystal X-ray diffraction. The absolute configurations of echinalides H, I, J and K were determined by CD spectroscopy. Additionally, the absolute configurations of echinalide L and M were determined by chemical conversion from echinalide H. These compounds were evaluated for inhibitory activity against nuclear factor κB (NF-κB). Echinalide M showed the most potent inhibitory activity (47±11% at 5μM) toward NF-κB-responsive gene expression.

  16. New neoclerodane diterpenoids isolated from the leaves of Salvia divinorum and their binding affinities for human kappa opioid receptors.

    PubMed

    Lee, David Y W; Ma, Zhongze; Liu-Chen, Lee-Yuan; Wang, Yulin; Chen, Yong; Carlezon, William A; Cohen, Bruce

    2005-10-01

    Bioactivity-guided fractionation of the leaves of Salvia divinorum has resulted in the isolation of three new neoclerodane diterpenoids: divinatorin D (1), divinatorin E (2), and salvinorin G (3), together with 10 known terpenoids, divinatorin C (4), hardwickiic acid (5), salvinorin-A (6), -B (7), -C (8), -D (9), -E (10), and -F (11), presqualene alcohol (12), and (E)-phytol (13). The structures of these three new compounds were characterized by spectroscopic methods. All these compounds were evaluated for their binding affinities to the human kappa opioid receptors. In comparison with divinatorin D (1), divinatorin E (2), and salvinorin G (3), salvinorin A (6) is still the most potent kappa agonist.

  17. Characterization by gas chromatography-mass spectrometry of diterpenoid resinous materials in Roman-age amphorae from northern Greece.

    PubMed

    Dimitrakoudi, Evagelia A; Mitkidou, Sofia A; Urem-Kotsou, Dushka; Kotsakis, Kostas; Stephanidou-Stephanatou, Julia; Stratis, John A

    2011-01-01

    A combined gas chromatography-mass spectrometry approach has been used for the characterization of two lumps of resin and 17 adsorbed residues on Roman-age vessels, mainly amphorae, from northern Greece. The data show that a diterpenic resin from plants of the Pinacae family is the main component of the tarry material associated with the analyzed archaeological samples. The identification and mass spectrometric fragmentation of several characteristic diterpenoid biomarkers is discussed. The abundance of secondary products identified in the archaeological samples suggests that the oxidative degradation of abietic acid and dehydroabietic acid to aromatic products was the main pathway. Of particular interest is the presence of characteristic saturated abietane hydrocarbons in one sample, which indicate that a reductive process also occurred on a small scale. The overall similarity in the composition of the residues suggests the common use of pine tar as a waterproofing and sealing agent at different sites in northern Greece during the Roman period.

  18. Antimicrobial Activity of neo-Clerodane Diterpenoids isolated from Lamiaceae Species against Pathogenic and Food Spoilage Microorganisms.

    PubMed

    Bozov, Petko; Girova, Tania; Prisadova, Natalia; Hristova, Yana; Gochev, Velizar

    2015-11-01

    Antimicrobial activity of nineteen neo-clerodane diterpenoids, isolated from the acetone extracts of the aerial parts of Scutellaria and Salvia species (Lamiaceae) were tested against thirteen strains belonging to nine different species of pathogenic and food spoilage bacteria Aeromonas hydrophila, Bacillus cereus, Escherichia coli, Listeria monocytogenes, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella abony and Staphylococcus aureus as well as against two yeast strains belonging to species Candida albicans. Seven of the evaluated compounds scutalpin A, scutalpin E, scutalpin F, salviarin, splenolide A, splenolide B and splendidin demonstrated antimicrobial activity against used test microbial strains, the rest of the compounds were inactive within the studied concentration range. Among all of the tested compounds the highest antimicrobial activity was detected for scutalpin A against Staphylococcus aureus (MIC 25 µg/mL).

  19. Analysis of diterpenoid compounds from the latex of two Euphorbiaceae by liquid chromatography‒electrospray ionisation mass spectrometry.

    PubMed

    Sobottka, A M; Görick, C; Melzig, M F

    2016-09-01

    The latex of Euphorbia papillosa A.St.-Hil. and Sapium glandulosum (L.) Morong was phytochemically investigated by liquid chromatography/mass spectrometry. The results reveal the presence of tigliane-type diterpenoid compounds, particularly 12-deoxyphorbol esters, in both species. In addition, ingenane-type diterpene esters were found in the latex of E. papillosa. The latex of S. glandulosum showed only tigliane-type diterpenes, confirming the literature data on this genus. According to mass data, we are proposing the presence of 10 compounds derived from 12-deoxyphorbol monoesters and diesters, from one 12-deoxyphorbaldehyde, from two ingenol derivatives and from one nitrogen-containing phorbol ester in the latex of the analysed species. Considering that 12-deoxy tigliane diterpenes are described as antitumour and antiviral agents, these results indicate a pharmacological potential for these two Euphorbiaceae species.

  20. Five new sesquiterpenoids and a new diterpenoid from Erigeron annuus (L.) PERS., Erigeron philadelphicus L. and Erigeron sumatrensis RETZ.

    PubMed

    Iijima, Takeyoshi; Yaoita, Yasunori; Kikuchi, Masao

    2003-05-01

    The aerial parts of Erigeron annuus (L.) PERS., E. philadelphicus L. and E. sumatrensis RETZ. (Compositae) have been investigated chemically. A new sesquiterpenoid, 6beta,14-epoxyeudesm-4(15)-en-1beta-ol (1), and a new diterpenoid, philadelphinone (6), have been isolated from E. philadelphicus. Four new sesquiterpenoids, (7R*)-opposit-4(15)-ene-1beta,7-diol (2), 11-methoxyopposit-4(15)-en-1beta-ol (3), 15-methoxyisodauc-3-ene-1beta,5alpha-diol (4) and 10alpha-hydroxycadin-4-en-15-al (5), have been isolated from E. annuus. Compounds 2 and 4 were also isolated from E. sumatrensis. The structures of the new compounds were elucidated on the basis of their spectral data.

  1. Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells.

    PubMed

    Li, Dahong; Cai, Hao; Jiang, Bowen; Liu, Guyue; Wang, Yuetong; Wang, Lei; Yao, Hequan; Wu, Xiaoming; Sun, Yijun; Xu, Jinyi

    2013-01-01

    A series of novel spirolactone-type diterpenoid derivatives of oridonin (12a-j) were designed and synthesized. All the target compounds showed improved anti-proliferative activity against a panel of human cancer cell lines and the most effective compound 12j was more potent than positive control Taxol in K562 and Bel-7402 cells with IC(50) values of 0.39 μM and 1.39 μM, respectively. The cellular mechanisms showed that compound 12j induced apoptosis at low micromolar concentrations in human hepatoma Bel-7402 cells. These results demonstrate that the spirolactone-type diterpenoid derivatives of oridonin have optimized growth inhibitory activity against cancer cells and interesting apoptosis-inducing ability.

  2. Determination of absolute configuration of an isopimarane-type diterpenoid by experimental and theoretical electronic circular dichroism and vibrational circular dichroism

    NASA Astrophysics Data System (ADS)

    Wang, Zhi-Qiang; Wu, Cheng-Jun; Wang, Zhen-Hui; Huang, Chao; Huang, Jian; Wang, Jin-Hui; Sun, Tie-Min

    2017-10-01

    In this study, the stereochemistry of a new isopimarane-type diterpenoid isolated from the Callicarpa macrophylla Vahl, Callicapene M3, was studied by experimental electronic circular dichroism and vibrational circular dichroism with the aid of TDDFT theoretical calculations. The good consistence between the experimental and simulated circular dichroism has clearly confirmed the absolute configuration of the title compound as (4S, 5S, 9S, 10S, 13S, 14S)-14α-hydroxy-7,15-isopimaradien-18-oic acid.

  3. Vulgarisin A, a new diterpenoid with a rare 5/6/4/5 ring skeleton from the Chinese medicinal plant Prunella vulgaris.

    PubMed

    Lou, Huayong; Zheng, Shan; Li, Tianlei; Zhang, Jianxin; Fei, Yue; Hao, Xiaojiang; Liang, Guangyi; Pan, Weidong

    2014-05-16

    Vulgarisin A (1), a new diterpenoid with an unprecedented 5/6/4/5 fused tetracyclic ring skeleton, has been isolated from the medicinal plant Prunella vulgaris Linn. Its structure was characterized by extensive spectroscopic methods, and the absolute configuration was secured by single crystal X-ray diffraction analysis. Compound 1 showed weak cytotoxicity against human lung carcinoma A549 cells with an IC50 value of 57.0 μM.

  4. Simultaneous determination of thirteen aminoalcohol-diterpenoid alkaloids in the lateral roots of Aconitum carmichaeli by solid-phase extraction-liquid chromatography-tandem mass spectrometry.

    PubMed

    Ding, Jia-Yu; Liu, Xiu-Xiu; Xiong, Dong-Mei; Ye, Li-Ming; Chao, Ruo-Bing

    2014-06-01

    Aminoalcohol-diterpenoid alkaloids have been reported as the cardioactive components in the lateral roots of Aconitum carmichaeli (Fuzi) according to recent studies. Determination of these effective components is of great significance for quality control purposes for Fuzi. Here we report, for the first, the development and validation of a new method to determine the 13 aminoalcohol-diterpenoid alkaloids in Fuzi by using a simple and accurate solid-phase extraction-liquid chromatography-tandem mass spectrometry. The chromatographic analysis was performed on an ODS column with methanol-0.1 % formic acid (80 : 20, v/v) as the mobile phase. The quantification was performed using MS/MS detection in the positive ion mode with multiple reaction monitoring. Linearity was observed within a range of concentrations of 20-2,000 ng/mL. For all the analytes, the r value was greater than 0.9990. The limit of detection and the limit of quantitation were less than 0.5 ng/mL and 2.0 ng/mL, respectively. The intraday and interday precisions were less than 5% and 10%, respectively. The accuracy was within the range of 90 to 105%. This method was successfully applied to determine the 13 aminoalcohol-diterpenoid alkaloids in Fuzi from different origins and with different processing methods.

  5. The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms' activities, a review of possible herb-drug interaction risks.

    PubMed

    Tan, Mei Lan; Lim, Lin Ee

    2015-01-01

    Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.

  6. A Cytochrome P450‐Mediated Intramolecular Carbon–Carbon Ring Closure in the Biosynthesis of Multidrug‐Resistance‐Reversing Lathyrane Diterpenoids

    PubMed Central

    Brown, Geoffrey D.; Gilday, Alison D.; Forestier, Edith; Larson, Tony R.

    2016-01-01

    Abstract The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids with potential applications in the treatment of pain, HIV and cancer. We report here a gene cluster from Jatropha curcas that contains the genes required to convert geranylgeranyl pyrophosphate into a number of diterpenoids, including the lathyranes jolkinol C and epi‐jolkinol C. The conversion of casbene to the lathyranes involves an intramolecular carbon–carbon ring closure. This requires the activity of two cytochrome P450s that we propose form a 6‐hydroxy‐5,9‐diketocasbene intermediate, which then undergoes an aldol reaction. The discovery of the P450 genes required to convert casbene to lathyranes will allow the scalable heterologous production of these potential anticancer drugs, which can often only be sourced in limited quantities from their native plant. PMID:27272333

  7. Phytotoxic effects of leukamenin E (an ent-kaurene diterpenoid) on root growth and root hair development in Lactuca sativa L. seedlings.

    PubMed

    Ding, Lan; Qi, Linlin; Jing, Hongwei; Li, Juan; Wang, Wei; Wang, Tao

    2008-11-01

    Leukamenin E, an ent-kaurene diterpenoid isolated from Isodon racemosa (Hemsl) Hara, showed phytotoxic effects on root growth and root hair development of lettuce seedlings (Lactuca sativa L.). Lower concentrations (10 microM) of leukamenin E did not affect root growth, but at concentrations higher than 50 microM, the rate was inhibited. The influence of leukamenin E on root growth rate was closely correlated with alterations in the mitotic index. A low incidence of aberrant mitosis image was observed when lettuce roots were treated with higher concentrations (100 and 200 microM) of leukamenin E. This suggests that inhibition of root growth may be due to inhibition of cell division. All tested concentrations of the diterpenoid (10 microM or more) inhibited root hair development in a dose-dependent manner. At a concentration of 80 microM, leukamenin E completely blocked root hair initiation. Application of Ag(+)-an ethylene action inhibitor-to lettuce seedlings inhibited root hair elongation similar to the diterpenoid. Enhanced root hair length was stimulated by exogenous ethephon-an ethylene-releasing agent-and could be reversed by addition of leukamenin E. This suggests that leukamenin E may act as a potential ethylene action antagonist in the inhibition of lettuce root hair development. We conclude that leukamenin E may curb root hair development by interfering with ethylene action at concentrations above 10 microM and inhibits root growth via inhibition of cell division at concentrations above 50 microM.

  8. 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.

  9. A Daphnane Diterpenoid Isolated from Wikstroemia polyantha Induces an Inflammatory Response and Modulates miRNA Activity

    PubMed Central

    Khong, Anthony; Forestieri, Roberto; Williams, David E.; Patrick, Brian O.; Olmstead, Andrea; Svinti, Victoria; Schaeffer, Emily; Jean, François; Roberge, Michel; Andersen, Raymond J.; Jan, Eric

    2012-01-01

    MicroRNAs (miRNAs) are endogenously expressed single-stranded ∼21–23 nucleotide RNAs that inhibit gene expression post-transcriptionally by binding imperfectly to elements usually within the 3′untranslated region (3′UTR) of mRNAs. Small interfering RNAs (siRNAs) mediate site-specific cleavage by binding with perfect complementarity to RNA. Here, a cell-based miRNA reporter system was developed to screen for compounds from marine and plant extracts that inhibit miRNA or siRNA activity. The daphnane diterpenoid genkwanine M (GENK) isolated from the plant Wikstroemia polyantha induces an early inflammatory response and can moderately inhibit miR-122 activity in the liver Huh-7 cell line. GENK does not alter miR-122 levels nor does it directly inhibit siRNA activity in an in vitro cleavage assay. Finally, we demonstrate that GENK can inhibit HCV infection in Huh-7 cells. In summary, the development of the cell-based miRNA sensor system should prove useful in identifying compounds that affect miRNA/siRNA activity. PMID:22761847

  10. WRKY45-dependent priming of diterpenoid phytoalexin biosynthesis in rice and the role of cytokinin in triggering the reaction.

    PubMed

    Akagi, Aya; Fukushima, Setsuko; Okada, Kazunori; Jiang, Chang-Jie; Yoshida, Riichiro; Nakayama, Akira; Shimono, Masaki; Sugano, Shoji; Yamane, Hisakazu; Takatsuji, Hiroshi

    2014-09-01

    Plant activators such as benzothiadiazole (BTH) protect plants against diseases by priming the salicylic acid (SA) signaling pathway. In rice, the transcription factor WRKY45 plays a central role in this process. To investigate the mechanism involved in defense-priming by BTH and the role of WRKY45 in this process, we analyzed the transcripts of biosynthetic genes for diterpenoid phytoalexins (DPs) during the rice-Magnaporthe oryzae interaction. The DP biosynthetic genes were barely upregulated in BTH-treated rice plants, but were induced rapidly after M. oryzae infection in a WRKY45-dependent manner. These results indicate that the DP biosynthetic genes were primed by BTH through WRKY45. Rapid induction of the DP biosynthetic genes was also observed after M. oryzae infection to WRKY45-overexpressing (WRKY45-ox) plants. The changes in gene transcription resulted in accumulation of DPs in WRKY45-ox and BTH-pretreated rice after M. oryzae infection. Previously, we reported that cytokinins (CKs), especially isopentenyladenines, accumulated in M. oryzae-infected rice. Here, we show that DP biosynthetic genes are regulated by the SA/CK synergism in a WRKY45-dependent manner. Together, we propose that CK plays a role in mediating the signal of M. oryzae infection to trigger the induction of DP biosynthetic genes in BTH-primed plants.

  11. hERG Channel Inhibitory Daphnane Diterpenoid Orthoesters and Polycephalones A and B with Unprecedented Skeletons from Gnidia polycephala.

    PubMed

    De Mieri, Maria; Du, Kun; Neuburger, Markus; Saxena, Priyanka; Zietsman, Pieter C; Hering, Steffen; van der Westhuizen, Jan H; Hamburger, Matthias

    2015-07-24

    The hERG channel is an important antitarget in safety pharmacology. Several drugs have been withdrawn from the market or received severe usage restrictions because of hERG-related cardiotoxicity. In a screening of medicinal plants for hERG channel inhibition using a two-microelectrode voltage clamp assay with Xenopus laevis oocytes, a dichloromethane extract of the roots of Gnidia polycephala reduced the peak tail hERG current by 58.8 ± 13.4% (n = 3) at a concentration of 100 μg/mL. By means of HPLC-based activity profiling daphnane-type diterpenoid orthoesters (DDOs) 1, 4, and 5 were identified as the active compounds [55.4 ± 7.0% (n = 4), 42.5 ± 16.0% (n = 3), and 51.3 ± 9.4% (n = 4), respectively, at 100 μM]. In a detailed phytochemical profiling of the active extract, 16 compounds were isolated and characterized, including two 2-phenylpyranones (15 and 16) with an unprecedented tetrahydro-4H-5,8-epoxypyrano[2,3-d]oxepin-4-one skeleton, two new DDOs (3 and 4), two new guaiane sesquiterpenoids (11 and 12), and 10 known compounds (1, 2, 5-10, 13, and 14). Structure elucidation was achieved by extensive spectroscopic analysis (1D and 2D NMR, HRMS, and electronic circular dichroism), computational methods, and X-ray crystallography.

  12. New Pesticidal Diterpenoids from Vellozia gigantea (Velloziaceae), an Endemic Neotropical Plant Living in the Endangered Brazilian Biome Rupestrian Grasslands.

    PubMed

    Ferreira, Mariana C; Cantrell, Charles L; Duke, Stephen O; Ali, Abbas; Rosa, Luiz H

    2017-01-21

    Vellozia gigantea is a rare, ancient, and endemic neotropical plant present in the Brazilian Rupestrian grasslands. The dichloromethane extract of V. gigantea adventitious roots was phytotoxic against Lactuca sativa, Agrostis stolonifera, and Lemna paucicostata, and showed larvicidal activity against Aedes aegypti. Phytotoxicity bioassay-directed fractionation of the extract revealed one new isopimaradiene, 8(9),15-isopimaradien-1,3,7,11-tetraone, and three new cleistanthane diterpenoids, 7-oxo-8,11,13-cleistanthatrien-3-ol, 3,20-epoxy-7-oxo-8,11,13-cleistanthatrien-3-ol, and 20-nor-3,7-dioxo-1,8,11,13-cleistanthatetraen-10-ol. These new structures are proposed based on interpretation of ¹H, (13)C, COSY, NOESY, HSQC, and HMBC NMR data. 8(9),15-isopimaradien-1,3,7,11-tetraone was especially phytotoxic with an IC50 value (30 μM) comparable to those of commercial herbicides clomazone, EPTC, and naptalam. In addition, 7-oxo-8,11,13-cleistanthatrien-3-ol provided 100% mortality at a concentration of 125 ppm against one-day-old Ae. aegypti larvae. Our results show that ancient and unique plants, like the endangered narrowly endemic neotropical species V. gigantea present in the Rupestrian grasslands, should also be protected because they can be sources of new bioactive compounds.

  13. CYP701A8: A Rice ent-Kaurene Oxidase Paralog Diverted to More Specialized Diterpenoid Metabolism1[W][OA

    PubMed Central

    Wang, Qiang; Hillwig, Matthew L.; Wu, Yisheng; Peters, Reuben J.

    2012-01-01

    All higher plants contain an ent-kaurene oxidase (KO), as such a cytochrome P450 (CYP) 701 family member is required for gibberellin (GA) phytohormone biosynthesis. While gene expansion and functional diversification of GA-biosynthesis-derived diterpene synthases into more specialized metabolism has been demonstrated, no functionally divergent KO/CYP701 homologs have been previously identified. Rice (Oryza sativa) contains five CYP701A subfamily members in its genome, despite the fact that only one (OsKO2/CYP701A6) is required for GA biosynthesis. Here we demonstrate that one of the other rice CYP701A subfamily members, OsKOL4/CYP701A8, does not catalyze the prototypical conversion of the ent-kaurene C4α-methyl to a carboxylic acid, but instead carries out hydroxylation at the nearby C3α position in a number of related diterpenes. In particular, under conditions where OsKO2 catalyzes the expected conversion of ent-kaurene to ent-kaurenoic acid required for GA biosynthesis, OsKOL4 instead efficiently reacts with ent-sandaracopimaradiene and ent-cassadiene to produce the corresponding C3α-hydroxylated diterpenoids. These compounds are expected intermediates in biosynthesis of the oryzalexin and phytocassane families of rice antifungal phytoalexins, respectively, and can be detected in rice plants under the appropriate conditions. Thus, it appears that OsKOL4 plays a role in the more specialized diterpenoid metabolism of rice, and our results provide evidence for divergence of a KO/CYP701 family member from GA biosynthesis. This further expands the range of enzymes recruited from the ancestral GA primary pathway to the more complex and specialized labdane-related diterpenoid metabolic network found in rice. PMID:22247270

  14. Simultaneous determination of seven major diterpenoids in Siegesbeckia pubescens Makino by high-performance liquid chromatography coupled with evaporative light scattering detection.

    PubMed

    Huo, Linan; Jiang, Zhen; Li, Huining; Wang, Mingsheng; Ye, Xiaoxia; Ji, Bin; Guo, Xingjie

    2012-10-01

    A novel HPLC method with evaporative light scattering detection was developed for the simultaneous quantification of seven major diterpenoids of two types, including ent-pimarane type: Kirenol, Hythiemoside B, Darutigenol, and ent-kaurane type: ent-16β,17,18-trihydroxy-kauran-19-oic acid, ent-17,18-dihydroxy-kauran-19-oic acid, ent-16β,17-dihydroxy-kauran-19-oic acid, 16α-hydro-ent-kauran-17,19-dioic acid in the aerial parts of Siegesbeckia pubescens Makino, an important traditional Chinese medicinal herb. Chromatographic separation was achieved on a Waters Symmetry Shield(TM) RP18 column (250 mm× 4.6 mm id, 5 μm) with a gradient mobile phase (A: 0.3% v/v aqueous formic acid and B: acetonitrile) at a flow rate of 1.0 mL/min. The drift tube temperature of evaporative light scattering detection was set at 103°C, and nitrogen flow rate was 3.0 L/min. The method was validated for accuracy, precision, LOD, and LOQ. All calibration curves showed a good linear relationship (r > 0.999) in test range. Precision was evaluated by intra- and interday tests that showed RSDs were less than 3.5%. Accuracy validation showed that the recovery was between 96.5 and 102.0% with RSDs below 2.8%. The validated method was successfully applied to determine the contents of seven diterpenoids in the different parts of Siegesbeckia pubescens Makino from two sources and to determine the contents of ent-pimarane, ent-kaurane, and total diterpenoids.

  15. Magnesiate Addition/Ring-Expansion Strategy To Access the 6-7-6 Tricyclic Core of Hetisine-Type C20-Diterpenoid Alkaloids.

    PubMed

    Pflueger, Jason J; Morrill, Louis C; deGruyter, Justine N; Perea, Melecio A; Sarpong, Richmond

    2017-09-01

    A synthetic strategy to access the fused 6-7-6 tricyclic core of hetisine-type C20-diterpenoid alkaloids is reported. This strategy employs a Diels-Alder cycloaddition to assemble a fused bicyclic anhydride intermediate, which is elaborated to a vinyl lactone-acetal bearing an aromatic ring in five steps. Aromatic iodination is followed by magnesium-halogen exchange with a trialkyl magnesiate species, which undergoes intramolecular cyclization. Subsequent oxidation provides the desired 6-7-6 tricyclic diketoaldehyde, with carbonyl groups at all three positions for eventual C-N bond formation and subsequent elaboration.

  16. Insect growth regulatory effects of linear diterpenoids and derivatives from Baccharis thymifolia.

    PubMed

    Juan Hikawczuk, Virginia E; Saad, J Roberto; Giordano, Oscar S; García, Celina; Martín, Tomás; Martín, Víctor S; Sosa, Marta E; Tonn, Carlos E

    2008-02-01

    Linear diterpenes isolated from aerial parts of Baccharis thymifolia ( 1- 3) were tested for insect growth inhibitory activity against Tenebrio molitor larvae. Compounds 4- 16 were prepared by various chemical transformations. The diterpenes 6,10-( E,E)-thymifodioic acid ( 1), the butenolide 3, and the derivatives 4, 11, and 14 produced developmental deficiencies in assays using topical application on fifth instar larvae of T. molitor. Compound 3 is a new natural product.

  17. Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of Opioid Receptor affinity.

    PubMed

    Fontana, Gianfranco; Savona, Giuseppe; Rodríguez, Benjamín; Dersch, Christina M; Rothman, Richard B; Prisinzano, Thomas E

    2008-12-20

    Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known non-nitrogenous and specific kappa-opioid agonist. Several structural congeners of 1 isolated from Salvia splendens (2 - 8) together with a series of semisynthetic derivatives (9 - 24), some of which possess a pyrazoline structural moiety (9, 19 - 22), have been tested for affinity at human mu, delta, and kappa opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for kappa receptors suggesting other naturally neoclerodanes from different Salvia species may possess opioid affinity.

  18. Next-generation transcriptome analysis in transgenic birch overexpressing and suppressing APETALA1 sheds lights in reproduction development and diterpenoid biosynthesis.

    PubMed

    Huang, Haijiao; Chen, Su; Li, Huiyu; Jiang, Jing

    2015-09-01

    Overexpression of BpAP1 could cause early flowering in birch. BpAP1 affected the expression of many flowering-related unigenes and diterpenoid biosynthesis in transgenic birch, and BpPI was a putative target gene of BpAP1. APETALA1 (AP1) is an MADS-box transcription factor that is involved in the flowering process in plants and has been a focus of genetic studies examining flower development. Here, we carried out transcriptome analysis of birch (Betula platyphylla Suk.), including BpAP1 overexpression lines, BpAP1 suppression lines, and non-transgenic line (NT). Compared with NT, we detected 8302 and 7813 differentially expressed unigenes in 35S::BpAP1 and 35S::BpAP1RNAi transgenic lines, respectively. Overexpression and suppression of BpAP1 in birch affected diterpenoid biosynthesis and altered expression of many flowering-related unigenes. Moreover, combining information from the RNA-seq database and the birch genome, we predicted downstream target genes of BpAP1. Among the 166 putative target genes of BpAP1, there was a positive correlation between BpAP1 and BpPI. These results provide references for further examining the relationship between BpAP1 and its target genes, and reveal that BpAP1 functions as a transcription regulator in birch.

  19. Extraction of three bioactive diterpenoids from Andrographis paniculata: effect of the extraction techniques on extract composition and quantification of three andrographolides using high-performance liquid chromatography.

    PubMed

    Kumar, Satyanshu; Dhanani, Tushar; Shah, Sonal

    2014-10-01

    Andrographis paniculata (Burm.f.) wall.ex Nees (Acanthaceae) or Kalmegh is an important medicinal plant finding uses in many Ayurvedic formulations. Diterpenoid compounds andrographolides (APs) are the main bioactive phytochemicals present in leaves and herbage of A. paniculata. The efficiency of supercritical fluid extraction (SFE) using carbon dioxide was compared with the solid-liquid extraction techniques such as solvent extraction, ultrasound-assisted solvent extraction and microwave-assisted solvent extraction with methanol, water and methanol-water as solvents. Also a rapid and validated reverse-phase high-performance liquid chromatography-diode array detection method was developed for the simultaneous determination of the three biologically active compounds, AP, neoandrographolide and andrograpanin, in the extracts of A. paniculata. Under the best SFE conditions tested for diterpenoids, which involved extraction at 60°C and 100 bar, the extractive efficiencies were 132 and 22 µg/g for AP and neoandrographolide, respectively. The modifier percentage significantly affected the extraction efficiency.

