Abstract
Kynurenic acid (KYNA) is an endogenous antagonist of the ionotropic glutamate receptors
and the α7 nicotinic acetylcholine receptor as well as an agonist of the G-protein-coupled
receptor GPR35. In this study, KYNA distribution and synthesis in plants as well as
its absorption was researched. KYNA level was determined by means of the high-performance
liquid chromatography with fluorescence detection. KYNA was found in leaves, flowers,
and roots of tested medicinal herbs: dandelion (Taraxacum officinale), common nettle (Urtica dioica), and greater celandine (Chelidonium majus). The highest concentration of this compound was detected in leaves of dandelion
– a mean value of 0.49 µg/g wet weight. It was shown that KYNA can be synthesized
enzymatically in plants from its precursor, L-kynurenine, or absorbed by plants from
the soil. Finally, the content of KYNA was investigated in 21 herbal tablets, herbal
tea, herbs in sachets, and single herbs in bags. The highest content of KYNA in a
maximum daily dose of herbal medicines appeared in St. John's wort – 33.75 µg (tablets)
or 32.60 µg (sachets). The pharmacological properties of KYNA and its presence in
high concentrations in medicinal herbs may suggest that it possesses therapeutic potential,
especially in the digestive system and should be considered a new valuable dietary
supplement.
Key words
kynurenic acid - medicinal plants - synthesis - absorption
References
- 1
Liebig J.
Über Kynurensäure.
Justus Liebigs Ann Chem.
1853;
86
125-126
- 2
Ganong A H, Cotman C W.
Kynurenic acid and quinolinic acid act at N-methyl-D-aspartate receptors in the rat
hippocampus.
J Pharmacol Exp Ther.
1986;
236
293-299
- 3
Hilmas C, Pereira E F, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque E X.
The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and
increases non-alpha7 nicotinic receptor expression: physiopathological implications.
J Neurosci.
2001;
21
7463-7473
- 4
Perkins M N, Stone T W.
An iontophoretic investigation of the actions of convulsant kynurenines and their
interaction with the endogenous excitant quinolinic acid.
Brain Res.
1982;
247
184-187
- 5
Turski W A, Nakamura M, Todd W P, Carpenter B K, Whetsell Jr W O, Schwarcz R.
Identification and quantification of kynurenic acid in human brain tissue.
Brain Res.
1988;
454
164-169
- 6
Schwarcz R, Pellicciari R.
Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities.
J Pharmacol Exp Ther.
2002;
303
1-10
- 7
Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L.
Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35.
J Biol Chem.
2006;
281
22021-22028
- 8
Scharfman H E, Goodman J H, Schwarcz R.
Electrophysiological effects of exogenous and endogenous kynurenic acid in the rat
brain: studies in vivo and in vitro.
Amino Acids.
2000;
19
283-297
- 9
Wonodi I, Schwarcz R.
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in
schizophrenia.
Schizophr Bull.
2010;
36
211-218
- 10
Vamos E, Pardutz A, Klivenyi P, Toldi J, Vecsei L.
The role of kynurenines in disorders of the central nervous system: possibilities
for neuroprotection.
J Neurol Sci.
2009;
283
21-27
- 11
Erhardt S, Olsson S K, Engberg G.
Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric
disorders.
CNS Drugs.
2009;
23
91-101
- 12
Kazda H, Taylor N, Healy D, Walker D.
Maternal, umbilical, and amniotic fluid concentrations of tryptophan and kynurenine
after labor or cesarean section.
Pediatr Res.
1998;
44
368-373
- 13
Milart P, Sikorski R.
Kynurenic acid concentration in blood and urine during normal pregnancy.
Ginekol Pol.
1998;
69
968-973
- 14
Milart P, Urbanska E M, Turski W A, Paszkowski T, Sikorski R.
Intrapartum levels of endogenous glutamate antagonist – kynurenic acid in amniotic
fluid, umbilical and maternal blood.
Neurosci Res Commun.
