Exploring the Interplay between Polyphenols and Lysyl Oxidase Enzymes for Maintaining Extracellular Matrix Homeostasis

Abstract

Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling the literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.

Use of Collagen in Cosmetic Products

“…As a result of the glycation process, the so-called AGE (advanced glycation end-product)—i.e., products of advanced glycation—compounds have the ability to create crosslinks in proteins [ 44 , 51 , 52 , 58 ]. Glycation ( Figure 7 ) is a non-enzymatic reaction between reducing sugars and proteins, lipids, or nucleic acids.…”

“…Glycation ( Figure 7 ) is a non-enzymatic reaction between reducing sugars and proteins, lipids, or nucleic acids. Enzymatic glycosylation of proteins in the body is a deliberate process and occurs in a specific place, while glycation, i.e., non-enzymatic glycosylation, is spontaneous [ 44 , 58 ]. Its severity depends on the content of simple sugars in the body, e.g., glucose.…”

“… Steps of glycation of collagen fibers, ( A ) Lysine glycation (red font—reduced glucose attached to lysine molecule and forming a Schiff base); ( B ) Collagen fibril via glycation cross-linking (red lines—bonds formed during the glycation process); ( C ) Abnormal collagen fiber (red lines—bonds formed between fibers) (reprinted from [ 58 ]). …”

Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences

“…Some polyphenols, such as chlorogenic acid, gallic acid, and caffeic acid, have been shown to have amine oxidase-like activity, which means that they can mimic the action of LOX and participate in collagen cross-linking. This suggests that polyphenols may contribute to the strengthening of the ECM and the maintenance of tissue integrity [ 244 ].…”

The effects of advanced glycation end‐products on skin and potential anti‐glycation strategies

“…Consumption of high‐sugar and high‐processed food diets can increase systemic AGEs levels, such as MGO, CEL and CML 7 . In diabetic patients, the expression levels of matrix metalloproteinase (MMP)‐1, MMP‐2 and lysyl oxidase (LOX) were elevated, and they enhanced the crosslink with collagen and elastin in the skin, destroying its integrity and losing the properties of mechanical support, 44 thereby leading to cellular senescence. The endogenous formation of AGEs was attributed to normal metabolic processes, oxidative stress and inflammation in the body.…”