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
Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Food Funct. 2023 Dec 11;14(24):10896-10909. doi: 10.1039/d3fo03568a.
Previous studies have indicated that NaIO 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 . The influence of BM on NaIO-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-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; it was mediated by significantly reduced NaIO-upregulated ROS, cellular HO 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-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 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 only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO-induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways.
先前的研究表明，碘酸钠可诱导细胞内活性氧（ROS）生成，并且由于其诱导的视网膜色素上皮（RPE）细胞选择性损伤，已被用作年龄相关性黄斑变性（AMD）的模型。β-山竹黄酮（BM）是一种从……中分离出的呫吨酮类天然化合物。BM对碘酸钠诱导的ARPE - 19细胞氧化应激损伤的影响尚未阐明。在本研究中，我们研究了BM如何保护ARPE - 19细胞免受碘酸钠诱导的ROS介导的细胞凋亡。我们的结果显示，BM显著提高了细胞活力，并预防了碘酸钠诱导的ARPE - 19细胞线粒体功能障碍介导的细胞凋亡；这是通过显著降低碘酸钠上调的ROS、细胞内HO生成以及改善下调的谷胱甘肽和过氧化氢酶活性来介导的。此外，我们发现BM可通过降低碘酸钠诱导的ARPE - 19细胞中MEK/ERK的磷酸化和p53表达，来抑制Bax、裂解的PARP和裂解的caspase - 3的表达。同时，我们还使用MEK抑制剂（PD98059）来证实上述现象。此外，我们的动物实验表明，BM可预防碘酸钠导致的视网膜变形；与仅接受碘酸钠的组相比，它使外核层和内核层更厚，并下调了裂解的caspase - 3表达。总体而言，这些结果表明，BM可通过涉及MEK/ERK和p53信号通路的ROS介导的线粒体功能障碍，保护RPE和视网膜免受碘酸钠诱导的细胞凋亡。
