Pharmacognostic Characteristics, Chemistry, Biological Activity And Toxicity of Lolium Species

  • Hussein Ali Hussein Al-Sa'idy Department of Environment and Pollution, Marshes research center, University of Thi-Qar, 64001, Nasiriya, Iraq.
  • Hussein Kamil Hamid College of pharmacy, National University of science and technology, Thi-Qar, Nasiriya, Iraq.


Around seven species of the genous lolium poisonous grasses belonging to the family Poaceae are mutually grown in corps field over the world. In Iraq the prennel ryegrass is locally called “rewatta”.The toxicity of these gasses are related to three chemically distinct alkaloids groups; the aminopyrrolizidine; lolines, indole-diterpenes (ergots, loliterms, and paxillines) as well as peramine alkaloids mostly concentrated in their seeds although indole-diterpene alkaloids loliterm B and paxilline biosynthesis requires endophytes symbiosis. The level of loline alkaloids enhances in both late summer-autumn of the year as well as in the infected dry plant materials up to 10 fold. However, paxilline and ergovaline are believed to be the precursor of the most toxic lolium species alkaloids, loliterm B, although, indole-diterpene alkaloids paxillines, loliterms and ergovaline are the actual indicators of Lolium species. In this review we summarize chemical characteristics, biological and toxicological influences as well as their interrelation of the plant of lolium genus. Central as well as peripheral biological/toxicological manifestations are summarized for both loline and indole-diterpene alkaloids. Finally, toxic influences of lolium alkaloids are function of their biological influences mostly exhibited via resembling molecular mechansims centrally as well as peripherallyare concluded.


Keywords: Pharmacognostic, lolium, alkaloids, chemistry, biological, phytochemicals, toxicity.


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Author Biographies

Hussein Ali Hussein Al-Sa'idy, Department of Environment and Pollution, Marshes research center, University of Thi-Qar, 64001, Nasiriya, Iraq.

Department of Environment and Pollution, Marshes research center, University of Thi-Qar, 64001, Nasiriya, Iraq.

Hussein Kamil Hamid, College of pharmacy, National University of science and technology, Thi-Qar, Nasiriya, Iraq.

College of pharmacy, National University of science and technology, Thi-Qar, Nasiriya, Iraq.


1. Schardl CL, Grossman RB, Nagabhyru P, Faulkner JR, Mallik UP. Loline alkaloids: currencies of mutualism. Phytochemistry. 2007; 68(7): 980-996.‏
2. Vikuk V, Fuchs B, Krischke M, Mueller M J, Rueb S, Krauss J. Alkaloid concentrations of Lolium perenne infected with Epichloë festucae var. lolii with different detection methods—A re-evaluation of intoxication risk in Germany?. Journal of Fungi. 2020; 6(3): 177.‏
3. Reddy P, Deseo MA, Ezernieks V, Guthridge K, Spangenberg G, Rochfort S. Toxic indole diterpenes from endophyte-infected perennial ryegrass Lolium perenne L.: Isolation and stability. Toxins. 2019; 11 :16.
4. Blankenship JD. (2004). Loline alkaloid biosynthesis in Neotyphodium uncinatum, a fungal endophyte of Lolium pratense.‏ Doctor of Philosophy dissertation, College of Agriculture at the University of Kentucky.
5. Arechavaleta M, Bacon CW, Hoveland CS, Radcliffe DE. Effect of the tall fescue endophyte on plant response to environmental stress. Agronomy Journal. 1989; 81: 83-90.
6. Leuchtmann A, Schmidt D, Bush L P. Different levels of protective alkaloids in grasses with stroma forming and seed-transmitted Epichloe/Neotyphodium endophytes. Journal of Chemical Ecology. 2000; 26 :1025-1036.
7. Siegel MR, Latch GCM, Bush LP, Fannin FF, Rowan DD, Tapper B A, Bacon C W, Johnson M C. Fungal endophyte-infected grasses: alkaloid accumulation and aphid response. Journal of Chemical Ecology. 1990; 16:3301-15.
8. Craven KD, Blankenship JD, Leuchtmann A, Hignight K, Schardl CL. Hybrid fungal endophytes symbiotic with the grass Lolium pratense. Sydowia. 2001; 53:44-73.
9. Bush LP, Fannin FF, Siegel M R, Dahlman DL, Burton HR. Chemistry, occurrence and biological effects of saturated pyrrolizidine alkaloids associated with endophyte-grass interactions. Agriculture, Ecosystems & Environment. 1993; 44(4-1): 81-102.
10. Justus M, Witte L, Hartmann T. Levels and tissue distribution of loline alkaloids in endophyte-infected Festuca pratensis. Phytochemistry. 1997; 44 :51-57.
11. Blakemore P R, Kim S-K, Schulze V K, White J D, Yokochi A F T. Asymmetric synthesis of (+)-loline, a pyrrolizidine alkaloid from rye grass and tall fescue. J. Chem. Soc., Perkin Trans. 2001; 1 :1831–1847.
12. Blankenship JD, Spiering MJ, Wilkinson HH, Fannin FF, Bush LP, Schardl CL. Production of loline alkaloids by the grass endophyte, Neotyphodium uncinatum, in defined media. Phytochemistry. 2001; 58 :395-401.
13. Bacon CW. Abiotic stress tolerances, moisture, nutrients, and photosynthesis in endophyte-infected tall fescue. Agriculture Ecosystems & Environment. 1993; 44 :123-141.
14. Yates SG, Tookey HL, Festucine, an alkaloid from tall fescue (Festuca arundinacea Schreb.): chemistry of the functional groups. Aust. J. Chem. 1965; 18(1): 53–60.
15. TePaske MR, Powell RG, Clement SL. Analyses of selected endophyte-infected grasses for the presence of loline-type and ergot-type alkaloids. Journal of Agricultural and Food Chemistry. 1993; 41 :2299-2303.
16. Yunusov SY, Akramov ST. Alkaloids of seeds of Lolium cuneatum. Zhurnal Obshchei Khimii. 1955; 25: 1765-71.
17. Dannhardt G, Steindl L. Alkaloids of Lolium temulentum: isolation, identification and pharmacological activity. Planta Medica. 1985; 51(3) :212-214.
18. Bush LP, Cornelius PL, Buckner RC, Varney SR, Chapman RA, et al. Association of N-acetyl loline and N-formylloline with Epichloe typhina in tall fescue. Crop Sci. 1982; 22:941-943.
19. Jones TA, Buckner RC, Burrus II, PB, Bush LP. Accumulation of pyrrolizidine alkaloids in benomyl-treated tall fescue parents and their untreated progenies. Crop Sci. 1983; 23: 1135-1140.