  20. Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

    PubMed Central

    Kemper, Katarina; Hirte, Max; Reinbold, Markus; Fuchs, Monika

    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. PMID:28546842

  1. 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.

  2. Strain Prioritization for Natural Product Discovery by a High-Throughput Real-Time PCR Method

    PubMed Central

    2015-01-01

    Natural products offer unmatched chemical and structural diversity compared to other small-molecule libraries, but traditional natural product discovery programs are not sustainable, demanding too much time, effort, and resources. Here we report a strain prioritization method for natural product discovery. Central to the method is the application of real-time PCR, targeting genes characteristic to the biosynthetic machinery of natural products with distinct scaffolds in a high-throughput format. The practicality and effectiveness of the method were showcased by prioritizing 1911 actinomycete strains for diterpenoid discovery. A total of 488 potential diterpenoid producers were identified, among which six were confirmed as platensimycin and platencin dual producers and one as a viguiepinol and oxaloterpin producer. While the method as described is most appropriate to prioritize strains for discovering specific natural products, variations of this method should be applicable to the discovery of other classes of natural products. Applications of genome sequencing and genome mining to the high-priority strains could essentially eliminate the chance elements from traditional discovery programs and fundamentally change how natural products are discovered. PMID:25238028

  3. Strain prioritization for natural product discovery by a high-throughput real-time PCR method.

    PubMed

    Hindra; Huang, Tingting; Yang, Dong; Rudolf, Jeffrey D; Xie, Pengfei; Xie, Guangbo; Teng, Qihui; Lohman, Jeremy R; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Duan, Yanwen; Shen, Ben

    2014-10-24

    Natural products offer unmatched chemical and structural diversity compared to other small-molecule libraries, but traditional natural product discovery programs are not sustainable, demanding too much time, effort, and resources. Here we report a strain prioritization method for natural product discovery. Central to the method is the application of real-time PCR, targeting genes characteristic to the biosynthetic machinery of natural products with distinct scaffolds in a high-throughput format. The practicality and effectiveness of the method were showcased by prioritizing 1911 actinomycete strains for diterpenoid discovery. A total of 488 potential diterpenoid producers were identified, among which six were confirmed as platensimycin and platencin dual producers and one as a viguiepinol and oxaloterpin producer. While the method as described is most appropriate to prioritize strains for discovering specific natural products, variations of this method should be applicable to the discovery of other classes of natural products. Applications of genome sequencing and genome mining to the high-priority strains could essentially eliminate the chance elements from traditional discovery programs and fundamentally change how natural products are discovered.

  4. Potential antitumor promoting diterpenoids from the stem bark of Thuja standishii.

    PubMed

    Iwamoto, Manabu; Minami, Toshifumi; Tokuda, Harukuni; Ohtsu, Hironori; Tanaka, Reiko

    2003-01-01

    Six diterpenes, including one new natural product, were isolated from a CHCl 3 extract of the stem bark of Thuja standishii. The new compound has been characterized as 15-oxolabda-8(17),13 Z-dien-19-oic acid. The known compounds were identified as ferruginol (2), sugiol (3), isocupressic acid (4), sandaracopimaric acid (5) and 15-oxolabda-8(17),13 E-dien-19-oic acid (6). Compounds 2-5 and the derivatives 4a and 4b were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Compounds 2, 3, 4 and 5 showed strong inhibitory effect on EBV-EA induction (100 % inhibition at 1000 mol ratio/TPA).

  5. A Simple and Sensitive LC-MS/MS Method for Determination of Four Major Active Diterpenoids from Andrographis paniculata in Human Plasma and Its Application to a Pilot Study.

    PubMed

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Satayavivad, Jutamaad

    2016-01-01

    Andrographis paniculata contains four major active diterpenoids, including andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4), which exhibit differences in types and/or degrees of their pharmacological activity. Previous pharmacokinetic studies in humans reported only the parameters of compound 1 and its analytical method in human plasma. The purpose of this study was to develop a simple, sensitive, and selective liquid chromatography tandem-mass spectrometry technique for the simultaneous determination of all four major active diterpenoids in the A. paniculata product in human plasma. These four diterpenoids in plasma samples were extracted by a simple protein precipitation method with methanol and separated on a Kinetex C18 column using a gradient system with a mobile phase of acetonitrile and water. The liquid chromatography tandem-mass spectrometry was performed in the negative mode, and the multiple reaction monitoring mode was used for the quantitation. The method showed a good linearity over a wide concentration range of 2.50-500 ng/mL for 1 and over the range of 1.00-500 ng/mL for the other diterpenoids with a correlation coefficient R(2) > 0.995. The lower limit of quantification of 1 was found to be 2.50 ng/mL, while those of the other diterpenoids were 1.00 ng/mL. The intraday and interday accuracy (relative error) ranged from 0.03 % to 10.03 %, and the intraday and interday precisions (relative standard deviation) were in the range of 2.05-9.67 %. The extraction recovery (86.54-111.56 %) with a relative standard deviation of 2.78-8.61 % and the matrix effect (85.15-112.36 %) were within the acceptance criteria. Moreover, these four major active diterpenoids were stable in plasma samples at the studied storage conditions with a relative error ≤-9.79 % and a relative standard deviation ≤ 9.26 %. Hence, this present method was successfully validated

  6. Andrographis paniculata extracts and major constituent diterpenoids inhibit growth of intrahepatic cholangiocarcinoma cells by inducing cell cycle arrest and apoptosis.

    PubMed

    Suriyo, Tawit; Pholphana, Nanthanit; Rangkadilok, Nuchanart; Thiantanawat, Apinya; Watcharasit, Piyajit; Satayavivad, Jutamaad

    2014-05-01

    Andrographis paniculata is an important herbal medicine widely used in several Asian countries for the treatment of various diseases due to its broad range of pharmacological activities. The present study reports that A. paniculata extracts potently inhibit the growth of liver (HepG2 and SK-Hep1) and bile duct (HuCCA-1 and RMCCA-1) cancer cells. A. paniculata extracts with different contents of major diterpenoids, including andrographolide, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and 14-deoxyandrographolide, exhibited a different potency of growth inhibition. The ethanolic extract of A. paniculata at the first true leaf stage, which contained a high amount of 14-deoxyandrographolide but a low amount of andrographolide, showed a cytotoxic effect to cancer cells about 4 times higher than the water extract of A. paniculata at the mature leaf stage, which contained a high amount of andrographolide but a low amount of 14-deoxyandrographolide. Andrographolide, not 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, or 14-deoxyandrographolide, possessed potent cytotoxic activity against the growth of liver and bile duct cancer cells. The cytotoxic effect of the water extract of A. paniculata at the mature leaf stage could be explained by the present amount of andrographolide, while the cytotoxic effect of the ethanolic extract of A. paniculata at the first true leaf stage could not. HuCCA-1 cells showed more sensitivity to A. paniculata extracts and andrographolide than RMCCA-1 cells. Furthermore, the ethanolic extract of A. paniculata at the first true leaf stage increased cell cycle arrest at the G0/G1 and G2/M phases, and induced apoptosis in both HuCCA-1 and RMCCA-1 cells. The expressions of cyclin-D1, Bcl-2, and the inactive proenzyme form of caspase-3 were reduced by the ethanolic extract of A. paniculata in the first true leaf stage treatment, while a proapoptotic protein Bax was increased. The cleavage of poly (ADP

  7. 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

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

    PubMed

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

    2017-01-13

    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.

  9. Diterpenoid, steroid, and triterpenoid agonists of liver X receptors from diversified terrestrial plants and marine sources.

    PubMed

    Jayasuriya, Hiranthi; Herath, Kithsiri B; Ondeyka, John G; Guan, Ziqiang; Borris, Robert P; Tiwari, Suroojnauth; de Jong, Wil; Chavez, Flor; Moss, Jeremy; Stevenson, Dennis W; Beck, Hans T; Slattery, Marc; Zamora, Nelson; Schulman, Marvin; Ali, Aisha; Sharma, Neelam; MacNaul, Karen; Hayes, Nancy; Menke, John G; Singh, Sheo B

    2005-08-01

    It has been demonstrated that liver X receptors (LXR) play a significant role in cholesterol homeostasis. Agonists of LXR are expected to increase cellular cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of plant extracts using a LXR-SPA binding assay and bioassay-guided fractionation of a number of plant and marine gorgonian extracts led to the isolation of a number of active compounds. These included acanthoic acid (1) and alcohol (2), viperidone (3), polycarpol (4), rosacea acid (5), a cycloartane derivative (6), a new cycloartane analogue (7), betulinic acid (8), and gorgostane derivatives (9, 10, and 11). Of these compounds, 1, 4, and 11 exhibited potent binding affinity for alpha-receptor with IC(50) values of 0.25, 0.12, and 0.07 microM, respectively. Functionally they also showed strong coactivator association stimulation for LXRalpha receptor with EC50 values of 0.18, 0.03, and 0.05 microM, respectively. They also exhibited 15-, 8-, and 13-fold induction of the alpha-receptor in a transactivation assay in HEK-293 cells, respectively. In general these compounds were selective for the LXR alpha-receptor over the beta-receptor in all assays and were much better stimulators of the alpha-receptor than the endogenous steroid ligands.

  10. Emission of ent-kaurene, a diterpenoid hydrocarbon precursor for gibberellins, into the headspace from plants.

    PubMed

    Otsuka, Minoru; Kenmoku, Hiromichi; Ogawa, Mikihiro; Okada, Kazunori; Mitsuhashi, Wataru; Sassa, Takeshi; Kamiya, Yuji; Toyomasu, Tomonobu; Yamaguchi, Shinjiro

    2004-09-01

    ent-Kaurene is a tetracyclic hydrocarbon precursor for gibberellins (GAs) in plants and fungi. To address whether fungal GA biosynthesis enzymes function in plants, we generated transgenic Arabidopsis plants overexpressing ent-kaurene synthase (GfCPS/KS) from a GA-producing fungus Gibberella fujikuroi. GfCPS/KS catalyzes a two-step reaction corresponding to ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS) activities in plants. When GfCPS/KS was overexpressed and targeted to plastids, a range of GA-deficient phenotypes of the ga1-3 and ga2-1 mutants (defective in CPS and KS, respectively) were restored to wild type. Unexpectedly, the transgenic lines overproducing GfCPS/KS emitted the GA precursor ent-kaurene into the headspace besides its accumulation in the plant body. When co-cultivated with the ent-kaurene overproducers in a closed environment, the airborne ent-kaurene was able to fully complement the dwarf phenotype of ga1-3 and ga2-1 mutants, but not that of the ga3-1 mutant (defective in ent-kaurene oxidase). These results suggest that ent-kaurene may be efficiently metabolized into bioactive GAs in Arabidopsis when supplied as a volatile. We also provide evidence that ent-kaurene is released in the headspace of wild-type Chamaecyparis obtusa and Cryptomeria japonica plants, suggesting the occurrence of this hydrocarbon GA precursor as a volatile in nature.

  11. Differentiation of Isodon japonica and Adulterants Based on Identification and Quantitation 14 Diterpenoids Using LC-MS-MS Library Search Approach and Hierarchical Cluster Analysis.

    PubMed

    Jin, Yiran; Tian, Tingting; Ma, Yinghua; Liu, Minyan; Xie, Weiwei; Wang, Xin; Xu, Huijun; Du, Yingfeng

    2016-03-01

    The aim of this study was to investigate the chemical differences between genunine Isodon japonica and its adulterants. A linear ion trap liquid chromatography with tandem mass spectrometry analytical method has been developed for the identification and quantification of 14 major diterpenoids in I. japonica. Data acquisition was multiple reaction monitoring transitions mode followed by an information-dependent acquisition using the enhanced product ion (EPI) scan in a single run. The target compounds were further identified and confirmed using an EPI spectral library. Overall validation of the assay was carried out including linearity, accuracy, precision, limits of detection and quantification. The results demonstrated that the method was selective, sensitive and reliable. The determination results of 21 batches of I. japonica and adulterants were then analyzed and differentiated by hierarchical clustering analysis.

  12. Bioactive (3Z,5E)-11,20-Epoxybriara-3,5-dien-7,18-olide Diterpenoids from the South China Sea Gorgonian Dichotella gemmacea

    PubMed Central

    Li, Cui; La, Ming-Ping; Sun, Peng; Kurtan, Tibor; Mandi, Attila; Tang, Hua; Liu, Bao-Shu; Yi, Yang-Hua; Li, Ling; Zhang, Wen

    2011-01-01

    Six new (3Z,5E)-11,20-epoxybriara-3,5-dien-7,18-olide diterpenoids, gemmacolides N–S (1–6), were isolated together with four known analogues, juncenolide D, and juncins R, S and U (7–10), from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by the detailed analysis of spectroscopic data in combination with the comparison with reported data. The absolute configuration of 1 was determined by a TDDFT calculation of its solution ECD spectrum, affording the determination of absolute configuration of other analogues by simply comparing their ECD spectra with that of 1. The cytotoxic and antimicrobial activities of these compounds were evaluated. In preliminary in vitro bioassays, compounds 4, 5, 6, 8 and 9 showed cytotoxicity against A549 and MG63, while compounds 1, 2, 4, 7–10 showed antimicrobial activity against the fungus Septoria tritici and the bacterium Escherichia coli. PMID:21892354

  13. Chemical constituents of malagasy liverworts, part V: prenyl bibenzyls and clerodane diterpenoids with nitric oxide inhibitory activity from Radula appressa and Thysananthus spathulistipus.

    PubMed

    Harinantenaina, Liva; Takahara, Yusuke; Nishizawa, Takashi; Kohchi, Chie; Soma, Gen-Ichiro; Asakawa, Yoshinori

    2006-07-01

    3Beta,4beta:15,16-diepoxy-13(16),14-clerodadiene (1) and a new clerodane diterpenoid designated thysaspathone (2) were isolated from the liverwort Thysananthus spathulistipus, while Radula appressa produced radulannin A (3), radulannin L (4), 2-geranyl-3,5-dihydroxybibenzyl (5), 2(S)-2-methyl-2-(4-methyl-3-pentenyl)-7-hydroxy-5-(2-phenylethyl) chromene (o-cannabichromene) (6), 6-hydroxy-4-(2-phenylethyl) benzofuran (7), and o-cannabicyclol (8). All of the isolated compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the greatest inhibition was attributed to compound 5, with an IC50 value of 4.5 microM.

  14. Seed dormancy breaking diterpenoids from the liverwort Plagiochila sciophila and their differentiation inducing activity in human promyelocytic leukemia HL-60 cells.

    PubMed

    Kenmoku, Hiromichi; Tada, Hiroyuki; Oogushi, Megumi; Esumi, Tomoyuki; Takahashi, Hironobu; Noji, Masaaki; Sassa, Takeshi; Toyota, Masao; Asakawa, Yoshinori

    2014-07-01

    To obtain the structural diversity of bioactive compounds similar to cotylenins and fusicoccins that modulate 14-3-3 protein-protein interactions in eukaryotes, screening tests were carried out using the lettuce seed dormancy breaking-assay. An acetone extract of the liverwort Plagiochila sciophila exhibited significant activity against the seeds in the presence of the plant hormone abscisic acid. Activity-guided fractionation of the extract afforded the isolation of seven novel fusicoccane-type diterpenoids, named fusicosciophins A-E (1-5), 8-deacetyl (6) and 9-deacetyl fusicosciophin E (7). Their structures were determined by spectroscopic methods and X-ray crystallographic analyses. All the pure isolated compounds (1-7) exhibited moderate lettuce seed dormancy breaking activity. In addition, the differentiation-inducing activity and cytotoxicity of these isolates, together with fusicoccin A (FC-A) and all-trans retinoic acid (ATRA), were evaluated in human promyelocytic leukemia HL-60 cells and human mouth epidermal carcinoma KB cells, respectively. Fusicosciophins (2 and 4) and FC-A exhibited moderate differentiation-inducing activity (EC50 31.2-59.1 microM) compared with ATRA (EC50 0.3 microM), while 2, 4 and ATRA exhibited higher selectivity indices (IC50/EC50 >3.38-667) than FC-A (IC50/EC50 1.05). This is the first report on the isolation of fusicoccane-type diterpenoids from liverworts having seed dormancy breaking activity and differentiation-inducing activity in mammal cells.

  15. 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...

  16. Targeting apoptosis pathway with natural terpenoids: implications for treatment of breast and prostate cancer.

    PubMed

    Yang, Huanjie; Dou, Q Ping

    2010-06-01

    Terpenoids represent a large and diverse class of naturally occurring compounds found in a variety of fruits, vegetables and medicinal plants. Structurally some of the terpenoids are similar to human hormones. A diet rich in terpenoids is inversely related with the risk of chronic diseases including cancers. Breast and prostate cancers are hormone-related diseases and the second leading cause of female and male cancer mortality. Diterpenoid paclitaxel, and its semi-synthetic analogue docetaxel, have entered clinical use against established breast and prostate cancers. Here we reviewed potential molecular targets and biological properties of natural terpenoids, including monoterpenoids, diterpenoids, triterpenoids and tetraterpenoids, and their applications in treatment of human breast and prostate cancers. These terpenoids are able to inhibit tumor cell proliferation and induce tumor cell death by inhibiting multiple cancer-specific targets including the proteasome, NF-kappaB, and antiapoptotic protein Bcl-2. The efficacy of these terpenoids against breast or prostate cancer cells, as demonstrated in pre-clinical studies support clinical application of these naturally occurring terpenoids in treatment of hormone-related human cancers.

  17. Anti-Melanogenic Activity of Gagunin D, a Highly Oxygenated Diterpenoid from the Marine Sponge Phorbas sp., via Modulating Tyrosinase Expression and Degradation

    PubMed Central

    Lee, Ho Yeon; Jang, Eun Jeong; Bae, Song Yi; Jeon, Ju-eun; Park, Hyen Joo; Shin, Jongheon; Lee, Sang Kook

    2016-01-01

    Tyrosinase is the rate-limiting enzyme critical for melanin synthesis and controls pigmentation in the skin. The inhibition of tyrosinase is currently the most common approach for the development of skin-whitening cosmetics. Gagunin D (GD), a highly oxygenated diterpenoid isolated from the marine sponge Phorbas sp., has exhibited cytotoxicity toward human leukemia cells. However, the effect of GD on normal cells and the molecular mechanisms remain to be elucidated. In the present study, we identified for the first time the anti-melanogenic activity of GD and its precise underlying mechanisms in mouse melan-a cells. GD significantly inhibited melanin synthesis in the melan-a cells and a reconstructed human skin model. Further analysis revealed that GD suppressed the expression of tyrosinase and increased the rate of tyrosinase degradation. GD also inhibited tyrosinase enzymatic activity. In addition, GD effectively suppressed the expression of proteins associated with melanosome transfer. These findings suggest that GD is a potential candidate for cosmetic formulations due to its multi-functional properties. PMID:27869664

  18. [Synthesis and antituberculosis activity of the derivatives of glycoside steviolbioside from the plant Stevia rebaudiana and diterpenoid isosteviol containing hydrazone, hydrazide and pyridinoyl moieties].

    PubMed

    Kataev, V E; Strobykina, I Iu; Andreeva, O V; Garifullin, B F; Sharipova, R R; Mironov, V F; Chestnova, R V

    2011-01-01

    Conjugates of antitubercular drug Isoniazid (hydrazide of isonicotinic acid), nicotinic and alpha-picolinic acid hydrazides and glycoside steviolbioside from the plant Stevia rebaudiana as well as the product of its acid hydrolysis, diterpenoid isosteviol, were synthesized. Besides, isosteviol hydrazide and hydrazone derivatives as well as conjugates containing two isosteviol moieties connected by dihydrazide linker were also obtained. Both initial compounds and their synthetic derivatives inhibit the growth of Mycobacterium tuberculosis (H37Rv in vitro). The minimum concentration at which the growth of M. tuberculosis was inhibited by 100% (MIC) for stevioside and steviolbioside equals 7.5 and 3.8 microg/mL, respectively. MIC values for conjugates of the hydrazides of pyridine carbonic acids and steviolbioside as well as isosteviol are in the ranges 5-10 and 10-20 microg/mL, respectively. Maximum inhibitory effect against M. tuberculosis showed the conjugates of isosteviol and adipic acid dihydrazide (MIC values ranged from 1.7 to 3.1 microg/mL). Antitubercular activity of the compounds studied is higher than the activity of antitubercular drug Pyrizanamide (MIC = 12.5-20 microg/mL) but lower than the activity of antitubercular drug Isoniazid (MIC = 0.02-0.04 microg/mL).

  19. Detection and identification of diterpenoid alkaloids, isoflavonoids and saponins in Qifu decoction and rat plasma by liquid chromatography-time-of-flight mass spectrometry.

    PubMed

    Tan, Guangguo; Jing, Jing; Zhu, Zhenyu; Lou, Ziyang; Li, Wuhong; Zhao, Liang; Zhang, Guoqing; Chai, Yifeng

    2012-02-01

    A liquid chromatography-time-of-flight mass spectrometric (LC-TOFMS) method has been developed for analysis of components in Qifu decoction (QFD), a traditional Chinese medical formula consisting of Radix Astragali and Acontium carmichaeli, and in rat plasma after oral administration. Based on accurate mass measurements within 3 ppm error for each molecular ion and subsequent fragment ions of TOFMS, as well as matching of empirical molecular formulae with those of published components in the in-house chemical library, a total of 44 major components including 21 diterpenoid alkaloids, 12 flavonoids and 11 saponins were identified in QFD. After oral administration of QFD, 22 components in rat plasma were detected and identified by comparing and contrasting the constituents measured in QFD with those in the plasma samples. The results provided valuable chemical information for further pharmacology and active mechanism research on QFD. LC-TOFMS was also applied for the comparison of relative peak area of major active components between QFD and the single herb extracts. The concentration ratios of major saponins detected in the crude herb Radix Astragali were found to be different from those in QFD. The experimental data indicated that the decocting process could result in differences in the amounts of active components. Copyright © 2011 John Wiley & Sons, Ltd.

  20. Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis.

    PubMed

    Chen, Xuexiang; Wu, Xian; Ouyang, Wen; Gu, Min; Gao, Zili; Song, Mingyue; Chen, Yunjiao; Lin, Yanyin; Cao, Yong; Xiao, Hang

    2017-03-01

    The tender leaves of Rubus corchorifolius L. f. have been consumed as tea for drinking in China since ancient times. In this study, a novel ent-kaurane diterpenoid was isolated and identified from R. corchorifolius L. f. leaves as ent-kaur-2-one-16β,17-dihydroxy-acetone-ketal (DEK). DEK suppressed the growth of HCT116 human colon cancer cells with an IC50 value of 40 ± 0.21 μM, while it did not cause significant growth inhibition on CCD-18Co human colonic myofibroblasts at up to100 μM. Moreover, DEK induced extensive apoptosis and S phase cell cycle arrest in the colon cancer cells. Accordingly, DEK caused profound effects on multiple signaling proteins associated with cell proliferation, cell death, and inflammation. DEK significantly upregulated the expression levels of pro-apoptotic proteins such as cleaved caspase-3, cleaved caspase-9, cleaved PARP, p53, Bax, and tumor suppressor p21(Cip1/Waf1), downregulated the levels of cell cycle regulating proteins such as cyclinD1, CDK2, and CDK4 and carcinogenic proteins such as EGFR and COX-2, and suppressed the activation of Akt. Overall, our results provide a basis for using DEK as a potential chemopreventive agent against colon carcinogenesis.

  1. 17-Hydroxy-jolkinolide B, a diterpenoid from Euphorbia fischeriana, inhibits inflammatory mediators but activates heme oxygenase-1 expression in lipopolysaccharide-stimulated murine macrophages.

    PubMed

    Uto, Takuhiro; Qin, Guo-Wei; Morinaga, Osamu; Shoyama, Yukihiro

    2012-01-01

    Jolkinolides are the main abietane-type diterpenoids isolated from the root of Euphorbia fischeriana Steud. In the present study, we investigated in vitro anti-inflammatory activity of four structural analogs of jolkinolide in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. Among these jolkinolides, 17-hydroxy-jolkinolide B (HJB) exhibited the most potent inhibition of LPS-induced production of inflammatory mediators such as prostaglandin E(2) (PGE(2)), nitric oxide (NO), and pro-inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)]. HJB could decrease LPS-induced protein levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the mRNA expressions of COX-2, iNOS, IL-6, and TNF-α in a concentration-dependent manner. These inhibitory effects were caused by suppression of MAPK phosphorylation and NF-κB activation. Furthermore, we demonstrated that HJB strongly induced heme oxygenase-1 (HO-1) protein and mRNA expressions. These findings suggest that HJB possesses anti-inflammatory actions in macrophages and may provide a potential therapeutic approach for inflammatory disorders.

  2. Gastroprotective effects of new diterpenoid derivatives from Azorella cuatrecasasii Mathias & Constance obtained using a β-cyclodextrin complex with microbial and chemical transformations.

    PubMed

    Sepúlveda, Beatriz; Quispe, Cristina; Simirgiotis, Mario; García-Beltrán, Olimpo; Areche, Carlos

    2016-07-15

    Mulinane diterpenoids isolated from Azorella species have displayed gastroprotective effects in animal models. In this study we have transformed the main constituent, mulin-11,13-dien-20 oic acid from this plant using the filamentous fungus Mucor plumbeus and a β-cyclodextrin inclusion complex and we have obtained two main products with good yields (33% and 15% for compound 4 and 5, respectively) for further preparation of semisynthetic derivatives to evaluate their gastroprotective effects. In addition, one of the compounds isolated from Azorella cuatrecasasii was new (9-epi-13α-hydroxymulinene 1). Six new derivatives 4a-4c and 5a-5c were then prepared by simple chemical transformations. The structures of all compounds were elucidated by spectroscopic means based on 1D and 2D-NMR techniques. Some 8 diterpenes were evaluated for their gastroprotective effects in the ethanol/HCl-induced ulcer model in mice at 20mg/kg. The highest gastroprotective activity was shown by 7α,16-dihydroxymulin-11,13-dien-20-oic acid 5, which was higher than the reference drug lansoprazole, while 16-hydroxymulin-11,13-dien-20-oic acid 4 was as active as lansoprazole.

  3. Polyandric acid A, a clerodane diterpenoid from the Australian medicinal plant Dodonaea polyandra, attenuates pro-inflammatory cytokine secretion in vitro and in vivo.

    PubMed

    Simpson, Bradley S; Luo, Xianling; Costabile, Maurizio; Caughey, Gillian E; Wang, Jiping; Claudie, David J; McKinnon, Ross A; Semple, Susan J

    2014-01-24

    Dodonaea polyandra is a medicinal plant used traditionally by the Kuuku I'yu (Northern Kaanju) indigenous people of Cape York Peninsula, Australia. The most potent of the diterpenoids previously identified from this plant, polyandric acid A (1), has been examined for inhibition of pro-inflammatory cytokine production and other inflammatory mediators using well-established acute and chronic mouse ear edema models and in vitro cellular models. Topical application of 1 significantly inhibited interleukin-1β production in mouse ear tissue in an acute model. In a chronic skin inflammation model, a marked reduction in ear thickness, associated with significant reduction in myeloperoxidase accumulation, was observed. Treatment of primary neonatal human keratinocytes with 1 followed by activation with phorbol ester/ionomycin showed a significant reduction in IL-6 secretion. The present study provides evidence that the anti-inflammatory properties of 1 are due to inhibition of pro-inflammatory cytokines associated with skin inflammation and may be useful in applications for skin inflammatory conditions including psoriasis and dermatitis.

