Action of pelargonidin on hyperglycemia and oxidative damage in diabetic rats: implication for glycation-induced hemoglobin modification

Glycation-modified hemoglobin in diabetes mellitus has been suggested to be a source of enhanced catalytic iron and free radicals causing pathological complications. The present study aims to verify this idea in experimental diabetes. Pelargonidin, an anthocyanidin, has been tested for its antidiabetic potential with emphasis on its role against pathological oxidative stress including hemoglobin-mediated free radical reactions. Male wistar rats were grouped as normal control, streptozotocin-induced diabetic control, normal treated with pelargonidin and diabetic treated with pelargonidin. Pelargonidin-treated rats received one time i.p injection of the flavonoid (3 mg/kg bodyweight). Biochemical parameters were assayed in blood samples of different groups of rats. Liver was used for histological examinations. Pelargonidin treatment normalized elevated blood glucose levels and improved serum insulin levels in diabetic rats. Glucose tolerance test appeared normal after treatment. Decreased serum levels of SOD and catalase, and increased levels of malondialdehyde and fructosamine in diabetic rats were reverted to their respective normal values after pelargonidin administration. Extents of hemoglobin glycation, hemoglobin-mediated iron release, iron-mediated free radical reactions and carbonyl formation in hemoglobin were pronounced in diabetic rats, indicating association between hemoglobin glycation and oxidative stress in diabetes. Pelargonidin counteracts hemoglobin glycation, iron release from the heme protein and iron-mediated oxidative damages, confirming glycated hemoglobin-associated oxidative stress in diabetes.     

From virgin education to real education

The now famous virgin headspace experiment from late Braja D. Mookherjee and Subha Patel, and its use in the creation of scent 'Virgin No 1' by Christophe Laudamiel and Christoph Hornetz for the novel by Patrick Süskind, and the movie by Tom Tykwer 'Perfume--The Story of a Murderer' (Constantin Film-Thierry Mugler Parfums-IFF, 2006) is discussed. Another fragrance from the luxury coffret, 'Salon Rouge', is described as well, illustrating how molecules and natural ingredients can be utilized, not only to create innovative or artistic fragrance compositions, but also to provide fundamental consumer education, improving the public image both of Chemistry and Perfumery.     

Identification and characterization of rabbit small intestinal villus cell brush border membrane Na-glutamine cotransporter

Glutamine, the primary metabolic fuel for the mammalian small intestinal enterocytes, is primarily assimilated by Na-amino acid cotransporters. Although Na-solute cotransport has been shown to exist in the brush border membrane (BBM) of the absorptive villus cells, the identity of Na-glutamine cotransport in rabbit small intestinal villus cells was unknown. Na-dependent glutamine uptake is present in villus BBM vesicles. An intravesicular proton gradient did not stimulate this Na-dependent glutamine uptake, whereas Li+ did not significantly suppress this uptake. These observations in concert with amino acid substitution studies suggested that Na-glutamine cotransporter in the villus cell BBM was the newly identified cotransporter B0AT1 (SLC6A19). Quantitative real-time PCR identified the message for this cotransporter in villus cells. Thus a full-length cDNA of B0AT1 was cloned and expressed in MDA-MB-231 cells. This expressed cotransporter exhibited characteristics similar to those observed in villus cells from the rabbit small intestine. Antibody was generated for B0AT1 that demonstrated the presence of this cotransporter protein in the villus cell BBM. Kinetic studies defined the kinetic parameters of this cotransporter. Thus this study describes the identification, cloning, and characterization of the Na-amino acid cotransporter responsible for the assimilation of a critical amino acid by the absorptive villus cells in the mammalian small intestine.     

A mercapto analogue of 5'-noraristeromycin.

5'-Noraristeromycin and its enantiomer have been found to possess a wide range of antiviral effects. In the search for analogues of and with improved activity, the synthesis of both enantiomers of 5'-mercapto-5'-deoxy-5'-noraristeromycin ( and ) has been accomplished. While (+)-7 was inactive, (-)- did show marginal activity against vaccinia virus, but not any other virus.     

Synthesis of [beta-(4-pyridyl-1-oxide)-L-alanine4]-angiotensin I as a potential suicide substrate for protein-tyrosine kinases

An asymmetric synthesis of [beta-(4-pyridyl-1-oxide)-L-alanine4]-angiotensin I (1a), which is a potential suicide substrate (mechanism-based inhibitor) for protein-tyrosine kinases, has been performed. Deprotonation of 6 with n-butyllithium in THF gave the anion 7, which was alkylated with 4-(chloromethyl)pyridine-1-oxide to afford intermediate 9 as a crystalline solid. Hydrolysis of 9 afforded a mixture of 11 and 12 in a ratio of 96:4 as estimated by conversion to the diastereomeric dipeptides 13 and 14 followed by HPLC analysis. The 96:4 mixture of 11 and 12 was used in the solid phase synthesis of the target angiotensin analog 1a and its diastereomer 1b, which were separated and tested for inhibitory activity against two thymocyte protein-tyrosine kinases: p40 and p56lck. Neither peptide displayed significant inhibitory activity toward p40 and both served as weak competitive inhibitors of p56lck.     

Protein kinase C dependent and independent activation of phospholipase A2 under calcium ionophore (A23187) exposure in rabbit pulmonary arterial smooth muscle cells

Exposure of rabbit pulmonary arterial smooth muscle cells to the calcium ionophore A23187, dose-dependently stimulates arachidonic acid (AA) release and phospholipase A2 (PLA2) activity. The protein kinase C (PKC) inhibitor, sphingosine does not prevents AA release and PLA2 activity caused by low doses of A23187. In contrast, sphingosine markedly prevents AA release and PLA2 activity caused by higher doses of A23187. PKC activity profile indicates that treatment of the cells with low doses of A23187 does not cause significant alteration of PKC translocation from cytosol to membrane whereas higher concentrations of the ionophore dose-dependently enhance PKC translocation from cytosol to membrane in the smooth muscle cells.     

Engineered Silybin Nanoparticles Educe Efficient Control in Experimental Diabetes

Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostrate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17±0.01 µg/lit to 0.57±0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.