College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
College of Life Sciences, Jilin Agricultural University, Changchun 130118, China.
Int J Mol Sci. 2024 Oct 24;25(21):11414. doi: 10.3390/ijms252111414.
Age-related macular degeneration (AMD) is marked by a progressive loss of central vision and is the third leading cause of irreversible blindness worldwide. The exact mechanisms driving the progression of this macular degenerative condition remain elusive, and as of now, there are no available preventative measures for dry AMD. According to ancient records, ginseng affects the eyes by brightening them and enhancing wisdom. Modern pharmacological research shows that the active ingredients in ginseng, ginsenosides, may be used to prevent or improve eye diseases that threaten vision. Some articles have reported that ginsenoside Rg3 can treat diabetic retinopathy in mice, but no reports exist on its effects and mechanisms in AMD. Therefore, the role and mechanism of ginsenoside Rg3 in AMD warrant further study. This study aims to investigate the effects of Rg3 on AMD and its underlying molecular mechanisms. We established a mouse model of AMD to examine the impact of ginsenoside Rg3 on NaIO-induced apoptosis in the retina and to explore the related intrinsic mechanisms. The in vivo results indicated that ginsenoside Rg3 prevents NaIO-induced apoptosis in retinal pigment epithelial cells by inhibiting reactive oxygen species production and preventing the reduction in mitochondrial membrane potential. Additionally, we assessed the levels of protein expression within the apoptosis pathway. Ginsenoside Rg3 decreased the expression of Bax, cleaved caspase-3, and cleaved caspase-9 proteins. Additionally, it increased the expression of Bcl-2 by decreasing P-JNK levels. Moreover, our in vivo results showed that ginsenoside Rg3 enhanced retinal structure, increased the relative thickness of the retina, and decreased the extent of disorganization in both the inner and outer nuclear layers. Ginsenoside Rg3 may safeguard the retina against NaIO-induced cell apoptosis by attenuating reactive-oxygen-species-mediated mitochondrial dysfunction, in which the JNK signaling pathway is also involved. These findings suggest that ginsenoside Rg3 has the potential to prevent or attenuate the progression of AMD and other retinal pathologies associated with NaIO-mediated apoptosis.
年龄相关性黄斑变性（AMD）的特征是中央视力逐渐丧失，是全球第三大致盲原因。导致这种黄斑退行性疾病进展的确切机制仍不清楚，目前对于干性 AMD 还没有可预防的措施。根据古代记载，人参能明目益智。现代药理研究表明，人参中的活性成分——人参皂苷可能用于预防或改善威胁视力的眼部疾病。有文章报道人参皂苷 Rg3 可治疗小鼠糖尿病视网膜病变，但在 AMD 中尚无其作用及机制的报道。因此，人参皂苷 Rg3 在 AMD 中的作用和机制值得进一步研究。本研究旨在探讨 Rg3 对 AMD 的作用及其潜在的分子机制。我们建立了 AMD 小鼠模型，研究了人参皂苷 Rg3 对 NaIO 诱导的视网膜细胞凋亡的影响，并探讨了相关的内在机制。体内结果表明，人参皂苷 Rg3 通过抑制活性氧的产生和防止线粒体膜电位降低，抑制 NaIO 诱导的视网膜色素上皮细胞凋亡。此外，我们评估了凋亡途径中的蛋白表达水平。人参皂苷 Rg3 降低 Bax、cleaved caspase-3 和 cleaved caspase-9 蛋白的表达，同时通过降低 P-JNK 水平增加 Bcl-2 的表达。此外，我们的体内结果表明，人参皂苷 Rg3 通过增强视网膜结构、增加视网膜相对厚度和减少内外核层的紊乱程度，来防止 NaIO 诱导的细胞凋亡。人参皂苷 Rg3 可能通过减轻活性氧介导的线粒体功能障碍来保护视网膜免受 NaIO 诱导的细胞凋亡，其中 JNK 信号通路也参与其中。这些发现表明，人参皂苷 Rg3 具有预防或减缓 AMD 及其他与 NaIO 介导的凋亡相关的视网膜病变进展的潜力。