20. Yu SY, Akramov ST. Alkaloids of seeds of Lolium cuneatum. Zh. Obshch. Khim.1955; 25 :1813-1820.
21. Khan RU. Mehmood S. Khan S U. Toxic effect of common poisonous plants of district Bannu, Khyber Pakhtunkhwa, Pakistan. Pakistan Journal of Pharmaceutical Sciences. 2018; 31(1) :57-67.
22. Holm LG, Plucknett DL, Pancho JV, Herberger JP. (1977) The World’s worst weeds. University Press of Hawaii, Honolulu
23. Senda T, Tominaga T. Genetic diversity of darnel (Lolium temulentum L.) in Malo, Ethiopia depends on traditional farming systems. Econ Bot. 2004; 58 :568–577.
24. Tackholm V. Students Flora of Egypt. Anglo-Egyptian Bookshop Cairo. 1965.
25. Tackholm V, Drar M, Täckholm G. Flora of Egypt (Vol. 1, pp. 113-114). Giza, Egypt: Fouad I University.‏ 1941.
26. Stegelmeier BL, Field R, Panter KE, Hall JO, Welch KD, Pfister JA. (2013). Selected poisonous plants affecting animal and human health. In Haschek and Rousseaux's Handbook of Toxicologic Pathology (pp. 1259-1314). Academic Press.‏
27. Thomas H, Archer E., Turely R. M., (2011), Evolution, Physiology and Phytochemistry of the Psychotoxic Arable Mimic Weed Darnel (Lolium temulentum L.). In Progress in Botany, genetics physiology, systematic ecology. Volume 72. Editors: Lu¨ttge U, Beyschlag W, Bu¨del B, Francis D. (pp. 76, 80) Springer-Verlag Berlin Heidelberg.
28. Yates SG, Fenster JC, Bartelt RJ. Assay of tall fescue seed extracts, fractions, and alkaloids using the large milkweed bug. J. Agric. Food Chem. 1989; 37:354–357.
29. Miles CO, Di Menna ME, Jacobs SWL, Garthwaite I, Lane GA, Prestidge RA, Marshall SL, et al. Endophytic fungi in indigenous Australasian grasses associated with toxicity to livestock. Appl. Environ. Microbiol. 1998; 64 :601–606.
30. Siegel, MR, Latch, GCM., Bush, LP, Fannin, FF, et al. Fungal endophyte infected grasses: alkaloid accumulation and aphid response. J. Chem. Ecol. 1990; 16 :3301–3315.
31. Robbins JD, Sweeny JG, Wilkinson SR, Burdick D. Volatile alkaloids of Kentucky 31 tall fescue seed (Festuca arundinancea). Journal of Agricultural and Food Chemistry. 1972; 20(5):1040-1043.‏
32. Hemken RW. Bush LP. Toxicants of Plant Origin, Vol. I, Cheeke PR, Ed., CRC Press, Boca Raton, Florida, 1989, pp. 281-289.
33. Powell RG, Petroski RJ. The loline group of pyrrolizidine alkaloids. Alkaloids: Chemical and Biological Perspectives. 1992; 8 :320-38. Powell RG, Petroski RJ. (1992). The loline group of pyrrolizidine alkaloids. In Alkaloids: chemical and biological perspectives (pp. 320-338). Springer, New York, NY.‏
34. Porter JK. Analysis of endophyte toxins - Fescue and other grasses toxic to livestock. Journal of Animal Science. 1995; 73 :871-880.
35. Bacon CW. Procedure for isolating the endophyte of tall fescue and screening isolates for ergot alkaloids. Applied and Environmental Microbiology. 1988; 54 :2615-2618.
36. Rowan DD. Lolitrems, perimine, and paxilline--mycotoxins of the ryegrass-endophyte interaction. Agriculture Ecosystems & Environment. 1993; 44 :103-122.
37. Gurney KA, Mantle PG, Penn J, Garthwaite I, Towers NR. Loss of toxic metabolites from Acremonium lolii, the endophyte of ryegrass, following mutagenesis. Naturwissenschaften. 1994; 81 :362-365.
38. Porter JK. (ed.) 1994. Chemical constituents of grass endophytes, pp. 103-123. CRC, Boca Raton, FL.
39. Bush LP, Wilkinson HH, Schardl CL. Bioprotective alkaloids of grass-fungal endophyte symbioses. Plant Physiology. 1997; 114:1-7.
40. Petroski RJ, Yates SG, Weisleder D, Powell RG. Isolation, semi-synthesis, and NMR spectral studies of loline alkaloids. Journal of Natural Products. 1989; 52(4):810-817.‏
41. Schardl CL, Young CA, Faulkner JR, Florea S, Pan J. Chemotypic diversity of Epichloë, fungal symbionts of grasses. Fungal Ecol. 2012; 5:331–344.
42. Burhan W. 1984. Development of Acremonium coenophialum and accumulation of N-acetyl and N-formyl loline in tall fescue (Festuca arundinacea Schreb. ). Master's Thesis, University of Kentucky, Lexington, KY, p. 64.
43. Belesky DP, Robbins JD, Stuedemann JA, Wilkinson SR, Devine OJ. Fungal endophyte infection-loline derivative alkaloid concentration of grazed tall fescue. Agron. J. 1987; 79 :217-220.
44. Buckner RC, Bush LP, Burrus II, PB. 1981. Improvement of forage quality of tall rescue through Lolium-Festuca hybridization. In: Smith JA, Hays VW (Editors), Proc. 14th Int. Grassland Congress 15-24 June, 1981, Lexington, KY, Westview Press, Boulder, CO, pp.157-159.
45. Belesky DP, Stringer WC, Plattner RD. Influence of endophyte and water regime upon tall fescue accessions. II. Pyrrolizidine and ergopeptine alkaloids. Ann. Bot. 1989; 64: 343-349.
46. Liu G, Casqueiro J, Banuelos O, Cardoza RE, Gutierrez S, Martin JF. Targeted inactivation of the mecB gene, encoding cystathionine-gamma-lyase, shows that the reverse transsulfuration pathway is required for high level cephalosporin biosynthesis in Acremonium chrysogenum C10 by not for methionine induction of the cephalosporin genes. Journal of Bacteriology. 2001; 183 :1765-1772.
47. Boettcher F, Ober D, Hartmann T. Biosynthesis of pyrrolizidine alkaloids: putrescine and spermidine are essential substrates of enzymatic homospermidine formation. Canadian Journal of Chemistry. 1994; 72 :80-5.
48. Siegel MR. Bush LP. (eds.).Toxin production in grass/endophyte associations. Springer-Verlag, New York. 1997; Vol.5, pp. 185-207.
49. Smith LS. Culvenor CCJ. Plant sources of hepatotoxic pyrrolizidine alkaloids. J. Nat. Prod. 1981; 44: 129-152.
50. Kennedy CW, Bush LP, Effect of environmental and management factors on the accumulation of N-acetyl and N-formyl loline alkaloids in tall fescue. Crop Sci. 1983; 23:547-552.
