Mol Biol Rep. 2026 Jan 20;53(1):309. doi: 10.1007/s11033-026-11476-9.
ABSTRACT
BACKGROUND: Diabetic retinopathy (DRP) is a leading cause of vision loss associated with chronic hyperglycemia-induced oxidative stress (OS), inflammation, and mitochondrial dysfunction in retinal pigment epithelium (RPE) cells. Zingerone (ZGN), a phenolic compound derived from Zingiber officinale, exhibits potent antioxidant and anti-inflammatory properties; however, its molecular targets in diabetic retinal damage remain unclear.
METHODS: This study investigated the protective effects of ZGN against high glucose (HG)-induced cytotoxicity in human ARPE-19 cells, focusing on the ROS/PARP-1/TRPM2 signaling pathway. The cells were exposed to HG (30 mM) and treated with ZGN (0-80 µM) for 24 h.
RESULTS: HG incubation significantly increased MDA, PARP-1, ROS, intracellular calcium ion ([Ca²⁺]i), and pro-inflammatory cytokines (IL-1β and TNF-α) in ARPE-19 cells, while decreasing GSH levels and cell viability. ZGN significantly restored OS, reduced cytokine release, [Ca²⁺]i, and preserved mitochondrial membrane potential. Western blot and fluorescence analyses showed that ZGN reduced TRPM2 protein expression and suppressed [Ca²⁺]i overload. Moreover, pharmacological inhibition of TRPM2 with 2-APB and of PARP-1 with DPQ enhanced the cytoprotective effects of ZGN, confirming that the ROS/PARP-1/TRPM2 axis mediates HG-induced oxidative damage.
CONCLUSIONS: These findings suggest that ZGN protects ARPE-19 cells by integrating OS with [Ca²⁺]i homeostasis, providing a mechanistic rationale for its potential therapeutic use in preventing OS-related retinal damage in DRP.
PMID:41557015 | DOI:10.1007/s11033-026-11476-9