Carnosic acid attenuates diabetic retinopathy via the SIRT1 signaling pathway: neuroprotection and endothelial cell preservation.

OBJECTIVE: To explore the therapeutic effects of Carnosic acid (CA) on diabetic retinopathy (DR), a complication of diabetes mellitus (DM) characterized by retinal neuronal damage induced by oxidative stress. METHODS: DR was induced in rodent models via streptozotocin (STZ) administration, while human retinal microvascular endothelial cells (HRMECs) were cultured in high-glucose (HG) conditions. The effects of CA on oxidative stress, inflammation, and apoptotic signaling were evaluated by quantifying relevant biomarkers. RESULTS: CA treatment significantly increased the expression of sirtuin 1, which was reduced in both STZ-treated rats and HG-exposed HRMECs, as confirmed by polymerase chain reaction (PCR) analysis. CA alleviated oxidative stress, inflammation, and apoptosis in STZ-induced DR models. In vitro, CA exhibited a dose-dependent enhancement of SIRT1 expression, providing substantial protection against HG-induced damage in HRMECs. This protective effect involved the suppression of oxidative mediators, reduction of pro-inflammatory cytokine release, and inhibition of apoptotic pathways. Additionally, CA prevented retinal ferroptosis by activating the SIRT1/p53/solute carrier family 7 member 11 (SLC7A11) pathway both in vivo and in vitro. CONCLUSION: This study suggests that CA alleviates DR by activating SIRT1, leading to decreased inflammation, apoptosis, and oxidative stress.