Ganoderic acid protects against diabetic retinal injury via modulating inflammatory, apoptotic, and antioxidant signaling pathways

Objective: To investigate whether ganoderic acid can alleviate streptozotocin-induced diabetic retinopathy and explore its underlying mechanisms. Methods: Streptozotocin (55 mg/kg) combined with nicotinamide (100 mg/kg body weight) was used to establish a diabetes mellitus rat model. Rats were then orally administered ganoderic acid at doses of 12.5, 25, and 50 mg/kg. Body weight, blood glucose, organ weights, and serum insulin levels were determined. Hepatic and renal biochemical indices, as well as markers related to oxidative stress, angiogenesis, inflammation, and apoptosis in retinal tissues, were also assessed. Results: Ganoderic acid treatment significantly ( P <0.001) lowered blood glucose and improved insulin levels and body and organ weights. The treatment remarkably attenuated blood-retinal barrier disruption, reduced acellular capillaries, and ameliorated hepatic and renal pathological changes, accompanied by decreased levels of IL-1β, TNF-α, IL-6, IL-17, COX-2, and PGE 2 . In addition, ganoderic acid upregulated Nrf2 and HO-1 and modulated the mRNA expression of Bax and Bcl-2 . Conclusions: Ganoderic acid ameliorates streptozotocin-induced diabetic retinopathy by inhibiting inflammation and apoptosis and enhancing antioxidant activities.