Quinoline alkaloids in honey: further analytical (HPLC-DAD-ESI-MS, multidimensional diffusion-ordered NMR spectroscopy), theoretical and chemometric studies.
The wound-healing properties of honey are well established and it has been suggested that, among its pharmaco-active constituents, kynurenic acid (KA) exerts antinociceptive action on injured tissue by antagonizing NMDA at peripheral GABA receptors. The aim of this study was to investigate the quantitative profile of KA and of two recently identified, structurally related derivatives, 3-pyrrolidinyl-kynurenic acid (3-PKA) and its gamma-lactamic derivative (gamma-LACT-3-PKA), by examining their mass spectrometric behavior, in honeys from different botanical sources. We used a combination of HPLC-DAD-ESI-MS and NMR techniques (one-dimensional (1)H NMR and diffusion-ordered spectroscopy NMR). Chestnut honey constantly contained KA (2114.9-23 g/kg), 3-PKA (482.8-80 mg/kg) and gamma-LACT-3-PKA (845.8-32 mg/kg), confirming their reliability as markers of origin. A new metabolite, 4-quinolone (4-QUIN), was identified for the first time in one chestnut honey sample (743.4 mg/kg). Small amounts of KA were found in honeydew, sunflower, multifloral, almond and eucalyptus honeys, in the range of 23.1-143 mg/kg, suggesting contamination with chestnut honey. Total phenol content (TPC) was in the range from 194.9 to 1636.3 mg(GAE)/kg and total antiradical activity (TAA) from 61 to 940 mg/(GAE)/kg), depending on the botanical origin. Principal component analysis (PCA) was then done on these data. The three different clusters depicted: (i) antinociceptive activity from KA and/or its derivatives, typical of chestnut honey; (ii) antioxidant/radical scavenging activity by antioxidants responsible for the antiinflammatory action (dark honeys); (iii) peroxide-dependent antibacterial activity due to H(2)O(2) production by glucose oxidase in honey. The PCA findings provide useful indications for the dermatologist for the treatment of topical diseases, and the profiling of KA and its derivatives may shed light on new aspects of the kynurenine pathway involved in tryptophan metabolism.
Beretta
Giangiacomo
G
Department of Pharmaceutical Sciences Pietro Pratesi, Faculty of Pharmacy, University of Milan, via Mangiagalli 25, 20133 Milan, Italy. giangiacomo.beretta@unimi.it
Artali
Roberto
R
Caneva
Enrico
E
Orlandini
Serena
S
Centini
Marisanna
M
Facino
Roberto Maffei
RM
D000470:Alkaloids / Q000032:analysis* / Q000302:isolation & purification; D000700:Analgesics / Q000032:analysis / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000302:isolation & purification; D000975:Antioxidants / Q000032:analysis / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006722:Honey / Q000032:analysis*; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010636:Phenols / Q000032:analysis / Q000302:isolation & purification; D025341:Principal Component Analysis; D011759:Pyrrolidines / Q000032:analysis / Q000302:isolation & purification; D011804:Quinolines / Q000032:analysis* / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
C540397:3-(2'-pyrrolidinyl)-kynurenic acid; D000470:Alkaloids; D000700:Analgesics; D000900:Anti-Bacterial Agents; D000975:Antioxidants; D010636:Phenols; D011759:Pyrrolidines; D011804:Quinolines; D007736:Kynurenic Acid