51. König J, Fuchs B, Krischke M, Mueller MJ, Krauss J. Hide and seek—Infection rates and alkaloid concentrations of Epichlö festucae var. lolii in Lolium perenne along a land-use gradient in Germany. Grass Forage Sci. 2018; 73: 510–516.
52. Fuchs B, Krischke M, Mueller MJ, Krauss J. Plant age and seasonal timing determine endophyte growth and alkaloid biosynthesis. Fungal Ecol. 2017; 29:52–58.
53. Jensen AMD. Endophyte persistence and toxin (lolitrem b) production in a Danish seed crop of perennial ryegrass. Eur. J. Agron. 2005; 23:68–78.
54. Repussard C, Zbib N, Tardieu D, Guerre P. Ergovaline and lolitrem B concentrations in perennial ryegrass in field culture in southern France: Distribution in the plant and impact of climatic factors. J. Agric. Food Chem. 2014; 62:12707–12712.
55. Bauer JI, Gross M, Cramer B, Humpf H-U, Hamscher G, Usleber E. Immunochemical analysis of paxilline and ergot alkaloid mycotoxins in grass seeds and plants. J. Agric. Food Chem. 2018; 66(1):315–322.
56. Hartmann T. Chemical ecology of pyrrolizidine alkaloids. Planta. 1999; 207:483-495.
57. Stuedemann JA, Rumsey TS, Bond J, Wilkinson SR, Bush LP, Williams DJ, Caudle AB. Association of blood cholesterol with occurrence of fat necrosis in cows and tall fescue summer toxicosis in steers. Am. J. Vet. Res. 1985; 46:1990-1995.
58. Putnam MR, Bransby DI, Schumacher J, Boosinger TR, et al. The effects of the fungal endophyte Acremonium coenophialum in fescue on pregnant mares and foal viability. Am. J. Vet. Res. 1991; 52:2071-2074.
59. Guglielmone AER, de Sanez AM, Carabelli MA, Guglielmoni MB, Basile EO, Severuga JO. Festucas toxicas e inocuas: diferencias en el contenido de alcaloides ysu relacion con un ensayo preliminar a campo. Rev. Asoc. Argent. Consorcios Regionales Experimentacion Agricola (CREA). 1981; 15:40-47.
60. Cakmak M, Mayer P, Trauner D. An efficient synthesis of loline alkaloids. Nature chemistry. 2011; 3(7):543-545.‏
61. Yates SG, Petroski RJ, Powell RG. Analysis of loline alkaloids in endophyte infected tall fescue by capillary gas chromatography. Journal of Agricultural and Food Chemistry. 1990; 38:182-5.
62. Dougherty CT, Knapp FW, Bush LP, Maul JE, Van Willigen J. Mortality of horn fly (Diptera: Muscidae) larvae in bovine during supplemented with loline alkaloids from tall fescue. Journal of Medical Entomology. 1998; 35:798-803.
63. Patterson CG, Potter DA, Fannin FF. Feeding deterrency of alkaloids from endophyte-infected grasses to Japanese beetle grubs. Entomologia Experimentalis et Applicata. 1991; 61:285-9.
64. Wilkinson HH, Siegel MR, Blankenship JD, Mallory AC, Bush LP, Schardl CL. Contribution of fungal loline alkaloids to protection from aphids in a grass endophyte mutualism. Molecular Plant-Microbe Interactions. 2000; 13 :1027-1033.
65. Hincks JR, Kim H-Y, Segall H J, Molyneux RJ, Stermitz FR, Coulombe Jr RA. DNA cross-linking in mammalian cells by pyrrolizidine alkaloids: Structure-activity relationships. Toxicology and Applied Pharmacology.1991; 111:90-98.
66. Kim H-Y, Stermitz FR, Li JK-K, Coulombe Jr RA. 1999. Comparative DNA Crosslinking by activated pyrrolizidine alkaloids. Food and Chemical Toxicology. 1999; 37:619-625.
67. Jones TA, Buckner R C, Burrus P B. Pyrrolizidine alkaloid levels in tall fescue seed as influenced by seed age, location, and variety. Journal of Seed Technology. 1983; 8: 47-54.
68. Hofmeister F. The active constituents of lolium temulentum. Arch. Exp. Pathol. Pharmakol. 1892; 30:203–230.
69. Yunusov SY, Akramov ST. Investigation of the alkaloids of the seeds of Lolium cuneatum (Nevski). J. Gen. Chem. (Moscow). 1955; 25, 1765–1771.
70. Katz, I., Contribution à l'étude de l'ivraie eniurante, Phytopathol. Z. 1949; 15 :495.
71. Akrarnov S T, Yunusov S Y. Chern Nat Cornpd, Engl Transl. 1965; 1:203.
72. Bates RB, Morehead SR. Absolute configurations of pyrrolizidine alkaloids of the loline group. Tetrahedron Lett. 1972; 17:1629-1630.
73. Aasen AJ, Culvenor CCJ. Abnormally low vicinal coupling constants for O–CH–CH in a highly strained five-membered-ring ether; the identity of loline and festucine. Aust. J. Chem. 1969; 22:2021–2024.
74. Yunusov SY, Akramov ST. Structure of norloline, loline, and lolinine. Doklady Akademii Nauk UzSSR. 1959; 24: 28-31.
75. Yunusov SY, Akramov ST. Alkaloids of Lolium cuneatum. II. Zhurnal Obshchei Khimii. 1960; 30:677-82.
76. Batirov EK, Khamidkhodzhaev SA, Malikov VM, Yunusov SY. Alkaloids of LoLium cuneatum. Khimiya Prirodnykh Soedinenii. 1976; 1:60-63.
77. Batirov EK, Malikov V M, Yunusov S Y. Khirn Prir Soedin. 1976; 1: 120.
78. Batirov, E’K, Malikov VM, Yunusov SY, Alkaloids of the seeds of Lolium cuneatum. Chem. Nat. Prod. 1977; 12:114–115.
79. Batirov EK, Malikov VM, Yunusov SY. Khirn Prir Soedin. 1976; 1: 63.
80. Batirov E’K, Malikov VM, Yunusov SY, Lolidine – a new chlorine-containing alkaloid from the seeds of Lolium cuneatum. Chem. Nat. Prod. 1977; 12(1):52–54.
