RESUMEN
Phytochemical investigation of the natural products from Xanthium strumarium led to the isolation of fourteen compounds including seven caffeoylquinic acid (CQA) derivatives. The individual compounds were screened for inhibition of α-glucosidase, protein tyrosine phosphatase 1ß (PTP1ß), advanced glycation end products (AGEs), and ABTS⺠radical scavenging activity using in vitro assays. Among the isolated compounds, methyl-3,5-di-caffeoyquinic acid exhibited significant inhibitory activity against α-glucosidase (18.42 µM), PTP1ß (1.88 µM), AGEs (82.79 µM), and ABTS⺠(6.03 µM). This effect was marked compared to that of the positive controls (acarbose 584.79 µM, sumarin 5.51 µM, aminoguanidine 1410.00 µM, and trolox 29.72 µM respectively). In addition, 3,5-di-O-CQA (88.14 µM) and protocatechuic acid (32.93 µM) had a considerable inhibitory effect against α-glucosidase and ABTSâº. Based on these findings, methyl-3,5-di-caffeoyquinic acid was assumed to be potentially responsible for the anti-diabetic actions of X. strumarium.
Asunto(s)
Benzotiazoles/química , Inhibidores de Glicósido Hidrolasas/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Ácidos Sulfónicos/química , Xanthium/química , alfa-Glucosidasas/química , Animales , Bovinos , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Productos Finales de Glicación Avanzada/química , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Humanos , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Proteínas de Saccharomyces cerevisiae/antagonistas & inhibidores , Proteínas de Saccharomyces cerevisiae/química , Albúmina Sérica BovinaRESUMEN
As part of our ongoing search for natural sources of therapeutic and preventive agents for diabetic complications, we evaluated the inhibitory effects of components of the fruit of Xanthium strumarium (X. strumarium) on aldose reductase (AR) and galactitol formation in rat lenses with high levels of glucose. To identify the bioactive components of X. strumarium, 7 caffeoylquinic acids and 3 phenolic compounds were isolated and their chemical structures were elucidated on the basis of spectroscopic evidence and comparison with published data. The abilities of 10 X. strumarium-derived components to counteract diabetic complications were investigated by means of inhibitory assays with rat lens AR (rAR) and recombinant human AR (rhAR). From the 10 isolated compounds, methyl-3,5-di-O-caffeoylquinate showed the most potent inhibition, with IC50 values of 0.30 and 0.67 µM for rAR and rhAR, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate, methyl-3,5-di-O-caffeoylquinate showed competitive inhibition of rhAR. Furthermore, methyl-3,5-di-O-caffeoylquinate inhibited galactitol formation in the rat lens and in erythrocytes incubated with a high concentration of glucose, indicating that this compound may be effective in preventing diabetic complications.