# Xanthone Derivatives and Their Potential Usage in the Treatment of Telangiectasia and Rosacea
## 1 Introduction
Furthermore, alterations in the glycocalyx have been implicated in various vascular pathologies, including endothelial dysfunction, atherosclerosis, and diabetic vascular complications. Damage to the glycocalyx, often induced by oxidative stress, inflammation, or hyperglycemia, compromises its protective and regulatory functions, contributing to vascular injury and disease progression [7]. Hyaluronic acid is a large, negatively charged glycosaminoglycan that contributes to the hydration, lubrication, and structural integrity of the glycocalyx. Through its ability to interact with water molecules and form a hydrated gel-like matrix, hyaluronic acid helps maintain the thickness and viscoelastic properties of the glycocalyx, which is crucial for its barrier function and mechanotransduction [8]. Hyaluronidase is an enzyme of the hydrolase class that depolymerizes the hyaluronic acid located in blood vessel walls (Scheme 1). Hyaluronidase is an endoglycosidase that breaks down hyaluronic acid into monosaccharides by cleaving its glycosidic bonds. Additionally, to some extent, it also breaks down other acid mucopolysaccharides in the connective tissue [9]. It is present both in organs and body fluids (e.g., tears and blood). There are six types of hyaluronages in the human body: hyaluronages 1-4, encoded by HYAL genes 1-4, PH-20 (SPAM-1), and HYALP1. Hyaluronidase 1 is present in human organs and acts as the major hyaluronidase in plasma, being activated at acidic pH levels. Hyaluronidase 2, on the other hand, has weaker enzymatic activity than hyaluronidase 1 and degrades only high molecular weight hyaluronic acid. It is mostly used in aesthetic medicine to dissolve tissue fillers based on high molecular weight hyaluronic acid. The role of hyaluronidase 3 remains unknown, as it is found only in the nucleus and bone marrow. Testicular hyaluronidase PH-20 is found on the surface of human sperm and the inner acrosomal membrane and serves to degrade hyaluronic acid in the egg cell during fertilization [10]. Recent studies have shed light on the intricate interplay between hyaluronidase, hyaluronic acid, and the vascular glycocalyx, providing valuable insights into their roles in vascular physiology and pathology. For instance, research by [PERSON] and [PERSON] found that enzymatic degradation of hyaluronic acid by hyaluronidase disrupts the glycocalyx structure, leading to increased vascular permeability and endothelial dysfunction [13]. Moreover, work by [PERSON] et al. demonstrated that hyaluronidase-mediated degradation of hyaluronic acid fragments can stimulate inflammatory responses and promote atherosclerosis progression in animal models [14]. Furthermore, clinical studies by [PERSON] et al. [15] have highlighted the association between elevated hyaluronidase activity and impaired glycocalyx function in patients with cardiovascular diseases, underscoring the potential clinical relevance of targeting hyaluronidase for vascular protection. Additionally, investigations by [PERSON] et al. [16] have identified dysregulated hyaluronidase expression in diabetic vasculopathy, suggesting a link between altered hyaluronic acid metabolism and diabetic vascular complications [15]. These findings collectively emphasize the importance of understanding the dynamic interactions between hyaluronidase, hyaluronic acid, and the glycocalyx in vascular health and disease. Future research efforts aimed at elucidating the molecular mechanisms underlying these interactions may pave the way for the development of novel therapeutic approaches for vascular disorders [16].