Review
A review on prevention of glycation of proteins: Potential therapeutic substances to mitigate the severity of diabetes complications

https://doi.org/10.1016/j.ijbiomac.2021.12.041Get rights and content

Highlights

  • An overview of glycation; characterization, complications and treatment approaches

  • Synthetic substances may prevent glycation in early, intermediate and final phases.

  • Plant extracts and polyphenols inhibit glycation and related pathology.

  • They lower blood sugar, scavenge free radicals/metal ions and trap carbonyls.

Abstract

Non-enzymatic reaction involving carbonyl of reducing sugars and amino groups in proteins produces advanced glycation end products (AGEs). AGE accumulation in vivo is a crucial factor in the progression of metabolic and pathophysiological mechanisms like obesity, diabetes, coronary artery disease, neurological disorders, and chronic renal failure. The body's own defense mechanism, synthetic inhibitors, and natural inhibitors can all help to prevent the glycation of proteins. Synthetic inhibitors have the potential to suppress the glycation of proteins through a variety of pathways. They could avoid Amadori product development by tampering with the addition of sugars to the proteins. Besides which, the free radical scavenging and blocking crosslink formation could be another mechanism behind their anti-glycation properties. In comparison with synthetic substances, naturally occurring plant products have been found to be comparatively non-toxic, cheap, and usable in an ingestible form. This review gives a brief introduction of the Maillard reaction; formation, characterization and pathology related to AGEs, potential therapeutic approaches against glycation, natural and synthetic inhibitors of glycation and their probable mechanism of action. The scientific community could get benefit from the combined knowledge about important molecules, which will further guide to the design and development of new pharmaceutical compounds.

Section snippets

Glycation of proteins: The Maillard reaction

Louis-Camille Maillard, a French scientist, in 1912, described the formation of yellow-brown coloration upon heating reducing sugars with amino acids [1]. The series of complex reactions involved in the browning was termed as Maillard reaction. As summarized by Hodge in 1953, the primary interest of the research associated with the Maillard reaction during that period was limited to the coloring and flavoring of the food when kept for a longer period of time [2]. Over the past few decades,

Advanced glycation end products (AGEs)

AGEs are complex, heterogeneous adducts generated during the course of glycation and are mostly characterized by their brown color and fluorescence characteristics. Many AGEs have been identified and characterized over the years in both in vivo and in vitro conditions; still, the chemistry associated with these are not clearly understood. Nε-carboxymethyl lysine (CML) was the first AGE isolated from glycated protein in vivo. It is derived from the lysine residues and has been detected in skin

Glycation and aggregation of proteins

Alzheimer's disease, amyotrophic lateral sclerosis, prion diseases and Parkinson's disease are crippling diseases that need extensive study. Protein misfolding, aggregation and precipitation all appear to be linked to neurotoxicity in these diseases [90], [91]. The physiological changes are linked to the development of fibrillar aggregates known as amyloid fibrils, which typically develop in the extracellular region or as intracellular deposits [92], [93]. Aggregation events are directly

Inhibition of glycation

In diabetic patients, glycation and the aggregation of AGEs are significant contributors to diabetes and related pathogenesis. As a result, finding effective antiglycating agents and preventing the development of intermediate or end products may be a useful and beneficial approach in the management of chronic complications. Anti-glycation biochemical pathways, in general, involve some mechanisms that may slow or suppress the glycation phase in vivo, thus inhibiting the formation of AGEs. Below

Inhibitors of glycation and AGE formation

Antiglycating agents may obstruct glycation and AGE development by interfering with various possible locations. Some could be able to compete for the protein's amino groups and others may attach directly to the protein or the glycation intermediates to halt the progression to AGE forming. Otherwise, they could have the ability to replace glycating sugars in the open-chain shape. A number of potential AGE inhibitors have also been suggested. Several inhibitors have been developed, and several

Natural and synthetic inhibitors: current shortcomings and potential prospects

Synthetic medicines are sometimes linked to drawbacks such as high expense, hypoglycemia, stomach disturbances, liver toxicity, exhaustion, fatigue, shortness of breath, vomiting, blurred vision, lactic acidosis, and kidney toxicity, to name a few. Such synthetic medications are not permitted to be taken by some renal patients. On the other hand, lack of dose-dependent standardization of inhibitors for effectiveness and protection, poor bioavailability, and weak aqueous solubility are some of

Conclusion

Increased AGE generation and occurrence have been linked to the development of diabetic complications and other pathologies. AGE levels are exceptionally high in people with diabetes, according to clinical research and experimental studies, and high blood sugar speeds up protein glycation and facilitates AGE development. Understanding the impact of diabetes in today's world and the wide variety of diabetes complications, medications to mitigate diabetes complications are urgently needed. The

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

ASR is highly grateful to the CSIR, Gov't of India, for financial support [File No. 01(2903)/17/EMR-II]. SS thanks TEQIP-III, NIT Meghalaya for his research fellowship.

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