Chrysanthemum morifolium extract attenuates pathological angiogenesis of age-related macular degeneration via VEGF...

Chrysanthemum morifolium has long been utilized in Traditional Chinese Medicine to improve visual acuity and alleviate ocular damage. Although recent pharmacological studies highlight its antioxidant and vasoprotective effects, its efficacy against neovascular processes in age-related macular degeneration (AMD) has not been established.

This study aimed to investigate the therapeutic potential and underlying mechanisms of Chrysanthemum morifolium extract (CME) in managing neovascular AMD, emphasizing its effects on vascular endothelial growth factor (VEGF)-mediated angiogenesis and oxidative stress regulation.

In vitro, ARPE-19 human retinal pigment epithelial cells underwent hypoxic and oxidative stress assays to measure VEGF, hypoxia-inducible factor 1-alpha (HIF-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Human umbilical vein endothelial cells (HUVECs) were treated with a conditioned medium (CM) from CME-exposed ARPE-19 cells to assess migration, invasion, and tube formation. In vivo therapeutic efficacy was validated in cobalt chloride (CoCl₂)-induced zebrafish and laser-induced rat choroidal neovascularization (CNV) models.

CME significantly attenuated hypoxia- and CoCl₂-induced upregulation of VEGF and HIF-1α, enhanced Nrf2 signaling, and reduced reactive oxygen species (ROS) in ARPE-19 cells. CME-CM markedly suppressed HUVEC migration, invasion, and angiogenesis. In zebrafish and rat CNV models, CME treatment significantly reduced neovascular lesion area and preserved retinal architecture in a dose-dependent manner, without evident toxicity.

CME exerts dual anti-angiogenic and antioxidant effects in AMD models by simultaneously targeting VEGF-driven angiogenesis and oxidative stress, supporting its therapeutic potential as a safe and effective herbal intervention for neovascular AMD.