  4. Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis

    PubMed Central

    Wangchuk, Phurpa; Navarro, Severine; Shepherd, Catherine; Keller, Paul A.; Pyne, Stephen G.; Loukas, Alex

    2015-01-01

    Aconitum laciniatum is used in Bhutanese traditional medicine for treating various chronic infections and inflammatory conditions. We carried out in-depth isolation and characterization of the phytochemicals from the root component and determined the anti-inflammatory effects of the isolated compounds against chemically-induced colitis in mice. Five diterpenoid alkaloids - pseudaconitine, 14-veratroylpseudaconine, 14-O-acetylneoline, neoline, and senbusine A - were isolated from A. laciniatum for the first time. Two of the alkaloids were tested for anti-inflammatory properties in the TNBS-induced colitis model in mice. Various parameters were measured to assess pathology including weight loss, clinical and macroscopic scores, histological structure and IFN-γ production in the gut. Of the two alkaloids tested, 14-O-acetylneoline showed significant protection against different parameters of colitic inflammation. Compared to control mice that received TNBS alone, mice treated with 14-O-acetylneoline experienced significantly less weight loss and had significantly lower clinical scores, macroscopic pathology and grades of histological inflammation. Moreover, colonic IFN-γ mRNA levels were significantly reduced in mice that received 14-O-acetylneoline compared to control mice that received TNBS alone. This alkaloid is now considered a novel anti-colitis drug lead compound. PMID:26240038

  5. Regulation of cell division and growth in roots of Lactuca sativa L. seedlings by the Ent-Kaurene diterpenoid rabdosin B.

    PubMed

    Ding, Lan; Jing, Hongwei; Qin, Bo; Qi, Linlin; Li, Jing; Wang, Tao; Liu, Guoan

    2010-05-01

    Rabdosin B, an ent-kaurene diterpenoid purified from the air-dried aerial parts of Isodon japonica (Burm.f) Hara var. galaucocalyx (maxin) Hara, showed a biphasic, dose-dependent effect on root growth and a strong inhibitory effect on root hair development in lettuce seedlings (Lactuca sativa L.). Lower concentrations of rabdosin B (20-80 microM) significantly promoted root growth, but its higher levels at 120-200 microM, by contrast, had inhibitory effects. Additionally, all tested concentrations (10-40 microM) inhibited root hair development of seedlings in a dose-dependent manner. Further investigations on the underlying mechanism revealed that the promotion effect of rabdosin B at the lower concentrations resulted from increasing the cell length in the mature region and enhancing the mitotic activity of meristematic cells in seedlings' root tips. In contrast, rabdosin B at higher concentrations inhibited root growth by affecting both cell length in the mature region and division of meristematic cells. Comet assay and cell cycle analysis demonstrated that the decrease of mitotic activity of root meristematic cells was due to DNA damage induced cell cycle retardation of the G(2) phase and S phase at different times.

  6. Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature.

    PubMed

    Millimouno, Faya M; Dong, Jia; Yang, Liu; Li, Jiang; Li, Xiaomeng

    2014-11-01

    Although the incidences are increasing day after day, scientists and researchers taken individually or by research group are trying to fight against cancer by several ways and also by different approaches and techniques. Sesquiterpenes, flavonoids, alkaloids, diterpenoids, and polyphenolic represent a large and diverse group of naturally occurring compounds found in a variety of fruits, vegetables, and medicinal plants with various anticancer properties. In this review, our aim is to give our perspective on the current status of the natural compounds belonging to these groups and discuss their natural sources, their anticancer activity, their molecular targets, and their mechanism of actions with specific emphasis on apoptosis pathways, which may help the further design and conduct of preclinical and clinical trials. Unlike pharmaceutical drugs, the selected natural compounds induce apoptosis by targeting multiple cellular signaling pathways including transcription factors, growth factors, tumor cell survival factors, inflammatory cytokines, protein kinases, and angiogenesis that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that they provide a novel opportunity for treatment of cancer, but clinical trials are still required to further validate them in cancer chemotherapy.

  7. Differential control of growth, cell cycle progression, and expression of NF-{kappa}B in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the chinese herb Rabdosia rubescens

    SciTech Connect

    Hsieh Tzechen; Wijeratne, E. Kithsiri; Liang Jingyu; Gunatilaka, A. Leslie; Wu, Joseph M. . E-mail: Joseph_Wu@nymc.edu

    2005-11-11

    Ponicidin and oridonin are novel diterpenoids isolated from Rabdosia rubescens. We tested their effects in MCF-7 and MDA-MB-231 cells, as representing low and high invasive breast carcinoma, with normal MCF-10A cells. Clonogenicity and proliferation in MCF-7 cells were inhibited more significantly by ponicidin than oridonin, while the reverse was observed in MCF-10A cells. Ponicidin and oridonin induced S/G{sub 2}M arrest and G{sub 1}/S block in MCF-7 cells. In MCF-10A cells treated with either diterpenoid, induction of apoptosis was observed. Moreover, oridonin almost completely blocked MCF-10A progression from S to G{sub 2}/M phase; in contrast, ponicidin-treated MCF-10A cells showed no discernable changes in cell cycle phase distribution. Neither diterpenoid affected growth of MDA-MB-231 cells, at the dose range effective for MCF-7 or MCF-10A cells. Ponicidin-treated MCF-7 cells expressed reduced levels of cyclin B1, cdc2, transcription factor E2F, and Rb including phosphorylation at S780. Less pronounced effects were found in cells treated with oridonin. Neither compound altered cyclin D1 and cdk4 in MCF-7 cells. In MCF-10A cells, oridonin was more active than ponicidin in inhibiting the expression of cyclin B1, cdc2, S780-phosphorylated Rb, and E2F. To further investigate induction of apoptosis in MCF-10A cells, we measured changes in NF-{kappa}B. Decreases in p65 or p50 forms of NF-{kappa}B and its upstream regulator I-{kappa}B were found in oridonin-treated MCF-10A and not MCF-7 cells. Taken together, these results provide a mechanistic framework for the cellular effects of ponicidin and oridonin in different stage breast cancer cells.

  8. LC-MS and 1H NMR as an improved dereplication tool to identify antifungal diterpenoids from Sagittaria latifolia

    USDA-ARS?s Scientific Manuscript database

    A dereplication strategy using a combination of liquid chromatography-mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy (1H NMR) to facilitate compound identification towards antifungal natural product discovery is presented. This analytical approach takes advantage of th...

  9. OsTGAP1 is responsible for JA-inducible diterpenoid phytoalexin biosynthesis in rice roots with biological impacts on allelopathic interaction.

    PubMed

    Yoshida, Yuri; Miyamoto, Koji; Yamane, Hisakazu; Nishizawa, Yoko; Minami, Eiichi; Nojiri, Hideaki; Okada, Kazunori

    2017-08-30

    Phytocassanes and momilactones are known as major diterpenoid phytoalexins (DPs), characterized by abundant production and antimicrobial activity and their biosynthetic genes are clustered in rice genomes. The basic leucine zipper transcription factor OsTGAP1 is known to act as a regulator of the coordinated production of DPs in cultured rice cells, but the in planta functions of OsTGAP1 remain largely unknown. Here, we present evidence on the biological function of OsTGAP1 in planta. In wild-type plants, OsTGAP1 is abundantly expressed in roots compared to that in shoots. Moreover, the inductive expression of OsTGAP1 under jasmonic acid (JA) treatment was only observed in a root-specific manner consistent with the JA-inductive expressions of DP biosynthetic genes in roots. In reverse genetic approaches on OsTGAP1 overexpressing and ostgap1 knockdown plants, expressions of the biosynthetic genes relevant for DP accumulation were found to be remarkably increased and decreased, respectively. Reporter analysis in planta revealed that OsTGAP1 activated the promoters of OsDXS3 and momilactone biosynthetic gene OsKSL4, presumably through binding to the TGACGT motif. Furthermore, co-cultivation experiments with barnyardgrass suggested that the allelopathic effect of knockdown and overexpression of OsTGAP1 was significantly changed compared to the controls. These results demonstrate that OsTGAP1 positively regulates DP accumulation via transcriptional regulation of DP biosynthetic genes in rice roots, and this is indispensable for maintaining of allelopathic interactions with paddy weeds by regulating the production of specialized metabolites like momilactones. This article is protected by copyright. All rights reserved.

  10. [Jaridonin, a new diterpenoid from Isodon rubescens, induces cell cycle arrest in gastric cancer cells through activating ataxia telangiectasia mutated kinase].

    PubMed

    Ma, Y C; Su, N; Zhao, N M; Li, Q Y; Zhang, M; Zhao, H W; Liu, H M; Qin, Y H

    2016-04-01

    To study the effects of Jaridonin, a novel diterpenoid from isodon rubescens, on the cell cycle of human gastric cancer cells and its molecular mechanism of action. Flow cytometry was used to analyze the cell cycle distribution and expression of ataxia telangiectasia mutated kinase (ATM) after Jaridonin treatment. Western blot was performed to detect the expression of cell cycle-related proteins. The results of flow cytometry showed that the percentages of MGC-803 cells in G(2)/M phase at 6 hours after 0, 10, 20 μmol/L Jaridonin-treatment were (10.8±2.2)%, (18.2±2.5)%, (27.3±3.2)%, respectively; those at 12 hours after Jaridonin-treatment were (12.0±1.5)%, (24.1±2.0)% and (39.7±5.2)%, respectively, indicating a G2/M phase arrest of MGC-803 cells was resulted in a time- and dose-dependent manner. The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up-regulated in the MGC-803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. KU-55933, an inhibitor of ATM, reversed the expression of relevant proteins and G(2)/M phase arrest induced by Jaridonin. Jaridonin can significantly induce G(2)/M arrest in gastric cancer MGC-803 cells. Its mechanism may be related to the activation of ATM and Chk1/2, and inactivation of Cdc2 and CDK2 phosphorylation.

  11. Diterpanes, triterpanes, steranes, and aromatic hydrocarbons in natural bitumens and pyrolysates from different humic coals

    NASA Technical Reports Server (NTRS)

    Lu, Shan-Tan; Kaplan, Isaac R.

    1992-01-01

    Data are presented on the distribution of diterpanes, triterpanes, steranes, and aromatic hydrocarbons in the natural bitumens extracted from unheated coals identified as Rocky Mountain coal (RMC), Australian Gippsland Latrobe Eocene coal (GEC), Australian Gippsland Latrobe Cretaceous coal (GCC), and Texas Wilcox lignite (WL), as well as from pyrolysates obtained from heating of these coals. It was found that pentacyclic triterpanes are dominant in GEC, GCC, and WL, whereas diterpanes strongly predominate in the bitumen of RMC, indicating that resin is a more important constituent of RMC than of the other coals and that it releases the diterpenoids at an early stage of diagenesis. It was also found that the composition of diterpanes is different among these coals and that the distributions of sterane and triterpane in the natural bitumen of coals are very different from those of pyrolysates.

  12. Diterpanes, triterpanes, steranes, and aromatic hydrocarbons in natural bitumens and pyrolysates from different humic coals

    NASA Technical Reports Server (NTRS)

    Lu, Shan-Tan; Kaplan, Isaac R.

    1992-01-01

    Data are presented on the distribution of diterpanes, triterpanes, steranes, and aromatic hydrocarbons in the natural bitumens extracted from unheated coals identified as Rocky Mountain coal (RMC), Australian Gippsland Latrobe Eocene coal (GEC), Australian Gippsland Latrobe Cretaceous coal (GCC), and Texas Wilcox lignite (WL), as well as from pyrolysates obtained from heating of these coals. It was found that pentacyclic triterpanes are dominant in GEC, GCC, and WL, whereas diterpanes strongly predominate in the bitumen of RMC, indicating that resin is a more important constituent of RMC than of the other coals and that it releases the diterpenoids at an early stage of diagenesis. It was also found that the composition of diterpanes is different among these coals and that the distributions of sterane and triterpane in the natural bitumen of coals are very different from those of pyrolysates.

  13. Discovery and development of natural product oridonin-inspired anticancer agents.

    PubMed

    Ding, Ye; Ding, Chunyong; Ye, Na; Liu, Zhiqing; Wold, Eric A; Chen, Haiying; Wild, Christopher; Shen, Qiang; Zhou, Jia

    2016-10-21

    Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic.

  14. A strategy for the separation of diterpenoid isomers from the root of Aralia continentalis by countercurrent chromatography: The distribution ratio as a substitute for the partition coefficient and a three-phase solvent system.

    PubMed

    Lee, Kyoung Jin; Song, Kwang Ho; Choi, Wonmin; Kim, Yeong Shik

    2015-08-07

    Aralia continentalis (Araliaceae) is widely used as a medicinal plant in East Asia. Previous studies have indicated that diterpenoid isomers (kaurenoic acid, continentalic acid, and ent-continentalic acid) are the major bioactive compounds of this plant. A new strategy was developed to alleviate difficulties in the separation of these isomers from this plant. A three-phase solvent system was applied to separate the isomers, and furthermore, the distribution ratio (Kc) was introduced as a substitute for the partition coefficient (KD). For compounds exhibiting a single equilibrium, their distributions in two immiscible phases were only affected by the partition coefficient of each solute. However, compounds that have a dissociating functional group (e.g., -COOH) are involved in two types of equilibrium in the two-phase system. In this case, the partitioning behaviors of the solutes are greatly affected by the pH of the solution. A mathematical prediction was applied for adjusting the solutions to the proper pH values. To prevent non-used phase (medium phase) waste, both the stationary phase (upper phase) and mobile phase (lower phase) were prepared on-demand without pre-saturation with the application of (1)H NMR. Each fraction obtained was collected and dried, yielding the following diterpenoid isomers from the 50mg injected sample: kaurenoic acid (19.7mg, yield: 39%) and ent-continentalic acid (21.3mg, yield: 42%). Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Apparent Contradiction: Psychrotolerant Bacteria from Hydrocarbon-Contaminated Arctic Tundra Soils That Degrade Diterpenoids Synthesized by Trees

    PubMed Central

    Yu, Zhongtang; Stewart, Gordon R.; Mohn, William W.

    2000-01-01

    Resin acids are tricyclic terpenoids occurring naturally in trees. We investigated the occurrence of resin acid-degrading bacteria on the Arctic tundra near the northern coast of Ellesmere Island (82°N, 62°W). According to most-probable-number assays, resin acid degraders were abundant (103 to 104 propagules/g of soil) in hydrocarbon-contaminated soils, but they were undetectable (<3 propagules/g of soil) in pristine soils from the nearby tundra. Plate counts indicated that the contaminated and the pristine soils had similar populations of heterotrophs (106 to 107 propagules/g of soil). Eleven resin acid-degrading bacteria belonging to four phylogenetically distinct groups were enriched and isolated from the contaminated soils, and representative isolates of each group were further characterized. Strains DhA-91, IpA-92, and IpA-93 are members of the genus Pseudomonas. Strain DhA-95 is a member of the genus Sphingomonas. All four strains are psychrotolerant, with growth temperature ranges of 4°C to 30°C (DhA-91 and DhA-95) or 4°C to 22°C (IpA-92 and IpA-93) and with optimum temperatures of 15 to 22°C. Strains DhA-91 and DhA-95 grew on the abietanes, dehydroabietic and abietic acids, but not on the pimaranes, isopimaric and pimaric acids. Strains IpA-92 and IpA-93 grew on the pimaranes but not the abietanes. All four strains grew on either aliphatic or aromatic hydrocarbons, which is unusual for described resin acid degraders. Eleven mesophilic resin acid degraders did not use hydrocarbons, with the exception of two Mycobacterium sp. strains that used aliphatic hydrocarbons. We conclude that hydrocarbon contamination in Arctic tundra soil indirectly selected for resin acid degraders, selecting for hydrocarbon degraders that coincidentally use resin acids. Psychrotolerant resin acid degraders are likely important in the global carbon cycle and may have applications in biotreatment of pulp and paper mill effluents. PMID:11097882

  16. Epigenetic genome mining of an endophytic fungus leads to the pleiotropic biosynthesis of natural products.

    PubMed

    Mao, Xu-Ming; Xu, Wei; Li, Dehai; Yin, Wen-Bing; Chooi, Yit-Heng; Li, Yong-Quan; Tang, Yi; Hu, Youcai

    2015-06-22

    The small-molecule biosynthetic potential of most filamentous fungi has remained largely unexplored and represents an attractive source for the discovery of new compounds. Genome sequencing of Calcarisporium arbuscula, a mushroom-endophytic fungus, revealed 68 core genes that are involved in natural product biosynthesis. This is in sharp contrast to the predominant production of the ATPase inhibitors aurovertin B and D in the wild-type fungus. Inactivation of a histone H3 deacetylase led to pleiotropic activation and overexpression of more than 75 % of the biosynthetic genes. Sampling of the overproduced compounds led to the isolation of ten compounds of which four contained new structures, including the cyclic peptides arbumycin and arbumelin, the diterpenoid arbuscullic acid A, and the meroterpenoid arbuscullic acid B. Such epigenetic modifications therefore provide a rapid and global approach to mine the chemical diversity of endophytic fungi. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Discovery of Highly Sweet Compounds from Natural Sources

    NASA Astrophysics Data System (ADS)

    Kinghorn, A. Douglas; Kennelly, Edward J.

    1995-08-01

    Sucrose, the most widely used sweetener globally, is of plant origin. In addition, a number of other plant constituents are employed as dietary sucrose substitutes in one or more countries, including the diterpenoid, stevioside, the triterpenoid, glycyrrhizin, and the protein, thaumatin. Accordingly, there has been much interest in discovering further examples of potently sweet compounds of natural origin, for potential use in foods, beverages, and medicines. Approximately 75 plant-derived compounds are presently known, mainly representative of the flavonoid, proanthocyandin, protein, steroidal saponin, and terpenoid chemotypes. In our program directed towards the elucidation of further highly sweet molecules from plants, candidate sweet-tasting plants for laboratory investigation are obtained from ethnobotanical observations in the field or in the existing literature. Examples of novel sweet-tasting compounds obtained so far are the sesquiterpenoids, hernandulcin and 4beta-hydroxyhemandulcin; the triterpenoids, abrusosides A-D; a semi-synthetic dihydroflavonol based on the naturally occurring substance, dihydroquercetin 3-acetate; and the proanthocyanidin, selligueain A. Natural product sweeteners may be of potential commercial use per se, and can be used for synthetic modification to produce improved sweeteners, and can also be of value scientifically to aid in the better understanding of structure-sweetness relationships.

  18. Immunofluorescence localization of levopimaradiene/abietadiene synthase in methyl jasmonate treated stems of Sitka spruce (Picea sitchensis) shows activation of diterpenoid biosynthesis in cortical and developing traumatic resin ducts.

    PubMed

    Zulak, Katherine G; Dullat, Harpreet K; Keeling, Christopher I; Lippert, Dustin; Bohlmann, Jörg

    2010-10-01

    Conifers produce terpenoid-rich oleoresin in specialized resin ducts as a main line of defence against pests and pathogens. In spruce species (Picea spp.), axial resin ducts are either present constitutively in the cortex tissue (cortical resin ducts, CRDs) or are formed de novo as traumatic resin ducts (TRDs) in the cambial zone upon attack by insects, fungi or treatment with methyl jasmonate (MeJA). Using immunofluorescence localization we tested if previously formed CRDs respond to MeJA treatment with increased capacity for diterpenoid biosynthesis. We also tested the dynamics of diterpene synthase localization in the cambial zone. Immunofluorescence localization was performed using an antibody against a diterpene synthase, levopimaradiene/abietadiene synthase (LAS), in stem cross-sections of untreated and 0.1% MeJA-treated 4-year old Sitka spruce (P. sitchensis) trees. No fluorescence signal was observed in untreated stem cross-sections; however, signal was present 2 days after treatment with MeJA exclusively in the epithelial cells of CRDs. Fluorescence steadily increased in the CRD epithelial cells 4 and 8 days after treatment. At 8days, additional fluorescence was observed in developing epithelial cells of traumatic resin ducts TRDs in the cambial zone. These results confirm that resin duct epithelial cells are the main site of diterpene biosynthesis in Sitka spruce, diterpenoid biosynthesis is induced in CRD epithelial cells early upon treatment with MeJA, and immature developing TRD epithelial cells produce diterpene synthase enzyme. Overall, the results of this work improve our understanding of spatial and temporal patterns of induced diterpene resin acid biosynthesis in conifers.

  19. Diterpenoid acids from Grindelia nana.

    PubMed

    Mahmoud, A A; Ahmed, A A; Tanaka, T; Iinuma, M

    2000-03-01

    Two new norditerpenoid acids of the labdane-type (norgrindelic acids), 4,5-dehydro-6-oxo-18-norgrindelic acid (1) and 4beta-hydroxy-6-oxo-19-norgrindelic acid (2), as well as a new grindelic acid derivative, 18-hydroxy-6-oxogrindelic acid (3), were isolated from the aerial parts of Grindelia nana. In addition, the known compounds, 6-oxogrindelic acid, grindelic acid, methyl grindeloate, 7alpha,8alpha-epoxygrindelic acid, and 4alpha-carboxygrindelic acid were also isolated. The structures of the new compounds were characterized on the basis of spectroscopic analysis.

  20. Natural organic compounds as tracers for biomass combustion in aerosols

    SciTech Connect

    Simoneit, B.R.T. |; Abas, M.R. bin |; Cass, G.R. |; Rogge, W.F. |; Mazurek, M.A.; Standley, L.J.; Hildemann, L.M.

    1995-08-01

    Biomass combustion is an important primary source of carbonaceous particles in the global atmosphere. Although various molecular markers have already been proposed for this process, additional specific organic tracers need to be characterized. The injection of natural product organic tracers to smoke occurs primarily by direct volatilization/steam stripping and by thermal alteration based on combustion temperature. The degree of alteration increases as the burn temperature rises and the moisture content of the fuel decreases. Although the molecular composition of organic matter in smoke particles is highly variable, the molecular structures of the tracers are generally source specific. The homologous compound series and biomarkers present in smoke particles are derived directly from plant wax, gum and resin by volatilization and secondarily from pyrolysis of biopolymers, wax, gum and resin. The complexity of the organic components of smoke aerosol is illustrated with examples from controlled burns of temperate and tropical biomass fuels. Burning of biomass from temperate regions (i.e., conifers) yields characteristic tracers from diterpenoids as well as phenolics and other oxygenated species, which are recognizable in urban airsheds. The major organic components of smoke particles from tropical biomass are straight-chain, aliphatic and oxygenated compounds and triterpenoids. The precursor-to-product approach of organic geochemistry can be applied successfully to provide tracers for studying smoke plume chemistry and dispersion.

  1. Natural Xanthones

    NASA Astrophysics Data System (ADS)

    Denisova-Dyatlova, O. A.; Glyzin, V. I.

    1982-10-01

    The available information on the abundance of natural xanthones in nature and the methods for the determination of their structure, biogenesis, and pharmacological properties is surveyed and described systematically. The bibliography includes 151 references.

  2. Genetic evidence for natural product mediated plant–plant allelopathy in rice

    PubMed Central

    Xu, Meimei; Galhano, Rita; Wiemann, Philipp; Bueno, Emilio; Tiernan, Mollie; Wu, William; Chung, Ill-Min; Gershenzon, Jonathan; Tudzynski, Bettina; Sesma, Ane; Peters, Reuben J.

    2011-01-01

    Summary A role for specific natural products in directly mediating antagonistic plant–plant interactions –that is, allelopathy –has been controversial. If proven, such phenomena would hold considerable promise for agronomic improvement of staple food crops such as rice (Oryza sativa).However, while substantiated by the presence of phytotoxic compounds at potentially relevant levels, demonstrating a direct role for specific natural products in allelopathy has been difficult due to the chemical complexity of root and plant litter exudates. This complexity can be bypassed via selective genetic manipulation to ablate production of putative allelopathic compounds, but such an approach previously has not been applied.The rice diterpenoid momilactones provide an example of natural products for which correlative biochemical evidence has been obtained for a role in allelopathy. Here, we apply reverse genetics, using knock-outs of the relevant diterpene synthases (OsCPS4 and OsKSL4), to demonstrate that rice momilactones are involved in allelopathy, including suppressing growth of the widespread rice paddy weed, barnyard grass (Echinochloa crus-galli).Thus, our results not only provide novel genetic evidence for natural product mediated allelopathy, but also furnish a molecular target for breeding and metabolic engineering of this important crop plant. PMID:22150231

  3. Genetic evidence for natural product-mediated plant-plant allelopathy in rice (Oryza sativa).

    PubMed

    Xu, Meimei; Galhano, Rita; Wiemann, Philipp; Bueno, Emilio; Tiernan, Mollie; Wu, William; Chung, Ill-Min; Gershenzon, Jonathan; Tudzynski, Bettina; Sesma, Ane; Peters, Reuben J

    2012-02-01

    • There is controversy as to whether specific natural products play a role in directly mediating antagonistic plant-plant interactions - that is, allelopathy. If proved to exist, such phenomena would hold considerable promise for agronomic improvement of staple food crops such as rice (Oryza sativa). • However, while substantiated by the presence of phytotoxic compounds at potentially relevant concentrations, demonstrating a direct role for specific natural products in allelopathy has been difficult because of the chemical complexity of root and plant litter exudates. This complexity can be bypassed via selective genetic manipulation to ablate production of putative allelopathic compounds, but such an approach previously has not been applied. • The rice diterpenoid momilactones provide an example of natural products for which correlative biochemical evidence has been obtained for a role in allelopathy. Here, we apply reverse genetics, using knock-outs of the relevant diterpene synthases (copalyl diphosphate synthase 4 (OsCPS4) and kaurene synthase-like 4 (OsKSL4)), to demonstrate that rice momilactones are involved in allelopathy, including suppressing growth of the widespread rice paddy weed, barnyard grass (Echinochloa crus-galli). • Thus, our results not only provide novel genetic evidence for natural product-mediated allelopathy, but also furnish a molecular target for breeding and metabolic engineering of this important crop plant. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  4. Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants.

    PubMed

    Crawford, Alexander D; Liekens, Sandra; Kamuhabwa, Appolinary R; Maes, Jan; Munck, Sebastian; Busson, Roger; Rozenski, Jef; Esguerra, Camila V; de Witte, Peter A M

    2011-02-17

    Natural products represent a significant reservoir of unexplored chemical diversity for early-stage drug discovery. The identification of lead compounds of natural origin would benefit from therapeutically relevant bioassays capable of facilitating the isolation of bioactive molecules from multi-constituent extracts. Towards this end, we developed an in vivo bioassay-guided isolation approach for natural product discovery that combines bioactivity screening in zebrafish embryos with rapid fractionation by analytical thin-layer chromatography (TLC) and initial structural elucidation by high-resolution electrospray mass spectrometry (HRESIMS). Bioactivity screening of East African medicinal plant extracts using fli-1:EGFP transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM) assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products.

  5. Zebrafish Bioassay-Guided Natural Product Discovery: Isolation of Angiogenesis Inhibitors from East African Medicinal Plants

    PubMed Central

    Crawford, Alexander D.; Liekens, Sandra; Kamuhabwa, Appolinary R.; Maes, Jan; Munck, Sebastian; Busson, Roger; Rozenski, Jef; Esguerra, Camila V.; de Witte, Peter A. M.

    2011-01-01

    Natural products represent a significant reservoir of unexplored chemical diversity for early-stage drug discovery. The identification of lead compounds of natural origin would benefit from therapeutically relevant bioassays capable of facilitating the isolation of bioactive molecules from multi-constituent extracts. Towards this end, we developed an in vivo bioassay-guided isolation approach for natural product discovery that combines bioactivity screening in zebrafish embryos with rapid fractionation by analytical thin-layer chromatography (TLC) and initial structural elucidation by high-resolution electrospray mass spectrometry (HRESIMS). Bioactivity screening of East African medicinal plant extracts using fli-1:EGFP transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM) assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products. PMID:21379387

  6. Firsthand Nature

    ERIC Educational Resources Information Center

    Gostev, Moses; Weiss, Francesca Michaelides

    2007-01-01

    It's no secret that many school programs don't give children enough opportunity to explore the natural world--i.e., to "mess about" and to have firsthand experience with nature and animals. Not so at the Muscota New School in New York City! This innovative public elementary school actively promotes inquiry-based learning and encourages…

  7. Nature plants.

    PubMed

    2014-06-01

    We welcome our new sister journal Nature Plants and the increased commitment to the plant science community that it represents. This is an opportunity for Nature Genetics to emphasize the use of genetic and genomic tools and resources in discovering new plant biology and solving major agricultural challenges.