81. Yunusov SY, Akramov ST. Investigation of alkaloids of Lolium cuneatum II. J. Gen. Chem. (Moscow). 1960; 30: 699–704.
82. Yunusov SY, Akramov ST, Structure of norloline, loline and lolinine IV. J. Gen. Chem. (Moscow). 1960; 30 :3105–3109.
83. Gribble GW. Occurrence of halogenated alkaloids. The Alkaloids: Chemistry and Biology. 2012; 71:1-165.‏
84. Hammouda FM. Rizk AM. El-Missiry MM. Ghaleb HA. Madkour MK. Pohland AE. Wood G. Poisonous plants contaminating edible ones and toxic substances in plant foods iv. phytochemistry and toxicity of Lolium temulentum. International Journal of Crude Drug Research. 1988; 26(4): 240-245.‏
85. Pammel LH. Manual of Poisonous Plants. Iowa, The Torch Press, Cedar Rapids. 1911.
86. Bull LB, Culvenor CCJ, Dick AT. The Pyrrolizidine Alkaloids. North Holland Publishing Company. 1969.
87. Takeda A, Suzuki E, Kamei K, Nakata H. Detection and identification of loline and its analogues in horse urine. Chem. Pharm. Bull. 1991; 39:964–968.
88. Tufariello JJ, Meckler H, Winzenberg K. Synthesis of the lolium alkaloids. The Journal of Organic Chemistry; 1986; 51(18):3556-3557.‏
89. Hume DE, Ryan GD, Gibert A, Helander M, Mirlohi A, Sabzalian MR. Epichloë fungal endophytes for grassland ecosystems. In Sustainable Agriculture Reviews; Sustainable Agriculture Reviews; Lichtfouse E, Ed.; Springer International Publishing: Cham, Switzerland, 2016; Volume 19, pp. 233–305.
90. Imlach WL, Finch SC, Dunlop J, Meredith AL, Aldrich RW, Dalziel JE. The molecular mechanism of “ryegrass staggers”, a neurological disorder of K+ channels. J. Pharmacol. Exp. Ther. 2008; 327:657–664.
91. Di Menna M, Finch SC, Popay AJ, Smith BL. A review of the Neotyphodium lolii/Lolium perenne symbiosis and its associated effects on animal and plant health, with particular emphasis on ryegrass staggers. N. Z. Vet. J. 2012; 60:315–328.
92. Young CA, Tapper BA, May K, Moon CD, Schardl CL, Scott B. Indole-diterpene biosynthetic capability of Epichloë endophytes as predicted by ltm gene analysis. Appl. Environ. Microbiol. 2009; 75:2200−2211.
93. Saikia S, Takemoto D, Tapper BA, Lane GA, Fraser K, Scott B. Functional analysis of an indole-diterpene gene cluster for lolitrem B biosynthesis in the grass endosymbiont. FEBS Lett. 2012; 586:2563−2569.
94. Schardl CL, Young CA, Hesse U, Amyotte S, Andreeva K, et al. Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid loci. PLoS Genet. 2013; 9:1−26.
95. Weedon CM, Mantle PG. Paxilline biosynthesis by Acremonium loliae; a step towards defining the origin of lolitrem neurotoxins. Phytochemistry 1987, 26:969−971.
96. Adhikari KB, Boelt B, Fomsgaard IS. Identification and quantification of loline-type alkaloids in endophyte-infected grasses by LC-MS/MS. J. Agric. Food Chem. 2016; 64:6212−6218.
97. Repussard C, Tardieu D, Alberich M, Guerre P. A new method for the determination of lolitrem B in plant materials. Anim. Feed Sci. Technol. 2014; 193:141−147.
98. Cagaš B, Flieger M, Olšowská J. Concentration of ergot alkaloids in Czech ecotypes of Lolium perenne and Festuca pratensis. Grass Forage Sci. 1999; 54:365−370.
99. Garthwaite I, Miles CO, Towers NR. Immunological detection of the indole diterpenoid tremorgenic mycotoxins. In Proceedings of the Second International Symposium on Acremonium/ Grass Interactions; Hume DE, Latch GCM, Easton HS, Eds.; AgResearch: Palmerston North, New Zealand, 1993; pp.77−80.
100. Davies E, Lane GA, Latch GCM, Tapper BA, et al. Alkaloid concentrations in field-grown synthetic perennial ryegrass endophyte associations. In Proceedings of the Second International Symposium on Acremonium/Grass Interactions; Hume DE, Latch GCM, Easton HS, Eds.; AgResearch: Palmerston North, New Zealand, 1993; pp.72−76.
101. Lewis GC, Clements ROA survey of ryegrass endophyte (Acremonium loliae) in the U.K. and its apparent ineffectuality on a seedling pest. J. Agric. Sci. 1986; 107:633−638.
102. Oldenburg E. Endophytic fungi and alkaloid production in perennial ryegrass in Germany. Grass Forage Sci. 1997; 52:425−431.
103. Dapprich P, Paul VH, Krohn K. Incidence of Acremonium endophytes in selected German pastures and the contents of alkaloids in Lolium perenne. In The 2nd International Conference on Harmful and Beneficial Microorganisms in Grassland, Pastures and Turf, Paderborn, Germany; Krohn K, Paul VH. Eds.; IOBC/WPRS Bulletin: Avignon, France, 1996; Vol 19, pp.103−114.
104. Duke JA. Wild lettuce: a bitter herb of biblical proportions. J. Med. Food. 2000; 3: 153−154.
105. Strickland JR, Bailey EM, Abney LK, Oliver JW. Assessment of the mitogenic potential of the alkaloids produced by endophyte (Acremonium coenophialum)-infected tall fescue (Festucaarundinacea) on bovine vascular smooth muscle in vitro. J. Anim. Sci. 1996; 74:1664–1671.
106. Larson BT, Samford MD, Camden JM, Piper EL, Kerley MS, Paterson JA, Turner JT. Ergovaline binding and activation of D2 dopamine receptors in GH4ZR7 cells. J Animal Sci. 1995; 73: 1396-1400.
107. Dew RK, Boissonneault GA, Gay N, Boling JA, CrossRJ, Cohen DA. The effect of the endophyte (Acremonium coenophialum) and associated toxin(s) of tall fescue on serum titer response to immunization and spleen cell flow cytometry analysis and response to mitogens. Vet Immunnol Immunopathol. 1990; 26:285-295.
108. Hornung R, Presek P, Glossmann H. Alpha adrenoceptors in rat brain: Direct identification with prazosin. Naunyn-Schmiedebergs Arch. Pharmakol. 1979; 308(3): 223-230.
109. Peroutka SJ. Snyder SH. Multiple serotonin receptors: differential binding of [3H] 5-hydroxytryptamine,[3H] lysergic acid diethylamide and [3H] spiroperidol. Molecular pharmacology. 1979; 16(3):687-699.‏
110. Yamamura HI, Snyder SH. Muscarinic cholinergic binding in rat brain. Proceedings of the National Academy of Sciences. 1974; 71(5):1725-1729.‏
111. Lukasiewicz RJ, Bennett EL. α-Bungarotoxin binding properties of a central nervous system nicotinic acetylcholine receptor. Biochimica et Biophysica Acta (BBA)-General Subjects. 1978; 544(2):294-308.‏
112. Squires RF. Braestrup C. Benzodiazepine receptors in rat brain. Nature. 1977; 266(5604):732-734.‏
113. Strickland JR. Cross DL. Jenkins TC. Petroski RJ. Powell RG. The effect of alkaloids and seed extracts of endophyte-infected tall fescue on prolactin secretion in an in vitro rat pituitary perfusion system. J. Anim. Sci. 1992; 70:2779–2786.
