1. Oxidative and carbonyl stress induced AMD and Codonopsis lanceolata ameliorates AMD via controlling oxidative and carbonyl stress.
- Author
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Lee SY, Cho YK, Bae CS, Kim G, Lee MJ, Cho SS, Jeon IC, and Park DH
- Subjects
- Humans, Plant Extracts pharmacology, Antioxidants pharmacology, Kelch-Like ECH-Associated Protein 1 metabolism, Cell Line, Aldehydes pharmacology, Retinal Pigment Epithelium drug effects, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology, Light adverse effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Codonopsis chemistry, Macular Degeneration drug therapy, Macular Degeneration metabolism, Macular Degeneration pathology, Oxidative Stress drug effects, Apoptosis drug effects, NF-E2-Related Factor 2 metabolism
- Abstract
Age-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 μM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 μg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 μM A2E and 20 mW/cm
2 blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent., (© 2024. The Author(s).)- Published
- 2024
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