Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population in the western countries1, which affects the macular and as a consequence results in central vision loss. AMD is characterized by including accumulation of extracellular deposits (drusen) in the macula, thickening of Bruch’s membrane, degeneration of retinal pigment epithelial (RPE) cells and photoreceptors, and even abnormal neovascularization (angiogenesis) growing into the central region of the retina2. Although the pathogenesis of AMD is still not well understood, oxidative stress is believed to accelerate the process of aging and contributes to the development of AMD3. The retina, a tissue with high levels of various lipid compounds4 in the environment with high oxygen tension5, along with high levels of light exposure, is particularly predisposed to produce reactive oxygen species (ROS). Mitochondria represent a major source of endogenous ROS in most cells of the retina6. ROS in turn damages mitochondria and lipids, leading to modification of retinal function. In recent studies, many evidences have suggested that light exposure can be involved in the progress of AMD7. Epidemiological studies on a population with similar lifestyle have indicated a positive correlation between AMD and the accumulated exposure to solar radiation8,9. In laboratory10,11, retina damages after light exposure in animal models which are generally similar to those seen in patients with AMD is induced by photochemical and photo-oxidative mechanisms. Furthermore, studies12,13 showed that the administration of antioxidants targeting ROS generation and oxidative damage can protect retina from light damage and play a therapeutic role in animal model of AMD. Therefore, the anti-oxidant strategy plays an important role in the treatment of AMD. Alpha-mangostin, a yellow color matter, is the major xanthone purified from mangosteen. Alpha-mangostin has health promoting benefits including anti-bacterial14, anti-inflammatory15, anti-oxidant16, anti-cancer17 and cardio protective18 activities. Researches showed that alpha-mangostin can inhibit the oxidation of low-density lipoprotein in vitro19 and scavenge singlet oxygen, superoxide anion and peroxynitrite anion20. This antioxidant as a free radical scavenger ameliorates the neuronal death induced by 3-nitropropionic acid (3-NP)21. Treatment of alpha-mangostin also provided a neuroprotective effect on cerebellar granule neurons (CGNs) which was associated with the induction of heme oxygenase-1 (HO-1)22. Although alpha-mangostin has showed several antioxidant properties, the effects on retina health have not been clarified yet. In our study, we investigated the effects of administration with alpha-mangostin in animal models of light–induced retina degeneration and the underlying mechanisms were discussed. Statistical analysis The results were presented as the means ± standard error of the mean (SEM). One-way ANOVA or Student’s t test was performed to assess the statistical differences between the groups using SPSS19.0 software and Graphpad Prism 5.0. Statistical significance was set at p < 0.05.