114. Larson BT, Harmon DL Piper EL Griffis LM Bush LP. Alkaloid binding and activation of D2 dopamine receptors in cell culture. J. Anim. Sci. 1999; 77:942–947.
115. Jackson JA, Hemken RW, Bush LP, Boling JA, Siegel MR, Zavos PM, Yates SG. Physiological responses in rats fed extracts of endophyte infected tall rescue seed. Drug Chem. Toxicol. 1987; 10:369-379.
116. Jackson JA, Yates SG, Powell RG, Hemken RW, Bush LP, Boling JA, Zavos PM, Siegel MR. Physiological responses in rats fed extracts of endophyte-free and endophyte-infected tall rescue seed relative to some known ergot alkaloids. Drug Chem. Toxicol. 1989; 12:147-164.
117. Strickland JR, Cross DL, Birrenkott GP, Grimes LW, Effect of ergovaline, loline, and dopamine antagonists on rat pituitary cell prolactin release in vitro. Am. J. Vet. Res. 1994; 55:716–721.
118. Strickland J, Cross D, Jenkins T, Petroski R,PowellR, The effect of alkaloids and seed extracts of endophyte infect fescue on prolactin secretion in an in vitro rat pituitary perfusion system. Journal of Animal Science. 1992; 70:2779-2786.
119. Oliver JW, Strickland JR, Waller JC, Fribourg HA, Linnabary RD, Abney LK, Endophytic fungal toxin effect on adrenergic receptors in lateral saphenous veins (cranial branch) of cattle grazing tall fescue. J. Anim. Sci. 1998; 76:2853–2856.
120. Solomons RN, Oliver JW, Linnabary RD, Reactivity of dorsal pedal vein of cattle to selected alkaloids associated with Acremoniumcoenophialum-infected fescue grass. Am. J. Vet. Res. 1989; 50:235–238.
121. Klotz J, Kirch B, Aiken G, Bush L, Strickland, J. Effects of selected combinations of tall fescue alkaloids on the vasoconstrictive capacity of fescue-naive bovine lateral saphenous veins. Journal of Animal Science. 2008; 86:1021-1028.
122. Abney L, Oliver J, Reinemeyer C, Vasoconstrictive effects of tall fescue alkaloids on equine vasaculature. Journal of Equine Veterinary Science. 1993; 13(6):334-340.
123. Oliver J. Physiological manifestations of endophyte toxicosis in ruminant and laboratory species. In: Bacon C, Hill N, Neotyphodium/Grass Interactions. 1997; (pp. 311-346). New York: Plenum Press.
124. Dougherty CT, Lauriault LM, Bradley NW, Gay N, Cornelius PL. Induction of tall fescue toxicosis in heat-stressed cattle and its alleviation with thiamin. J. Anim. Sci. 1991; 69:1008-1018.
125. Edwin EE. Jackman R. Ruminant thiamin requirements in perspective. Vet. Res. Commun. 1982; 5:237-250.
126. Karimov VA, Kamilov IK, Pharmacology of the new loline alkaloid and of its derivative. Dok. Akad. Nauk Uzb. SSR. 1961; 12:43-47.
127. Petroski RJ, Powell RG, Ratnayake S, McLaughlin JL. Note: Cytotoxic Activities of N-Acyllolines. International journal of pharmacognosy. 1994; 32(4):409-412.‏
128. Ruan J, Liao C, Ye Y, Lin G. Lack of metabolic activation and predominant formation of an excreted metabolite of nontoxic platynecine-type pyrrolizidine alkaloids. ChemicalResearch in Toxicology. 2014; 27:7-16.
129. Rowan DD. Lolitrems, peramine and paxilline: mycotoxins of the ryegrass/endophyte interaction. Agriculture, Ecosystems & Environment. 1993; 44(1-4):103-122.‏
130. Reddy P, Rochfort S, Read E, Deseo M, Jaehne E, Van Den Buuse M, et al. Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates. Scientific reports. 2019; 9(1):1-17.‏
131. Gallagher RT, Hawkes AD. The potent tremorgenic neurotoxins lolitrem B and aflatrem: a comparison of the tremor response in mice. Experientia.1986;42:823–825.
132. McLeay LM, Mith BL, Munday-Finch SC. Tremorgenic mycotoxins paxilline, penitrem and lolitrem B, the non-tremorgenic 31-epilolitrem B and electromyographic activity of the reticulum and rumen of sheep. Res. Vet. Sci. 1999; 66:119–127.
133. Combs MD,et al. Development of a model for investigation of perennial ryegrass toxicosis in sheep. N Z Vet J. 2018;66:281–289.
134. Sallam AA,et al. Bioguided discovery and pharmacophore modeling of the mycotoxic indole diterpene alkaloids penitrems as breast cancer proliferation, migration, and invasion inhibitors. Med Chem Comm.2013; 4:1360–1369.
135. Sallam AA,et al. Indole diterpene alkaloids as novel inhibitors of the Wnt/β-catenin pathway in breast cancer cells. Eur J Med Chem. 2013;70:594–606.
136. Goda AA,et al. Astaxanthin and docosahexaenoic acid reverse the toxicity of the maxi-K (BK) channel antagonist mycotoxin penitrem A. Mar Drugs. 2016;14: 208.
137. Johnstone LK, Mayhew IG, Fletcher LR. Clinical expression of lolitrem B (perennial ryegrass) intoxication in horses. Equine Vet. J. 2012; 44:304–309.
138. Knaus H-G. et al. Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry. 1994;33:5819–5828.
139. Imlach WL, Finch SC, Dunlop J, Dalziel JE. Structural determinants of lolitrems for inhibition of BK large conductance Ca2+-activated K+ channels. Eur. J. Pharmacol. 2009; 605:36–45.
140. Miles CO, Wilkins AL, Gallagher RT, Hawkes AD, Munday SC, Towers NR, Synthesis and Tremorgenicity of Paxitriols and Lolitriol: Possible Biosynthetic Precursors of Lolitrem B. J. Agric. Food Chem. 1992; 40:234–238.
141. Cole RJ, Cox RH. Handbook of Toxic Fungal Metabolites (Academic Press, New York, NY). 1981; p.355.
142. Finch SC, Fletcher LR, Babu JV. The evaluation of endophyte toxin residues in sheep fat. N Z Vet J. 2011;60: 56–60.
143. Miyazaki S, Ishizaki I, Ishizaka M, Kanbara T, Ishiguro-Takeda Y. Lolitrem B residue in fat tissues of cattle consuming endophyte-infected perennial ryegrass straw. J. Vet. Diagn. Invest. 2004; 16:340–342.
