No abstract

No abstract

The positive glycation inhibitory and antioxidative activities of these tropical herbs suggest a possible role in targeting ageing, diabetic complications and oxidative stress related diseases.

Diabetes mellitus is characterised by hyperglycaemia, lipidaemia and oxidative stress and predisposes affected individuals to long-term complications afflicting the eyes, skin, kidneys, nerves and blood vessels. Increased protein glycation and the subsequent build-up of tissue advanced glycation endproducts (AGEs) contribute towards the pathogenesis of diabetic complications. Protein glycation is accompanied by generation of free radicals through autoxidation of glucose and glycated proteins and via interaction of AGEs with their cell surface receptors (referred to as RAGE). Glycationderived free radicals can damage proteins, lipids and nucleic acids and contribute towards oxidative stress in diabetes. There is interest in compounds with anti-glycation activity as they may offer therapeutic potential in delaying or preventing the onset of diabetic complications. Although many different compounds are under study, only a few have successfully entered clinical trials but none have yet been approved for clinical use. Whilst the search for new synthetic inhibitors of glycation continues, little attention has been paid to anti-glycation compounds from natural sources. In the last few decades the traditional system of medicine has become a topic of global interest. Various studies have indicated that dietary supplementation with combined anti-glycation and antioxidant nutrients may be a safe and simple complement to traditional therapies targeting diabetic complications. Data for forty two plants/constituents studied for anti-glycation activity is presented in this review and some commonly used medicinal plants that possess anti-glycation activity are discussed in detail including their active ingredients, mechanism of action and therapeutic potential.

No abstract

Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia and long-term complications affecting the eyes, nerves, blood vessels, skin, and kidneys. Increased glycation of proteins and accumulation of advanced glycation endproducts (AGEPs) have been implicated in the pathogenesis of diabetic complications. Glycation and AGEP formation are also accompanied by formation of free radicals via autoxidation of glucose and glycated proteins. Compounds with combined antiglycation and antioxidant properties may offer therapeutic potential. Recent studies suggest that aged garlic extract (AGE) inhibits formation of AGEPs in vitro and formation of glycation-derived free radicals. S-Allylcysteine, a key component of aged garlic, is a potent antioxidant and can inhibit AGEP formation. Aged garlic extract and S-allylcysteine deserve more attention and should be investigated to see whether they can reduce AGEPs in vivo.

Protein glycation involves formation of early (Amadori) and late advanced glycation endproducts (AGEs) together with free radicals via autoxidation of glucose and Amadori products. Glycation and increased free radical activity underlie the pathogenesis of diabetic complications. This study investigated whether aged garlic has more potent antiglycation and antioxidant properties compared to fresh garlic extract in vitro in a cell-free system. Proteins were glycated by incubation with sugars (glucose, methylglyoxal or ribose) ±5–15 mg/mL of aged and fresh garlic extracts. Advanced glycation endproducts were measured using SDS-PAGE gels and by ELISA whereas Amadori products were assessed by the fructosamine method. Colorimetric methods were used to assess antioxidant activity, free radical scavenging capacity, protein-bound carbonyl groups, thiol groups and metal chelation activities in addition to phenolic, total flavonoid and flavonol content of aged and fresh garlic extracts. Aged garlic inhibited AGEs by 56.4% compared to 33.5% for an equivalent concentration of fresh garlic extract. Similarly, aged garlic had a higher total phenolic content (129 ± 1.8 mg/g) compared to fresh garlic extract (56 ± 1.2 mg/g). Aged garlic has more potent antiglycation and antioxidant properties compared to fresh garlic extract and is more suitable for use in future in vivo studies.

Diabetic patients have increased likelihood of developing breast cancer. Advanced glycation endproducts (AGEs) underlie the pathogenesis of diabetic complications but their impact on breast cancer cells is not understood. This study aims to determine the effects of methylglyoxal-derived bovine serum albumin AGEs (MG-BSA-AGEs) on the invasive MDA-MB-231 breast cancer cell line. By performing cell counting, using wound-healing assay, invasion assay and zymography analysis, we found that MG-BSA-AGEs increased MDA-MB-231 cell proliferation, migration and invasion through Matrigel™ associated with an enhancement of matrix metalloproteinase (MMP)-9 activities, in a dose-dependent manner. Using Western blot and flow cytometry analyses, we demonstrated that MG-BSA-AGEs increased expression of the receptor for AGEs (RAGE) and phosphorylation of key signaling protein extracellular signal-regulated kinase (ERK)-1/2. Furthermore, in MG-BSA-AGE-treated cells, phospho-protein micro-array analysis revealed enhancement of phosphorylation of the ribosomal protein 70 serine S6 kinase beta 1 (p70S6K1), which is known to be involved in protein synthesis, the signal transducer and activator of transcription (STAT)-3 and the mitogen-activated protein kinase (MAPK) p38, which are involved in cell survival. Blockade of MG-BSA-AGE/RAGE interactions using a neutralizing anti-RAGE antibody inhibited MG-BSA-AGE-induced MDA-MB-231 cell processes, including the activation of signaling pathways. Throughout the study, non-modified BSA had a negligible effect. In conclusion, AGEs might contribute to breast cancer development and progression partially through the regulation of MMP-9 activity and RAGE signal activation. The up-regulation of RAGE and the concomitant increased phosphorylation of p70S6K1 induced by AGEs may represent promising targets for drug therapy to treat diabetic patients with breast cancer.