AUTHOR=Shi Jiemei , Liu Min , Zhao Jiajie , Tan Ye , Jiang Chunhui 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1485831

DOI=10.3389/fphar.2024.1485831

ISSN=1663-9812

ABSTRACT=<sec><title>Introduction</title><p>Mitochondrial dysfunction and oxidative stress play important roles in diabetic retinal vascular injuries. Honokiol (HKL) is a small-molecule polyphenol that exhibits antioxidant effects and has a beneficial effect in diabetes. This study aimed to explore the potential ability of HKL to ameliorate vascular injury in diabetic retinopathy (DR) and its possible mechanisms of action.</p></sec><sec><title>Methods</title><p>The effect of HKL was evaluated in vascular injury in an <italic>in vivo</italic> type 2 diabetic (db/db) mouse model. <italic>In vitro</italic>, retinal microvascular endothelial cells were treated with high glucose (HG) to simulate the pathological diabetic environment. Cell viability, expression of apoptosis-related proteins, cellular reactive oxygen species, mitochondrial membrane potential, and morphological changes in the mitochondria were examined.</p></sec><sec><title>Results</title><p>The diabetic mice exhibited severe retinal vascular damage, including vascular leakage <italic>in vivo</italic> and capillary endothelial cell apoptosis <italic>in vitro</italic>. HKL reversed the retinal vascular leakage in the diabetic mice. <italic>In vitro</italic>, HKL improved retinal capillary endothelial cell viability, decreased apoptosis, and reversed the HG-induced increased cellular oxidative stress and mitochondrial fragmentation. The sirtuin 3 (SIRT3) inhibitor 3-TYP blocked all the <italic>in vivo</italic> and <italic>in vitro</italic> protective effects of HKL against diabetic retinal vascular leakage and capillary endothelium and eliminated the decrease in oxidative stress levels and reduction of mitochondrial fragmentation.</p></sec><sec><title>Discussion</title><p>In conclusion, these findings suggest that HKL inhibits vascular injury in DR, which was likely achieved through SIRT3-mediated mitochondrial fusion. This study provides a potential new strategy for the treatment of DR.</p></sec>