144. Shimada N, et al. Toxicological evaluation and bioaccumulation potential of lolitrem B, endophyte mycotoxin in Japanese black steers. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2013; 30:1402–1406.
145. Munday-Finch SC, Garthwaite I. Toxicology of Ryegrass Endophyte in Livestock. Ryegrass Endophyte Essent. N. Z. Symbiosis Grassl. Res. Pract. Ser. 1999; 7:63–67.
146. Finch S, Thom E, Babu J, Hawkes A, Waugh C. The Evaluation of Fungal Endophyte Toxin Residues in Milk. N. Z. Vet. J. 2013; 61:11–17.
147. Zbib N, Repussard C, Tardieu D, Priymenko N, Domange C, Guerre P. Toxicity of Endophyte-Infected Ryegrass Hay Containing High Ergovaline Level in Lactating Ewes. J. Anim. Sci. 2015; 93:4098–4109.
148. Dalziel JE. Dunstan K E. Finch S C. Combined Effects of Fungal Alkaloids on Intestinal Motility in an in Vitro Rat Model. J. Anim. Sci. 2013; 91:5177–5182.
149. Fletcher LR, Easton HS. The Evaluation and Use of Endophytes for Pasture Improvement. In Neotyphodium/Grass Interactions; Bacon CW. Hill NS. Eds.; Springer: New York, NY, USA, 1997; pp. 209–227.
150. Bluett SJ, Thom ER, Clark DA, Macdonald KA, Minneé EMK. Effects of Perennial Ryegrass Infected with Either AR1 or Wild Endophyte on Dairy Production in the Waikato. N. Z. J. Agric. Res. 2005; 48:197–212.
151. Thom ER, Waugh CD, Minneé EMK. Dairy Cow Responses to the Wild-Type Endophyte in Perennial Ryegrass. In Proceedings of the 4th Australasian Dairy Science Symposium 2010, Hamilton, New Zealand, 2010; pp. 370–375.
152. Ruckebusch Y, Malbert CH, Crichlow EC. Hexamethonium: A Probe to Assess Autonomic Nervous System Involvement in Upper Gastrointestinal Functions in Conscious Sheep. Vet. Res. Commun. 1987; 11:293–303.
153. Dalziel JE, Dunlop J, Finch SC, Wong SS. Immune Response Inhibition Using Indole Diterpene Compound. WO2006115423A1, 2006. Available online: (accessed on 2 November 2018).
154. Betina V. Indole derived tremorgenic toxins. In: Betina V. (Editor), Mycotoxins Production, Isolation, Separation and Purification. Developments in Food Science, 8. Elsevier Scientific Publishing Company, Amsterdam/Oxford/New York, pp. 415-442.
155. Munday-Finch SC, Wilkins AL, Miles CO, Tomoda H, O’mura S. Isolation and Structure Elucidation of Lolilline, a Possible Biosynthetic Precursor of the Lolitrem Family of Tremorgenic Mycotoxins. J. Agric. Food Chem. 1997; 45:199–204.
156. Wang L, Cross AL, Allen KL, Smith BL, McLeay LM. Tremorgenic Mycotoxins Increase Gastric Smooth Muscle Activity of Sheep Reticulum and Rumen in Vitro. Res. Vet. Sci. 2003; 74:93–100.
157. Gallagher RT, White EP, Mortimer PH. Ryegrass Staggers: Isolation of Potent Neurotoxins Lolitrem A and Lolitrem B from Staggers-Producing Pastures. N. Z. Vet. J. 1981; 29:189–190.
158. Easton HS, Lane GA, Tapper BA, Keogh RG, Cooper BM, Blackwell M, Fletcher LR. Ryegrass Endophyte-Related Heat Stress in Cattle. Proc. N. Z. Grassland Assoc. 1995; 57:37–41.
159. Auldist MJ, Thom ER. Effects of Endophyte Infection of Perennial Ryegrass on Somatic Cell Counts, Mammary Inflammation, and Milk Protein Composition in Grazing Dairy Cattle. N. Z. J. Agric. Res. 2000; 43:345–349.
160. Hovermale JT, Craig AM. Correlation of Ergovaline and Lolitrem B Levels in Endophyte-Infected Perennial Ryegrass Lolium Perenne. J. Vet. Diagn. Investig. 2001; 13:323–327.
161. Benkhelil A, Grancher D, Giraud N, Bezille P, Bony S. Intoxication Par Des Toxines de Champignons Endophytes Chez Des Taureaux Reproducteurs. Rev. Méd. Vét. 2004; 156:243–247.
162. Zbib N, Repussard C, Tardieu D, Priymenko N, Domange C, Guerre P. Ergovaline in Tall Fescue and Its Effect on Health, Milk Quality, Biochemical Parameters, Oxidative Status, and Drug Metabolizing Enzymes of Lactating Ewes. J. Anim. Sci. 2014; 92:5112–5123.
163. Gadberry MS, Denard TM, Spiers DE, Piper EL. Effects of Feeding Ergovaline on Lamb Performance in a Heat Stress Environment. J. Anim. Sci. 2003; 81:1538–1545.
164. Tor-Agbidye J, Blythe LL, Craig AM, Correlation of Endophyte Toxins ergovaline and Lolitrem B. with Clinical Disease: Fescue Foot and Perennial Ryegrass Staggers. Vet. Hum. Toxicol. 2001; 43:140–146.
165. Guerre P. Ergot Alkaloids Produced by Endophytic Fungi of the Genus Epichloë. Toxins. 2015; 7:773–790.
166. Easton HS, Christensen MJ, Eerens JPJ, Fletcher LR, Hume DE, Keogh RG, et al. Ryegrass Endophyte: A New Zealand Grassland Success Story. Proc. N. Z. Grassl. Assoc. 2001; 63:37–46.
167. Springer JP, Clardy J, Wells JM, Cole RJ, Kirksey JW. The structure of paxilline, a tremorgenic metabolite of Penicillium paxilli Bainier. Tetrahedron. Lett. 1975; 16:2531–2534.
168. Garcia ML, Galvez A, Garcia-Calvo M, King VF, Vazquez J, Kaczorowski GJ. Use of toxins to study potassium channels, J. Biomembr. Bioenerg. 1991; 23:615.
169. Giangiacomo KM, Garcia ML, McManus O. Mechanism of the iberiotoxin block of the large conductance calcium-activated potassium channel from bovine aortic smooth muscle. Biochemistry. 1992; 31:6719.
170. Selala MI, Laekeman GM, Loendrs B, Musuku A, Herman A, Schenfens P. In vitro effects of tremorgenic mycotoxins. J. Nat. Prod. 1991; 54:207-212.