  8. Natural death.

    PubMed

    Oehmichen, M; Meissner, C

    2000-01-01

    The increasing age of every human being is the beginning of the end of life, an obviously natural process, but any attempt to define the term 'natural death' soon encounters difficulties in defining what is meant by 'natural'. In the industrialized countries of the West, for example 'natural death' is thought of as the opposite of non-natural types of death such as accidental death, suicide, and homicide. The aim of our present survey is to discuss the meaning of the term 'natural death' under a clinical, a forensic and a scientific point of view with regard to recent developments especially in molecular biology. If there are 'external' physical influences, a medical-technical manipulation, a therapeutic or molecular biological intervention cannot be definitely ruled out as the cause of death, then use of the term 'natural death' in general is open to question. It will only remain meaningful if it can be applied with a specific meaning in definite practical situations. Current research and medical technology, however, do not allow use of the term 'natural death' in its conventional sense: it can thus be stricken from the medical vocabulary. Copyright 2000 S. Karger AG, Basel

  9. Firsthand Nature

    ERIC Educational Resources Information Center

    Gostev, Moses; Weiss, Francesca Michaelides

    2007-01-01

    It's no secret that many school programs don't give children enough opportunity to explore the natural world--i.e., to "mess about" and to have firsthand experience with nature and animals. Not so at the Muscota New School in New York City! This innovative public elementary school actively promotes inquiry-based learning and encourages…

  10. Nature Detectives

    ERIC Educational Resources Information Center

    Harr, Natalie; Lee, Richard E.; Jr.

    2010-01-01

    Richard Louv's "Last Child in the Woods" (2008) added to a growing consensus to get children outside and experiencing nature. Using ideas from place-based education, the authors present a simple year-long project that brings science, nature, and other curriculum standards to life right in your school yard. With a focus on journaling, this project…

  11. Matematica Natural.

    ERIC Educational Resources Information Center

    Lozano, Patricia; Medearis, Linda

    Matematica Natural (Natural Mathematics) is a mathematics curriculum for young children based on the assumption that they learn mathematics through concrete, real life, relevant experiences and that educational differences rather than cultural differences influence math achievement. The curriculum uses hands-on materials and activities to teach…

  12. Natural Beauty

    ERIC Educational Resources Information Center

    Coy, Mary

    2006-01-01

    In this article, the author describes how her art class students were able to create, in just four class periods, clay relief plaques depicting nature. A lesson on texture speeds up the completion of such a project. Seeing that clay is a natural material with its own unique texture, it seemed fitting that the final product should depict a variety…

  13. Natural Beauty

    ERIC Educational Resources Information Center

    Coy, Mary

    2006-01-01

    In this article, the author describes how her art class students were able to create, in just four class periods, clay relief plaques depicting nature. A lesson on texture speeds up the completion of such a project. Seeing that clay is a natural material with its own unique texture, it seemed fitting that the final product should depict a variety…

  14. Matematica Natural.

    ERIC Educational Resources Information Center

    Lozano, Patricia; Medearis, Linda

    Matematica Natural (Natural Mathematics) is a mathematics curriculum for young children based on the assumption that they learn mathematics through concrete, real life, relevant experiences and that educational differences rather than cultural differences influence math achievement. The curriculum uses hands-on materials and activities to teach…

  15. Nature Detectives

    ERIC Educational Resources Information Center

    Harr, Natalie; Lee, Richard E.; Jr.

    2010-01-01

    Richard Louv's "Last Child in the Woods" (2008) added to a growing consensus to get children outside and experiencing nature. Using ideas from place-based education, the authors present a simple year-long project that brings science, nature, and other curriculum standards to life right in your school yard. With a focus on journaling, this project…

  16. Bharangin, a Diterpenoid Quinonemethide, Abolishes Constitutive and Inducible Nuclear Factor-κB (NF-κB) Activation by Modifying p65 on Cysteine 38 Residue and Reducing Inhibitor of Nuclear Factor-κB α Kinase Activation, Leading to Suppression of NF-κB-Regulated Gene Expression and Sensitization of Tumor Cells to Chemotherapeutic Agents

    PubMed Central

    Gupta, Subash C.; Kannappan, Ramaswamy; Kim, Jihye; Rahman, Ghazi M.; Francis, Sajin K.; Raveendran, Reshma; Nair, Mangalam S.; Das, Joydip

    2011-01-01

    Although inflammatory pathways have been linked with various chronic diseases including cancer, identification of an agent that can suppress these pathways has therapeutic potential. Herein we describe the identification of a novel compound bharangin, a diterpenoid quinonemethide that can suppress pro-inflammatory pathways specifically. We found that bharangin suppresses nuclear factor (NF)-κB activation induced by pro-inflammatory cytokine, tumor promoter, cigarette smoke, and endotoxin. Inhibition of NF-κB activation was mediated through the suppression of phosphorylation and degradation of inhibitor of nuclear factor-κB (IκBα); inhibition of IκBα kinase activation; and suppression of p65 nuclear translocation, and phosphorylation. The diterpenoid inhibited binding of p65 to DNA. A reducing agent reversed the inhibitory effect, and mutation of the Cys38 of p65 to serine abrogated the effect of bharangin on p65-DNA binding. Molecular docking revealed strong interaction of the ligand with the p65 via two hydrogen bonds one with Lys37 (2.204 Å) and another with Cys38 (2.023 Å). The inhibitory effect of bharangin on NF-κB activation was specific, inasmuch as binding of activator protein-1 and octameric transcription factor 1 to DNA was not affected. Suppression of NF-κB activation by this diterpenoid caused the down-regulation of the expression of proteins involved in tumor cell survival, proliferation, invasion, and angiogenesis, leading to potentiation of apoptosis, suppression of proliferation, and invasion of tumor cells. Furthermore, the genetic deletion of p65 and mutation of p65Cys38 residue to Ser abolished the affect of bharangin. Overall, our results demonstrate that bharangin specifically inhibits the NF-κB activation pathway by modifying p65 and inhibiting IκBα kinase activation and potentiates apoptosis in tumor cells. PMID:21795584

  17. The Nature of Natural Languages.

    ERIC Educational Resources Information Center

    Pierce, Joe E.

    A variety of types of evidence are examined to help determine the true nature of "deep structure" and what, if any, implications this has for linguistic theory as well as culture theory generally. The evidence accumulated over the past century on the nature of phonetic and phonemic systems is briefly discussed, and the following areas of…

  18. Natural disasters.

    PubMed

    Cullen, J M

    1980-09-01

    This presentation covers the various types of natural disasters which are faced by investigators throughout the world. Each geophysical substance is discussed, including earth, air and water, and secondary effects including fire. Additionally, four myths associated with disasters are reviewed.

  19. Natural aphrodisiacs.

    PubMed

    Shamloul, Rany

    2010-01-01

    The search for a remedy or a prescription that can enhance sexual function and/or treat male erectile dysfunction has been an obsession throughout known history. Whether it was an Eastern civilization or a Western one, religious or atheist, man's aspiration for a better or best "manhood" has been a history-time goal. This review will discuss the current research done on the most popular natural aphrodisiacs and examine the weight of evidence to support or discourage the use of any of these substances to enhance sexual desire and/or function. Review of the current evidence on the use of natural substances as aphrodisiacs. Efficacy of natural aphrodisiacs in enhancing sexual function in men and women. There is little evidence from literature to recommend the usage of natural aphrodisiacs for the enhancement of sexual desire and/or performance. Data on yohimbine's efficacy does not support the wide use of the drug, which has only mild effects in the treatment of psychogenic ED. Although there's a positive trend towards recommending ginseng as an effective aphrodisiac, however, more in depth studies involving large number of subjects and its mechanism of action are needed before definite conclusions could be reached. Data on the use of natural aphrodisiacs in women is limited. The current body of objective evidence does not support the use of any natural aphrodisiac as an effective treatment for male or female sexual dysfunctions. Potent men and men with ED will continue the search for natural aphrodisiacs despite the current disappointing data on their effectiveness. Care should be taken regarding the fraud addition of sildenafil analogues to natural aphrodisiacs.

  20. Cloning, molecular characterization and functional analysis of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) gene for diterpenoid tanshinone biosynthesis in Salvia miltiorrhiza Bge. f. alba.

    PubMed

    Hao, Gangping; Shi, Renjiu; Tao, Ru; Fang, Qian; Jiang, Xingyu; Ji, Haiwei; Feng, Lei; Huang, Luqi

    2013-09-01

    The enzyme 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) is a terminal-acting enzyme in the plastid MEP pathway, which produce isoprenoid precursors. The full-length cDNA of HDR, designated SmHDR1 (Genbank Accession No. JX516088), was isolated for the first time from Salvia miltiorrhiza Bge. f. alba. SmHDR1 contains a 1389-bp open reading frame encoding 463 amino acids. The deduced SmHDR1 protein, which shows high identity to HDRs of other plant species, is predicted to possess a chloroplast transit peptide at the N-terminus and four conserved cysteine residues. Transcription pattern analysis revealed that SmHDR1 has high levels of transcription in leaves and low levels of transcription in roots and stems. The expression of SmHDR1 was induced by 0.1 mM methyl-jasmonate (MeJA) and salicylic acid (SA), but not by 0.1 mM abscisic acid (ABA), in the hairy roots of S. miltiorrhiza Bge. f. alba. Complementation of SmHDR1 in the Escherichia coli HDR mutant MG1655 ara < > ispH demonstrated the function of this enzyme. A functional color assay in E. coli showed that SmHDR1 accelerates the biosynthesis of β-carotene, indicating that SmHDR1 encodes a functional protein. Overexpression of SmHDR1 enhanced the production of tanshinones in cultured hairy roots of S. miltiorrhiza Bge. f. alba. These results indicate that SmHDR1 is a novel and important enzyme involved in the biosynthesis of diterpenoid tanshinones in S. miltiorrhiza Bge. f. alba.

  1. Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH{sub 2}-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells

    SciTech Connect

    Miyata, Yoshiki; Sato, Takashi . E-mail: satotak@ps.toyaku.ac.jp; Ito, Akira

    2005-11-04

    Triptolide, a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook f., exerts antitumorigenic actions against several tumor cells, but the intracellular target signal molecule(s) for this antitumorigenesis activity of triptolide remains to be identified. In the present study, we demonstrated that triptolide, in a dose-dependent manner, inhibited the proliferation of human fibrosarcoma HT-1080, human squamous carcinoma SAS, and human uterine cervical carcinoma SKG-II cells. In addition, triptolide was found to decrease phosphatidylinositol 3-kinase (PI3K) activity. A PI3K inhibitor, LY-294002, mimicked the triptolide-induced antiproliferative activity in HT-1080, SAS, and SKG-II cells. There was no change in the activity of Akt or protein kinase C (PKC), both of which are downstream effectors in the PI3K pathway. Furthermore, the phosphorylation of Ras, Raf, and mitogen-activated protein/extracellular signal-regulated kinase 1/2 was not modified in HT-1080 cells treated with triptolide. However, the phosphorylation of c-Jun NH{sub 2}-terminal kinase 1 (JNK1) was found to increase in both triptolide- and LY-294002-treated cells. Furthermore, the triptolide-induced inhibition of HT-1080 cell proliferation was not observed by JNK1 siRNA-treatment. These results provide novel evidence that PI3K is a crucial target molecule in the antitumorigenic action of triptolide. They further suggest a possible triptolide-induced inhibitory signal for tumor cell proliferation that is initiated by the decrease in PI3K activity, which in turn leads to the augmentation of JNK1 phosphorylation via the Akt and/or PKC-independent pathway(s). Moreover, it is likely that the activation of JNK1 is required for the triptolide-induced inhibition of tumor proliferation.

  2. Synthesis of antimalarial amide analogues based on the plant serrulatane diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid.

    PubMed

    Kumar, Rohitesh; Duffy, Sandra; Avery, Vicky M; Davis, Rohan A

    2017-09-01

    A plant-derived natural product scaffold, 3,7,8-trihydroxyserrulat-14-en-19-oic acid (1) was isolated in high yield from the aerial parts of the endemic Australian desert plant Eremophila microtheca. This scaffold (1) was subsequently used in the generation of a series of new amide analogues via a one-pot mixed anhydride amidation using pivaloyl chloride. The structures of all analogues were characterized using MS, NMR, and UV data. The major serrulatane natural products (1-3), isolated from the plant extract, and all amide analogues (6-15) together with several pivaloylated derivatives of 3,7,8-trihydroxyserrulat-14-en-19-oic acid (16-18) were evaluated for their antimalarial activity against 3D7 (chloroquine sensitive) and Dd2 (chloroquine resistant) Plasmodium falciparum strains, and preliminary cytotoxicity data were also acquired using the human embryonic kidney cell line HEK293. The natural product scaffold (1) did not display any antimalarial activity at 10µM. Replacing the carboxylic acid of 1 with various amides resulted in moderate activity against the P. falciparum 3D7 strain with IC50 values ranging from 1.25 to 5.65µM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Nature's Code

    NASA Astrophysics Data System (ADS)

    Hill, Vanessa J.; Rowlands, Peter

    2008-10-01

    We propose that the mathematical structures related to the `universal rewrite system' define a universal process applicable to Nature, which we may describe as `Nature's code'. We draw attention here to such concepts as 4 basic units, 64- and 20-unit structures, symmetry-breaking and 5-fold symmetry, chirality, double 3-dimensionality, the double helix, the Van der Waals force and the harmonic oscillator mechanism, and our explanation of how they necessarily lead to self-aggregation, complexity and emergence in higher-order systems. Biological concepts, such as translation, transcription, replication, the genetic code and the grouping of amino acids appear to be driven by fundamental processes of this kind, and it would seem that the Platonic solids, pentagonal symmetry and Fibonacci numbers have significant roles in organizing `Nature's code'.

  4. Nature's Palette

    ERIC Educational Resources Information Center

    McBride, Brooke B.; Brewer, Carol A.

    2010-01-01

    Flower petals, acorn hats, exoskeletons of beetles, and lichens are just a few of the objects students may find in a surprising array of vivid colors. These tiny examples from nature's palette can be discovered in a school yard, a park, or even along the edges of a paved sidewalk...it simply takes careful observation! This article describes a…

  5. Natural fibers

    Treesearch

    Craig M. Clemons; Daniel F. Caulfield

    2005-01-01

    The term “natural fibers” covers a broad range of vegetable, animal, and mineral fibers. However, in the composites industry, it usually refers to wood fiber and agrobased bast, leaf, seed, and stem fibers. These fibers often contribute greatly to the structural performance of the plant and, when used in plastic composites, can provide significant reinforcement. Below...

  6. Natural restoration

    SciTech Connect

    Kamlet, K.S.

    1993-02-01

    After a company pays millions of dollars to clean up contaminated site, its liability may not be over. It may have to spend tens of millions more to restore damaged natural resources under an oft-overlooked Superfund program. Examples of liability are cited in this report from the Exxon Valdez oil spill and a pcb leak which contaminated a harbor.

  7. Natural ecosystems

    USGS Publications Warehouse

    Fleishman, Erica; Belnap, Jayne; Cobb, Neil; Enquist, Carolyn A.F.; Ford, Karl; MacDonald, Glen; Pellant, Mike; Schoennagel, Tania; Schmit, Lara M.; Schwartz, Mark; van Drunick, Suzanne; Westerling, Anthony LeRoy; Keyser, Alisa; Lucas, Ryan

    2013-01-01

    Natural Ecosystems analyzes the association of observed changes in climate with changes in the geographic distributions and phenology (the timing of blossoms or migrations of birds) for Southwestern ecosystems and their species, portraying ecosystem disturbances—such as wildfires and outbreaks of forest pathogens—and carbon storage and release, in relation to climate change.

  8. Nature Watch

    ERIC Educational Resources Information Center

    Sterling, Donna R.

    2010-01-01

    Children are naturally curious about the world in which they live. To focus this sense of wonder, have your students investigate their local habitat as it changes over the year. This multiseason study will build connections and add relevance to the habitats that children learn about. This series of activities for grades 4-6 explores the changing…

  9. Uranium, natural

    Integrated Risk Information System (IRIS)

    Uranium , natural ; CASRN 7440 - 61 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  10. Nature Watch

    ERIC Educational Resources Information Center

    Sterling, Donna R.

    2010-01-01

    Children are naturally curious about the world in which they live. To focus this sense of wonder, have your students investigate their local habitat as it changes over the year. This multiseason study will build connections and add relevance to the habitats that children learn about. This series of activities for grades 4-6 explores the changing…

  11. Nature's Palette

    ERIC Educational Resources Information Center

    McBride, Brooke B.; Brewer, Carol A.

    2010-01-01

    Flower petals, acorn hats, exoskeletons of beetles, and lichens are just a few of the objects students may find in a surprising array of vivid colors. These tiny examples from nature's palette can be discovered in a school yard, a park, or even along the edges of a paved sidewalk...it simply takes careful observation! This article describes a…

  12. Evident and latent plasticity across the rice diterpene synthase family with potential implications for the evolution of diterpenoid metabolism in the cereals

    PubMed Central

    Morrone, Dana; Hillwig, Matthew L.; Mead, Matthew E.; Lowry, Luke; Fulton, D. Bruce; Peters, Reuben J.

    2013-01-01

    SYNOPSIS The evolution of natural products biosynthetic pathways can be envisioned to occur via a number of mechanisms. Here we provide evidence that latent plasticity plays a role in such metabolic evolution. In particular, rice (Oryza sativa) produces both ent- and syn-copalyl diphosphate (CPP), which are substrates for downstream diterpene synthases. Here we report that several members of this enzymatic family exhibit dual reactivity with some pairing of ent-, syn-, or normal CPP stereochemistry. Evident plasticity was observed, as a previously reported ent-sandaracopimaradiene synthase also converts syn-CPP to syn-labda-8(17),12E,14-triene, which can be found in planta. Notably, normal CPP is not naturally found in rice. Thus, the presence of diterpene synthases that react with this non-native metabolite reveals latent enzymatic/metabolic plasticity, providing biochemical capacity for utilization of such a novel substrate (i.e., normal CPP) that may arise during evolution, the implications of which are discussed. PMID:21323642

  13. Natural thermodynamics

    NASA Astrophysics Data System (ADS)

    Annila, Arto

    2016-02-01

    The principle of increasing entropy is derived from statistical physics of open systems assuming that quanta of actions, as undividable basic build blocks, embody everything. According to this tenet, all systems evolve from one state to another either by acquiring quanta from their surroundings or by discarding quanta to the surroundings in order to attain energetic balance in least time. These natural processes result in ubiquitous scale-free patterns: skewed distributions that accumulate in a sigmoid manner and hence span log-log scales mostly as straight lines. Moreover, the equation for least-time motions reveals that evolution is by nature a non-deterministic process. Although the obtained insight in thermodynamics from the notion of quanta in motion yields nothing new, it accentuates that contemporary comprehension is impaired when modeling evolution as a computable process by imposing conservation of energy and thereby ignoring that quantum of actions are the carriers of energy from the system to its surroundings.

  14. Natural fibers

    Treesearch

    Craig M. Clemons

    2010-01-01

    The term “natural fibers” covers a broad range of vegetable, animal, and mineral fibers. However, in the composites industry, it usually refers to wood fiber and plant-based bast, leaf, seed, and stem fibers. These fibers often contribute greatly to the structural performance of the plant and, when used in plastic composites, can provide significant reinforcement....

  15. Nature's pumps

    NASA Astrophysics Data System (ADS)

    Vogel, Steven

    1994-10-01

    Although diverse in both form and function, the fluid-forcing devices in organisms have many of the capabilities and limitations of pumps of human design. Nature's pumps certainly look quite different from those of our technology, but all of them perform the same task. The author examines a few of these with an eye toward technological parallels and the two functional classes -- positive-displacement pumps and fluid-dynamic pumps.

  16. Satellite (Natural)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    In its most general sense, any celestial object in orbit around a similar larger object. Thus, for example, the Magellanic Clouds are satellite galaxies of our own Milky Way galaxy. Without qualification, the term is used to mean a body in orbit around a planet; an alternative term is moon. The term natural satellite distinguishes these bodies from artificial satellites—spacecraft placed in orbi...

  17. Natural inflation

    SciTech Connect

    Frieman, J.A.

    1991-02-01

    A pseduo-Nambu-Goldstone boson, with a potential of the form V({phi}) = {Lambda}{sup 4}(1 {plus minus} cos({phi}/f)), can naturally give rise to an epoch of inflation in the early universe. Successful inflation can be achieved if f {approximately} m{sub pl} and {Lambda} {approximately} m{sub GUT}. Such mass scales arise in particle physics models with a gauge group that becomes strongly interacting a the GUT scale, e.g., as is expected to happen in the hidden sector of superstring theories. The density fluctuation spectrum is a non-scale-invariant power law, with extra power on large scales. 12 refs., 3 figs.

  18. Natural Strain

    NASA Technical Reports Server (NTRS)

    Freed, Alan D.

    1995-01-01

    The purpose of this paper is to present a consistent and thorough development of the strain and strain-rate measures affiliated with Hencky. Natural measures for strain and strain-rate, as I refer to them, are first expressed in terms of of the fundamental body-metric tensors of Lodge. These strain and strain-rate measures are mixed tensor fields. They are mapped from the body to space in both the Eulerian and Lagrangian configurations, and then transformed from general to Cartesian fields. There they are compared with the various strain and strain-rate measures found in the literature. A simple Cartesian description for Hencky strain-rate in the Lagrangian state is obtained.

  19. Natural relaxation

    NASA Astrophysics Data System (ADS)

    Marzola, Luca; Raidal, Martti

    2016-11-01

    Motivated by natural inflation, we propose a relaxation mechanism consistent with inflationary cosmology that explains the hierarchy between the electroweak scale and Planck scale. This scenario is based on a selection mechanism that identifies the low-scale dynamics as the one that is screened from UV physics. The scenario also predicts the near-criticality and metastability of the Standard Model (SM) vacuum state, explaining the Higgs boson mass observed at the Large Hadron Collider (LHC). Once Majorana right-handed neutrinos are introduced to provide a viable reheating channel, our framework yields a corresponding mass scale that allows for the seesaw mechanism as well as for standard thermal leptogenesis. We argue that considering singlet scalar dark matter extensions of the proposed scenario could solve the vacuum stability problem and discuss how the cosmological constant problem is possibly addressed.

  20. [Naturalizing empathy].

    PubMed

    Decety, J

    2002-01-01

    Empathy is the ability to share emotions with others. It is acknowledged to be a powerful means of tacit communication, a key ingredient in any therapeutic relationship as well as in psychotherapy. Empathy is the cornerstone in the humanist perspective (Ego-psychology) in clinical psychology. This approach is often considered as poorly grounded on scientific and objective evidence. It is however acknowledged that empathetic therapists are more effective than less empathetic therapists. I shall argue that this paradox, i.e. it is the least scientific and the less validated psychotherapeutic approach that is the most efficient, can be eliminated if one considers the nature of empathy, its biological foundation, its evolutionary origin and its cognitive architecture. In this paper I will suggest that empathy is based on specific information processing modules which have been designed by natural selection to cope with social regularities in expressing and reading emotional states. This has provided adaptive benefits to individuals living in large groups bestowing them with mechanisms for cooperativity, altruism and more generally various aspects of prosocial behaviour. The capacity to express emotions, and to read and understand emotions of others also ensures implicit communication with others and may be at the root of intersubjectivity. This perspective on empathy is then articulated with two concurrent hypotheses regarding theory of mind (the simulation and the theory-theory) which aim to explain the human capacity to understand that the behaviors of other intelligent agents are caused by intentions, desires and beliefs. In this context, empathy can be considered as a simulation (or analogical) process that is necessary to understand but not sufficient to interpret other people. This last issue is relevant to clinical practice.

  1. Theoretical and experimental study of aparisthman: A natural product with anti-ulcer activity

    NASA Astrophysics Data System (ADS)

    Brasil, D. S. B.; Moreira, R. Y. O.; Müller, A. H.; Alves, C. N.

    Aparisthman is a furan diterpenoid with a clerodane skeleton isolated from Aparisthmium cordatum (Juss.) Bail. (Euphorbiaceae). This natural product presents significant anti-ulcer activity to the level of cimetidine (Tagamet®), a compound used for the treatment of ulcers provoked by stress. The structure of X-ray diffraction of the aparisthman was compared with theoretical calculations and the results showed that the theory is in accordance with the experimental data. The infrared (IR) and nuclear magnetic resonance (NMR) spectra also were obtained and compared with theoretical calculations. The B3LYP theory level, with the 6-31G(d,p) basis set, leads the value to the IR absorption close to the value experimentally observed. NMR theoretical obtained with HF/6-311+G(2d,p) shows little deviation of experimental results. Calculations of molecular electrostatic potential and stabilization energies suggest that the protonation of aparisthman will be able to occur on carbonyl oxygen atom (O4).

  2. Antibacterial profiling of abietane-type diterpenoids.

    PubMed

    Helfenstein, Andreas; Vahermo, Mikko; Nawrot, Dorota A; Demirci, Fatih; İşcan, Gökalp; Krogerus, Sara; Yli-Kauhaluoma, Jari; Moreira, Vânia M; Tammela, Päivi

    2017-01-01

    Abietic and dehydroabietic acid are interesting diterpenes with a highly diverse repertoire of associated bioactivities. They have, among others, shown antibacterial and antifungal activity, potentially valuable in the struggle against the increasing antimicrobial resistance and imminent antibiotic shortage. In this paper, we describe the synthesis of a set of 9 abietic and dehydroabietic acid derivatives containing amino acid side chains and their in vitro antimicrobial profiling against a panel of human pathogenic microbial strains. Furthermore, their in vitro cytotoxicity against mammalian cells was evaluated. The experimental results showed that the most promising compound was 10 [methyl N-(abiet-8,11,13-trien-18-yl)-d-serinate], with an MIC90 of 60μg/mL against Staphylococcus aureus ATCC 25923, and 8μg/mL against methicillin-resistant S. aureus, Staphylococcus epidermidis and Streptococcus mitis. The IC50 value for compound 10 against Balb/c 3T3 cells was 45μg/mL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Labdane diterpenoid glycosides from Aster veitchianus.

    PubMed

    Li, Er-Wei; Gao, Xue; Gao, Kun; Jia, Zhong-Jian

    2007-03-01

    Four new labdane-type rhamnopyranosides derived from 13-epimanool, compounds 1-4, with differently acetylated sugar moieties, were isolated from A. veitchianus. Their structures and absolute configurations were elucidated by chemical transformation, spectroscopic and mass-spectrometric analyses (IR, 1D- and 2D-NMR, HR-ESI-MS), as well as by single-crystal X-ray diffraction (compound 1). The isolates 2-4 were investigated for their cytotoxic properties against cultured human hepatoma (SMMC-7721), ovarian neoplasm (HO-8910), and leukemia (HL-60) cells, and for their antibacterial activities against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus.

  4. The social nature of natural childbirth.

    PubMed

    Mansfield, Becky

    2008-03-01

    This paper aims to develop a better understanding of what proponents of natural childbirth mean by "natural." Using a biosocial approach to birth that posits that all birth is both social and natural, the paper investigates how proponents represent the relationship between nature and society. The study asks about what kinds of nature-society relationships are expressed in proponents' representations of natural childbirth. The study examines how natural childbirth is represented by proponents in popular non-fictional English language books written for pregnant women. Claims in these books are not taken as reality, but are analyzed as ideas about nature-society relations. The central finding is that these authors simultaneously emphasize the naturalness of birth and showcase three types of social practices that they describe as being integral to natural childbirth: (1) activity during birth, (2) preparation before birth, and (3) social support, both in an individual and in a broader socio-cultural sense. At least for these authors, it is these social practices that allow natural childbirth to be natural. These findings on the social nature of natural childbirth challenge current social science scholarship, in which natural childbirth is characterized as an essentializing and nostalgic attempt to return to nature.

