Global Perspectives on Poisonous Plants: The 9th ... - ACS Publications

Mar 25, 2014 - days of oral and poster presentations, followed by a tour of the Xilinhot Region of the Mongolian Grasslands, encompassing grazing cond...
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Global Perspectives on Poisonous Plants: The 9th International Symposium on Poisonous Plants ABSTRACT: The 9th International Symposium on Poisonous Plants (ISOPP9) was held July 15−21, 2013, at the Inner Mongolia Agricultural University in Hohhot, Inner Mongolia Autonomous Region of China. The symposium consisted of three days of oral and poster presentations, followed by a tour of the Xilinhot Region of the Mongolian Grasslands, encompassing grazing conditions consisting of desert, grassland, and steppes. This was the first time that an ISOPP meeting has been held in Asia and provided an opportunity for visitors from outside China to become aware of livestock poisonings caused by plant species with which they were previously not familiar while at the same time demonstrating that many of the problems experienced around the world have a common etiology. Presentations focused on botany, veterinary science, toxicology, mechanism of action, and chemistry. As is appropriate for the Journal of Agricultural and Food Chemistry, this cluster of papers consists of selected oral and poster presentations in which the chemistry of the toxins played a significant role. The symposium revealed that there is considerable scope for isolation, structural elucidation, and analysis of the toxins from the numerous poisonous plant species that have been identified in China. It became apparent that there are abundant opportunities for chemists both within China and abroad to collaborate with Chinese scientists working on biological aspects of livestock poisonings.

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defined in grams per kilogram of animal body weight, a measure that could be highly variable, depending on plant location, growth stage, and environment. It was not until the 1960s that chemistry assumed its essential place in plant toxicity studies. In this period, Dr. Richard Keeler at the USDA Poisonous Plant Research Laboratory (PPRL) in Logan, Utah, established that the toxin responsible for cyclopic lambs born from ewes that grazed Veratrum californicum was a steroidal alkaloid, cyclopamine.4,5 In subsequent research he showed that piperidine alkaloids occurring in Lupinus, Conium, and Nicotiana species caused skeletal malformations and cleft palate in livestock,6−8 studies that are still ongoing.9 Over the same time period, Dr. Claude Culvenor and colleagues at the CSIRO Animal Health Laboratory in Parkville, Australia, investigated widespread species of the families Compositae, Leguminosae, and Boraginaceae responsible for liver damage in livestock, establishing the structures, subclasses, and occurrence of numerous hepatotoxic pyrrolizidine alkaloids and their metabolism and mode of action. 10 Such findings, in combination with modern instrumental techniques for structure determination, stimulated an explosion of chemistry research on poisonous plants, resulting in numerous scientific publications and comprehensive volumes defining the specific toxins associated with the major poisonous plant species in the United States, Australia, South Africa, and Brazil.11−14 Analytical chemistry can now be used to accurately assess the toxic potential of plant species at any particular location and period of growth. In recent years, the availability of many of these toxins and their derivatives has led to their use in studying biochemical functionality and potential use as pharmaceuticals for treatment of animals and humans. In 1973, Dr. Lynn F. James, then Director of the PPRL, traveled to Australia and met with members of the Queensland Poisonous Plant Committee, in particular Drs. Selwyn Everist

oisonous plants have been a major cause of economic losses to livestock producers in many parts of the world. Ingestion of such plants by animals can result not only in death but also reproductive disruption, abortions, teratogenicity, and failure to thrive. These effects were particularly noted by European settlers in countries such as the United States, Australia, and South Africa. As these settlers migrated from coastal areas where pastoral grazing was dominant to the more arid interiors, their animals were exposed to diverse ecosystems with nutritious grasses and poisonous plants intermixed. In certain seasons and locations the toxic plants predominated, and losses were often catastrophic. Such situations led producers to call on their respective governments for assistance in understanding the causes of losses and how they might be avoided. For example, in the United States a Department of Agriculture scientist, Dr. C. Dwight Marsh, was assigned to the problem and conducted investigations in the western United States over a period of 20 years, commencing in 1910. Although based in Washington, DC, Marsh traveled annually to various locations in Colorado, Montana, Nebraska, or Utah, in each case setting up a field station focused on specific problems, such as locoweed disease or larkspur poisoning. The temporary nature of these research sites required forethought and careful experimental design because it would be impossible for the work to be repeated under identical conditions in subsequent years. On his return to Washington for the winter months, Marsh compiled and published his studies in a series of monographs, which even now provide a major resource in describing the plant species implicated; physiological effects on cattle, sheep, and horses; and the periods of greatest hazard or relative safety.1−3 Analogous studies were undertaken by others in Australia and South Africa, resulting in compendia of toxic plants relevant to those countries. Although the importance of establishing the specific toxic constituents was well appreciated by Marsh and co-workers, the field stations were not conducive to performing the necessary wet chemistry, and instrumentation was virtually nonexistent. The relative toxicity of any particular plant was therefore © 2014 American Chemical Society