171. Matsui C, Ikeda Y,Iinuma H, Kushida N, Kunisada T, Simizu S, Umezawa K. Isolation of a novel paxilline analog pyrapaxilline from fungus that inhibits LPS-induced NO production. The Journal of Antibiotics. 2014; 67(11):787-790.
172. Papavlassopoulos M, et al. MaxiK blockade selectively inhibits the lipopolysaccharide induced I kappa B-alpha/NF-kappa B signaling pathway in macrophages. J. Immunol. 2006; 177:4086–4093.
173. Fan Y, Wang Y, Liu P, Fu P, Zhu T, Wang W,Zhu W. Indole-diterpenoids with anti-H1N1 activity from the aciduric fungus Penicillium camemberti OUCMDZ-1492. J. Nat. Prod. 2013; 76: 1328–1336.
174. DeFarias F P. Carvalho M F. Lee S H. Kaczorowski G J. Suarez-Kurtz G. Effects of the K+ channel blockers paspalitrem-C and paxilline on mammalian smooth muscle. European journal of pharmacology. 1996; 314(1-2):123-128.‏
175. Smith BL, McLeay LM, Embling PP. Effect of the Mycotoxins Penitrem, Paxilline and Lolitrem B on the Electromyographic Activity of Skeletal and Gastrointestinal Smooth Muscle of Sheep. Res. Vet. Sci. 1997; 62:111–116.
176. McLeay LM, Smith BL. Effects of the Mycotoxins Lolitrem B and Paxilline on Gastrointestinal Smooth Muscle, the Cardiovascular and Respiratory Systems, and Temperature in Sheep. Ryegrass Endophyte: An Essential New Zealand Symbiosis. Grassland Res. Pract. Ser. 1999; 7:69–76.
177. Sanchez M, McManus OB. Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel. Neuropharmacology. 1996; 35:963–968.
178. Imlach WL, Finch SC, Zhang Y, Dunlop J, Dalziel JE. Mechanism of action of lolitrem B, a fungal endophyte derived toxin that inhibits BK large conductance Ca2+-activated K+ channels. Toxicon. 2011; 57:686–694.
179. Gant DB, Cole RJ, Valdes JJ, Eldefrawi ME, Eldefrawi AT. Action of Tremorgenic Mycotoxins on GABAA Receptor. Life Sci. 1987; 41:2207–2214.
180. Norris PJ, Smith CCT, De Belleroche J, Bradford HF, Mantle PG, Thomas AJ, Penny RHC. Actions of Tremorgenic Fungal Toxins on Neurotransmitter Release. J. Neurochem. 1980; 34:33–42.
181. Cole RJ, Kirksey JW, Wells JM. A new tremorgenic metabolite from Penicillium paxilli. Can. J. Microbial. 1974; 20:1159-1162.
182. Gallagher RT, Keogh RG, Latch GCM, Reid CSW. The role of fungal tremorgens in ryegrass staggers. NZ J. Agric. Res. 1977; 20:431-440.
183. Lee US, Cui J. BK Channel Activation: Structural and Functional Insights. Trends Neurosci. 2010; 33:415–423.
184. Munday-Finch SC, Wilkins AL, Miles CO, Ede, Thomson RA. Structure Elucidation of Lolitrem F, a Naturally Occurring Stereoisomer of the Tremorgenic Mycotoxin Lolitrem B, Isolated from Lolium Perenne Infected with Acremonium Lolii. J. Agric. Food Chem. 1996; 44:2782–2788.
185. Dalziel JE, Finch SC, Dunlop J. The Fungal Neurotoxin Lolitrem B Inhibits the Function of Human Large Conductance Calcium-Activated Potassium Channels. Toxicol. Lett. 2005; 155:421–426.
186. McMillan LK, Carr RL, Young CA, Astin JW, Lowe RG, et al. Molecular analysis of two cytochrome P450 monooxygenase genes required for paxilline biosynthesis in Penicillium paxilli, and e_ects of paxilline intermediates on mammalian maxi-K ion channels. Mol. Genet. Genomics. 2003; 270: 9–23.
187. Aniszewski T. Alkaloids - Secrets of Life. Amsterdam: Elsevier Science. 2007.
188. Froehlich KA. Metabolism of loline in ruminants and their potential effects on microflora, and gastrointestinal nematodes. In Animal Science; Lincoln University: Lincoln, New Zealand, 2020; p. 120.
189. Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv. Drug. Deliv. Rev. 2009; 61:158–171.
190. Rudolph W, Remane D, Wissenbach DK, Peters FT. Development and validation of an ultrahigh performance liquid chromatography-high resolution tandem mass spectrometry assay for nine toxic alkaloids from endophyte-infected pasture grasses in horse serum. J. Chromatogr. A. 2018; 1560:35–44.
191. TePaske MR, Powell RG, Clement SL, Quantitative analyses of bovine urine and blood plasma for loline alkaloids. J. Agric. Food Chem. 1993; 41:231–234.
192. Froehlich KA.Metabolism of loline in ruminants and their potential effects on microflora, and gastrointestinal nematodes. PhD thesis submitted to Lincoln University. 2020; pp: i-iii.
193. Seawright A, Hrdlicka J, Wright J, Kerr D. The identification of hepatic pyrrolizidine alkaloids in horse by the demonstration of sulfur bound pyrrolic metabolites to their haemoglobin. Veterinary and Human Toxicology. 1991; 33(3):286-287.
194. Gooneratne SR, Patchett BJ, Wellby M, Fletcher LR. Excretion of loline alkaloids in urine and faeces of sheep dosed with meadow fescue (Festuca pratensis) seed containing high concentrations of loline alkaloids. N. Z. Vet. J. 2012; 60:176–182.
195. Westendorf M, Mitchell G, Tucker R, Bush L. In Vitro and In Vivo Ruminal and Physiological Responses to Endophyte-Infected Tall Fescue. Journal of Dairy Science. 1993; 76:555-563.
196. Rudolph W, Remane D, Wissenbach DK, Peters FT. Liquid chromatography-mass spectrometry-based determination of ergocristine, ergocryptine, ergotamine, ergovaline, hypoglycin A, lolitrem B, methylene cyclopropyl acetic acid carnitine, N-acetylloline, Nformylloline, paxilline, and peramine in equine hair. Journal of Chromatography B,.2019; 1117:127-135.
197. Grancher D, Durix A, Moulard Y, Bonnaire Y. Carcelen M. Camier Y. Bony S. Distribution Du Lolitrème B et de L’ergovaline Après Un Bolus Intraruminal Chez La Chèvre En Lactation; Rencontres Recherches Ruminants: Paris, France, 2004; Volume 11, p. 37.
