Plumbagin Protects Diabetogenic Cataract Formation by Mitigating Lens Aldose Reductase and Oxidative Stress.

The polyol pathway plays an important pathophysiological role in diabetic-related ocular complications, including cataracts, one of the major causes of ocular blindness. The current paper investigated the protective effects of plumbagin against diabetogenic cataract formation, focusing on exploring its possible mechanism of action. The study investigates antioxidant activity, aldose reductase inhibitory activity, and anticataract activity in experimental pharmacological models. In the ex-vivo study, goat lenses were incubated in artificial aqueous humor with high concentrations of glucose (55.5 mM) and plumbagin (20, 50, and 100 µg/mL), which was assessed against cataract control lenses. The in-vitro study showed that plumbagin inhibits 2,2-Diphenyl-1-Picrylhydrazyl free radical and lens aldose reductase activity. The ex-vivo study showed that plumbagin prevents lenticular opacity against the glucose-induced model. The plumbagin exposure significantly (p < 0.05) increased the antioxidant activity (catalase, superoxide dismutase and reduced glutathione) and reduced the malonaldehyde level. Moreover, plumbagin treatment significantly (p < 0.05) restored the lens protein content. Additionally, network pharmacological approaches suggested that SLC2A1, STAT3, and TP53 are the major target proteins for plumbagin in the prevention of cataract. The results concluded that plumbagin has promising anticataract activity by inhibiting lens aldose reductase and mitigating lenticular oxidative stress, making it a potential anticataract agent for diabetic conditions.