A Review of the Health Benefits of Food Enriched with Kynurenic Acid

Kynurenic acid (KYNA), a metabolite of tryptophan, is an endogenous substance produced intracellularly by various human cells. In addition, KYNA can be synthesized by the gut microbiome and delivered in food. However, its content in food is very low and the total alimentary supply with food accounts for only 1–3% of daily KYNA excretion. The only known exception is chestnut honey, which has a higher KYNA content than other foods by at least two orders of magnitude. KYNA is readily absorbed from the gastrointestinal tract; it is not metabolized and is excreted mainly in urine. It possesses well-defined molecular targets, which allows the study and elucidation of KYNA’s role in various pathological conditions. Following a period of fascination with KYNA’s importance for the central nervous system, research into its role in the peripheral system has been expanding rapidly in recent years, bringing some exciting discoveries. KYNA does not penetrate from the peripheral circulation into the brain; hence, the following review summarizes knowledge on the peripheral consequences of KYNA administration, presents data on KYNA content in food products, in the context of its daily supply in diets, and systematizes the available pharmacokinetic data. Finally, it provides an analysis of the rationale behind enriching foods with KYNA for health-promoting effects

Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease

Paraoxonase 1 (PON1) is the high density lipoprotein-associated esterase which inhibits the development of atherosclerosis by metabolizing lipid peroxidation products as well as hydrolyzing proatherogenic metabolite of homocysteine (Hcy), Hcy thiolactone, which otherwise reacts with lysine groups of proteins, thus forming N-Hcy-protein in a process referred to as protein N-homocysteinylation. Rheumatoid arthritis (RA) is the chronic inflammatory autoimmune disease associated with increased risk of cardiovascular complications, but the underlying mechanisms are incompletely understood. We examined PON1 status and N-homocysteinylation of serum proteins in patients with RA. Blood was collected from 74 RA patients and 70 control subjects. PON1 activity was measured toward synthetic (paraoxon, phenyl acetate) and natural (Hcy thiolactone) substrates. PON1 protein concentration was measured by ELISA. Total Hcy as well as N-Hcy-protein were measured in serum as well. PON1 activity toward Hcy thiolactone was lower in RA patients than in control subjects which was accompanied by increased concentration of N-Hcy-protein despite normal total Hcy concentration. PON1 protein concentration was unchanged in the RA group, but the specific enzyme activity was reduced. When RA patients were categorized according to the DAS28-ESR score, PON1 concentration and enzymatic activity were lower whereas N-Hcy-protein was higher in those with high disease activity. PON1 activity and Hcy thiolactone were correlated with DAS28-ESR score and myeloperoxidase concentration. In conclusion, RA is associated with deficiency of PON1 activity and increased protein N-homocyseinylation which may contribute to accelerated development of cardiovascular diseases

Kynurenic Acid in the Digestive System—New Facts, New Challenges

This review provides information on the most recent findings concerning presence, origin, and role of kynurenic acid (KYNA), a tryptophan metabolite, in the digestive system. KYNA is an antagonist of both the ionotropic glutamate receptors and the alpha7 nicotinic acetylcholine receptor, as well as an agonist of G-protein coupled GPR35 receptor. Since the GPR35 receptor is mainly present in the gastrointestinal tract, researchers have concentrated on the digestive system in recent years. They have found that KYNA content increases gradually and significantly along the gastrointestinal tract. Interestingly, the concentration of KYNA in the lumen is much higher than in the wall of intestine. It has been documented that KYNA may have a positive influence on the number of pathologies in the gastrointestinal tract, in particular ulcers, colon obstruction, or colitis. Future studies might determine whether it is advisable to supplement KYNA to a human organism

Copyright © 2007 by Institute of Pharmacology Polish Academy of Sciences

Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cell

Kynurenic Acid Protects against Thioacetamide-Induced Liver Injury in Rats

Acute liver failure (ALF) is a life-threatening disorder of liver function. Kynurenic acid (KYNA), a tryptophan metabolite formed along the kynurenine metabolic pathway, possesses anti-inflammatory and antioxidant properties. Its presence in food and its potential role in the digestive system was recently reported. The aim of this study was to define the effect of KYNA on liver failure. The Wistar rat model of thioacetamide-induced liver injury was used. Morphological and biochemical analyses as well as the measurement of KYNA content in liver and hepatoprotective herbal remedies were conducted. The significant attenuation of morphological disturbances and aspartate and alanine transaminase activities, decrease of myeloperoxidase and tumor necrosis factor-α, and elevation of interleukin-10 levels indicating the protective effect of KYNA in thioacetamide (TAA) - induced liver injury were discovered. In conclusion, the hepatoprotective role of KYNA in an animal model of liver failure was documented and the use of KYNA in the treatment of ALF was suggested