1999;
24
173-178
- 15
Parada-Turska J, Rzeski W, Zgrajka W, Majdan M, Kandefer-Szerszen M, Turski W.
Kynurenic acid, an endogenous constituent of rheumatoid arthritis synovial fluid,
inhibits proliferation of synoviocytes in vitro.
Rheumatol Int.
2006;
26
422-426
- 16
Kuc D, Zgrajka W, Parada-Turska J, Urbanik-Sypniewska T, Turski W A.
Micromolar concentration of kynurenic acid in rat small intestine.
Amino Acids.
2008;
35
503-505
- 17
Glavin G B, Pinsky C.
Kynurenic acid attenuates experimental ulcer formation and basal gastric acid secretion
in rats.
Res Commun Chem Pathol Pharmacol.
1989;
64
111-119
- 18
Glavin G B, Pinsky C, Bose R.
Gastrointestinal effects of contaminated mussels and putative antidotes thereof.
Can Dis Wkly Rep.
1990;
16 (Suppl. 1E)
111-115
- 19
Kaszaki J, Palasthy Z, Erczes D, Racz A, Torday C, Varga G, Vecsei L, Boros M.
Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during
experimental colon obstruction in dogs.
Neurogastroenterol Motil.
2008;
21
53-62
- 20
Varga G, Erces D, Fazekas B, Fulop M, Kovacs T, Kaszaki J, Fulop F, Vecsei L, Boros M.
N-Methyl-D-aspartate receptor antagonism decreases motility and inflammatory activation
in the early phase of acute experimental colitis in the rat.
Neurogastroenterol Motil.
2010;
22
217-225
- 21
Turski M P, Turska M, Zgrajka W, Kuc D, Turski W A.
Presence of kynurenic acid in food and honeybee products.
Amino Acids.
2009;
36
75-80
- 22
Shibata K.
Fluorimetric micro-determination of kynurenic acid, an endogenous blocker of neurotoxicity,
by high-performance liquid chromatography.
J Chromatogr.
1988;
430
376-380
- 23
Drieu K.
Preparation and definition of Ginkgo biloba extract.
Presse Med.
1986;
15
1455-1457
- 24
al-Khalil S, Alkofahi A, al-Eisawi D, al-Shibib A.
Transtorine, a new quinoline alkaloid from Ephedra transitoria.
J Nat Prod.
1998;
61
262-263
- 25
Beretta G, Artali R, Caneva E, Orlandini S, Centini M, Facino R M.
Quinoline alkaloids in honey: further analytical (HPLC-DAD-ESI-MS, multidimensional
diffusion-ordered NMR spectroscopy), theoretical and chemometric studies.
J Pharm Biomed Anal.
2009;
50
432-439
- 26
Nemeth H, Toldi J, Vecsei L.
Role of kynurenines in the central and peripheral nervous systems.
Curr Neurovasc Res.
2005;
2
249-260
- 27
Paluszkiewicz P, Zgrajka W, Saran T, Schabowski J, Valverde Piedra J L, Fedkiv O,
Rengman S, Pierzynowski S G, Turski W A.
High concentration of kynurenic acid in bile and pancreatic juice.
Amino Acids.
2009;
37
637-641
- 28
Turski W A, Schwarcz R.
On the disposition of intrahippocampally injected kynurenic acid in the rat.
Exp Brain Res.
1988;
71
563-567
- 29
Horibata K, Taniuchi H, Tashiro M, Kuno S, Hayaishi O.
The metabolism of kynurenic acid. II. Tracer experiments on the mechanism of kynurenic
acid degradation and glutamic acid synthesis by Pseudomonas extracts.
J Biol Chem.
1961;
236
2991-2995
Waldemar A. Turski
Department of Toxicology
Institute of Agricultural Medicine
Jaczewskiego 2
20-950 Lublin
Poland
Phone: +48 8 17 18 45 43
Fax: +48 8 17 47 86 46
Email: turskiwa@op.pl