Enhancing ocular protection against UVB: The role of irigenin in modulating oxidative stress and apoptotic pathways In Vivo
Year: 2024
Type: article
Abstract: Oxidative damage contributes to age-related macular degeneration. Irigenin possesses diverse pharmacologic properties, including antioxidative and antiapoptotic effects. Our in vivo experiments indicated that irigenin mitigates UVB-induced histopathologic changes and oxidative DNA damage. Histologic analyses and TUNEL staining revealed that this compound dose-dependently ameliorated UVB-induced retinal damage and apoptosis. Furthermore, irigenin substantially reduced the level of 8-hydroxyguanosine, a biomarker of UVB-induced oxidative DNA damage. We further explored the molecular mechanisms that mediate the protective effects of irigenin. Our findings suggested that UVB-induced generation of ROS disrupts the stability of the mitochondrial membrane, activating intrinsic apoptotic pathways; the underlying mechanisms include the release of cytochrome c, activation of caspase-9 and caspase-3, and subsequent degradation of PARP-1. Notably, irigenin reversed mitochondrial disruption and apoptosis. It also modulated the Bax and Bcl-2 expression but influenced the mitochondrial apoptotic pathways. Our study highlights the role of the Nrf2 pathway in mitigating the effects of oxidative stress. We found that UVB exposure downregulated, but irigenin treatment upregulated the expression of Nrf2 and antioxidant enzymes. Therefore, irigenin activates the Nrf2 pathway to address oxidative stress. In conclusion, irigenin exhibits protective effects against UVB-induced ocular damage, evidenced by the diminution of histological alterations. It mitigates oxidative DNA damage and apoptosis in the retinal tissues by modulating the intrinsic apoptotic pathways and the AIF mechanisms. Furthermore, irigenin effectively reduces lipid peroxidation, enhancing the activity of antioxidant enzymes by stimulating the Nrf2 pathway. This protective mechanism underscores the potential benefit of irigenin in combating UVB-mediated ocular damage.
Source: Biomedicine & Pharmacotherapy
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,420
Awards: Investigation of the Molecular Mechanisms of Cardiovascular Diseases Induced by Indium Chloride through Oxidative Stress and Ferroptosis in Endothelial Cells and Zebrafish Model, Exploring a Sars-Cov-2-Like Cardiopulmonary Model: Assessing Mulberry Leaf Extracts and Solanesol in Modulating Immune Responses and Molecular Mechanism to Improve Acute Respiratory Distress Syndrome and Myocarditis, To Investigate the Molecular Mechanism of Sepsis Induced Acute Kidney Injury Improved by Visnagin via the Network Pharmacology Development Platform and Experiment Mode, G5722973056, Nonaisoprenol Reduces Panoptosis by Regulating Ripk1 and Improves the Molecular Mechanisms Associated with Acute Kidney Injury (Aki), Investigation of the Molecular Mechanism of Septic Acute Lung Injury via the Cgas/Sting Dna Sensing Pathway on the Artificial Intelligence Network Health Care Material Efficacy Platform, Experimental Cellular and Animal Models
OpenAlex ID: W4402193044