# Xanthone Derivatives and Their Potential Usage in the Treatment of Telangiectasia and Rosacea
## 2 Xanthone Derivatives and Their Vascular Activity
### Sealing Blood Vessel Activity
#### 2.1.1 Antiangiogenic Activity  
Angiogenesis refers to the formation of new blood vessels from existing ones, and inhibiting this process holds promise in combating cancer. Tumor angiogenesis, a complex series of events involving endothelial cell activation, invasion, migration, proliferation, and the formation of capillary networks, is crucial for cancer progression and metastasis. Without the formation of new blood vessels, tumors typically remain small and are less likely to metastasize. Consequently, targeting angiogenesis is a significant strategy in cancer treatment with regard to skin lesions as well.  
In one of the studies conducted by [PERSON] et al., a few gambogic acid derivatives were obtained and evaluated in terms of antiangiogenic activity. Four derivatives effectively inhibited the development of new segmental blood vessels in zebrafish assays and showed lower toxicity to zebrafish than gambogic acid (GA) (Figure 2). They also demonstrated stronger inhibitory effects on the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro compared with GA [27].  
Another xanthone derivative, \(\alpha\)-mangostin (Figure 3), exhibits significant inhibitory effects on various aspects of angiogenesis and vascular permeability in retinal endothelial cells (RECs). Specifically, it suppresses VEGF-induced permeability increases, proliferation, migration, and tube formation, as well as vascular sprouting in the aortic ring assay. This compound also hampers the phosphorylation of VEGF receptor 2 (VEGFR2) as well as extracellular signal-regulated kinase 1 and 2-mitogen-activated protein kinase (ERK1/2-MAPK) induced by VEGF. Furthermore, \(\alpha\)-mangostin has been found to inhibit reactive oxygen species (ROS) formation induced by hypoxia treatment in RECs. This suggests its potential in mitigating oxidative stress associated with hypoxia and preventing neovascularization in the retina. The inhibition of VEGF-induced angiogenic responses by \(\alpha\)-mangostin is associated with its ability to block VEGFR and ERK1/2-MAPK activation. These findings underscore the antioxidant and anti-angiogenic properties of \(\alpha\)-mangostin, indicating its potential as a natural therapeutic agent for reducing oxidative stress and preventing retinal neovascularization. Moreover, \(\alpha\)-mangostin's selective inhibition of specific signaling path  
Figure 1: Structure of xanthone (dibenzo-\(\gamma\)-pyrone).  
ways like VEGFR2 and ERK1/2-MAPK without affecting Akt and p38 phosphorylation provides insights into its mechanism of action in regulating angiogenesis and vascular permeability in microvascular endothelial cells. It was successfully demonstrated that \(\alpha\)-mangostin possesses both antioxidant and anti-angiogenic properties when applied to RECs. Specifically, our findings reveal that \(\alpha\)-mangostin effectively reduces the formation of ROS triggered by hypoxia treatment in RECs, \(\alpha\)-mangostin inhibits various angiogenic responses induced by VEGF, such as enhanced REC permeability, proliferation, migration, tube formation, and vascular sprouting in the aortic ring assay, and \(\alpha\)-mangostin attenuates the phosphorylation of the VEGFR2 and ERK1/2-MAPK pathways in RECs stimulated by VEGF [28].