  5. Analysis of diterpenoic compounds in natural resins applied as binders in museum objects by capillary electrophoresis.

    PubMed

    Findeisen, Anna; Kolivoska, Viliam; Kaml, Isabella; Baatz, Wolfgang; Kenndler, Ernst

    2007-07-20

    The exudates of conifers consist mainly of diterpenoic acids of the abietane and pimarane type (abietic, neoabietic, dehydroabietic, palustric, pimaric, isopimaric, levopimaric and sandaracopimaric acid) and larixol acetate. These natural resins were used as adhesives, coatings, varnishes or plasticizers in artistic and historic works since ancient times. For the purpose of conservation and restoration and for art historic examination of such museum objects the identification of the binding media used is undoubtedly of paramount importance. In the present paper, the characterization of these resins based on the pattern of their diterpenoid constituents is carried out by capillary electrophoresis. For separation a background electrolyte which has been initially introduced for the analysis of chlorinated and natural resin acids in waste water was modified and the experimental conditions were adjusted in terms of resolution and analysis time. Separation was carried out in borate buffer at pH 9.25 (ionic strength 20 mmol L(-1)) with methyl-beta-cyclodextrin and sulfobutylether-beta-cyclodextrin as additives to increase selectivity and enhance the solubility of the analytes. With this electrophoretic system the resin acids of interest and larixol acetate--all as anionic cyclodextrin complexes--were separated within 5 min and detected at 200, 250 and 270 nm with a diode array detector. The electrophoretic patterns served for the characterisation of the relevant diterpenoic resins, balsams and copals. Sample pre-treatment was limited to sonication in methanol at 55 degrees C for 30 min. This enables the identification of the resins in mixtures with other binders like plant gums, animal glues or drying oils, even when these media are present in excess. Colophony was identified as resinous constituent of a modelling mass for gilded frames originating from the 19th century.

  6. Two new natural products from Croton kongensis Gagnep.

    PubMed

    Sun, Lin; Meng, Zhaoqing; Li, Zhaoliang; Yang, Biao; Wang, Zhenzhong; Ding, Gang; Xiao, Wei

    2014-01-01

    A new diterpenoid, 14β-hydroxy-3-oxo-ent-kaur-16-ene (1), and a new nor-lignan, 8S-( - )-8-(4-hydroxy-3-methoxybenzoyl)-dihydrofuran-8(8'H)-one (4), along with five known compounds were isolated from the twigs and leaves of Croton kongensis Gagnep. Their isolations were clarified and structures were elucidated by the extensive spectroscopic analyses, especially 2D NMR experiments.

  7. Rapid screening of bioactive compounds from natural products by integrating 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays.

    PubMed

    Zhang, Yufeng; Xiao, Shun; Sun, Lijuan; Ge, Zhiwei; Fang, Fengkai; Zhang, Wen; Wang, Yi; Cheng, Yiyu

    2013-05-13

    A high throughput method was developed for rapid screening and identification of bioactive compounds from traditional Chinese medicine, marine products and other natural products. The system, integrated with five-channel chromatographic separation and dual UV-MS detection, is compatible with in vitro 96-well microplate based bioassays. The stability and applicability of the proposed method was validated by testing radical scavenging capability of a mixture of seven known compounds (rutin, dihydroquercetin, salvianolic acid A, salvianolic acid B, glycyrrhizic acid, rubescensin A and tangeretin). Moreover, the proposed method was successfully applied to the crude extracts of traditional Chinese medicine and a marine sponge from which 12 bioactive compounds were screened and characterized based on their anti-oxidative or anti-tumor activities. In particular, two diterpenoid derivatives, agelasine B and (-)-agelasine D, were identified for the first time as anti-tumor compounds from the sponge Agelas mauritiana, showing a considerable activity toward MCF-7 cells (IC50 values of 7.84±0.65 and 10.48±0.84 μM, respectively). Our findings suggested that the integrated system of 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays can be a versatile and high efficient approach for the discovery of active compounds from natural products. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Natural Language Processing.

    ERIC Educational Resources Information Center

    Chowdhury, Gobinda G.

    2003-01-01

    Discusses issues related to natural language processing, including theoretical developments; natural language understanding; tools and techniques; natural language text processing systems; abstracting; information extraction; information retrieval; interfaces; software; Internet, Web, and digital library applications; machine translation for…

  9. Natural Gas Emergencies

    MedlinePlus

    Natural Gas Emergencies Extinguish cigarettes and do not light matches. You can help prevent natural gas emergencies by calling the utility locator service ... Health through the Cities Readiness Initiative (CRI) English – Natural Gas Emergencies - Last reviewed 2014

  10. Natural Language Processing.

    ERIC Educational Resources Information Center

    Chowdhury, Gobinda G.

    2003-01-01

    Discusses issues related to natural language processing, including theoretical developments; natural language understanding; tools and techniques; natural language text processing systems; abstracting; information extraction; information retrieval; interfaces; software; Internet, Web, and digital library applications; machine translation for…

  11. The nature and ethics of natural experiments.

    PubMed

    Dawson, Angus; Sim, Julius

    2015-10-01

    Natural experiments are an important methodology often used to answer research questions that would, otherwise, be impossible to address, or employed because of ethical concerns about the use of randomisation to interventions that carry known risks. The UK Medical Research Council (MRC) recently produced an extremely useful document discussing the nature and significance of natural experiments within medical and public health research. In this paper, however, we suggest that the MRC document's definition of the term 'natural experiment' is insufficiently precise. In response, we offer a taxonomy of different types of natural experiments and related methods, and explore the ethical implications of these different types. We argue that while the ethical issues that may arise within natural experiments in relation to risks of harm or informed consent may differ from those within the randomised controlled trial, they are not thereby less pressing. The implications of the argument are explored and recommendations made for those involved in research governance.

  12. Immune up regulatory response of a non-caloric natural sweetener, stevioside.

    PubMed

    Sehar, Irum; Kaul, Anpurna; Bani, Sarang; Pal, Harish Chandra; Saxena, Ajit Kumar

    2008-05-28

    Immunomodulation is a process, which alters the immune system of an organism by interfering with its functions. This interference results in either immunostimulation or immunosuppression. An immunomodulator is any substance that helps to regulate the immune system. This "regulation" is a normalization process, so that an immunomodulator helps to optimise immune response. Immunomodulators are becoming very popular in the worldwide natural health industry as these do not tend to boost immunity, but to normalize it. Keeping this in view, major efforts have to be directed to modulate the immune responses, to permit effective treatment of various ailments associated with immune system and thus the development of a safe and effective immunomodulator for clinical us. Leaves of Stevia rebaudiana are a source of several sweet glycosides of steviol. The major glycoside, stevioside, diterpenoid glycoside--is used in oriental countries as a food sweetener. Its medical use is also reported as a heart tonic. Besides, it is used against obesity, hypertension, and stomach burn and to lower uric acid levels. Here in this study, stevioside was tested for its immunomodulatory activity on different parameters of the immune system at three different doses (6.25, 12.5 and 25 mg/kg p.o.) on normal as well as cyclophosphamide treated mice. Stevioside was found effective in increasing phagocytic activity, haemagglutination antibody titre and delayed type hypersensitivity. In parallel, stevioside substantially increase proliferation in the LPS and Con A stimulated B and T cells, respectively. Present study, therefore, reveals that the drug holds promise as immunomodulating agent, which acts by stimulating both humoral as well as cellular immunity and phagocytic function.

  13. Engaging Nature Aesthetically

    ERIC Educational Resources Information Center

    Kupfer, Joseph H.

    2003-01-01

    For the most part, most people appreciate nature as spectators. Some portion of a natural scene is viewed as if it were a painting or photograph. However, thinking of nature solely or chiefly as an aesthetic scene to be observed is unnecessarily limiting. Regarding natural phenomena as material for detached, pictorial observation overlooks the…

  14. Naturally occurring chemical carcinogens

    USDA-ARS?s Scientific Manuscript database

    Natural products are chemicals found in nature which have unique pharmacological effects. Humans are exposed to many of these bioactive naturally occurring chemicals via the air breathed, the water drunk and the food eaten. Exposure also occurs in clinical settings. Naturally occurring chemicals ...

  15. Natural and near natural tropical forest values

    Treesearch

    Daniel H. Henning

    2011-01-01

    This paper identifies and describes some of the values associated with tropical rain forests in their natural and near-natural conditions. Tropical rain forests are moist forests in the humid tropics where temperature and rainfall are high and the dry season is short. These closed (non-logged) and broad-leaved forests are a global resource. Located almost entirely in...

  16. The Nature of Natural Hazards Communication (Invited)

    NASA Astrophysics Data System (ADS)

    Kontar, Y. Y.

    2013-12-01

    Some of the many issues of interest to natural hazards professionals include the analysis of proactive approaches to the governance of risk from natural hazards and approaches to broaden the scope of public policies related to the management of risks from natural hazards, as well as including emergency and environmental management, community development and spatial planning related to natural hazards. During the talk we will present results of scientific review, analysis and synthesis, which emphasize same new trends in communication of the natural hazards theories and practices within an up-to-the-minute context of new environmental and climate change issues, new technologies, and a new focus on resiliency. The presentation is divided into five sections that focus on natural hazards communication in terms of education, risk management, public discourse, engaging the public, theoretical perspectives, and new media. It includes results of case studies and best practices. It delves into natural hazards communication theories, including diffusion, argumentation, and constructivism, to name a few. The presentation will provide information about: (1) A manual of natural hazards communication for scientists, policymakers, and media; (2) An up-to-the-minute context of environmental hazards, new technologies & political landscape; (3) A work by natural hazards scientists for geoscientists working with social scientists and communication principles; (4) A work underpinned by key natural hazards communication theories and interspersed with pragmatic solutions; (5) A work that crosses traditional natural hazards boundaries: international, interdisciplinary, theoretical/applied. We will further explore how spatial planning can contribute to risk governance by influencing the occupation of natural hazard-prone areas, and review the central role of emergency management in risk policy. The goal of this presentation is to contribute to the augmentation of the conceptual framework

  17. A Natural Love of Natural Products

    PubMed Central

    2008-01-01

    Recent research on the chemistry of natural products from the author’s group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies with the epothilones suggest that the current tubulin-binding model needs to be modified. Examples of natural products discovery and biodiversity conservation in Suriname and Madagascar are also presented, and it is concluded that natural products chemistry will continue to make significant contributions to drug discovery. PMID:18459734

  18. Nature's Nature: Ideas of Nature in Curricula for Environmental Education

    ERIC Educational Resources Information Center

    St Maurice, Henry

    2006-01-01

    Two contrasting sets of ideas about nature in environmental education are described. An analytical framework is developed from inter-disciplinary histories of ideas and used in evaluating a specific curriculum. In conclusion, some general implications are suggested for curricula in environmental education. [This article was reprinted from…

  19. Nature's Nature: Ideas of Nature in Curricula for Environmental Education

    ERIC Educational Resources Information Center

    St Maurice, Henry

    2006-01-01

    Two contrasting sets of ideas about nature in environmental education are described. An analytical framework is developed from inter-disciplinary histories of ideas and used in evaluating a specific curriculum. In conclusion, some general implications are suggested for curricula in environmental education. [This article was reprinted from…

  20. Crystal structure and theoretical study of IR and 1H and 13C NMR spectra of cordatin, a natural product with antiulcerogenic activity

    NASA Astrophysics Data System (ADS)

    Brasil, Davi S. B.; Alves, Cláudio N.; Guilhon, Giselle M. S. P.; Muller, Adolfo H.; Secco, Ricardo De S.; Peris, Gabriel; Llusar, Rosa

    Cordatin is a furan diterpenoid with a clerodane skeleton isolated from Croton palanostigma Klotzsch (Euphorbiaceae). This natural product shows significant antiulcerogenic activity, similar to cimetidine (Tagamet®), a compound used for the treatment of peptic ulcers. The crystal structure of cordatin was obtained by X-ray diffraction and its geometrical parameters were compared with theoretical calculations at the B3LYP theory level. The IR and NMR (1H and 13C chemical shifts and coupling constants) spectra were obtained and compared with the theoretical calculations. The B3LYP theory level, with the 6-31G(d,p) and 6-311G(d,p) basis set, provided IR absorption values close to the experimental data. Moreover, theoretical NMR parameters obtained in both gas phase and chloroform solvent at the B3PW91/DGDZVP, B3LYP/6-311+G(2d,p), and B3PW91/6-311+G(2d,p) levels showed good correlations with the experimental results.

  1. Natural Gas Monthly

    EIA Publications

    2017-01-01

    Highlights activities, events, and analyses associated with the natural gas industry. Volume and price data are presented each month for natural gas production, distribution, consumption, and interstate pipeline activities. Producer related activities and underground storage data are also reported.

  2. Fine Arts through Nature.

    ERIC Educational Resources Information Center

    Gentry, Carol

    1986-01-01

    Describes how high school students are involved in using natural materials found in the local environment for art projects. The materials used include wood, clay, and natural fibers. Provides photographs of ten students' projects. (JDH)

  3. Colours From Nature

    ERIC Educational Resources Information Center

    Simon, Wilma

    1974-01-01

    In reference to American Indian ceremonial art, the importance of using natural pigments is emphasized, since the superior color values of natural dyes better reflect religious and philosophical depth and meaning. (JC)

  4. Demonstrating Natural Selection

    ERIC Educational Resources Information Center

    Hinds, David S.; Amundson, John C.

    1975-01-01

    Describes laboratory exercises with chickens selecting their food from dyed and natural corn kernels as a method of demonstrating natural selection. The procedure is based on the fact that organisms that blend into their surroundings escape predation. (BR)

  5. Natural Resource Damages: Trustees

    EPA Pesticide Factsheets

    CERCLA and OPA authorize the United States, States, and Indian Tribes to act on behalf of the public as Natural Resource Trustees for natural resources under their respective trusteeship. OPA also authorizes foreign governments to act as Trustees.

  6. Breast reconstruction - natural tissue

    MedlinePlus

    ... flap; TUG; Mastectomy - breast reconstruction with natural tissue; Breast cancer - breast reconstruction with natural tissue ... it harder to find a tumor if your breast cancer comes back. The advantage of breast reconstruction with ...

  7. Natural gas annual 1996

    SciTech Connect

    1997-09-01

    This document provides information on the supply and disposition of natural gas to a wide audience. The 1996 data are presented in a sequence that follows natural gas from it`s production to it`s end use.

  8. Demonstrating Natural Selection

    ERIC Educational Resources Information Center

    Hinds, David S.; Amundson, John C.

    1975-01-01

    Describes laboratory exercises with chickens selecting their food from dyed and natural corn kernels as a method of demonstrating natural selection. The procedure is based on the fact that organisms that blend into their surroundings escape predation. (BR)

  9. Colours From Nature

    ERIC Educational Resources Information Center

    Simon, Wilma

    1974-01-01

    In reference to American Indian ceremonial art, the importance of using natural pigments is emphasized, since the superior color values of natural dyes better reflect religious and philosophical depth and meaning. (JC)

  10. Natural gas annual 1995

    SciTech Connect

    1996-11-01

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1995 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1991 to 1995 for each Census Division and each State. Annual historical data are shown at the national level.

  11. Natural gas annual 1994

    SciTech Connect

    1995-11-17

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1994 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1990 to 1994 for each Census Division and each State. Annual historical data are shown at the national level.

  12. Natural Gas Basics

    SciTech Connect

    2016-06-01

    Natural gas powers about 150,000 vehicles in the United States and roughly 22 million vehicles worldwide. Natural gas vehicles (NGVs) are a good choice for high-mileage fleets -- such as buses, taxis, and refuse vehicles -- that are centrally fueled or operate within a limited area or along a route with natural gas fueling stations. This brochure highlights the advantages of natural gas as an alternative fuel, including its domestic availability, established distribution network, relatively low cost, and emissions benefits.

  13. Natural Gas Basics

    SciTech Connect

    2016-06-08

    Natural gas powers about 150,000 vehicles in the United States and roughly 22 million vehicles worldwide. Natural gas vehicles (NGVs) are a good choice for high-mileage fleets -- such as buses, taxis, and refuse vehicles -- that are centrally fueled or operate within a limited area or along a route with natural gas fueling stations. This brochure highlights the advantages of natural gas as an alternative fuel, including its domestic availability, established distribution network, relatively low cost, and emissions benefits.

  14. Natural language processors

    SciTech Connect

    Rauzino, V.C.

    1983-09-05

    The development of natural language processors has required a shift in the perception of language structures to bring the user interface closer to the ultimate ease of natural language dialogue. This article explains the principles of these new natural language processors which are increasingly becoming commercially available.

  15. Learning in Nature

    ERIC Educational Resources Information Center

    Brody, Michael

    2005-01-01

    This paper traces the evolution of a theory of learning in nature in order to explain how people learn in natural settings. The intellectual roots of the theory in informal learning, cognition, affective development, experiential and meaningful learning are described and the synthesis into a comprehensive theory of learning in nature are…

  16. Nature in the City.

    ERIC Educational Resources Information Center

    Ferbert, Mary Lou

    1981-01-01

    Describes a science program developed by the Cleveland Museum of Natural History, "Nature in the City," in which students and teachers learn together about the natural community surrounding their school. Includes program's rationale, list of "adventures," and methods. Discusses strategies of Sherlock Holmes'"adventure" focusing on animal tracks…

  17. Nature in the City.

    ERIC Educational Resources Information Center

    Ferbert, Mary Lou

    1981-01-01

    Describes a science program developed by the Cleveland Museum of Natural History, "Nature in the City," in which students and teachers learn together about the natural community surrounding their school. Includes program's rationale, list of "adventures," and methods. Discusses strategies of Sherlock Holmes'"adventure" focusing on animal tracks…

  18. Learning in Nature

    ERIC Educational Resources Information Center

    Brody, Michael

    2005-01-01

    This paper traces the evolution of a theory of learning in nature in order to explain how people learn in natural settings. The intellectual roots of the theory in informal learning, cognition, affective development, experiential and meaningful learning are described and the synthesis into a comprehensive theory of learning in nature are…

  19. On nature and bioethics.

    PubMed

    Peterson, Paul Silas

    2010-01-01

    The account of nature and humanity's relationship to nature are of central importance for bioethics. The Scientific Revolution was a critical development in the history of this question and many contemporary accounts of nature find their beginnings here. While the innovative approach to nature going out of the seventeenth century was reliant upon accounts of nature from the early modern period, the Middle Ages, late-antiquity and antiquity, it also parted ways with some of the understandings of nature from these epochs. Here I analyze this development and suggests that some of the insights from older understandings of nature may be helpful for bioethics today, even if there can be no simple return to them.

  20. Nature and health.

    PubMed

    Hartig, Terry; Mitchell, Richard; de Vries, Sjerp; Frumkin, Howard

    2014-01-01

    Urbanization, resource exploitation, and lifestyle changes have diminished possibilities for human contact with nature in urbanized societies. Concern about the loss has helped motivate research on the health benefits of contact with nature. Reviewing that research here, we focus on nature as represented by aspects of the physical environment relevant to planning, design, and policy measures that serve broad segments of urbanized societies. We discuss difficulties in defining "nature" and reasons for the current expansion of the research field, and we assess available reviews. We then consider research on pathways between nature and health involving air quality, physical activity, social cohesion, and stress reduction. Finally, we discuss methodological issues and priorities for future research. The extant research does describe an array of benefits of contact with nature, and evidence regarding some benefits is strong; however, some findings indicate caution is needed in applying beliefs about those benefits, and substantial gaps in knowledge remain.

  1. Natural vacuum electronics

    NASA Technical Reports Server (NTRS)

    Leggett, Nickolaus

    1990-01-01

    The ambient natural vacuum of space is proposed as a basis for electron valves. Each valve is an electron controlling structure similiar to a vacuum tube that is operated without a vacuum sustaining envelope. The natural vacuum electron valves discussed offer a viable substitute for solid state devices. The natural vacuum valve is highly resistant to ionizing radiation, system generated electromagnetic pulse, current transients, and direct exposure to space conditions.

  2. Natural gas annual 1997

    SciTech Connect

    1998-10-01

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1997 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1993 to 1997 for each Census Division and each State. Annual historical data are shown at the national level. 27 figs., 109 tabs.

  3. Natural gas monthly

    SciTech Connect

    Not Available

    1983-08-01

    The Natural Gas Monthly (NGM) highlights activities, events, and analyses of interest to public and private sector organizations associated with the natural gas industry. The NGM replaces three EIA reports previously published annually: Underground Natural Gas Storage in the United States; US Imports and Exports of Natural Gas; Main Line Sales of Natural Gas to Industrial Users. Some of the highlights are: marketed production of natural gas during June 1983 was estimated at 1307 billion cubic feet (Bcf), 178 Bcf (12.0 percent) below the June 1982 level; consumption of natural gas during June 1983 was an estimated 1060 Bcf, a decrease of 55 Bcf (4.9 percent) compared to June 1982 consumption; natural gas consumption in May 1983, compared to the previous May, was up 14.0 percent in the residential sector, up 7.9 percent in the commercial sector, and up 14.2 percent in the industrial sector; the volume of working gas in underground storage reservoirs at the end of June 1983 was 3.1 percent above the June 30, 1982 level; the average wellhead price of natural gas in April 1983 was $2.63 per thousand cubic feet (Mcf) compared to $2.35 per Mcf for April 1982; in June 1983, the US city average residential price for 100 therms of natural gas was $64.70 ($6.63 per Mcf), the comparable price in June 1982 was $54.80 ($5.62 per Mcf); the average wellhead (first sale) price for natural gas purchases projected for July 1983 by selected interstate pipeline companies was $2.72 per Mcf, in July 1982 the average price was $2.45 per Mcf.

  4. Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation.

    PubMed

    An, Jing; Yang, Hao; Zhang, Qian; Liu, Cuicui; Zhao, Jingjing; Zhang, Lingling; Chen, Bo

    2016-02-15

    Osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass, bone quality, and microarchitectural deterioration. An imbalance in bone remodeling that is caused by more osteoclast-mediated bone resorption than osteoblast-mediated bone formation results in such pathologic bone disorder. Traditional Chinese medicines (TCM) have long been used to prevent and treat osteoporosis and have received extensive attentions and researches at home and abroad, because they have fewer adverse reactions and are more suitable for long-term use compared with chemically synthesized medicines. Here, we put the emphasis on osteoblasts, summarized the detailed research progress on the active compounds derived from TCM with potential anti-osteoporosis effects and their molecular mechanisms on promoting osteoblast-mediated bone formation. It could be concluded that TCM with kidney-tonifying, spleen-tonifying, and stasis-removing effects all have the potential effects on treating osteoporosis. The active ingredients derived from TCM that possess effects on promoting osteoblasts proliferation and differentiation include flavonoids, glycosides, coumarins, terpenoids (sesquiterpenoids, monoterpenoids, diterpenoids), phenolic acids, phenols and others (tetrameric stilbene, anthraquinones, diarylheptanoids). And it was confirmed that the bone formation effect induced by the above natural products was regulated by the expressions of bone specific matrix proteins (ALP, BSP, OCN, OPN, COL I), transcription factor (Runx2, Cbfa1, Osx), signal pathways (MAPK, BMP), local factors (ROS, NO), OPG/RANKL system of osteoblasts and estrogen-like biological activities. All the studies provided theoretical basis for clinical application, as well as new drug research and development on treating osteoporosis.

  5. Nature Experience and Education

    ERIC Educational Resources Information Center

    Rathunde, Kevin

    2013-01-01

    Kevin Rathunde turns his research lens to the task of finding out the relevance of the natural world, its impact on adolescent motivation, and its positive sustaining of concentration and focus. He cites "disembodiment and denaturing" as needing to be countered by contact with nature, leading to higher creativity, less drudgery, and more…

  6. Modeling Natural Selection

    ERIC Educational Resources Information Center

    Bogiages, Christopher A.; Lotter, Christine

    2011-01-01

    In their research, scientists generate, test, and modify scientific models. These models can be shared with others and demonstrate a scientist's understanding of how the natural world works. Similarly, students can generate and modify models to gain a better understanding of the content, process, and nature of science (Kenyon, Schwarz, and Hug…

  7. Island Natural Science School.

    ERIC Educational Resources Information Center

    Toronto Board of Education (Ontario).

    Prepared for students in grade six attending the Island Natural Science School, Toronto, Ontario, Canada, this booklet offers information and suggests activities in the areas of ecology, conservation, natural resources, and outdoor recreation. Introductory material describes island lore, its formation and significant features, followed by units of…

  8. Natural gas monthly

    SciTech Connect

    Not Available

    1982-12-01

    This report presents data on the supply and disposition of natural gas in the USA during August 1982, as well as data on production, storage, imports, exports, and consumption. Selected data are also presented on the activities of the major interstate pipeline companies. Marketed production of natural gas decreased 18.2% during August 1982, compared to August 1981, from 1706 billion cubic feet (Bcf) to 1471 Bcf. Consumption during the same period declined as well, from 1314 Bcf to 1153 Bcf. Commencing with this issue of the Natural Gas Monthly (NGM), estimates of marketed production are provided for two more recent months, September and October. Volumes of natural gas in storage continue to run slightly ahead of year-ago levels. The volume of natural gas purchased from producers and imported by major interstate natural gas pipeline companies continues to decline. In August 1981, 864 Bcf were purchased from producers, compared to 793 Bcf in August 1982. Imports during the same period declined from 62 Bcf to 46 Bcf. Applications for determination of a maximum lawful price under the Natural Gas Policy Act (NGPA) showed a significant increase between September and October 1982. The increase occurred principally for Section 103 classification wells (new onshore production wells), and for Section 107 classification wells (high-cost natural gas).

  9. Natural gas monthly

    SciTech Connect

    Not Available

    1983-04-01

    This document highlights activities, events, and analysis results of interest to public and private sector organizations associated with natural gas industry operations. Data highlights: (1) Marketed production of natural gas during February 1983 was estimated at 1387 billion cubic feet (Bcf), 178 Bcf (11.4 percent) below the February 1982 level; (2) Consumption of natural gas during February 1983 was an estimated 1709 Bcf, a decrease of 258 Bcf (13.1 percent) compared to February 1982 consumption; (3) Consumption declined in all market sectors in January 1983 compared to January 1982; (4) The volume of working gas in underground storage reservoirs at the end of February 1983 was 31.7 percent above the February 28, 1982 level; (5) The average wellhead price of natural gas in December 1982 was $2.56 per thousand cubic feet (Mcf). In December 1981 the average was $2.16 per Mcf; (6) In February 1983, the US city average residential price for 100 therms of natural gas was $59.99; and (7) The average wellhead (first sale) price for natural gas purchases projected for March 1983 by selected interstate pipeline companies was $2.79 per Mcf. The feature article in this issue is entitled Recent Trends in Natural Gas Well Costs. Information is presented under the headings: industry overview, explanatory notes, data sources, and selected recurring natural gas and related reports. 5 figures, 24 tables. (DMC)

  10. Introduction to Exploring Nature

    ERIC Educational Resources Information Center

    Early Childhood Today, 2006

    2006-01-01

    Children are fascinated with the world of nature. From the tiniest of seeds to the highest of birds, they wonder "Why?" "How?" and "What can I do with it?" This paper provides intriguing nature activities that provide a solid starting point for expanding children's thinking and learning. Through these activities, children will be building skills…

  11. Natural Resources Bibliography.

    ERIC Educational Resources Information Center

    Hoadley, Irene Braden

    This bibliography presents a modern definition of the conceptual framework from which to view natural resources, and affords access to information which examines resources from the social scientists point of view. It presents five broad divisions of activity or variables which include (1) Natural and Human Resources, (2) Epistomological and…

  12. Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    The birds of New England and their particular habitats are explored in this guide which is part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is designed for…

  13. On Teaching Natural Law.

    ERIC Educational Resources Information Center

    Forte, David F.

