s-allylcysteine and Hyperglycemia

Alternative medicine or herbal therapies have been in use for blood glucose control in patients with diabetes for considerable time. Effect of garlic, more specifically its biologically active component s-allyl cysteine, on amelioration of hyperglycemia has also been reported. However, the cellular or molecular target of this compound is little known. This study was designed to determine the action of s-allyl cysteine sulfoxide (SACSO) at the cellular and molecular level in the widely reported HUVEC model when activated with advanced glycation end products (AGEs).. AGE-HSA was derived from non-enzymatic glycation of human serum albumin in the presence of 20 mM glucose. AGE-HSA induced expression of receptors of AGEs, namely RAGE and galectin-3 has been assayed. Activity of endothelial nitric oxide synthase (NOS) denoting normal endothelial function and expression of AGE-RAGE triggered inflammatory marker sICAM-1 is also evaluated in the presence or absence of SACSO.. In presence of SACSO, AGE-HSA induced expression of RAGE was down-regulated, galectin-3 was significantly up-regulated, NOS activity was enhanced and sICAM-1 expression was reduced.. The data suggest that SACSO exerts an attenuating effect on 20 mM glucose derived AGE-HSA induced inflammation, by selectively inhibiting RAGE while stimulating galectin-3 expression. The former triggers inflammatory pathways while the latter sequesters AGE molecules and prevents AGE-RAGE engagement. This may form the basis for its therapeutic action.

Topics: Cysteine; Diabetes Complications; Down-Regulation; Endothelial Cells; Galectin 3; Garlic; Glucose; Glycation End Products, Advanced; Humans; Hyperglycemia; In Vitro Techniques; Phytotherapy; Plant Extracts; Receptor for Advanced Glycation End Products; Serum Albumin; Serum Albumin, Human; Sulfoxides; Up-Regulation

Hyperglycaemia causes increased protein glycation and the formation of advanced glycation endproducts which underlie the complications of diabetes and ageing. Glycation is accompanied by metal-catalysed oxidation of glucose and Amadori products to form free radicals capable of protein fragmentation. Aged garlic extract is a potent antioxidant with established lipid-lowering effects attributed largely to a key ingredient called S-allyl cysteine. This study investigated the ability of aged garlic extract and S-allyl cysteine to inhibit advanced glycation in vitro. Bovine serum albumin (BSA) was glycated in the presence of Cu(2+) ions and different concentrations of aged garlic extract and protein fragmentation was examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Lysozyme was glycated by glucose or methylglyoxal in the presence of different concentrations of aged garlic extract or S-allyl cysteine with subsequent analysis of glycation-derived crosslinking using SDS-PAGE. Amadori-rich protein was prepared by dialysing lysozyme that had been glycated by ribose for 24 h. This ribated lysozyme was reincubated and the effects of aged garlic extract, S-allyl cysteine and pyridoxamine on glycation-induced crosslinking was monitored. Aged garlic extract inhibited metal-catalysed protein fragmentation. Both aged garlic extract and S-allyl cysteine inhibited formation of glucose and methylglyoxal derived advanced glycation endproducts and showed potent Amadorin activity when compared to pyridoxamine. S-allyl cysteine inhibited formation of carboxymethyllysine (CML), a non-crosslinked advanced glycation endproduct derived from oxidative processes. Further studies are required to assess whether aged garlic extract and S-allyl cysteine can protect against the harmful effects of glycation and free radicals in diabetes and ageing.

Topics: Aging; Antioxidants; Cysteine; Diabetes Complications; Electrophoresis, Polyacrylamide Gel; Free Radicals; Garlic; Glucose; Glycation End Products, Advanced; Humans; Hyperglycemia; Muramidase; Peptide Fragments; Plant Extracts; Pyridoxamine; Pyruvaldehyde; Ribose