Chitosan-based Moringa oleifera nanoparticles attenuate hyperglycemia-induced vascular endothelial growth factor upregulation in human lens epithelial cells

Chronic hyperglycemia induces oxidative stress and stress-responsive signaling in ocular tissues, contributing to the progression of diabetic eye complications. Vascular endothelial growth factor (VEGF) is a key mediator of hyperglycemia-induced cellular dysfunction. Moringa oleifera, rich in antioxidant flavonoids and phenolics, exhibits potential protective effects against metabolic stress. This study evaluated whether chitosan-based M. oleifera nanoparticles attenuate hyperglycemia-induced upregulation of VEGF in human lens epithelial (HLE) cells. HLE-B3 cells were exposed to high glucose to establish an in vitro model of hyperglycemia. Chitosan nanoparticles loaded with M. oleifera seed (NMS) and leaf (NML) extracts were fabricated and characterized for physicochemical properties and bioactive compound content. Cytotoxicity was assessed using MTT assays under normoglycemic and hyperglycemic conditions. VEGF expression was evaluated by immunofluorescence and semi-quantitative image analysis following nanoparticle treatment. Nanoparticle characterization confirmed successful encapsulation of flavonoids and phenolic compounds with stable physicochemical properties. Both NMS and NML were well tolerated under normoglycemic conditions (IC₅₀ >3500 µg/mL), while hyperglycemia-induced cells exhibited greater sensitivity (IC_50: 1517 µg/mL for NMS; 1943 µg/mL for NML). High glucose exposure significantly increased VEGF expression, whereas treatment with NMS and NML markedly attenuated VEGF upregulation. Chitosan-based M. oleifera nanoparticles attenuate hyperglycemia-induced VEGF expression in HLE cells, indicating a protective effect against epithelial stress signaling. These findings highlight the potential of nanoencapsulated M. oleifera as a strategy to modulate hyperglycemia-driven ocular epithelial dysfunction.