    1978-01-01

    A brief look at Columbia, Harvard, and Notre Dame law schools shows that the American tradition in teaching natural law has not been strong. The value of teaching natural law is discussed, a separate course or seminar is seen as the most effective option, and a selection of available sources for such a course is appended. (JMD)

  14. Modeling Natural Selection

    ERIC Educational Resources Information Center

    Bogiages, Christopher A.; Lotter, Christine

    2011-01-01

    In their research, scientists generate, test, and modify scientific models. These models can be shared with others and demonstrate a scientist's understanding of how the natural world works. Similarly, students can generate and modify models to gain a better understanding of the content, process, and nature of science (Kenyon, Schwarz, and Hug…

  15. Nature Foil Reliefs

    ERIC Educational Resources Information Center

    Lane, Shaw J.

    2012-01-01

    Nature has always been a source of inspiration for artists across the centuries. Artists such as Leonardo da Vinci, Georgia O'Keeffe, Ansel Adams, and Andy Goldsworthy all drew inspiration for their work from nature. Seeds come from the dried pods, which when planted and cared for, bear fruit. In this article, the author describes how her…

  16. Nature's Advice Book

    ERIC Educational Resources Information Center

    Mahlin, Kathryn; Robertson, Amy

    2005-01-01

    What do can people learn from the world around them? Can a tree really teach something about life? Many times teachers provide students with facts about nature but fail to consider what one can learn from the natural world around them. After many months of exploring various ecosystems such as the prairie, rain forest, and desert, one of the…

  17. Nature's Advice Book

    ERIC Educational Resources Information Center

    Mahlin, Kathryn; Robertson, Amy

    2005-01-01

    What do can people learn from the world around them? Can a tree really teach something about life? Many times teachers provide students with facts about nature but fail to consider what one can learn from the natural world around them. After many months of exploring various ecosystems such as the prairie, rain forest, and desert, one of the…

  18. Introduction to Exploring Nature

    ERIC Educational Resources Information Center

    Early Childhood Today, 2006

    2006-01-01

    Children are fascinated with the world of nature. From the tiniest of seeds to the highest of birds, they wonder "Why?" "How?" and "What can I do with it?" This paper provides intriguing nature activities that provide a solid starting point for expanding children's thinking and learning. Through these activities, children will be building skills…

  19. Nature Foil Reliefs

    ERIC Educational Resources Information Center

    Lane, Shaw J.

    2012-01-01

    Nature has always been a source of inspiration for artists across the centuries. Artists such as Leonardo da Vinci, Georgia O'Keeffe, Ansel Adams, and Andy Goldsworthy all drew inspiration for their work from nature. Seeds come from the dried pods, which when planted and cared for, bear fruit. In this article, the author describes how her…

  20. Natural Concepts in Pigeons

    ERIC Educational Resources Information Center

    Herrnstein, R. J.; And Others

    1976-01-01

    Pigeons learned discrimination rapidly and responded differentially to pictures seen for the first time. The essential feature of a natural discrimination--which is the ability to cope with natural ranges of variation--was approached and earlier experimental results were extended using other classes of stimuli. (Author/RK)

  1. Nature of Science Is...

    ERIC Educational Resources Information Center

    Lederman, Judith Sweeney; Lederman, Norman G.

    2005-01-01

    The phrase "nature of science" refers to the characteristics of scientific knowledge that necessarily result from the scientific investigations that scientists conduct to develop knowledge. Yet, these characteristics are assumed by many to be "difficult" to teach. Not so. Many important aspects of nature of science can be directly linked to…

  2. Sketching in Nature

    ERIC Educational Resources Information Center

    Hobart, April

    2005-01-01

    Nature journaling is a useful skill for science students, independent of whether they also consider themselves artists. A pencil and sketchbook can be carried anywhere to record ecological information in many ways. A traditional page in a nature journal may consist of quick studies of plant and animal life sketched out as rudimentary line drawings…

  3. Natural Language Information Retrieval.

    ERIC Educational Resources Information Center

    Strzalkowski, Tomek

    1995-01-01

    Describes an information retrieval system in which advanced natural language processing is used to enhance the effectiveness of term-based document retrieval by preprocessing the documents; discovering interterm dependencies and build a conceptual hierarchy specific to database domain; and processing the user's natural language requests into…

  4. Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    The birds of New England and their particular habitats are explored in this guide which is part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is designed for…

  5. On Teaching Natural Law.

    ERIC Educational Resources Information Center

    Forte, David F.

    1978-01-01

    A brief look at Columbia, Harvard, and Notre Dame law schools shows that the American tradition in teaching natural law has not been strong. The value of teaching natural law is discussed, a separate course or seminar is seen as the most effective option, and a selection of available sources for such a course is appended. (JMD)

  6. Agriculture: Natural Events and Disasters

    EPA Pesticide Factsheets

    Natural Events and DiasastersInformation on Natural Events and Disasters. Every year natural disasters, such as hurricanes, floods, fires, earthquakes, and tornadoes, challenge agricultural production.

  7. Thermoacoustic natural gas liquefier

    SciTech Connect

    Swift, G.; Gardner, D.; Hayden, M.; Radebaugh, R.; Wollan, J.

    1996-07-01

    This is the final report of a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This project sought to develop a natural-gas-powered natural-gas liquefier that has absolutely no moving parts and requires no electrical power. It should have high efficiency, remarkable reliability, and low cost. The thermoacoustic natural-gas liquefier (TANGL) is based on our recent invention of the first no-moving-parts cryogenic refrigerator. In short, our invention uses acoustic phenomena to produce refrigeration from heat, with no moving parts. The required apparatus comprises nothing more than heat exchangers and pipes, made of common materials, without exacting tolerances. Its initial experimental success in a small size lead us to propose a more ambitious application: large-energy liquefaction of natural gas, using combustion of natural gas as the energy source. TANGL was designed to be maintenance-free, inexpensive, portable, and environmentally benign.

  8. Naturally occurring insecticides.

    PubMed Central

    Soloway, S B

    1976-01-01

    Naturally occurring insecticides are abundant and varied in their effects, though but a few are articles of commerce. Even for these, pyrethrum, nicotine, rotenone, hellebore, ryania, and sabadilla, there is a paucity of information on mammalian toxicology and environmental effects. In general, these materials are characterized favorably by low acute toxicity and ready dissipation in nature. Unfavorable aspects of natural insecticides are the contained mixture of active and inactive components and the low active ingredient content on a crop yield basis pointing to a high unit cost. Natural insecticides can serve additionally as leads to unnatural mimics, of which the commercially successful synthetic pyrethroids are prime examples. The chemical nature, relationship of insecticidal activity to chemical structure, occurrence, production, and utilization, registered uses, metabolism, and insect and mammalian toxicity are reviewed. PMID:789058

  9. Unnaturalised racial naturalism.

    PubMed

    Hochman, Adam

    2014-06-01

    Quayshawn Spencer (2014) misunderstands my treatment of racial naturalism. I argued that racial naturalism must entail a strong claim, such as "races are subspecies", if it is to be a substantive position that contrasts with anti-realism about biological race. My recognition that not all race naturalists make such a strong claim is evident throughout the article Spencer reviews (Hochman, 2013a). Spencer seems to agree with me that there are no human subspecies, and he endorses a weaker form of racial naturalism. However, he supports his preferred version of 'racial naturalism' with arguments that are not well described as 'naturalistic'. I argue that Spencer offers us an unnaturalised racial naturalism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Natural language parsing systems

    SciTech Connect

    Bole, L.

    1987-01-01

    The objective of this book is to enable scientists from different countries to present the results of their research on natural language parsing in the form of more detailed papers than would be possible in professional journals. The contents include: Robust Parsing Using Multiple Construction-Specific Strategies.- Parsing with Logical Variables.- Knowledge-Based Parsing.- Using Declarative Knowledge for Understanding Natural Language.- Weighted Parsing.- A Distributed Word-Based Approach to Parsing.- Parsing by Means of Uppsala Chart Processor.- Preliminary Analysis of a Breadth-First Parsing Algorithm: Theoretical and Experimental Results.- Syntax Directed Translation in the Natural Language Information System PLIDIS.- Subject Index.

  11. On nature's scaling effects

    NASA Technical Reports Server (NTRS)

    Wilkins, Dick J.

    1994-01-01

    This presentation afforded the opportunity to look back in the literature to discover scaling effects in nature that might be relevant to composites. Numerous examples were found in nature's approaches to wood, teeth, horns, leaves, eggs, feathers, etc. Nature transmits tensile forces rigidly with cohesive bonds, while dealing with compression forces usually through noncompressible hydraulics. The optimum design scaling approaches for aircraft were also reviewed for comparison with similitude laws. Finally, some historical evidence for the use of Weibull scaling in composites was reviewed.

  12. Living in cities, naturally.

    PubMed

    Hartig, Terry; Kahn, Peter H

    2016-05-20

    Natural features, settings, and processes in urban areas can help to reduce stress associated with urban life. In this and other ways, public health benefits from, street trees, green roofs, community gardens, parks and open spaces, and extensive connective pathways for walking and biking. Such urban design provisions can also yield ecological benefits, not only directly but also through the role they play in shaping attitudes toward the environment and environmental protection. Knowledge of the psychological benefits of nature experience supports efforts to better integrate nature into the architecture, infrastructure, and public spaces of urban areas.

  13. A New Fungal Diterpene Induces VDAC1-dependent Apoptosis in Bax/Bak-deficient Cells.

    PubMed

    Huang, Li; Han, Junjie; Ben-Hail, Danya; He, Luwei; Li, Baowei; Chen, Ziheng; Wang, Yueying; Yang, Yanlei; Liu, Lei; Zhu, Yushan; Shoshan-Barmatz, Varda; Liu, Hongwei; Chen, Quan

    2015-09-25

    The pro-apoptotic Bax and Bak proteins are considered central to apoptosis, yet apoptosis occurs in their absence. Here, we asked whether the mitochondrial protein VDAC1 mediates apoptosis independently of Bax/Bak. Upon screening a fungal secondary metabolite library for compounds inducing apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts, we identified cyathin-R, a new cyathane diterpenoid compound able to activate apoptosis in the absence of Bax/Bak via promotion of the VDAC1 oligomerization that mediates cytochrome c release. Diphenylamine-2-carboxilic acid, an inhibitor of VDAC1 conductance and oligomerization, inhibited cyathin-R-induced VDAC1 oligomerization and apoptosis. Similarly, Bcl-2 overexpression conferred resistance to cyathin-R-induced apoptosis and VDAC1 oligomerization. Silencing of VDAC1 expression prevented cyathin-R-induced apoptosis. Finally, cyathin-R effectively attenuated tumor growth and induced apoptosis in Bax/Bak-deficient cells implanted into a xenograft mouse model. Hence, this study identified a new compound promoting VDAC1-dependent apoptosis as a potential therapeutic option for cancerous cells lacking or presenting inactivated Bax/Bak. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Automatic natural language parsing

    SciTech Connect

    Sprack-Jones, K.; Wilks, Y.

    1985-01-01

    This collection of papers on automatic natural language parsing examines research and development in language processing over the past decade. It focuses on current trends toward a phrase structure grammar and deterministic parsing.

  15. Web life: Ask Nature

    NASA Astrophysics Data System (ADS)

    2012-11-01

    Ask Nature is a site devoted to biomimicry, an interdisciplinary field in which practitioners study how animals and plants solve problems, and then use those solutions to develop better human technologies.

  16. Is image steganography natural?

    PubMed

    Martín, Alvaro; Sapiro, Guillermo; Seroussi, Gadiel

    2005-12-01

    Steganography is the art of secret communication. Its purpose is to hide the presence of information, using, for example, images as covers. We experimentally investigate if stego-images, bearing a secret message, are statistically "natural." For this purpose, we use recent results on the statistics of natural images and investigate the effect of some popular steganography techniques. We found that these fundamental statistics of natural images are, in fact, generally altered by the hidden "nonnatural" information. Frequently, the change is consistently biased in a given direction. However, for the class of natural images considered, the change generally falls within the intrinsic variability of the statistics, and, thus, does not allow for reliable detection, unless knowledge of the data hiding process is taken into account. In the latter case, significant levels of detection are demonstrated.

  17. Parallels with nature

    NASA Astrophysics Data System (ADS)

    2014-10-01

    Adam Nelson and Stuart Warriner, from the University of Leeds, talk with Nature Chemistry about their work to develop viable synthetic strategies for preparing new chemical structures in parallel with the identification of desirable biological activity.

  18. Natural radioactivity. Proceedings

    SciTech Connect

    de Bettencourt, A.O.; Galvao, J.P.; Lowder, W.; Olast, M.; Sinnaeve, J.

    1988-12-31

    This volume provides the Proceedings of the Fourth International Symposium on the Natural Radiation Environment held in Lisbon, Portugal December 7--11, 1987. Individual papers of the symposium are abstracted and indexed for the database.

  19. Make a Nature Trail

    ERIC Educational Resources Information Center

    Johnson, Janice K.

    1973-01-01

    Discusses the planning, construction, use, and maintenance of a nature trail. Ideal for demonstrating interrelationships between plants and animals, conservation practices, wildlife management, plant succession, forestry, geologic features and other scientific phenomena. (JR)

  20. Make a Nature Trail

    ERIC Educational Resources Information Center

    Johnson, Janice K.

    1973-01-01

    Discusses the planning, construction, use, and maintenance of a nature trail. Ideal for demonstrating interrelationships between plants and animals, conservation practices, wildlife management, plant succession, forestry, geologic features and other scientific phenomena. (JR)

  1. Tifft Farm Nature Preserve.

    ERIC Educational Resources Information Center

    Benjamin, Thomas B.; Gannon, David J.

    1980-01-01

    Described are the creation, development, activities, and programs of Tifft Farm, a 264-acre nature preserve and environmental education center in Buffalo, New York, constructed on a sanitary landfill. (BT)

  2. The "Natural Law Tradition."

    ERIC Educational Resources Information Center

    Finnis, John

    1986-01-01

    A discussion of natural law outlines some of the theory and tradition surrounding it and examines its relationship to the social science and legal curriculum and to the teaching of jurisprudence. (MSE)

  3. Tifft Farm Nature Preserve.

    ERIC Educational Resources Information Center

    Benjamin, Thomas B.; Gannon, David J.

    1980-01-01

    Described are the creation, development, activities, and programs of Tifft Farm, a 264-acre nature preserve and environmental education center in Buffalo, New York, constructed on a sanitary landfill. (BT)

  4. Natural Language Sourcebook

    DTIC Science & Technology

    1990-01-01

    HyperCard Database for the Natural Language Sourcebook. Center for Technology Assessment , UCLA Center for the Study of Evaluation. Herl, H. September 1990...Designing a HyperCard Database for the Natural Language Sourcebook. Center for Technology Assessment , UCLA Center for the Study of Evaluation. DD...Patricia Mutch, Frances Butler, Alex Quilici, John Reeves Center for Technology Assessment UCLA Center for the Study of Evaluation - UCLA Computer

  5. Lesson "Balance in Nature

    NASA Astrophysics Data System (ADS)

    Chapanova, V.

    2012-04-01

    Lesson "Balance in Nature" This simulation game-lesson (Balance in Nature) gives an opportunity for the students to show creativity, work independently, and to create models and ideas. It creates future-oriented thought connected to their experience, allowing them to propose solutions for global problems and personal responsibility for their activities. The class is divided in two teams. Each team chooses questions. 1. Question: Pollution in the environment. 2. Question: Care for nature and climate. The teams work on the chosen tasks. They make drafts, notes and formulate their solutions on small pieces of paper, explaining the impact on nature and society. They express their points of view using many different opinions. This generates alternative thoughts and results in creative solutions. With the new knowledge and positive behaviour defined, everybody realizes that they can do something positive towards nature and climate problems and the importance of individuals for solving global problems is evident. Our main goal is to recover the ecological balance, and everybody explains his or her own well-grounded opinions. In this work process the students obtain knowledge, skills and more responsible behaviour. This process, based on his or her own experience, dialogue and teamwork, helps the participant's self-development. Making the model "human↔ nature" expresses how human activities impact the natural Earth and how these impacts in turn affect society. Taking personal responsibility, we can reduce global warming and help the Earth. By helping nature we help ourselves. Teacher: Veselina Boycheva-Chapanova " Saint Patriarch Evtimii" Scholl Str. "Ivan Vazov"-19 Plovdiv Bulgaria

  6. Natural Object Categorization.

    DTIC Science & Technology

    1987-11-01

    of leaves and is found to be sensitive to the structure of the natural categories corresponding to the different species . We next develop a...categories are recovered; by means of recursively invoking the categorization procedure both the genera and species are recovered in population of...function is tested in the domain of leaves and is found to be sensitive to the structure of the natural categories corresponding to the different species . We

  7. [Natural toxin poisoning].

    PubMed

    Tsunematsu, Satoshi

    2012-08-01

    Natural toxin poisoning often occurs when amateur who has no expert knowledge of food collects and cooks the wrong material. In many cases, the symptoms of natural toxin poisoning are mild and the patients recover from illness within a day. However, if the patients have respiratory or neurological symptoms after several hours of intake, the patients must go to hospital immediately. Mushroom poisoning is often reported and puffer fish poisoning is sometimes reported in Japan.

  8. Nature's ups and downs

    NASA Astrophysics Data System (ADS)

    Rodgers, Peter

    2015-12-01

    When Norman Lockyer, an astronomer and science writer with a day job as a clerk at the War Office in London, approached the publishing house Macmillan and Company in 1869 with a proposal for a new weekly journal about science, few could have predicted the outcome. The journal in question was Nature, and given its influence over the past 146 years, it is hard to believe that Melinda Baldwin's Making Nature is the first full-length book to be written about it.

  9. Induction of the mitochondria-mediated apoptosis in human esophageal cancer cells by DS2, a newly synthetic diterpenoid analog, is regulated by Bax and caused by generation of reactive oxygen species

    PubMed Central

    Zi, Xiaolin; Zhao, Fei; Yuan, Lin; Zhu, Ying-Li; Fan, Xia-Xia; Zhao, Ning-Min; Li, Qiao-Yan; Qin, Yu-Hua; Liu, Hong-Min

    2016-01-01

    Ent-kaurane diterpene compounds have attracted considerable attention in recent years due to its antitumor, antibacterial, and antiviral activities. However, the clinical development of natural kaurane diterpenes, for example, oridonin for cancer therapy has been hampered by its relatively moderate potency, limited bioavailability. Herein, we report a newly synthetic analog of natural ent-kaurane diterpene, DS2, which exhibits significantly improved activity of antiproliferation against various cancer cell lines relative to oridonin. DS2 treatment triggers the mitochondria-mediated apoptosis and cell cycle arrest in human esophageal cancer cell lines (EC9706, EC109). Interestingly, normal human esophageal epithelial cells (HEECs) and normal human liver cells (HL-7702) are both significantly more resistant to the growth inhibition by DS2 compared with esophageal cancer cells. The DS2-induced apoptosis in EC9706 cells correlated with the drop of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol and activation of caspase-9 and -3. The induction of proapoptotic proteins p21 and Bax were also observed in DS2-treated cells. The DS2-induced apoptosis was significantly attenuated by knockdown of Bax proteins. Meanwhile, the DS2 treatment caused generation of reactive oxygen species (ROS) in human esophageal cancer cells, but not in HEECs, which was attenuated by pretreatment with ROS scavenger N-acetylcysteine (NAC). More interestingly, the antioxidants pretreatment completely attenuated DS2 mediated loss of the MMP and apoptosis, as well as Bax expression and growth inhibition. In conclusion, the present study reveals that the mitochondria-mediated cell death by DS2 is associated with Bax regulation and ROS generation, and understanding the function and mechanism of DS2 will help us to design better anti-cancer drugs. PMID:27863415

  10. Induction of the mitochondria-mediated apoptosis in human esophageal cancer cells by DS2, a newly synthetic diterpenoid analog, is regulated by Bax and caused by generation of reactive oxygen species.

    PubMed

    Ma, Yong-Cheng; Ke, Yu; Zi, Xiaolin; Zhao, Fei; Yuan, Lin; Zhu, Ying-Li; Fan, Xia-Xia; Zhao, Ning-Min; Li, Qiao-Yan; Qin, Yu-Hua; Liu, Hong-Min

    2016-12-27

    Ent-kaurane diterpene compounds have attracted considerable attention in recent years due to its antitumor, antibacterial, and antiviral activities. However, the clinical development of natural kaurane diterpenes, for example, oridonin for cancer therapy has been hampered by its relatively moderate potency, limited bioavailability. Herein, we report a newly synthetic analog of natural ent-kaurane diterpene, DS2, which exhibits significantly improved activity of antiproliferation against various cancer cell lines relative to oridonin. DS2 treatment triggers the mitochondria-mediated apoptosis and cell cycle arrest in human esophageal cancer cell lines (EC9706, EC109). Interestingly, normal human esophageal epithelial cells (HEECs) and normal human liver cells (HL-7702) are both significantly more resistant to the growth inhibition by DS2 compared with esophageal cancer cells. The DS2-induced apoptosis in EC9706 cells correlated with the drop of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol and activation of caspase-9 and -3. The induction of proapoptotic proteins p21 and Bax were also observed in DS2-treated cells. The DS2-induced apoptosis was significantly attenuated by knockdown of Bax proteins. Meanwhile, the DS2 treatment caused generation of reactive oxygen species (ROS) in human esophageal cancer cells, but not in HEECs, which was attenuated by pretreatment with ROS scavenger N-acetylcysteine (NAC). More interestingly, the antioxidants pretreatment completely attenuated DS2 mediated loss of the MMP and apoptosis, as well as Bax expression and growth inhibition. In conclusion, the present study reveals that the mitochondria-mediated cell death by DS2 is associated with Bax regulation and ROS generation, and understanding the function and mechanism of DS2 will help us to design better anti-cancer drugs.

  11. Natural Resource Management Plan

    SciTech Connect

    Green, T.; Schwager, K.

    2016-10-01

    This comprehensive Natural Resource Management Plan (NRMP) for Brookhaven National Laboratory (BNL) was built on the successful foundation of the Wildlife Management Plan for BNL, which it replaces. This update to the 2003 plan continues to build on successes and efforts to better understand the ecosystems and natural resources found on the BNL site. The plan establishes the basis for managing the varied natural resources located on the 5,265-acre BNL site, setting goals and actions to achieve those goals. The planning of this document is based on the knowledge and expertise gained over the past 15 years by the Natural Resources management staff at BNL in concert with local natural resource agencies including the New York State Department of Environmental Conservation, Long Island Pine Barrens Joint Planning and Policy Commission, The Nature Conservancy, and others. The development of this plan works toward sound ecological management that not only benefits BNL’s ecosystems but also benefits the greater Pine Barrens habitats in which BNL is situated. This plan applies equally to the Upton Ecological and Research Reserve (Upton Reserve). Any difference in management between the larger BNL area and the Upton Reserve are noted in the text.

  12. Blackouts and natural risks

    NASA Astrophysics Data System (ADS)

    Danihelka, P.; Paldusová, E.; Dobeš, P.

    2009-04-01

    "Blackout" has become the common definition for the situation when electricity supply and demand are not balanced and security of supply fails. These failures have many impacts besides the lights going out, but this term is used commonly. Blackouts have drastic impacts for the society on whole and its citizens and some of them can influence big areas and last for long period, so the consequences are catastrophic. Even if at the European scale, the large extend blackouts are supposed to be exceptional, real frequency is relatively high, approximately once per two years. According to statistics, blackouts are often caused by natural causes, especially lightning. An example of lightning caused blackout is New York blackout 1977, leading to the stand-by of nuclear power plant Indian Point and with overall cost more than 300 mil. USD. There is a clear a distinction between those blackouts caused by nature and those that were caused by other faults. Usually, the nature-caused disturbances as Canada 1988, Sweden 2005 and France 1999, stay inside one country. However, their duration can extend to several weeks, and thus the costs of the interruptions and social impacts are high. Blackouts of only technologic and/or anthropogenic origin are frequently shorter, but may concern more end-users, when cascading from one country to another. Lightning is not the only natural event causing blackouts. Eighteen various case studies of blackout caused by natural events different then lightning were studied and following natural phenomenon found as a root causes: 1x forest fire, 1x snow calamity, 1x ice storm, 1x landslide, 1x high temperature, 1x geomagnetic storm, 2x earthquake, 2x inundation, 2x contact of line with trees, 6x storm (wind, hurricane…). We can conclude, that natural event are frequent cause of blackout of medium or large extend and this phenomena should be studied more in details. This contribution was supported by Ministry of Environment of the Czech Republic.

  13. Natural Dietary Phytosterols.

    PubMed

    Racette, Susan B; Lin, Xiaobo; Ma, Lina; Ostlund, Richard E

    2015-01-01

    Most clinical phytosterol studies are performed by adding purified supplements to smaller phytosterol amounts present in the natural diet. However, natural dietary phytosterols themselves may also have important effects on cholesterol metabolism. Epidemiological work using food frequency questionnaires to estimate dietary intake suggest that extremes of normal consumption may be associated with 3-14% changes in LDL cholesterol. Standardized food databases do not have enough phytosterol values to allow calculation of phytosterol intake for individuals outside of specialized studies. Natural diets contain phytosterol amounts ranging from less than 60 mg/2000 kcal to over 500 mg/2000 kcal. Physiological studies in which whole body cholesterol metabolism is investigated show large effects of natural dietary phytosterols on cholesterol absorption efficiency, cholesterol biosynthesis and cholesterol excretion which exceed the magnitude of changes in LDL cholesterol. The dual effects of natural phytosterols on both LDL-C and whole body cholesterol metabolism need to be considered in relating them to potential protection from coronary heart disease risk.

  14. Natural flow wing

    NASA Technical Reports Server (NTRS)

    Wood, Richard M. (Inventor); Bauer, Steven X. S. (Inventor)

    1992-01-01

    The invention is a natural flow wing and a method for constructing the same. The method comprises contouring a three-dimensional upper surface and a three-dimensional lower surface of the natural flow wing independently of one another into a prescribed shape. Experimental data and theoretical analysis show that flow and pressure-loading over an upper surface of a wing tend to be conical about an apex of the wing, producing favorable and unfavorable regions of performance based on drag. The method reduces these unfavorable regions by shaping the upper surface such that the maximum thickness near a tip of the natural flow wing moves aft, thereby, contouring the wing to coincide more closely with the conical nature of the flow on the upper surface. Nearly constant compressive loading characterizes the flow field over a lower surface of the conventional wing. Magnitude of these compressive pressures on the lower surface depends on angle of attack and on a streamwise curvature of the lower surface of the wing and not on a cross-sectional spanwise curvature. The method, thereby, shapes the lower surface to create an area as large as possible with negative slopes. Any type of swept wing may be used to obtain the final, shaped geometry of the upper and lower surfaces of the natural flow wing.

  15. Natural competence for transformation.

    PubMed

    Blokesch, Melanie

    2016-11-07

    While most molecular biologists are familiar with the artificial transformation of bacteria in the context of laboratory cloning experiments, natural competence for transformation refers to a specific physiological state in which prokaryotes are able to take up genetic material from their surroundings. Occasionally, such absorbed DNA is recombined into the organism's own genome, resulting in natural transformation (Figure 1). As a consequence, natural competence for transformation is considered a primary mode of horizontal gene transfer (HGT) in prokaryotes, together with conjugation (direct cell to cell transfer of DNA via a specialized conjugal pilus) and phage transduction (DNA transfer mediated by viruses). HGT plays a major role in bacterial evolution, and past research has demonstrated that HGT, including natural competence for transformation, contributes to the emergence of pathogens and the spread of virulence factors. Indeed, Frederick Griffith discovered natural competence for transformation in 1928 while he was investigating the exchange of pathogenic traits in pneumococci. Due to the increase in the abundance and spread of multidrug-resistant microbes, research on HGT is even more important today than ever before.

