rhodanine and pimagedine

Topics: Aldehyde Reductase; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Chronic Disease; Diabetic Neuropathies; Enzyme Inhibitors; gamma-Linolenic Acid; Glycation End Products, Advanced; Guanidines; Humans; Insulin; Oxidative Stress; Rhodanine; Thiazolidines

Topics: Aldehyde Reductase; Arteriosclerosis; Blood Glucose; Diabetes Mellitus; Enzyme Inhibitors; Guanidines; Humans; Hypoglycemic Agents; Insulin Resistance; Rhodanine; Thiazolidines

Important targets for the prevention and treatment of diabetic complications include aldose reductase (AR) inhibitors (ARIs) and inhibitors of advanced glycation endproduct (AGE) formation. Here we evaluate the inhibitory activities of prenylated flavonoids isolated from Sophora flavescens, a traditional herbal medicine, on rat lens AR (RLAR), human recombinant AR (HRAR) and AGE formation. Among the tested compounds, two prenylated chalcones--desmethylanhydroicaritin (1) and 8-lavandulylkaempferol (2)--along with five prenylated flavanones--kurarinol (8), kurarinone (9), (2S)-2'-methoxykurarinone (10), (2S)-3beta,7,4'-trihydroxy-5-methoxy-8-(gamma,gamma-dimethylally)-flavanone (11), and kushenol E (13) were potent inhibitors of RLAR, with IC50 values of 0.95, 3.80, 2.13, 2.99, 3.77, 3.63 and 7.74 microM, respectively, compared with quercetin (IC50 7.73 microM). In the HRAR assay, most of the prenylated flavonoids tested showed marked inhibitory activity compared with quercetin (IC50 2.54 microM). In particular, all tested prenylated flavonols, such as desmethylanhydroicaritin (1, IC50 0.45 microM), 8-lavandulylkaempferol (2, IC50 0.79 microM) and kushenol C (3, IC50 0.85 microM), as well as a prenylated chalcone, kuraridin (5, IC50 0.27 microM), and a prenylated flavanone, (2S)-7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylally)-flavanone (12, IC50 0.37 microM), showed significant inhibitory activities compared with the potent AR inhibitor epalrestat (IC50 0.28 microM). Interestingly, prenylated flavonoids 1 (IC50 104.3 microg mL(-1)), 2 (IC50 132.1 microg mL(-1)), 3 (IC50 84.6 microg mL(-1)) and 11 (IC50 261.0 microg mL(-1)), which harbour a 3-hydroxyl group, also possessed good inhibitory activity toward AGE formation compared with the positive control aminoguanidine (IC50 115.7 microg mL(-1)). Thus, S. flavescens and its prenylated flavonoids inhibit the processes that underlie diabetic complications and related diseases and may therefore have therapeutic benefit.

Topics: Aldehyde Reductase; Animals; Chalcones; Flavones; Flavonoids; Glycation End Products, Advanced; Guanidines; Humans; Inhibitory Concentration 50; Medicine, Traditional; Plant Extracts; Quercetin; Rats; Rats, Sprague-Dawley; Rhodanine; Sophora; Thiazolidines

We examined the effects of high glucose concentrations on the expression of adhesion molecules in human aortic endothelial cells. Expression levels of both mRNA and protein of intercellular adhesion molecule-1 (ICAM-1) were increased after incubation of endothelial cells with 30 mM glucose for 24 h. The effect of glucose on ICAM-1 was concentration dependent, partially attributable to osmolarity, and enhanced by glycated-collagen. Staurosporine (10 nM), epalrestat (10 microM) suppressed the expression of ICAM-1 mRNA and protein induced by high glucose to variable extents. Aminoguanidine (50 mM) suppressed the expression of ICAM-1 protein. It is thought that soluble ICAM-1 protein is produced by shedding in human aortic endothelial cells because RNA for the soluble form of ICAM-1 formed by variant splicing has not been detected. These results show that glucose is an important determinant of ICAM-1 expression in endothelial cells, and suggest that ICAM-1 molecules induced by hyperglycemia may contribute to the development of atherosclerosis in diabetes mellitus.

Topics: Aldehyde Reductase; Aorta; Collagen; Endothelium, Vascular; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Glucose; Guanidines; Humans; Intercellular Adhesion Molecule-1; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Protein Synthesis Inhibitors; Reverse Transcriptase Polymerase Chain Reaction; Rhodanine; RNA, Messenger; Staurosporine; Thiazolidines

The relation between ventricular histamine concentrations and the occurrence of early ventricular arrhythmias during acute myocardial ischaemia was investigated in pentobarbitone-anaesthetized rats. There was significant decrease in the left, but not the right, ventricular histamine level at 5 min following acute left coronary artery ligation. Pretreatment with rhodanine caused remarkable reduction in ventricular histamine concentrations as well as significantly lower incidence and slower onset of ventricular tachycardia and fibrillation resulting from acute myocardial ischaemia. On the contrary, aminoguanidine pretreatment did not significantly alter ventricular histamine levels nor did it influence the occurrence of early ventricular arrhythmias induced by coronary artery ligation. The responses of blood pressure and heart rate to acute coronary artery ligation were not noticeably affected by rhodanine or aminoguanidine pretreatment. These findings support the hypothesis that histamine release from cardiac tissues may contribute to the genesis of early ventricular arrhythmias, but not to the changes in blood pressure and heart rate, during acute myocardial ischaemia.

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Blood Pressure; Coronary Disease; Guanidines; Heart Rate; Heart Ventricles; Histamine; Histamine Release; Male; Myocardium; Rats; Rats, Inbred Strains; Rhodanine; Thiazoles