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United States Department of Agriculture

Agricultural Research Service

Research Project: Chemistry of Natural Products for Nutraceutical Use, Pest Management and Crop Development

Location: Natural Products Utilization Research

2011 Annual Report

1a. Objectives (from AD-416)
The long-term objective of this project is to identify and chemically characterize secondary metabolites from natural sources with nutraceutical and/or pesticidal properties as chemical markers for selection of high value crops and/or lead compounds for structure-activity optimization. Over the next 5 years, we will focus on the following objectives: Objective 1. Profile phytochemicals of selected crops (blueberry and rice) to identify species or cultivars with high contents of compounds with beneficial health and/or fungicidal properties to promote development as high value crops. Objective 2. Discover and identify technologies based on secondary metabolites that facilitate the development of commercially viable herbicides, fungicides, insecticides, insect repellants, fish bacterides, and health promoters.

1b. Approach (from AD-416)
Blueberry and rice samples will be extracted with appropriate solvents and the extracts will be analyzed by liquid chromatography-mass spectrometry, as well as by gas chromatography-mass spectrometry. The extracts will also be tested for antioxidant activity using a cell-based antioxidant assay. The chemical profiles of the extracts will be correlated with disease resistance of the samples, as well as antioxidant activity. A bioassay-guided investigative approach will be performed on bioactive extracts in efforts to discover herbicides, fungicides, insecticides, insect repellents, fish bactericides and health promoters. General procedures for isolation of active compounds such as solvent extractions, distillations, column chromatography and thin layer chromatography will be employed. Extracts, fractions and pure compounds will be tested for phytotoxicity, antifungal and insecticidal activity in assays being carried out routinely at NPURU and at collaborator's laboratories. Identification of active compounds will be done using spectroscopic methods (Ultraviolet (UV), Infrared (IR), Mass Spectroscopy (MS), Nuclear Magnetic Resonance (NMR)). Chemical studies modification will be performed on compound(s) that will be identified as "highly active" to improve activity or bioavailability.

3. Progress Report
This report is for the first year of our renewed in-house project. Field-grown blueberry cultivars Duke, Spartan, Berkeley and Brigitta Blue were received from a collaborator. Extraction and preliminary chemical profiling is on-going. In continuing studies to discover health beneficial properties of pterostilbene, it was shown to have anti-anxiety effects in animal models for anxiety. Biochemical experiments supported behavior observed in the animal, as pterostilbene inhibited enzymes in the pathway that play a role in producing anxiety. An efficient synthesis of the natural insect repellant callicarpenal was devised, which allows optimization of its structure and repellency. Analysis by 1H NMR, 13C NMR, HPLC-RI, and GC-FID of Jatropha curcas seed oil, burned in oil lamps in India and parts of Africa to repel biting insects, as well tests using an oil condensation trap demonstrated that free fatty acids and triglycerides are the active compounds in Aedes aegypti biting deterrent assays. Oleic, palmitic, and linoleic acids were more active than stearic acid in this bioassay. Oleic acid was the only fatty acid that had larvicidal activity against 1-day old Aedes (Ae.) aegypti larvae. In another study, the effects of 10 insect repellents and a pyrethroid insecticide with known repellent activity on two highly specific odorant receptors (ORs) of Aedes aegypti, was investigated. Results showed that a range of insect repellents belonging to structurally diverse chemical classes modulate the function of mosquito ORs through multiple molecular mechanisms. This study identifies the mode of action for callicarpenal and its activity on odorant receptors. More importantly, this study specifies a difference between the insect repelling mode of action of callicarpenal and DEET. In another study, compounds were prepared by synthetic modification of the structure of the natural compound lycorine and were tested for inhibition of the fish pathogen Flavobacterium columnare. Several new analogs were synthesized; specifically a carbamate analog showed greater activity than lycorine. Research involvement in Deployed War-Fighter Protection (DWFP) Program continued to expand in 2010 as we increased our output of extracts and pure compounds for evaluation as insectides and/or mosquito deterrent agents through collaboration with the Center for Medical, Agricultural, and Veterinary Entomology. This collaboration demonstrated the strong mosquito deterrent activity of z-ligustilide from Angelica spp. A total of 39 crude extracts of endophytic fungi associated with American medicinal plant Echinacea purpurea were screened for antifungal activity against the plant pathogens Colletotrichum (C.) fragariae, C. gloeosporioides, and C. acutatum. Of the 39 extracts, 16 extracts showed antifungal activities to at least one of these pathogens; among them, seven were strongly active against C. acutatum, six against C. fragariae, and eight againt C. gloeosporioides.

