Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Comprehensive multi-omics and pharmacokinetics reveal sclareol's role in inhibiting ocular neovascularization.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yang Chong-Chao, Jiang Qin, Xue Jin-Song
Аннотация
BACKGROUND: Ocular neovascularization, a hallmark of several vision-threatening diseases, including retinopathy of prematurity (ROP) and wet age-related macular degeneration (wet AMD), is commonly treated with intravitreal injections of anti-VEGF agents. However, these treatments are limited by invasiveness and drug resistance, highlighting the need for alternative therapies. Sclareol (SCL), a labdane diterpenoid derived from Salvia sclarea, exhibits various biological activities, but its potential role in angiogenesis and pharmacokinetics after oral administration remain unexplored.
METHODS: Hypoxia-induced endothelial cells (ECs) were used as an in vitro model, while mouse oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were used as in vivo models. The pharmacokinetics of SCL in plasma, retina, and choroid were analyzed after oral administration in mice. Furthermore, the underlying mechanisms were elucidated through an integrative approach combining transcriptomics, metabolomics, network pharmacology, molecular docking, and molecular dynamics simulation.
RESULTS: SCL inhibited hypoxia-induced EC proliferation, permeability, migration, tube formation, sprouting, glycolysis, mitochondrial respiration, and oxidative stress by modulating the PI3K-AKT-FOXO1 pathway. Additionally, Oral administration of SCL significantly inhibited OIR and CNV progression in mice, demonstrating enhanced therapeutic efficacy when combined with intravitreal aflibercept (Eylea) injection.
CONCLUSION: SCL is a promising orally administered natural compound for ocular neovascularization, offering a potential alternative or adjunctive therapy to existing anti-VEGF treatments.
METHODS: Hypoxia-induced endothelial cells (ECs) were used as an in vitro model, while mouse oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were used as in vivo models. The pharmacokinetics of SCL in plasma, retina, and choroid were analyzed after oral administration in mice. Furthermore, the underlying mechanisms were elucidated through an integrative approach combining transcriptomics, metabolomics, network pharmacology, molecular docking, and molecular dynamics simulation.
RESULTS: SCL inhibited hypoxia-induced EC proliferation, permeability, migration, tube formation, sprouting, glycolysis, mitochondrial respiration, and oxidative stress by modulating the PI3K-AKT-FOXO1 pathway. Additionally, Oral administration of SCL significantly inhibited OIR and CNV progression in mice, demonstrating enhanced therapeutic efficacy when combined with intravitreal aflibercept (Eylea) injection.
CONCLUSION: SCL is a promising orally administered natural compound for ocular neovascularization, offering a potential alternative or adjunctive therapy to existing anti-VEGF treatments.