Special Issue: Poisonous Plant Symposium, Inner Mongolia Received: January 30, 2014 Published: March 25, 2014 7323

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Symposium Introduction

livestock in the region is regarded as being on a par with sandstorms and soil salinization, all three of which can be catastrophic to producers. Other poisonous plant species, such as Stellera chamaejasme (Thymelaeaceae) are unique to China and surrounding regions, or specifically Inner Mongolia. These species have been extensively described and their effects on livestock defined. On the other hand, the role of chemistry in isolating the toxins, elucidating their structures, and determining their mode of action has not become fully integrated into poisonous plant research process. This collection of papers from the ISOPP9 meeting focuses on research that has taken advantage of modern chemistry techniques to fully understand the deleterious nature of plant toxins on animals and perhaps provide structural leads in areas such as pest control, invasive plant management, and new pharmaceuticals. It is anticipated that the presentations at the very successful Hohhot meeting will provide opportunities for collaboration not only within China but also internationally, so that subsequent ISOPP meetings will reveal novel chemistry. A return to Brisbane, Australia, in 2016 is planned for the ISOPP10 meeting, 32 years after the previous meeting there.

and Alan Seawright. Recognizing many of the commonalities between the two countries in livestock poisoning problems, he proposed a Joint U.S.−Australian Symposium on Poisonous Plants, which was held in Logan, Utah, in 1977. A reciprocal meeting took place in Brisbane, Australia, in 1984. At this meeting it was noted that a number of participants were from countries other than the United States or Australia, and a subsequent meeting, held once again in Logan in 1989, was titled the 3rd International Symposium on Poisonous Plants. The fourth such meeting was held in Fremantle, Western Australia, in 1993, and the Chair of that meeting, Dr. Peter Dorling, proposed that the meetings henceforth adopt the name of International Symposium on Poisonous Plants, codified as ISOPP, followed by the meeting number. Subsequent meetings have been held in San Angelo, Texas, in 1997 (ISOPP5); Glasgow, Scotland, in 2001 (ISOPP6); Logan, Utah, in 2005 (ISOPP7); and João Pessoa, Brazil, in 2009 (ISOPP8). The broadening international scope of these symposia has shown that other countries have gone or are going through a progression of poisonous plant research analogous to that experienced by the United States and Australia, albeit at a much more rapid pace. This consists of documentation of poisoning occurrences, identification of the plant and animal species involved, syndromes of toxicity, and ultimately isolation and structural identification of the specific toxins. It is noteworthy that the ISOPP meetings have led to international collaborations, such as that between the research group of Dr. Franklin Riet Correa in Brazil and chemists at the PPRL in Logan, Utah, currently leading to the identification of new plant toxins. In July 2013, the 9th International Symposium on Poisonous Plants (ISOPP9) was held under the sponsorship of Inner Mongolia Agricultural University and the USDA/ARS Poisonous Plant Research Laboratory at the West Campus of Inner Mongolia Agricultural University in Hohhot, the capital of the Inner Mongolia Autonomous Region of China. After a series of symposia held on the continents of North and South America, Australia, and Europe over more than 30 years, this was the first time that an ISOPP meeting had been held in Asia, a very appropriate venue because the history of poisonous plants in China is well established. It is estimated that there are more than 900 such plant species, belonging to about 100 plant families, affecting livestock. It is noteworthy that many of these species are used in traditional Chinese medicine (TCM). In Inner Mongolia alone, where livestock production is a major economic enterprise, 270 poisonous plant species encompassing 57 plant families have been identified on the extensive grasslands characteristic of the region. The major hazards to grazing livestock are the widespread species Oxytropis glabra, Stellera chamaejasme, and Datura stramonium. O. glabra is a member of one of the two plant genera (Astragalus and Oxytropis) of which certain species have been identified as responsible for locoweed toxicity in the United States, illustrating the common interests in poisonous plant species in disparate parts of the world. In fact, the endophytic toxin, swainsonine, first isolated from Swainsona spp. in Australia15 and subsequently shown to be present in Astragalus and Oxytropis locoweeds in the United States,16,17 has recently been identified in O. glabra and other Chinese Astragalus and Oxytropis species.18 In some areas of western Inner Mongolia 15−30% of the grassland is contaminated by O. glabra, and the direct economic loss due to this plant alone has been estimated at RMB 3 million per year (U.S. $0.5 million/year). Its effect on

Russell J. Molyneux*,† Kip E. Panter‡ Mengli Zhao§ †



Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, Hawaii 96720, United States ‡ Poisonous Plant Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, 1150 East 1400 North, Logan, Utah 84341, United States § Inner Mongolia Agricultural University, 306 Zhaowuda Road, Hohhot, Inner Mongolia, People’s Republic of China 010018

AUTHOR INFORMATION

Corresponding Author

*(R.J.M.) Phone: (808) 933-1661. Fax: (808) 963-2974. Email: [email protected]. Notes

The authors declare no competing financial interest.



