Pomegranate peel extract alleviates diabetic retinopathy by suppressing the PI3K/AKT/HIF-1α/VEGF pathway and gut microbiota modulation

作者：Qi‐dong Ren, Meirong Li, Mohamed A. Farag, Linlin Qiu, Yan-ao Wang, Dan Liu, Haoran Liu, Jinyue Sun, Ningyang Li, Chao Liu · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.10.048 · 被引用次数：4 · 研究领域：Pomegranate: compositions and health benefits、Retinal Diseases and Treatments、Natural Antidiabetic Agents Studies

• PPE attenuated ocular lesions and preserved retinal structure in DR rats. • Network pharmacology analysis identified that PPE’s anti-DR effects primarily involved the HIF-1 and ROS pathways. • PPE suppressed oxidative stress and inhibited the PI3K/AKT/HIF-1α/VEGF pathway in the retinas of DR rats and high-glucose-exposed ARPE-19 cells. • PPE ameliorated gut microbiota dysbiosis and improved metabolic functions associated with inflammation and oxidative stress in DR rats. Diabetic retinopathy (DR) is a severe microvascular complication of diabetes mellitus. Pomegranate peel extract (PPE) has shown potential in mitigating various diabetic complications, yet its role in DR remains unexplored. To investigate the beneficial effects and underlying action mechanisms of PPE in managing DR. PPE was extracted using 50% ethanol. The effects and underlying mechanisms of PPE on DR were evaluated in streptozotocin (STZ)-induced DR rats and high-glucose-incubated adult retinal pigment epithelial cell line (ARPE-19) cells. Phenotypic parameters, network pharmacology (NP), and gut microbiota metagenomic analysis were employed to elucidate the impact and mechanisms of PPE in DR. In DR rats, oral administration of PPE significantly mitigated retinal damage. NP analysis indicated potential mechanisms, involving the hypoxia-inducible factor-1/vascular endothelial growth factor (HIF-1/VEGF), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and reactive oxygen species (ROS) pathways. PPE su...