Honokiol protects against diabetic retinal microvascular injury via sirtuin 3-mediated mitochondrial fusion

Introduction: Mitochondrial dysfunction and oxidative stress are critical contributors to diabetic retinal vascular injuries. Honokiol (HKL), a small-molecule polyphenol with antioxidant properties, has shown promise in managing diabetes. This study aimed to investigate the potential of HKL to mitigate vascular injury in diabetic retinopathy (DR) and elucidate its underlying mechanisms.

Methods: The protective effects of HKL were evaluated using an in vivo type 2 diabetic (db/db) mouse model and an in vitro system involving retinal microvascular endothelial cells exposed to high glucose (HG) to mimic the diabetic environment. Key assessments included cell viability, apoptosis-related protein expression, cellular reactive oxygen species levels, mitochondrial membrane potential, and mitochondrial morphological changes.

Results: Diabetic mice exhibited significant retinal vascular damage, characterized by vascular leakage in vivo and capillary endothelial cell apoptosis in vitro. HKL treatment attenuated retinal vascular leakage in diabetic mice. In vitro, HKL improved retinal capillary endothelial cell viability, reduced apoptosis, and alleviated HG-induced oxidative stress and mitochondrial fragmentation. Notably, the protective effects of HKL, both in vivo and in vitro, were abolished by the sirtuin 3 (SIRT3) inhibitor 3-TYP. This included the loss of HKL-induced reductions in oxidative stress and mitochondrial fragmentation.

Discussion: These findings demonstrate that HKL protects against vascular injury in DR, likely through SIRT3-mediated mitochondrial fusion. This study highlights a potential therapeutic strategy for managing DR.