  16. Nature/culture/seawater.

    PubMed

    Helmreich, Stefan

    2011-01-01

    Seawater has occupied an ambiguous place in anthropological categories of "nature" and "culture." Seawater as nature appears as potentiality of form and uncontainable flux; it moves faster than culture - with culture frequently figured through land-based metaphors - even as culture seeks to channel water's (nature's) flow. Seawater as culture manifests as a medium of pleasure, sustenance, travel, disaster. I argue that, although seawater's qualities in early anthropology were portrayed impressionistically, today technical, scientific descriptions of water's form prevail. For example, processes of globalization - which may also be called "oceanization" - are often described as "currents," "flows," and "circulations." Examining sea-set ethnography, maritime anthropologies, and contemporary social theory, I propose that seawater has operated as a “theory machine” for generating insights about human cultural organization. I develop this argument with ethnography from the Sargasso Sea and in the Sea Islands. I conclude with a critique of appeals to water's form in social theory.

  17. Natural photonic crystals

    NASA Astrophysics Data System (ADS)

    Vigneron, Jean Pol; Simonis, Priscilla

    2012-10-01

    Photonic structures appeared in nature several hundred millions years ago. In the living world, color is used for communication and this important function strongly impacts the individual chances of survival as well as the chances to reproduce. This has a statistical influence on species populations. Therefore, because they are involved in evolution, natural color-generating structures are - from some point of view - highly optimized. In this short review, a survey is presented of the development of natural photonic crystal-type structures occurring in insects, spiders, birds, fishes and other marine animals, in plants and more, from the standpoint of light-waves propagation. One-, two-, and three-dimensional structures will be reviewed with selected examples.

  18. Natural Cycles, Gases

    NASA Technical Reports Server (NTRS)

    Douglass, Anne R.; Jackman, Charles H.; Rood, R. B.; Aikin, A. C.; Stolarski, R. S.; Mccormick, M. P.; Fahey, David W.

    1992-01-01

    The major gaseous components of the exhaust of stratospheric aircraft are expected to be the products of combustion (CO2 and H2O), odd nitrogen (NO, NO2 HNO3), and products indicating combustion inefficiencies (CO and total unburned hydrocarbons). The species distributions are produced by a balance of photochemical and transport processes. A necessary element in evaluating the impact of aircraft exhaust on the lower stratospheric composition is to place the aircraft emissions in perspective within the natural cycles of stratospheric species. Following are a description of mass transport in the lower stratosphere and a discussion of the natural behavior of the major gaseous components of the stratospheric aircraft exhaust.

  19. Natural language modeling

    SciTech Connect

    Sharp, J.K.

    1997-11-01

    This seminar describes a process and methodology that uses structured natural language to enable the construction of precise information requirements directly from users, experts, and managers. The main focus of this natural language approach is to create the precise information requirements and to do it in such a way that the business and technical experts are fully accountable for the results. These requirements can then be implemented using appropriate tools and technology. This requirement set is also a universal learning tool because it has all of the knowledge that is needed to understand a particular process (e.g., expense vouchers, project management, budget reviews, tax, laws, machine function).

  20. Natural environment analysis

    NASA Technical Reports Server (NTRS)

    Frost, W.

    1985-01-01

    The influence of terrain features on wind loading of the space shuttle while on the launch pad, or during early liftoff, was investigated both qualitatively and quantitatively. The climatology and meteorology producing macroscale wind patterns and characteristics for the Vandenburg Air Force Base launch site are described. Field test data are analyzed, and the nature and characteristic of flow disturbances due to the various terrain features, both natural and man-made, are reviewed. The magnitude of these wind loads are estimated. Finally, effects of turbulence are discussed. It is concluded that the influence of complex terrain can create significant wind loading on the vehicle.

  1. Enhance Nature Exploration with Technology

    ERIC Educational Resources Information Center

    Holloway, Patricia; Mahan, Carol

    2012-01-01

    Kids and nature seem like a natural combination, but what was natural a generation ago is different today. Children are spending less time outdoors but continue to need nature for their physical, emotional, and mental development. This fact has led author Richard Louv to suggest that today's children are suffering from "nature-deficit disorder"…

  2. Enhance Nature Exploration with Technology

    ERIC Educational Resources Information Center

    Holloway, Patricia; Mahan, Carol

    2012-01-01

    Kids and nature seem like a natural combination, but what was natural a generation ago is different today. Children are spending less time outdoors but continue to need nature for their physical, emotional, and mental development. This fact has led author Richard Louv to suggest that today's children are suffering from "nature-deficit disorder"…

  3. Nature in the City.

    ERIC Educational Resources Information Center

    Melber, Leah W.

    2000-01-01

    Presents three science activities targeted to help urban students learn about nature: (1) observing coloration patterns of pigeons; (2) measuring local rainfall and comparing it to other areas; and (3) conducting a biodiversity study by observing a patch of lawn. (YDS)

  4. Natural disturbance production functions

    Treesearch

    Jeffrey P. Prestemon; D. Evan Mercer; John M. Pye

    2008-01-01

    Natural disturbances in forests are driven by physical and biological processes. Large, landscape scale disturbances derive primarily from weather (droughts, winds, ice storms, and floods), geophysical activities (earthquakes, volcanic eruptions), fires, insects, and diseases. Humans have invented ways to minimize their negative impacts and reduce their rates of...

  5. New force in nature

    SciTech Connect

    Fischbach, E.; Sudarsky, D.; Szafer, A.; Talmadge, C.; Aronson, S.H.

    1986-10-15

    We review recent experimental and theoretical work dealing with the proposed fifth force. Further analysis of the original Eoetvoes experiments has uncovered no challenges to our original assertion that these data evidence a correlation characteristic of the presence of a new coupling to baryon number or hypercharge. Various models suggest that the proposed fifth force could be accomodated naturally into the existing theoretical framework.

  6. Nature as Inspiration

    ERIC Educational Resources Information Center

    Tank, Kristina; Moore, Tamara; Strnat, Meg

    2015-01-01

    This article describes the final lesson within a seven-day STEM and literacy unit that is part of the Picture STEM curriculum (pictureSTEM. org) and uses engineering to integrate science and mathematics learning in a meaningful way (Tank and Moore 2013). For this engineering challenge, students used nature as a source of inspiration for designs to…

  7. Demystifying Nature of Science

    ERIC Educational Resources Information Center

    Lederman, Judith; Bartels, Selina; Lederman, Norman; Gnanakkan, Dionysius

    2014-01-01

    With the emergence of the "Next Generation Science Standards" ("NGSS"; NGSS Lead States 2013), it is apparent that teaching and learning about nature of science (NOS) continues to be an important goal of science education for all K-12 students. With this emphasis on NOS, early childhood teachers are asking how to design…

  8. A Biospheric Natural History.

    ERIC Educational Resources Information Center

    Thomashow, Mitchell

    2001-01-01

    A group of Maine birdwatchers recognizes that the presence or absence of migrating songbirds is related to complex biospheric patterns. For schoolchildren, community groups, and environmental scientists, such local natural history observations can be a pathway to perceiving and understanding global ecological change and then to developing…

  9. Radioactivity: A Natural Phenomenon.

    ERIC Educational Resources Information Center

    Ronneau, C.

    1990-01-01

    Discussed is misinformation people have on the subject of radiation. The importance of comparing artificial source levels of radiation to natural levels is emphasized. Measurements of radioactivity, its consequences, and comparisons between the risks induced by radiation in the environment and from artificial sources are included. (KR)

  10. Natural generalized mirage mediation

    NASA Astrophysics Data System (ADS)

    Baer, Howard; Barger, Vernon; Serce, Hasan; Tata, Xerxes

    2016-12-01

    In the supersymmetric scenario known as mirage mediation (MM), the soft supersymmetry (SUSY) breaking terms receive comparable anomaly-mediation and moduli-mediation contributions leading to the phenomenon of mirage unification. The simplest MM SUSY breaking models which are consistent with the measured Higgs mass and sparticle mass constraints are strongly disfavored by fine-tuning considerations. However, while MM makes robust predictions for gaugino masses, the scalar sector is quite sensitive to specific mechanisms for moduli stabilization and potential uplifting. We suggest here a broader setup of generalized mirage mediation (GMM), where heretofore discrete parameters are allowed as continuous to better parametrize these other schemes. We find that natural SUSY spectra consistent with both the measured value of mh as well as LHC lower bounds on superpartner masses are then possible. We explicitly show that models generated from natural GMM may be beyond the reach of even high-luminosity LHC searches. In such a case, the proposed International Linear e+e- Collider will be required for natural SUSY discovery via higgsino pair production reactions. We also outline prospects for detection of higgsino-like WIMPs from natural GMM.

  11. Natural fracture systems studies

    SciTech Connect

    Lorenz, J.C.; Warpinski, N.R.

    1992-09-01

    The objectives of this program are (1) to develop a basinal-analysis methodology for natural fracture exploration and exploitation, and (2) to determine the important characteristics of natural fracture systems for use in completion, stimulation, and production operations. Natural-fracture basinal analysis begins with studies of fractures in outcrop, core and logs in order to determine the type of fracturing and the relationship of the fractures to the lithologic environment. Of particular interest are the regional fracture systems that are pervasive in western US tight sand basins. A Methodology for applying this analysis is being developed, with the goal of providing a structure for rationally characterizing natural fracture systems basin-wide. Such basin-wide characterizations can then be expanded and supplemented locally, at sites where production may be favorable. Initial application of this analysis is to the Piceance basin where there is a wealth of data from the Multiwell Experiment (MWX), DOE cooperative wells, and other basin studies conducted by Sandia, CER Corporation, and the USGS (Lorenz and Finley, 1989, Lorenz et aI., 1989, and Spencer and Keighin, 1984). Such a basinal approach has been capable of explaining the fracture characteristics found throughout the southern part of the Piceance basin and along the Grand Hogback.

  12. Nature's engines: active matter

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    2017-03-01

    Active materials, bacteria, molecular motors, and self-propelled colloids, continuously transform chemical energy from the environment to mechanical work. Dense active matter, from layers of cells to flocks of birds, self-assembles into intricate patterns. Nature's engines are complex and efficient, and we would like to exploit her ideas to fabricate nano-machines.

  13. Natural Language Generation,

    DTIC Science & Technology

    1986-02-01

    modified with adverbs or adjectives, or elaborated by subordinated clauses. The natural recourse in this situation is to use a phrasal lexicon. This notion...Representation of Grammatical Relations, MIT Press, Cambridge, Mass., 1984. 171 G. Brown, Some Problems in German to English Machine Translation, MIT LCS TR 142

  14. Drawing Closer to Nature

    ERIC Educational Resources Information Center

    London, Peter

    2004-01-01

    This article discusses how drawing closer to nature, two profoundly important and powerful qualities are experienced. First, the entire world takes on a new degree of poignancy, luminosity, preciousness, subtlety, mystery, and intimacy. Second, the author points out how we increasingly experience ourselves in just the same way: poignant, luminous,…

  15. Picturing the Natural World

    ERIC Educational Resources Information Center

    Salia, Hannah

    2011-01-01

    How is the natural environment in the neighborhood representative of the larger biosphere in which people live? Studying the local birds and flora of the Pacific Northwest in the context of the local parks and ponds provided a rich opportunity for third-grade students at St. Thomas School in Medina, Washington, to explore and learn about…

  16. A Natural Hazards Workbook.

    ERIC Educational Resources Information Center

    Kohler, Fred

    This paper discusses the development of and provides examples of exercises from a student workbook for a college-level course about natural hazards. The course is offered once a year to undergraduates at Western Illinois University. Students are introduced to 10 hazards (eight meteorological plus earthquakes and volcanoes) through slides, movies,…

  17. The Nature of Evolution

    ERIC Educational Resources Information Center

    Alles, David L.

    2005-01-01

    The nature of evolution, the historical change in the universe, and the change that is caused by the workings of the dynamic processes at the smallest and largest scales are studied. It is viewed that the cumulative change in the historical systems is caused by evolution, which is a type of causal relationship and evolutionary processes could be…

  18. The Natural Learning Process

    ERIC Educational Resources Information Center

    Criss, Ellen

    2008-01-01

    Teacher-educator and researcher Daniel L. Kohut suggests in "Musical Performance: Learning Theory and Pedagogy" that there are many problems that result from the way music teachers often teach. Most teachers focus on the process, not the goal. The Natural Learning Process that Kohut advocates is the same process that young children use when they…

  19. Saving Natural Areas.

    ERIC Educational Resources Information Center

    Buchinger, Maria

    This manual serves as a handbook for those involved in the art of land saving. The various topics in the booklet are dealt with in great detail since little has been published on the preservation of natural areas in international publications. Most of the document is derived from articles, books, and publications published by, or describing the…

  20. Natural Resources Education Notebook.

    ERIC Educational Resources Information Center

    Weber, Eldon C.

    This notebook was developed cooperatively by the United States Soil Conservation Service and Iowa State University to be used by teachers in providing instruction regarding certain aspects of natural resources. It includes four sections which provide: (1) an instructional plan about the conservation provisions of the 1985 Food Security Act; (2) an…

  1. Natural disasters in Australia.

    PubMed

    Leivesley, S

    1984-06-01

    The history of natural hazards in Australia and their physical, economic and social consequences are discussed in this paper. The lack of any national programme for hazard mitigation is identified, alongside an overview of Australia as a country where major disasters are accepted as a part of everyday life.

  2. Reinventing Natural Selection

    ERIC Educational Resources Information Center

    Geraedts, Caspar L.; Boersma, Kerst Th.

    2006-01-01

    Although many research studies report students' Lamarckian misconceptions, only a few studies present learning and teaching strategies that focus on the successful development of the concept of natural selection. The learning and teaching strategy for upper secondary students (aged 15-16) presented in this study conducted in The Netherlands is…

  3. Natural Language Generation

    DTIC Science & Technology

    1992-12-01

    34 "* Generalization of the Work to Multiple Media ................................ 48 "* Toward Multimodal Presentation Planning...support human-computer interactions of the most powerful kind: using human language and additional media , as natural and appropriate. The work presented in...within normal English texts. The study involved 3ome hundreds of paragraphs (ranging over advertisements , scientific articles, letters, newspaper texts

  4. Picturing the Natural World

    ERIC Educational Resources Information Center

    Salia, Hannah

    2011-01-01

    How is the natural environment in the neighborhood representative of the larger biosphere in which people live? Studying the local birds and flora of the Pacific Northwest in the context of the local parks and ponds provided a rich opportunity for third-grade students at St. Thomas School in Medina, Washington, to explore and learn about…

  5. Fertilizing natural stands

    Treesearch

    L. R. Auchmoody

    1989-01-01

    Given our present knowledge, and under current costs and returns, there appears to be little reason to fertilize natural stands of central hardwoods. Yet, some of the numerous fertilizer tests conducted with hardwoods over the past 50 years have shown very positive--but short-lived-growth responses. One "operational" (nonexperimental) use of nitrogen and...

  6. Nitrogen and nature.

    PubMed

    Vitousek, Peter M; Hättenschwiler, Stephan; Olander, Lydia; Allison, Steven

    2002-03-01

    Anthropogenic changes to the global N cycle are important in part because added N alters the composition, productivity, and other properties of many natural ecosystems substantially. Why does added N have such a large impact? Why is N in short supply in so many natural ecosystems? Processes that slow the cycling of N relative to other elements and processes that control ecosystem-level inputs and outputs of N could cause N supply to limit the dynamics of ecosystems. We discuss stoichiometric differences between terrestrial plants and other organisms, the abundance of protein-precipitating plant defenses, and the nature of the C-N bond in soil organic matter as factors that can slow N cycling. For inputs, the energetic costs of N fixation and their consequences, the supply of nutrients other than N, and preferential grazing on N-fixers all could constrain the abundance and/or activity of biological N-fixers. Together these processes drive and sustain N limitation in many natural terrestrial ecosystems.

  7. Nature, Education and Things

    ERIC Educational Resources Information Center

    Rømer, Thomas Aastrup

    2013-01-01

    In this essay it is argued that the educational philosophy of John Dewey gains in depth and importance by being related to his philosophy of nature, his metaphysics. The result is that any experiental process is situated inside an event, an existence, a thing, and I try to interpret this "thing" as schools or major cultural events such…

  8. Picturing the Natural Environment

    ERIC Educational Resources Information Center

    Johnson, Phyllis Scott

    2011-01-01

    Around Scout Island Education Center, a site used by schools in Fresno County to explore the area's natural environment, a total of 200 cylinder-shaped concrete stools display tiles representing small mammals, flying insects, birds, wildflowers, and more. Twenty sets have been created by elementary, middle, and high-school art students as part of…

  9. Natural Resources Management Program

    DTIC Science & Technology

    1989-01-24

    Program, activity, or opportunity dependent on the natural environment. Examples are hunting, fishing, trapping, picnick- ing, birdwatching , off-road...fair market value. d. Planned forest products sales shall continue on land reported as excess until actual disposal or transfer occurs. When forested

  10. Nature, Education and Things

    ERIC Educational Resources Information Center

    Rømer, Thomas Aastrup

    2013-01-01

    In this essay it is argued that the educational philosophy of John Dewey gains in depth and importance by being related to his philosophy of nature, his metaphysics. The result is that any experiental process is situated inside an event, an existence, a thing, and I try to interpret this "thing" as schools or major cultural events such…

  11. Nature Conservation in Bophuthatswana.

    ERIC Educational Resources Information Center

    Motaung, Maria

    1992-01-01

    This presentation to the International Girl Guides Jamboree, July 1991, addressed the issue of nature conservation and the role of the National Parks and Wildlife Management Board of Bophuthatswana in creating parks and conserving wildlife. Describes three national parks and the boards' achievements in preserving wildlife. (MDH)

  12. The Nature of Atoms.

    ERIC Educational Resources Information Center

    Holden, Alan

    This monograph was written for the purpose of presenting physics to college students who are not preparing for careers in physics. It deals with the nature of atoms, and treats the following topics: (1) the atomic hypothesis, (2) the chemical elements, (3) models of an atom, (4) a particle in a one-dimensional well, (5) a particle in a central…

  13. A Natural Integration

    ERIC Educational Resources Information Center

    Coskie, Tracy; Hornof, Michelle; Trudel, Heidi

    2007-01-01

    A five-week study taught students how to write a field guide that identified the plants in a small wooded area they passed through on their way to their school playground. By creating this authentic genre of science writing, students came to understand and care for the natural world in their immediate environment. They also developed important…

  14. Connecting Latinos with nature

    Treesearch

    Deborah J. Chavez

    2008-01-01

    Experts around the world have identified ecosystem services that benefit humans. Ecosystem services provided by natural areas include cultural (such as providing outdoor recreation locations) and regulating (such as protecting water quality) services. It is important to understand both public perceptions about the importance of particular ecosystem services and the...

  15. Designing Nature's Way

    ERIC Educational Resources Information Center

    Fisher, Diane

    2005-01-01

    In the case of cars and other engineered objects, humans go about the design process in a very intentional way. They pretty much know what they are aiming for. The activity described in this article demonstrates how a computer can simulate biological evolution and the laws of natural selection. The article is divided into the following sections:…

  16. Regenerating Longleaf Pine Naturally

    Treesearch

    Thomas C. Croker; William D. Boyer

    1975-01-01

    Research has developed guides for consistent natural regeneration of longleaf pine by a shelterwood system. Key measures include hardwood control by fire and other means, timely preparatory and seed cuts, seed crop monitoring, seedbed preparation, protection of established seedlings, prompt removal of parent trees when reproduction is adequate, and control of...

  17. Designing Nature's Way

    ERIC Educational Resources Information Center

    Fisher, Diane

    2005-01-01

    In the case of cars and other engineered objects, humans go about the design process in a very intentional way. They pretty much know what they are aiming for. The activity described in this article demonstrates how a computer can simulate biological evolution and the laws of natural selection. The article is divided into the following sections:…

  18. Gaia and natural selection

    NASA Astrophysics Data System (ADS)

    Lenton, Timothy M.

    1998-07-01

    Evidence indicates that the Earth self-regulates at a state that is tolerated by life, but why should the organisms that leave the most descendants be the ones that contribute to regulating their planetary environment? The evolving Gaia theory focuses on the feedback mechanisms, stemming from naturally selected traits of organisms, that could generate such self-regulation.

  19. Nature Conservation in Bophuthatswana.

    ERIC Educational Resources Information Center

    Motaung, Maria

    1992-01-01

    This presentation to the International Girl Guides Jamboree, July 1991, addressed the issue of nature conservation and the role of the National Parks and Wildlife Management Board of Bophuthatswana in creating parks and conserving wildlife. Describes three national parks and the boards' achievements in preserving wildlife. (MDH)

  20. The Nature of Diamonds

    NASA Astrophysics Data System (ADS)

    Harlow, George E.

    1997-10-01

    The paragon of physical perfection and a sparkling example of Earth's forces at work, the diamond has fascinated all realms of society, from starlets to scientists. The Nature of Diamonds is a comprehensive look at nature's most coveted gem. A handsome, large-format book, The Nature of Diamonds is an authoritative and richly-illustrated tribute to the diamond. Leading geologists, gemologists, physicists, and cultural observers cover every facet of the stone, from its formation in the depths of the Earth, its ascent to the surface, and its economic, regal, social, and technological roles. Cutting-edge research takes the reader to the frontiers of diamond exploration and exploitation, from the Arctic wastes to the laboratories where diamonds are created for massive road shredders that rip up and then re-create superhighways. Here also is an overview of cutting, from the rough stones in Roman rings to the highly-faceted stones we see today, and a glimpse into the business of diamonds. Finally, The Nature of Diamonds chronicles scientific and cultural history and explores the diamond as both a sacred and a social symbol, including a picture history of betrothal rings. Wide-ranging illustrations explain the geology of diamonds, chart the history of mining from its origins in India and Brazil through the diamond rush in South Africa and today's high-tech enterprises, and capture the brilliance and beauty of this extraordinary gem. _

  1. Natural vegetation inventory

    NASA Technical Reports Server (NTRS)

    Schrumpf, B. J.

    1973-01-01

    Unique characteristics of ERTS imagery can be used to inventory natural vegetation. While satellite images can seldom be interpreted and identified directly in terms of vegetation types, such types can be inferred by interpretation of physical terrain features and through an understanding of the ecology of the vegetation.

  2. The Nature of Evolution

    ERIC Educational Resources Information Center

    Alles, David L.

    2005-01-01

    The nature of evolution, the historical change in the universe, and the change that is caused by the workings of the dynamic processes at the smallest and largest scales are studied. It is viewed that the cumulative change in the historical systems is caused by evolution, which is a type of causal relationship and evolutionary processes could be…

  3. Explaining Immigrant Naturalization.

    ERIC Educational Resources Information Center

    Yang, Philip Q.

    1994-01-01

    Proposes a broad analytical framework in the study of immigrant naturalization that incorporates an immigrant's individual characteristics with the larger social contexts in the country of origin and the country of destination to explain the likelihood of citizenship acquisition. Results testing of this framework show that such considerations are…

  4. Radioactivity: A Natural Phenomenon.

    ERIC Educational Resources Information Center

    Ronneau, C.

    1990-01-01

    Discussed is misinformation people have on the subject of radiation. The importance of comparing artificial source levels of radiation to natural levels is emphasized. Measurements of radioactivity, its consequences, and comparisons between the risks induced by radiation in the environment and from artificial sources are included. (KR)

  5. Demystifying Nature of Science

    ERIC Educational Resources Information Center

    Lederman, Judith; Bartels, Selina; Lederman, Norman; Gnanakkan, Dionysius

    2014-01-01

    With the emergence of the "Next Generation Science Standards" ("NGSS"; NGSS Lead States 2013), it is apparent that teaching and learning about nature of science (NOS) continues to be an important goal of science education for all K-12 students. With this emphasis on NOS, early childhood teachers are asking how to design…

  6. Nature as Inspiration

    ERIC Educational Resources Information Center

    Tank, Kristina; Moore, Tamara; Strnat, Meg

    2015-01-01

    This article describes the final lesson within a seven-day STEM and literacy unit that is part of the Picture STEM curriculum (pictureSTEM. org) and uses engineering to integrate science and mathematics learning in a meaningful way (Tank and Moore 2013). For this engineering challenge, students used nature as a source of inspiration for designs to…

  7. Rehabilitating Afghanistan's natural resources

    Treesearch

    George Hernandez

    2011-01-01

    The Soviet Union invaded Afghanistan in late 1979. During the next 23 years, the war between the Mujahideen Resistance and the Soviet forces, the ensuing civil war, and eventual take over by the Taliban caused enormous harm to the natural resources of Afghanistan. In 2003, the USDA Forest Service (USFS) was asked by the USDA Foreign Agricultural Service to provide...

  8. The Natural Learning Process

    ERIC Educational Resources Information Center

    Criss, Ellen

    2008-01-01

    Teacher-educator and researcher Daniel L. Kohut suggests in "Musical Performance: Learning Theory and Pedagogy" that there are many problems that result from the way music teachers often teach. Most teachers focus on the process, not the goal. The Natural Learning Process that Kohut advocates is the same process that young children use when they…

  9. Saving Natural Inflation

    SciTech Connect

    Croon, Djuna; Sanz, Verónica E-mail: v.sanz@sussex.ac.uk

    2015-02-01

    Slow-roll inflation requires the inflaton field to have an exceptionally flat potential, which combined with measurements of the scale of inflation demands some degree of fine-tuning. Alternatively, the flatness of the potential could be due to the inflaton's origin as a pseudo-Goldstone boson, as in Natural Inflation. Alas, consistency with Planck data places the original proposal of Natural Inflation in a tight spot, as it requires a trans-Planckian excursion of the inflaton. Although one can still tune the renormalizable potential to sub-Planckian values, higher order corrections from quantum gravity or sources of breaking of the Goldstone symmetry would ruin the predictivity of the model. In this paper we show how in more realistic models of Natural Inflation one could achieve inflation without a trans-Planckian excursion of the field. We show how a variant of Extra-natural inflation with bulk fermions can achieve the desired goal and discuss its four-dimensional duals. We also present a new type of four dimensional models inspired in Little Higgs and Composite Higgs models which can lead to sub-Planckian values of the inflaton field.

  10. Picturing the Natural Environment

    ERIC Educational Resources Information Center

    Johnson, Phyllis Scott

    2011-01-01

    Around Scout Island Education Center, a site used by schools in Fresno County to explore the area's natural environment, a total of 200 cylinder-shaped concrete stools display tiles representing small mammals, flying insects, birds, wildflowers, and more. Twenty sets have been created by elementary, middle, and high-school art students as part of…

  11. Natural Gas Annual

    EIA Publications

    2016-01-01

    Provides information on the supply and disposition of natural gas in the United States. Production, transmission, storage, deliveries, and price data are published by state for the current year. Summary data are presented for each state for the previous 5 years.

  12. Natural hazards science strategy

    USGS Publications Warehouse

    Holmes, Jr., Robert R.; Jones, Lucile M.; Eidenshink, Jeffery C.; Godt, Jonathan W.; Kirby, Stephen H.; Love, Jeffrey J.; Neal, Christina A.; Plant, Nathaniel G.; Plunkett, Michael L.; Weaver, Craig S.; Wein, Anne; Perry, Suzanne C.

    2012-01-01

    The mission of the U.S. Geological Survey (USGS) in natural hazards is to develop and apply hazard science to help protect the safety, security, and economic well-being of the Nation. The costs and consequences of natural hazards can be enormous, and each year more people and infrastructure are at risk. USGS scientific research—founded on detailed observations and improved understanding of the responsible physical processes—can help to understand and reduce natural hazard risks and to make and effectively communicate reliable statements about hazard characteristics, such as frequency, magnitude, extent, onset, consequences, and where possible, the time of future events.To accomplish its broad hazard mission, the USGS maintains an expert workforce of scientists and technicians in the earth sciences, hydrology, biology, geography, social and behavioral sciences, and other fields, and engages cooperatively with numerous agencies, research institutions, and organizations in the public and private sectors, across the Nation and around the world. The scientific expertise required to accomplish the USGS mission in natural hazards includes a wide range of disciplines that this report refers to, in aggregate, as hazard science.In October 2010, the Natural Hazards Science Strategy Planning Team (H–SSPT) was charged with developing a long-term (10-year) Science Strategy for the USGS mission in natural hazards. This report fulfills that charge, with a document hereinafter referred to as the Strategy, to provide scientific observations, analyses, and research that are critical for the Nation to become more resilient to natural hazards. Science provides the information that decisionmakers need to determine whether risk management activities are worthwhile. Moreover, as the agency with the perspective of geologic time, the USGS is uniquely positioned to extend the collective experience of society to prepare for events outside current memory. The USGS has critical statutory

  13. Natural hazards science strategy

    USGS Publications Warehouse

    Holmes, Jr., Robert R.; Jones, Lucile M.; Eidenshink, Jeffery C.; Godt, Jonathan W.; Kirby, Stephen H.; Love, Jeffrey J.; Neal, Christina A.; Plant, Nathaniel G.; Plunkett, Michael L.; Weaver, Craig S.; Wein, Anne; Perry, Suzanne C.

