Abstract
Cataracts are a major cause of human blindness. Aldose reductase (AR) is an important rate-limiting enzyme that contributes to cataract induction in diabetic patients. Scopoletin is the main bioactive constituent of flower buds from Magnolia fargesii and is known to inhibit AR activity. To assess scopoletin's ability to mitigate sugar cataract formation in vivo, we studied its effects in a rat model of dietary galactose-induced sugar cataracts. Galactose-fed rats were orally dosed with scopoletin (10 or 50 mg/kg body weight) once a day for 2 weeks. Administering scopoletin delayed the progression of the cataracts that were induced by dietary galactose. Scopoletin also prevented galactose-induced changes in lens morphology, such as lens fiber swelling and membrane rupture. Scopoletin's protective effect against sugar cataracts was mediated by inhibiting both AR activity and oxidative stress. These results suggest that scopoletin is a useful treatment for sugar cataracts.
Highlights
Cataracts are the leading cause of blindness worldwide
All of the animals fed on the galactose diet developed mature cataracts after two weeks (70% were in grade III and 30% were in grade IV, Figures 2(a) and 2(b))
The highest dose of scopoletin treatment (50 mg/kg/day) delayed the onset of cataracts (80% were in grade I and 20% were in grade II, Figures 2(a) and 2(b))
Summary
Hyperglycemia and diabetes increase the risk of developing cataracts [1]. Cataractogenesis under diabetic or galactosemic conditions is directly linked to the aldose-reductase- (AR-) catalyzed accumulation of sorbitol or galactitol from glucose or galactose, respectively. Accumulating excess sorbitol or galactitol initiates osmotic stress, altering lens cell permeability and redox homeostasis, as well as decreasing ATPase activity and crystallin synthesis [2, 3]. Cataracts can be successfully treated with surgery, it remains important to find nonsurgical treatments for this condition. Synthetic AR inhibitors (ARIs) have been studied to treat diabetic cataracts. Consuming foods or medicinal plants containing micronutrients with potential anti-AR activities may protect against cataracts [5,6,7,8,9]
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