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.