4. Accomplishments
1. Anxiety is one of the most common psychiatric disorders in the U.S. ARS scientists in Oxford, MS, in collaboration with University of Mississippi scientists, discovered that pterostilbene, a phenolic compound found in blueberries and grapes, reduced anxiety in mice at low doses using an established behavioral model for assessing anxiety. The anti-anxiety activity of pterostilbene was comparable to that of the clinically used drug Diazepam. The locomotor activity of the animals given pterostilbene was unaffected even at the higher doses used, suggesting favorable effects of this compound. Biochemical analysis corroborated the observed animal behavior, revealing a decrease in activity of enzymes involved in the pathway for anxiety. Pterostilbene was also detected in the serum and brain of the test animals. This study provides a natural compound that could alleviate anxiety. A patent was filed for this new activity (U.S. Patent Application Serial No. 13/105,470 filed on May 11, 2011) and was licensed by Chromadex on June 3, 2011.

2. Efficient synthesis of the nautral insect repellent callicarpenal devised. ARS scientists in Oxford, MS, have shown that callicarpenal, a natural terpenoid isolated from American beautyberry (Callicarpa americana), has significant repellent activities against mosquitoes, ticks, and imported fire ants. The yield of this compound from beautyberry is low, so a synthetic method of production is needed. An efficient synthetic approach to this natural product was accomplished, and a study of the mosquito biting deterrent effect of callicarpenal as well as its synthetic precursors and related compounds was conducted. This synthetic method allows rapid access to various analogues of the natural product that can be used to explore its structure activity relationship and optimize its biological properties.

Review Publications
Zheljazkov, V.D., Cantrell, C.L., Astatkie, T., Cannon, J.B. 2011. Lemongrass productivity oil content and composition as a function of nitrogen sulfur and harvest time. Agronomy Journal. 103(3):805-812.

Ling, T., Xu, J., Smith, R., Ali, A., Cantrell, C.L., Theodorakis, E.A. 2011. Synthesis of (-)-callicarpenal a natural arthropod-repellent terpenoid. Tetrahedron. 67:3023-3029.

Zheljazkov, V.D., Cantrell, C.L., Astatkie, T. 2010. Yield and composition of oil from japanese cornmint fresh and dry material harvested successively. Agronomy Journal. 102(6):1652-1656.

Amin, E., El-Hawary, S.S., Fathy, M.M., Mohammed, R., Ali, Z., Tabanca, N., Wedge, D.E., Becnel, J.J., Khan, I.A. 2011. Triterpenoidal saponins: bioactive secondary metabolites from Zygophyllum coccineum L. Planta Medica. 77:485-488.

Tan, C., Schrader, K., Mizuno, C.S., Rimando, A.M. 2011. Activity of lycorine analogs against the fish bacterial pathogen Flavobacterium columnare. Journal of Agricultural & Food Chemistry. 59:5977-5985.

Tabanca, N., Demirci, B., Gurbuz, I., Demirci, F., Becnel, J.J., Wedge, D.E., Baser, K. 2011. Essential oil composition of five collections of Achillea biebersteinii from central Turkey and their antifungal and insecticidal activity. Natural Product Communications. 6(5):701-706.

Castro, A., Cantrell, C.L., Hale, A.L., Duke, S.O. 2010. Phytotoxic activity of flavonoids from dicranostyles ampla. Natural Product Communications. 5(8):1233-1237.

Crockett, S.L., Poller, B., Tabanca, N., Pferschy-Wenzig, E., Kunert, O., Wedge, D.E., Bucar, F. 2010. Bioactive xanthones from the roots of Hypericum perforatum (common St John's Wort). Journal of the Science of Food and Agriculture. 91:428-434.

Sobolev, V.S., Khan, S.I., Tabanca, N., Wedge, D.E., Manly, S.P., Cutler, S.J., Coy, M.R., Becnel, J.J., Neff, S.A., Gloer, J.B. 2011. Biological Activity of Peanut (Arachis hypogaea) Phytoalexins and Selected Natural and Synthetic Stilbenoids. Journal of Agricultural and Food Chemistry. 59(5):1673-1682.

Last Modified: 07/25/2017
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