Jiang Guan-Cheng, Pan Hong-Ye, Gu Lei, Cheng Tian-Tian, Zhu Bing-Xue, Wang Xuan-Qi, Yu Jia-Yu, Zhu Feng, Lin Ming, Hu Jiang-Ning, Wang Xia-Wei
Department of Ophthalmology, First Affiliated Hospital, Zhejiang University School of Medicine, 310003, China.
Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, 310051, China; Zhejiang Key Laboratory of Chinese Medicine Modernization, Hangzhou, 310051, China.
J Ethnopharmacol. 2026 Jan 30;355(Pt B):120660. doi: 10.1016/j.jep.2025.120660. Epub 2025 Sep 26.
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 (CoCl)-induced zebrafish and laser-induced rat choroidal neovascularization (CNV) models.
CME significantly attenuated hypoxia- and CoCl-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.
菊花长期以来被用于传统中药中，以提高视力和减轻眼部损伤。尽管最近的药理学研究强调了其抗氧化和血管保护作用，但其对年龄相关性黄斑变性（AMD）新生血管形成过程的疗效尚未确定。
本研究旨在探讨菊花提取物（CME）在治疗新生血管性AMD方面的治疗潜力和潜在机制，重点关注其对血管内皮生长因子（VEGF）介导的血管生成和氧化应激调节的影响。
在体外，对ARPE-19人视网膜色素上皮细胞进行缺氧和氧化应激试验，以测量VEGF、缺氧诱导因子1α（HIF-1α）和核因子红细胞2相关因子2（Nrf2）途径的激活。用人脐静脉内皮细胞（HUVECs）处理来自CME处理的ARPE-19细胞的条件培养基（CM），以评估迁移、侵袭和管形成。在体内，在氯化钴（CoCl）诱导的斑马鱼和激光诱导的大鼠脉络膜新生血管（CNV）模型中验证了治疗效果。
CME显著减弱了缺氧和CoCl诱导的ARPE-19细胞中VEGF和HIF-1α的上调，增强了Nrf2信号传导，并减少了活性氧（ROS）。CME-CM显著抑制了HUVEC的迁移、侵袭和血管生成。在斑马鱼和大鼠CNV模型中，CME治疗以剂量依赖的方式显著减少了新生血管病变面积并保留了视网膜结构，且无明显毒性。
CME通过同时靶向VEGF驱动的血管生成和氧化应激，在AMD模型中发挥双重抗血管生成和抗氧化作用，支持其作为新生血管性AMD安全有效的草药干预措施的治疗潜力。
