Non-enzymatic glycation of proteins is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid, or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce Amadori products. The Amadori product further undergoes various reactions, including dehydration and rearrangements, to develop a cross-link between adjacent proteins, resulting in the formation of advanced glycation end products (AGEs). AGEs can also accumulate in the body through a diet rich in AGEs. Irrespective of how AGEs accumulate, they exert harmful physiological effects by interacting and engaging with their membrane-bound receptor for advanced glycation end products (RAGE), expressed on various cell types including macrophages, fibroblasts, and endothelial cells. The AGE-RAGE interaction is involved in the activation of various pro-inflammatory cascades and production of reactive oxygen species via the JAK/STAT, MAPK, and ERK1/2 signaling pathways and can result in various complications of diabetes, such as neuropathy, nephropathy, retinopathy, and vascular complications. The effects of AGEs are also implicated in various diseases including neurodegenerative diseases, chronic kidney disease, cancer, liver diseases, and atherosclerosis.

Despite their complexity and extensive pathological interactions, the chemical outcome produced by the AGEs, i.e., the crosslinking of proteins, remains the chief underlying mechanism of inducing damage. Novel compounds, both synthetic and non-synthetic, have been evaluated for their effects against the formation of AGEs, with varying degrees of success and side effects. Phytochemicals are now being considered as a promising avenue for the development of potent AGE inhibitors, as various phytochemicals have been shown to possess therapeutic potential towards oxidative stress and inflammation, thereby preventing further harmful ramifications caused by the formation of AGEs.

The aim of this Special Issue is to explore the role of various phytochemicals in inhibiting the formation of AGEs and in reducing physiological levels of AGEs. We welcome both original research and review articles.

Potential topics include but are not limited to the following:

• Basic molecular and cellular mechanisms regulating inflammation in diabetes
• Oxidative stress and renal health
• Metabolic mechanisms involved in diabetic complications, and its management by phytochemicals,
• Advanced glycation end products and diabetic complications
• Antioxidants and their role in inhibiting the formation of advanced glycation end products
• Role of ER stress in diabetic complications, and possible interventions by phytochemicals
• AGEs and mitochondrial health in diabetes
• Identifying the role of novel phytochemicals as inhibitors of AGEs
• Role of AGEs in renal, neuronal and endothelial cell death
• Dietary phytochemicals in combating oxidative stress inflammation, and formation of AGEs