Assuntos
Antitussígenos , COVID-19 , Oftalmopatias , Humanos , Descongestionantes Nasais/uso terapêutico , Face , Doença AgudaAssuntos
Tosse , Surtos de Doenças , Humanos , Hong Kong/epidemiologia , Tosse/tratamento farmacológico , FaceAssuntos
COVID-19 , Oclusão da Artéria Retiniana , COVID-19/sangue , COVID-19/complicações , COVID-19/epidemiologia , Humanos , Assistência ao Paciente/métodos , Oclusão da Artéria Retiniana/epidemiologia , Oclusão da Artéria Retiniana/etiologia , Oclusão da Artéria Retiniana/fisiopatologia , Oclusão da Artéria Retiniana/terapia , Fatores de Risco , SARS-CoV-2RESUMO
BACKGROUND AND PURPOSE: Angiogenesis is a crucial step in tumour growth and metastasis. Ginsenoside-Rb1 (Rb1), the major active constituent of ginseng, potently inhibits angiogenesis in vivo and in vitro. However, the underlying mechanism remains unknown. We hypothesized that the potent anti-angiogenic protein, pigment epithelium-derived factor (PEDF), is involved in regulating the anti-angiogenic effects of Rb1. EXPERIMENTAL APPROACHES: Rb1-induced PEDF was determined by real-time PCR and western blot analysis. The anti-angiogenic effects of Rb1 were demonstrated using endothelial cell tube formation assay. Competitive ligand-binding and reporter gene assays were employed to indicate the interaction between Rb1 and the oestrogen receptor (ER). KEY RESULTS: Rb1 significantly increased the transcription, protein expression and secretion of PEDF. Targeted inhibition of PEDF completely prevented Rb1-induced inhibition of endothelial tube formation, suggesting that the anti-angiogenic effect of Rb1 was PEDF specific. Interestingly, the activation of PEDF occurred via a genomic pathway of ERbeta. Competitive ligand-binding assays indicated that Rb1 is a specific agonist of ERbeta, but not ERalpha. Rb1 effectively recruited transcriptional activators and activated an oestrogen-responsive reporter gene. Furthermore, Rb1-mediated PEDF activation and the subsequent inhibition of tube formation were blocked by the ER antagonist ICI 182,780 or transfection of ERbeta siRNA, indicating ERbeta dependence. CONCLUSIONS AND IMPLICATIONS: Here we show for the first time that the Rb1 suppressed the formation of endothelial tube-like structures through modulation of PEDF via ERbeta. These findings demonstrate a novel mechanism of the action of this ginsenoside that may have value in anti-cancer and anti-angiogenesis therapy.