198. Mantle PG, Burt SJ, Bilton JN. The role of the ryegrass endophyte (Acremonium loliae) in ruminant neurotoxicosis. Proc. Jpn. Assoc. Mycotoxicol. 1988; (Suppl. 1):115-116.
199. Cheeke PR. Pyrrolizidine alkaloid toxicity and metabolism in laboratory animals and livestock. In: Cheeke P R. (Editor), Toxicants of Plant Origin. Vol I. Alkaloids. CRC Press, Boca Raton, FL, 1989; pp. 1-22.
200. Ruan J, Yang M, Fu P, Yang Y, Lin G. Metabolic activation of pyrrolizidine alkaloids: insights into the structural and enzymatic basis. Chemical Research in Toxicology. 2014; 27:1030-1039.
201. Stegelmeier BL, Edgar JA, Colegate SM, Gardner DR, Schoch TK, Coulombe RA, Molyneux RJ. Pyrrolizidine alkaloids plants, metabolism and toxicity. Journal ofNatural Toxins. 1991; 8(1):95-116.
202. Mattocks AR. Chemistry and toxicology of pyrrolizidine alkaloids. Orlando: Academic Press. 1986.
203. Dominguez-Bello MG. Detoxification in the rumen. Annales De Zootechnie. 1996; 45(suppl):323-327.
204. Mattocks RA, Jukes R. Recovery of the pyrrolic nucleus of pyrrolizidine alkaloid metabolites from sulphur conjugates in tissues and body fluids. Chemical-BiologicalInteractions. 1990; 75:225-239.
205. Jackson JA, Varney DR, Petroski RJ, Powell RG, Bush LP, Siegel MR, Hemken RW, Zavos PM. Physiological responses of rats fed loline and ergot alkaloids from endophyte-infected tall fescue. Drug and Chemical Toxicology. 1996; 19(1&2):85-96.
206. Wang T, Frandsen HL, Christiansson NR, Rosendal SE, Pedersen M, Smedsgaard J. Pyrrolizidine alkaloids in honey: Quantification with and without standards. Food Control. 2019; 98:227–237.
207. König J, Fuchs B, Krischke M, Mueller MJ, Krauss J. Hide and seek—Infection rates and alkaloid concentrations of Epichloe festucae var. lolii in Lolium perenne along a land-use gradient in Germany. Grass Forage Sci. 2018; 73:510–516.
208. Byam W, Archibald RG. The Practice of Medicine in Tropics. Frowde, Hodder. and Stoughlon, London (1921-1923).
209. Watt JM, Breyer-Brandwijk MG. The Medicinal and Poisonous Plants of Southern and Eastern Africa. E. & S. Livingstone, London. 1962. 2nd edition.
210. Katz I. Contribution à l'étude de l'ivraie eniurante. Phytopathol. Z. 1949;15: 495.
211. Casabuono AC, Pomilio AB. Alkaloids from endophyte-infected Festuca argentina. Journal of Ethnopharmacology. 1997; 57:1-9.
212. Finch S, Munday J, Munday R. Kerby J. Short-term toxcity studies of loline alkaloids in mice. Food and Chemical Toxicology. 2016; 94:243-249.
213. Vikuk V, Young CA, Lee ST, Nagabhyru P, Krischke M, Mueller MJ, Krauss J. Infection rates and alkaloid patterns of different grass species with systemic Epichloë endophytes. Appl. Environ. Microbiol. 2019; 85:e00465-19.
214. Gallagher RT, Campbell AG, Hawkes AD, Holland PT, McGaveston DA, Pansier EA, Ryegrass staggers: The presence of lolitrem neurotoxins in perennial ryegrass seed. N. Z. Vet. J. 1982; 30:183–184.
215. Philippe G. Lolitrem B and indole diterpene alkaloids produced by endophytic fungi of the genus Epichloë and their toxic effects in livestock. Toxins. 2016; 8(2):47.‏
216. Craig AM, Blythe LL, Duringer JM. The role of the Oregon State University Endophyte Service Laboratory in diagnosing clinical cases of endophyte toxicoses. J. Agric. Food Chem. 2014; 62:7376–7381.
217. Miles CO, Lane GA, Di Menna ME, Garthwaite I, et al. High levels of ergonovine and lysergic acid amide in toxic Achnatherum inebrians accompany infection by an Acremonium-like endophytic fungus. J. Agric. Food Chem. 1996; 44:1285−1290.
218. Rowan DD, Shaw GJ. Detection of ergopeptine alkaloids in endophyte-infected perennial ryegrass by tandem mass spectrometry. N. Z. Vet. J. 1987; 35:197−198.
219. Fletcher LR, Garthwaite I, Towers NR. Ryegrass staggers in the absence of lolitrem B. In Proceedings of the Second International Symposium on Acremonium/Grass Interactions; Hume D E, Latch G C M, Easton H S, Eds.; AgResearch: Palmerston North, New Zealand, 1993; pp.119−121.
220. Saikkonen K, Lehtonen P, Helander M, Koricheva J, Faeth SH. Model systems in ecology: Dissecting the endophyte-grass literature. Trends Plant Sci. 2006; 11:428–433.
221. Rowan DD, Dymock JJ, Brimble MA. Effect of fungal metabolite peramine and analogs on feeding and development of Argentine stem weevil (Listronotus bonariensis). J. Chem. Ecol. 1990; 16:1683-1695
222. Vamey DR, Prestidge RA, Jones DD, Varney LA, Zavos PM, Siegel MR. Effect of endophyte-infected perennial ryegrass seed diets on growth and reproduction in mice. NZ J. Agric. Res. 1989; 32:547-554.
223. Cunningham IJ, Hartley WJ. Ryegrass staggers. NZ Vet. J. 1959; 7:1-7.
224. Aboling S, Drotleff AM, Cappai MG, Kamphues J. Contamination with ergot bodies (Claviceps purpurea sensu lato) of two horse pastures in Northern Germany. Mycotoxin Res. 2016; 32:207−219.
225. Lorenzo-Velazquez B, Dominguez L A. Estudio experimental sobre la ototoxicidad de los fármacos: y sal sódica del acido fusídico. Arch. Inst. Farmacol. Exptl. (Madrid); 1965; 17(1):83.
226. Page MG, Ankona-Sey V, Coulson WF, Bender DA. Brain glutamate and gamma-aminobutyrate (GABA) metabolism in thiamin-deficient rats. Br. J. Nutr. 1989; 62:245- 253.
227. Porter JK, Stuedemann JA, Thompson Jr. FN, Lipham LB. Neuroendocrine measurements in steers grazed on endophyte-infected fescue. J. Anim. Sci. 1990; 68:3285-3292.
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Al-Sa’idy, H. A. H., & Hamid, H. K. (2022). Pharmacognostic Characteristics, Chemistry, Biological Activity And Toxicity of Lolium Species. Asian Journal of Pharmaceutical Research and Development, 10(6), 77-94.