Investigations on selected natural product classes as inhibitors of Advanced Glycation Endproducts (AGEs) and modulators of autophagy

During previous investigations in the host laboratory it has been found that several classes of natural products, i.e. polymethoxy-flavones, biflavonoids, xanthones and quinazoline alkaloids, exhibited AGEs inhibiting properties. AGEs (or Advanced Glycation Endproducts) are implicated in many age-related chronic diseases and in protein ageing, and are associated with diabeticcomplications, atherosclerosis, neurodegenerative diseases, cancer and the normal ageing processes. AGEs have been found to induce autophagy, a favourable subcellular process contributing to cellular homeostasis and adaptation to stress by removing damaged or unwanted intracellular material. Similar to AGEs, autophagy has been associated with different pathologicalconditions including heart disease, cancer and neurodegeneration. Autophagy is stimulated in atherosclerosis and in oxidative stress conditions. Therefore, AGEs inhibition and modulation of autophagy were selected as targets to be evaluated and to establish structure-activity relationships for the product classes mentioned above. Both AGEs inhibition and modulation of autophagy are relatively new targets in natural product research. AGEs inhibitors and inducers of autophagy, or a combination of both, may be potentially useful products against degenerative diseases in a broad sense, such as the ones mentioned above.

Keywords:AUTOPHAGY

Disciplines:Other chemical sciences, Nutrition and dietetics, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences, Agricultural animal production, Food sciences and (bio)technology