REFERENCES

(1) Marsh, C. D. The Locoweed Disease of the Plains; Bureau of Animal Industry Bulletin 112; U.S. Department of Agriculture: Washington, DC, USA, 1909; 130 pp. (2) Marsh, C. D.; Clawson, A. B.; Marsh, H. Larkspur Poisoning of Livestock; Bureau of Animal Industry Bulletin 365; U.S. Department of Agriculture: Washington, DC, USA, 1916; 91 pp. (3) Marsh, C. D. Stock-Poisoning Plants of the Range; Bureau of Animal Industry Bulletin 1245; U.S. Department of Agriculture: Washington, DC, USA, 1924; 75pp. (4) Keeler, R. F. Teratogenic compounds of Veratrum californicum (Durand). VI. The structure of cyclopamine. Phytochemistry 1969, 8, 223−225. (5) Keeler, R. F. Cyclopamine and related steroidal alkaloid teratogens: their occurrence, structural relationship, and biologic effects. Lipids 1978, 13, 708−715. (6) Keeler, R. F. Lupin alkaloids from teratogenic and nonteratogenic lupins. III. Identification of anagyrine as the probable teratogen by feeding trials. J. Toxicol. Environ. Health 1976, 1, 887−889. 7324

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(7) Keeler, R. F.; Balls, L. D. Teratogenic effects in cattle of Conium maculatum and Conium alkaloids and analogs. Clin. Toxicol. 1978, 12, 49−64. (8) Keeler, R. F.; Balls, L. D.; Panter, K. E. Teratogenic effects of Nicotiana glauca and concentration of anabasine, the suspect teratogen in plants. Cornell Vet. 1981, 71, 47−53. (9) Lee, S. T.; Cook, D.; Panter, K. E.; Gardner, D. R.; Ralphs, M. H.; Motteram, E. S.; Pfister, J. A.; Gay, C. C. Lupine induced “crooked calf disease” in Washington and Oregon: identification of the alkaloid profiles in Lupinus sulf ureus, Lupinus leucophyllus, and Lupinus sericeus. J. Agric. Food Chem. 2007, 55, 10649−10655. (10) Bull, L. B.; Culvenor, C. C. J.; Dick, A. T. The Pyrrolizidine Alkaloids: Their Chemistry, Pathogenicity and Other Biological Properties; North-Holland Publishing: Amsterdam, The Netherlands, 1968; 293 pp. (11) Burrows, G. E.; Tyrl, R. J. Toxic Plants of North America, 2nd ed.; Wiley-Blackwell: Ames, IA, USA, 2013; 1390 pp. (12) McKenzie, R. Australia’s Poisonous Plants, Fungi and Cyanobacteria: A Guide to Species of Medical and Veterinary Importance; CSIRO Publishing: Melbourne, Australia, 2012; 976 pp. (13) Kellerman, T. S.; Coetzer, J. A. W.; Naude, T. W.; Botha, C. J. Plant Poisonings and Mycotoxicoses of Livestock in South Africa, 2nd ed.; Oxford University Press Southern Africa: Cape Town, South Africa, 2005; 256 pp. (14) Tokarnia, C. H.; Dobereiner, J.; Peixoto, P. V. Plantas Toxicas do Brasil; Editoria Helianthus: Rio de Janeiro, Brazil, 2000; 310 pp. (15) Colegate, S. M.; Dorling, P. R.; Huxtable, C. R. A spectroscopic investigation of swainsonine: an α-mannosidase inhibitor isolated from Swainsona canescens. Aust. J. Chem. 1979, 32, 2257−2264. (16) Molyneux, R. J.; James, L. F. Loco intoxication: indolizidine alkaloids of spotted locoweed (Astragalus lentiginosus). Science 1982, 216, 190−191. (17) Grum, D. S.; Cook, D.; Gardner, D. R.; Roper, J. M.; Pfister, J. A.; Ralphs, M. H. Influence of seed endophyte amounts on swainsonine concentrations in Astragalus and Oxytropis locoweeds. J. Agric. Food Chem. 2012, 60, 8083−8089. (18) Yu, Y.; Zhao, Q.; Wang, J.; Wang, J.; Wang, Y.; Song, Y.; Geng, G.; Li, Q. Swainsonine-producing fungal endophytes from major locoweed species in China. Toxicon 2010, 56, 330−338.

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