    2012-01-01

    The mission of the U.S. Geological Survey (USGS) in natural hazards is to develop and apply hazard science to help protect the safety, security, and economic well-being of the Nation. The costs and consequences of natural hazards can be enormous, and each year more people and infrastructure are at risk. USGS scientific research - founded on detailed observations and improved understanding of the responsible physical processes - can help to understand and reduce natural hazard risks and to make and effectively communicate reliable statements about hazard characteristics, such as frequency, magnitude, extent, onset, consequences, and where possible, the time of future events. To accomplish its broad hazard mission, the USGS maintains an expert workforce of scientists and technicians in the earth sciences, hydrology, biology, geography, social and behavioral sciences, and other fields, and engages cooperatively with numerous agencies, research institutions, and organizations in the public and private sectors, across the Nation and around the world. The scientific expertise required to accomplish the USGS mission in natural hazards includes a wide range of disciplines that this report refers to, in aggregate, as hazard science. In October 2010, the Natural Hazards Science Strategy Planning Team (H-SSPT) was charged with developing a long-term (10-year) Science Strategy for the USGS mission in natural hazards. This report fulfills that charge, with a document hereinafter referred to as the Strategy, to provide scientific observations, analyses, and research that are critical for the Nation to become more resilient to natural hazards. Science provides the information that decisionmakers need to determine whether risk management activities are worthwhile. Moreover, as the agency with the perspective of geologic time, the USGS is uniquely positioned to extend the collective experience of society to prepare for events outside current memory. The USGS has critical statutory

  14. Natural products as photoprotection.

    PubMed

    Saewan, Nisakorn; Jimtaisong, Ampa

    2015-03-01

    The rise in solar ultraviolet radiation on the earth's surface has led to a depletion of stratospheric ozone over recent decades, thus accelerating the need to protect human skin against the harmful effects of UV radiation such as erythema, edema, hyperpigmentation, photoaging, and skin cancer. There are many different ways to protect skin against UV radiation's harmful effects. The most popular way to reduce the amount of UV radiation penetrating the skin is topical application of sunscreen products that contain UV absorbing or reflecting active molecules. Based on their protection mechanism, the active molecules in sunscreens are broadly divided into inorganic and organic agents. Inorganic sunscreens reflect and scatter UV and visible radiation, while organic sunscreens absorb UV radiation and then re-emit energy as heat or light. These synthetic molecules have limited concentration according to regulation concern. Several natural compounds with UV absorption property have been used to substitute for or to reduce the quantity of synthetic sunscreen agents. In addition to UV absorption property, most natural compounds were found to act as antioxidants, anti-inflammatory, and immunomodulatory agents, which provide further protection against the damaging effects of UV radiation exposure. Compounds derived from natural sources have gained considerable attention for use in sunscreen products and have bolstered the market trend toward natural cosmetics. This adds to the importance of there being a wide selection of active molecules in sunscreen formulations. This paper summarizes a number of natural products derived from propolis, plants, algae, and lichens that have shown potential photoprotection properties against UV radiation exposure-induced skin damage. © 2015 Wiley Periodicals, Inc.

  15. Tails of Natural Hazards

    NASA Astrophysics Data System (ADS)

    Malamud, B. D.

    2003-12-01

    There is increasing evidence that many natural hazards satisfy power-law frequency-size statistics. Examples include earthquakes, volcanic eruptions, landslides, snow avalanches, forest and wildfires, meteorite impacts, and possibly floods. Although power-law (fat-tail) distributions are commonly associated with the frequency-size distribution of earthquakes, the frequency-size statistics of many other natural hazards are presently associated (e.g. by government agencies and reinsurance companies) with distributions that are more thin-tailed. The occurrence risk for large and very-large events using power-law frequency-size distributions is often much more conservative, with a greater chance of a large event occurring in a given period of time, compared to thinner tail distributions. One potential explanation for the frequent occurrence of power-law (fractal) frequency-size distributions among natural hazards lies in cellular-automata models, and their association with self-organized criticality and inverse cascades. The power-law behavior of the sandpile cellular-automata model has been associated by some with landslides, the forest-fire model with actual forest fires, and the slider-block model with earthquakes. A relatively simple inverse-cascade of metastable regions can explain the behavior of both models and the actual natural hazards. Metastable regions grow by coalescence and are lost in `avalanches'. However, the losses are dominated by the largest events and have little influence on the inverse cascade of metastable region coalescence. This inverse cascade of metastable regions is self-similar and the number-area statistics are power-law. Although the theoretical explanations are still being debated, the increasing evidence for power-law statistics means that government agencies and reinsurance companies should include this much more conservative frequency-size distribution when calculating the occurrence risk of large natural hazards.

  16. Natural Freedom and Wilderness Survival

    ERIC Educational Resources Information Center

    Welton, George E.

    1978-01-01

    The "naturalism" of Jean Jacques Rousseau offers a philosophical base for wilderness survival: the renewal of participants in nature so that they can reenter civilization with a proper balance of natural and civil liberty. (MJB)

  17. Natural light illumination system.

    PubMed

    Whang, Allen Jong-Woei; Chen, Yi-Yung; Yang, Shu-Hua; Pan, Po-Hsuan; Chou, Kao-Hsu; Lee, Yu-Chi; Lee, Zong-Yi; Chen, Chi-An; Chen, Cheng-Nan

    2010-12-10

    In recent years, green energy has undergone a lot of development and has been the subject of many applications. Many research studies have focused on illumination with sunlight as a means of saving energy and creating healthy lighting. Natural light illumination systems have collecting, transmitting, and lighting elements. Today, most daylight collectors use dynamic concentrators; these include Sun tracking systems. However, this design is too expensive to be cost effective. To create a low-cost collector that can be easily installed on a large building, we have designed a static concentrator, which is prismatic and cascadable, to collect sunlight for indoor illumination. The transmission component uses a large number of optical fibers. Because optical fibers are expensive, this means that most of the cost for the system will be related to transmission. In this paper, we also use a prismatic structure to design an optical coupler for coupling n to 1. With the n-to-1 coupler, the number of optical fibers necessary can be greatly reduced. Although this new natural light illumination system can effectively guide collected sunlight and send it to the basement or to other indoor places for healthy lighting, previously there has been no way to manage the collected sunlight when lighting was not desired. To solve this problem, we have designed an optical switch and a beam splitter to control and separate the transmitted light. When replacing traditional sources, the lighting should have similar characteristics, such as intensity distribution and geometric parameters, to those of traditional artificial sources. We have designed, simulated, and optimized an illumination lightpipe with a dot pattern to redistribute the collected sunlight from the natural light illumination system such that it equals the qualities of a traditional lighting system. We also provide an active lighting module that provides lighting from the natural light illumination system or LED auxiliary

  18. Design, science and naturalism

    NASA Astrophysics Data System (ADS)

    Deming, David

    2008-09-01

    The Design Argument is the proposition that the presence of order in the universe is evidence for the existence of God. The Argument dates at least to the presocratic Greek philosophers, and is largely based on analogical reasoning. Following the appearance of Aquinas' Summa Theologica in the 13th century, the Christian Church in Europe embraced a Natural Theology based on observation and reason that allowed it to dominate the entire world of knowledge. Science in turn advanced itself by demonstrating that it could be of service to theology, the recognized queen of the sciences. During the heyday of British Natural Theology in the 17th and 18th centuries, the watchmaker, shipbuilder, and architect analogies were invoked reflexively by philosophers, theologians, and scientists. The Design Argument was not systematically and analytically criticized until David Hume wrote Dialogues on Natural Religion in the 1750s. After Darwin published Origin of Species in 1859, Design withered on the vine. But in recent years, the Argument has been resurrected under the appellation "intelligent design," and been the subject of political and legal controversy in the United States. Design advocates have argued that intelligent design can be formulated as a scientific hypothesis, that new scientific discoveries validate a design inference, and that naturalism must be removed as a methodological requirement in science. If science is defined by a model of concentric epistemological zonation, design cannot be construed as a scientific hypothesis because it is inconsistent with the core aspects of scientific methodology: naturalism, uniformity, induction, and efficient causation. An analytical examination of claims by design advocates finds no evidence of any type to support either scientific or philosophical claims that design can be unambiguously inferred from nature. The apparent irreducible complexity of biological mechanisms may be explained by exaptation or scaffolding. The argument

  19. Why Is Nature Beneficial?: The Role of Connectedness to Nature

    ERIC Educational Resources Information Center

    Mayer, F. Stephan; Frants, Cynthia McPherson; Bruehlman-Senecal, Emma; Dolliver, Kyffin

    2009-01-01

    Three studies examine the effects of exposure to nature on positive affect and ability to reflect on a life problem. Participants spent 15 min walking in a natural setting (Studies 1, 2, & 3), an urban setting (Study 1), or watching videos of natural and urban settings (Studies 2 & 3). In all three studies, exposure to nature increased…

  20. The nature of beamstrahlung

    SciTech Connect

    Chen, P.

    1987-04-01

    The physical nature of beamstrahlung during beam-beam interaction in linear colliders is reviewed. We first make the distinction between a dense beam and a dilute beam. We then review the characteristics of synchrotron radiation (SR) and bremsstrahlung, and argue that for a wide range of beam parameters beamstrahlung is SR in nature, even if the beam is dilute. Some issues concerning the specific conditions in beamstrahlung as SR are then discussed. Finally we suggest that in order to suppress beamstrahlung energy loss and to improve energy resolution, it is desirable to partition a bunch into a train of bunchlets, where the length of each bunchlet is shorter than the SR convergence length.

  1. Epidemics after natural disasters.

    PubMed

    Watson, John T; Gayer, Michelle; Connolly, Maire A

    2007-01-01

    The relationship between natural disasters and communicable diseases is frequently misconstrued. The risk for outbreaks is often presumed to be very high in the chaos that follows natural disasters, a fear likely derived from a perceived association between dead bodies and epidemics. However, the risk factors for outbreaks after disasters are associated primarily with population displacement. The availability of safe water and sanitation facilities, the degree of crowding, the underlying health status of the population, and the availability of healthcare services all interact within the context of the local disease ecology to influence the risk for communicable diseases and death in the affected population. We outline the risk factors for outbreaks after a disaster, review the communicable diseases likely to be important, and establish priorities to address communicable diseases in disaster settings.

  2. Natural environment analysis

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Qualitative analyses (and quantitatively to the extend possible) of the influence of terrain features on wind loading of the space shuttle while on the launch pad, or during early liftoff, are presented. Initially, the climatology and meteorology producing macroscale wind patterns and characteristics fot he Vandenburg Air Force Base (VAFB) launch site are described. Also, limited field test data are analyzed, and then the nature and characteristic of flow disturbances due to the various terrain features, both natural and man-made, are then reviewed. Following this, the magnitude of these wind loads are estimated. Finally, effects of turbulence are discussed. The study concludes that the influence of complex terrain can create significant wind loading on the vehicle. Because of the limited information, it is not possible to quantify the magnitude of these loads.

  3. Hybrid Natural Inflation

    NASA Astrophysics Data System (ADS)

    Ross, Graham G.; Germán, Gabriel; Vázquez, J. Alberto

    2016-05-01

    We construct two simple effective field theory versions of Hybrid Natural Inflation (HNI) that illustrate the range of its phenomenological implications. The resulting inflationary sector potential, V = Δ4(1 + acos( ϕ/f)), arises naturally, with the inflaton field a pseudo-Nambu-Goldstone boson. The end of inflation is triggered by a waterfall field and the conditions for this to happen are determined. Also of interest is the fact that the slow-roll parameter ɛ (and hence the tensor r) is a non-monotonic function of the field with a maximum where observables take universal values that determines the maximum possible tensor to scalar ratio r. In one of the models the inflationary scale can be as low as the electroweak scale. We explore in detail the associated HNI phenomenology, taking account of the constraints from Black Hole production, and perform a detailed fit to the Planck 2015 temperature and polarisation data.

  4. Natural Products for Antithrombosis

    PubMed Central

    Chen, Cen; Zhang, Qian; Wang, Feng-Qin; Hu, Yuan-Jia; Xia, Zhi-Ning

    2015-01-01

    Thrombosis is considered to be closely related to several diseases such as atherosclerosis, ischemic heart disease and stroke, as well as rheumatoid arthritis, hyperuricemia, and various inflammatory conditions. More and more studies have been focused on understanding the mechanism of molecular and cellular basis of thrombus formation as well as preventing thrombosis for the treatment of thrombotic diseases. In reality, there is considerable interest in the role of natural products and their bioactive components in the prevention and treatment of thrombosis related disorders. This paper briefly describes the mechanisms of thrombus formation on three aspects, including coagulation system, platelet activation, and aggregation, and change of blood flow conditions. Furthermore, the natural products for antithrombosis by anticoagulation, antiplatelet aggregation, and fibrinolysis were summarized, respectively. PMID:26075003

  5. Safer Liquid Natural Gas

    NASA Technical Reports Server (NTRS)

    1976-01-01

    After the disaster of Staten Island in 1973 where 40 people were killed repairing a liquid natural gas storage tank, the New York Fire Commissioner requested NASA's help in drawing up a comprehensive plan to cover the design, construction, and operation of liquid natural gas facilities. Two programs are underway. The first transfers comprehensive risk management techniques and procedures which take the form of an instruction document that includes determining liquid-gas risks through engineering analysis and tests, controlling these risks by setting up redundant fail safe techniques, and establishing criteria calling for decisions that eliminate or accept certain risks. The second program prepares a liquid gas safety manual (the first of its kind).

  6. Epidemics after Natural Disasters

    PubMed Central

    Gayer, Michelle; Connolly, Maire A.

    2007-01-01

    The relationship between natural disasters and communicable diseases is frequently misconstrued. The risk for outbreaks is often presumed to be very high in the chaos that follows natural disasters, a fear likely derived from a perceived association between dead bodies and epidemics. However, the risk factors for outbreaks after disasters are associated primarily with population displacement. The availability of safe water and sanitation facilities, the degree of crowding, the underlying health status of the population, and the availability of healthcare services all interact within the context of the local disease ecology to influence the risk for communicable diseases and death in the affected population. We outline the risk factors for outbreaks after a disaster, review the communicable diseases likely to be important, and establish priorities to address communicable diseases in disaster settings. PMID:17370508

  7. Biofouling: lessons from nature.

    PubMed

    Bixler, Gregory D; Bhushan, Bharat

    2012-05-28

    Biofouling is generally undesirable for many applications. An overview of the medical, marine and industrial fields susceptible to fouling is presented. Two types of fouling include biofouling from organism colonization and inorganic fouling from non-living particles. Nature offers many solutions to control fouling through various physical and chemical control mechanisms. Examples include low drag, low adhesion, wettability (water repellency and attraction), microtexture, grooming, sloughing, various miscellaneous behaviours and chemical secretions. A survey of nature's flora and fauna was taken in order to discover new antifouling methods that could be mimicked for engineering applications. Antifouling methods currently employed, ranging from coatings to cleaning techniques, are described. New antifouling methods will presumably incorporate a combination of physical and chemical controls.

  8. Natural convective mixing flows

    NASA Astrophysics Data System (ADS)

    Ramos, Eduardo; de La Cruz, Luis; del Castillo, Luis

    1998-11-01

    Natural convective mixing flows. Eduardo Ramos and Luis M. de La Cruz, National University of Mexico and Luis Del Castillo San Luis Potosi University. The possibility of mixing a fluid with a natural convective flow is analysed by solving numerically the mass, momentum and energy equations in a cubic container. Two opposite vertical walls of the container are assumed to have temperatures that oscillate as functions of time. The phase of the oscillations is chosen in such a way that alternating corrotating vortices are formed in the cavity. The mixing efficiency of this kind of flow is examined with a Lagrangian tracking technique. This work was partially financed by CONACyT-Mexico project number GE0044

  9. Principles of Natural Photosynthesis.

    PubMed

    Krewald, Vera; Retegan, Marius; Pantazis, Dimitrios A

    2016-01-01

    Nature relies on a unique and intricate biochemical setup to achieve sunlight-driven water splitting. Combined experimental and computational efforts have produced significant insights into the structural and functional principles governing the operation of the water-oxidizing enzyme Photosystem II in general, and of the oxygen-evolving manganese-calcium cluster at its active site in particular. Here we review the most important aspects of biological water oxidation, emphasizing current knowledge on the organization of the enzyme, the geometric and electronic structure of the catalyst, and the role of calcium and chloride cofactors. The combination of recent experimental work on the identification of possible substrate sites with computational modeling have considerably limited the possible mechanistic pathways for the critical O-O bond formation step. Taken together, the key features and principles of natural photosynthesis may serve as inspiration for the design, development, and implementation of artificial systems.

  10. Notes on natural inflation

    NASA Astrophysics Data System (ADS)

    Yonekura, Kazuya

    2014-10-01

    In the so-called natural inflation, an axion-like inflaton is assumed to have a cosine-type periodic potential. This is not the case in a very simple model in which the axion-like inflaton is coupled to an SU(N) (or other) pure Yang-Mills, at least in the large N limit as pointed out by Witten. It has a multi-valued potential, which is effectively quadratic, i.e., there is only a mass term in the large N limit. Thanks to this property, chaotic inflation can be realized more naturally with the decay constant of the axion-like inflaton less than the Planck scale. We demonstrate these points explicitly by using softly broken Script N=1 Super-Yang-Mills which allows us to treat finite N. This analysis also suggests that moderately large gauge groups such as E8 are good enough with a Planck scale decay constant.

  11. Nature and nurture

    PubMed Central

    Mann, Janet; Krützen, Michael; Connor, Richard C; Bejder, Lars; Sherwin, William B

    2011-01-01

    The debate about the relative importance of nature versus nurture has been around for decades, but despite this, there has been very little evidence about how these might in fact interact to drive evolution in the wild. Recently, the identification of a comparable methodology for analyzing both genetic and social effects of phenotypic variation revealed that fitness variation in a free-living population of dolphin was driven by a strong social and genetic interaction. This study not only provides evidence that nature and nurture do interact to drive phenotypic evolution but also represents a step towards partitioning the effects of genetic, social, environmental factors and their multiway interactions to better understand phenotypic evolution in the wild. PMID:21655437

  12. Mysteries of nature.

    PubMed

    Molnar, Michael

    2011-01-01

    This article examines a group photograph of the Psychiatry and Neurology section of the 66th Meeting of the Society of German Natural Scientists and Doctors in Vienna, 24-30 September 1894 which Sigmund Freud attended. The society's origins in Naturphilosophie are indicated and a number of the participants are identified on the photo. They and the events at the conference are related to Sigmund Freud's work at the time and to his gradual abandonment of anatomy and of heredity and degeneration as significant aetiological factors in the neuroses. Philosophical problems, such as how phenomena should be described and how 'nature' is conceptualized, are also considered in the light of their implications for Freud's life and thought at that period.

  13. Responses to natural disasters

    NASA Astrophysics Data System (ADS)

    Maggs, William Ward

    Since 1964, natural disasters caused by earthquakes, volcanic eruptions, or extreme weather in the form of floods, droughts, or hurricanes, have been responsible for more than 2,756,000 deaths worldwide in nations other than the United States, the Soviet Union, and the Eastern European Bloc, according to figures tabulated by the Office of Foreign Disaster Assistance (OFDA) of the Agency for International Development (AID). Over 95% of these fatalities occurred in developing or third world countries. Damage resulting from these calamities has been severe but extremely difficult to estimate in monetary terms. In 1986, U.S. government and voluntary agencies spent $303 million on natural disaster assistance around the world, 79% of total world assistance. In 1985 the U.S. total was nearly $900 million, 48% of the $1.84 billion world total.

  14. Clathrate hydrates in nature.

    PubMed

    Hester, Keith C; Brewer, Peter G

    2009-01-01

    Scientific knowledge of natural clathrate hydrates has grown enormously over the past decade, with spectacular new findings of large exposures of complex hydrates on the sea floor, the development of new tools for examining the solid phase in situ, significant progress in modeling natural hydrate systems, and the discovery of exotic hydrates associated with sea floor venting of liquid CO2. Major unresolved questions remain about the role of hydrates in response to climate change today, and correlations between the hydrate reservoir of Earth and the stable isotopic evidence of massive hydrate dissociation in the geologic past. The examination of hydrates as a possible energy resource is proceeding apace for the subpermafrost accumulations in the Arctic, but serious questions remain about the viability of marine hydrates as an economic resource. New and energetic explorations by nations such as India and China are quickly uncovering large hydrate findings on their continental shelves.

  15. Naturally selecting solutions

    PubMed Central

    Manning, Timmy; Sleator, Roy D; Walsh, Paul

    2013-01-01

    For decades, computer scientists have looked to nature for biologically inspired solutions to computational problems; ranging from robotic control to scheduling optimization. Paradoxically, as we move deeper into the post-genomics era, the reverse is occurring, as biologists and bioinformaticians look to computational techniques, to solve a variety of biological problems. One of the most common biologically inspired techniques are genetic algorithms (GAs), which take the Darwinian concept of natural selection as the driving force behind systems for solving real world problems, including those in the bioinformatics domain. Herein, we provide an overview of genetic algorithms and survey some of the most recent applications of this approach to bioinformatics based problems. PMID:23222169

  16. Thermoacoustic natural gas liquefier

    SciTech Connect

    Swift, G.W.

    1997-05-01

    Cryenco and Los Alamos are collaborating to develop a natural-gas-powered natural-gas liquefier that will have no moving parts and require no electrical power. It will have useful efficiency, remarkable reliability, and low cost. The liquefaction of natural gas, which occurs at only 115 Kelvin at atmospheric pressure, has previously required rather sophisticated refrigeration machinery. The 1990 invention of the thermoacoustically driven orifice pulse-tube refrigerator (TA-DOPTR) provides cryogenic refrigeration with no moving parts for the first time. In short, this invention uses acoustic phenomena to produce refrigeration from heat. The required apparatus consists of nothing more than helium-filled heat exchangers and pipes, made of common materials, without exacting tolerances. In the Cryenco-Los Alamos collaboration, the authors are developing a version of this invention suitable for use in the natural-gas industry. The project is known as acoustic liquefier for short. The present program plans call for a two-phase development. Phase 1, with capacity of 500 gallon per day (i.e., approximately 40,000 scfd, requiring a refrigeration power of about 7 kW), is large enough to illuminate all the issues of large-scale acoustic liquefaction without undue cost, and to demonstrate the liquefaction of 60--70% of input gas, while burning 30--40%. Phase 2 will target versions of approximately 10{sup 6} scfd = 10,000 gallon per day capacity. In parallel with both, they continue fundamental research on the technology, directed toward increased efficiency, to build scientific foundations and a patent portfolio for future acoustic liquefiers.

  17. Natural Underwater Adhesives.

    PubMed

    Stewart, Russell J; Ransom, Todd C; Hlady, Vladimir

    2011-06-01

    The general topic of this review is protein-based underwater adhesives produced by aquatic organisms. The focus is on mechanisms of interfacial adhesion to native surfaces and controlled underwater solidification of natural water-borne adhesives. Four genera that exemplify the broad range of function, general mechanistic features, and unique adaptations are discussed in detail: blue mussels, acorn barnacles, sandcastle worms, and freshwater caddisfly larva. Aquatic surfaces in nature are charged and in equilibrium with their environment, populated by an electrical double layer of ions as well as adsorbed natural polyelectrolytes and microbial biofilms. Surface adsorption of underwater bioadhesives likely occurs by exchange of surface bound ligands by amino acid sidechains, driven primarily by relative affinities and effective concentrations of polymeric functional groups. Most aquatic organisms exploit modified amino acid sidechains, in particular phosphorylated serines and hydroxylated tyrosines (dopa), with high-surface affinity that form coordinative surface complexes. After delivery to the surfaces as a fluid, permanent natural adhesives solidify to bear sustained loads. Mussel plaques are assembled in a manner superficially reminiscent of in vitro layer-by-layer strategies, with sequentially delivered layers associated through Fe(dopa)(3) coordination bonds. The adhesives of sandcastle worms, caddisfly larva, and barnacles may be delivered in a form somewhat similar to in vitro complex coacervation. Marine adhesives are secreted, or excreted, into seawater that has a significantly higher pH and ionic strength than the internal environment. Empirical evidence suggests these environment triggers could provide minimalistic, fail-safe timing mechanisms to prevent premature solidification (insolubilization) of the glue within the secretory system, yet allow rapid solidification after secretion. Underwater bioadhesives are further strengthened by secondary covalent

  18. New force in nature

    SciTech Connect

    Fischbach, E.; Sudarsky, D.; Szafer, A.; Talmadge, C.; Aronson, S.H.

    1986-01-01

    We review recent experimental and theoretical work dealing with the proposed fifth force. Further analysis of the original Eotvos experiments has uncovered no challenges to our original assertion that these data evidence a correlation characteristic of the presence of a new coupling to baryon number or hypercharge. Various models suggest that the proposed fifth force could be accommodated naturally into the existing theoretical framework. 40 refs.

  19. Natural sampling strategy

    NASA Technical Reports Server (NTRS)

    Hallum, C. R.; Basu, J. P. (Principal Investigator)

    1979-01-01

    A natural stratum-based sampling scheme and the aggregation procedures for estimating wheat area, yield, and production and their associated prediction error estimates are described. The methodology utilizes LANDSAT imagery and agrophysical data to permit an improved stratification in foreign areas by ignoring political boundaries and restratifying along boundaries that are more homogeneous with respect to the distribution of agricultural density, soil characteristics, and average climatic conditions. A summary of test results is given including a discussion of the various problems encountered.

  20. Natural Underwater Adhesives

    PubMed Central

    Stewart, Russell J.; Ransom, Todd C.; Hlady, Vladimir

    2011-01-01

    The general topic of this review is protein-based underwater adhesives produced by aquatic organisms. The focus is on mechanisms of interfacial adhesion to native surfaces and controlled underwater solidification of natural water-borne adhesives. Four genera that exemplify the broad range of function, general mechanistic features, and unique adaptations are discussed in detail: blue mussels, acorn barnacles, sandcastle worms, and freshwater caddisfly larva. Aquatic surfaces in nature are charged and in equilibrium with their environment, populated by an electrical double layer of ions as well as adsorbed natural polyelectrolytes and microbial biofilms. Surface adsorption of underwater bioadhesives likely occurs by exchange of surface bound ligands by amino acid sidechains, driven primarily by relative affinities and effective concentrations of polymeric functional groups. Most aquatic organisms exploit modified amino acid sidechains, in particular phosphorylated serines and hydroxylated tyrosines (dopa), with high-surface affinity that form coordinative surface complexes. After delivery to the surfaces as a fluid, permanent natural adhesives solidify to bear sustained loads. Mussel plaques are assembled in a manner superficially reminiscent of in vitro layer-by-layer strategies, with sequentially delivered layers associated through Fe(dopa)3 coordination bonds. The adhesives of sandcastle worms, caddisfly larva, and barnacles may be delivered in a form somewhat similar to in vitro complex coacervation. Marine adhesives are secreted, or excreted, into seawater that has a significantly higher pH and ionic strength than the internal environment. Empirical evidence suggests these environment triggers could provide minimalistic, fail-safe timing mechanisms to prevent premature solidification (insolubilization) of the glue within the secretory system, yet allow rapid solidification after secretion. Underwater bioadhesives are further strengthened by secondary covalent