title: Aldose reductase inhibitory compounds from Xanthium strumarium.
abstract: 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.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, 200-702, Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Yoon
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002726:Chlorogenic Acid / Q000031:analogs & derivatives; D048909:Diabetes Complications / Q000517:prevention & control; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020834:Ethnopharmacology; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005638:Fruit / Q000737:chemistry*; D004376:Galactitol / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D056910:Republic of Korea; D031210:Xanthium / Q000737:chemistry*
chemical_list: D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D011994:Recombinant Proteins; D011801:Quinic Acid; D004376:Galactitol; D002726:Chlorogenic Acid; C478100:3,4-di-O-caffeoylquinic acid; C580929:AKR1A1 protein, human; D000449:Aldehyde Reductase