The protective effects of beta-mangostin against sodium iodate-induced retinal ROS-mediated apoptosis through MEK/ERK and p53 signaling pathways

• Published in: Food & function Vol. 14; no. 24; pp. 1896 - 199
• Main Authors: Chang, Yuan-Yen, Wang, Meilin, Yeh, Jui-Hsuan, Tsou, Shang-Chun, Chen, Tzu-Chun, Hsu, Min-Yen, Lee, Yi-Ju, Wang, Inga, Lin, Hui-Wen
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 11.12.2023
• Subjects: Age; Age related diseases; Animals; Apoptosis; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; Catalase; Cell viability; Cellular manufacture; Damage; Down-regulation; Epithelium; Eye diseases; Glutathione; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Intracellular signalling; Macular degeneration; MEK inhibitors; Mitochondrial Diseases; Mitogen-Activated Protein Kinase Kinases - metabolism; Oxidative Stress; p53 Protein; Phosphorylation; Reactive oxygen species; Reactive Oxygen Species - metabolism; Retina; Retinal Pigment Epithelium; Signal Transduction; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 2042-6496; 2042-650X; 2042-650X
• DOI: 10.1039/d3fo03568a

Previous studies have indicated that NaIO 3 induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces. Beta-mangostin (BM) is a xanthone-type natural compound isolated from Cratoxylum arborescens . The influence of BM on NaIO 3 -induced oxidative stress damage in ARPE-19 cells has not yet been elucidated. In this study, we investigated how BM protects ARPE-19 cells from NaIO 3 -induced ROS-mediated apoptosis. Our results revealed that BM notably improved cell viability and prevented ARPE-19 cell mitochondrial dysfunction mediated-apoptosis induced by NaIO 3 ; it was mediated by significantly reduced NaIO 3 -upregulated ROS, cellular H 2 O 2 production and improved downregulated glutathione and catalase activities. Furthermore, we found that BM could suppress the expression of Bax, cleaved PARP, and cleaved caspase-3 by decreasing phosphorylation of MEK/ERK and p53 expression in NaIO 3 -induced ARPE-19 cells. At the same time, we also used MEK inhibitors (PD98059) to confirm the above phenomenon. Moreover, our animal experiments revealed that BM prevented NaIO 3 from causing retinal deformation; it led to thicker outer and inner nuclear layers and downregulated cleaved caspase-3 expression compared to the group receiving NaIO 3 only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO 3 -induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways. Previous studies have indicated that NaIO 3 induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces.