Diosgenin, a Natural Steroidal Sapogenin, Alleviates the Progression of Diabetic Retinopathy in Diabetic Mice

Abstract Background/Aim: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and a major cause of blindness in working-age adults. Diosgenin (DG), a natural steroidal sapogenin extracted from fenugreek seeds and wild yam roots, has hypolipidemic, hypoglycemic, anticancer, and anti-inflammatory properties. Given its pharmacological effects, we speculated that DG may be a promising treatment for DR. Therefore, this study was aimed at evaluating the effectiveness of DG in preventing or slowing DR progression in a mouse model (+Leprdb/+Leprdb strain) of type 2 diabetes (T2D). Materials and Methods: DG (5.0 mg/kg body weight) or phosphate-buffered saline (PBS) was administered to 8-week-old T2D mice via oral gavage daily for 24 weeks. Paraffin-embedded eye tissues from the mice were collected and stained with hematoxylin and eosin to evaluate retinal histopathology. Apoptosis-related proteins BCL2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 were evaluated by western blotting of mouse retinas. Results: Body weight was slightly reduced in the DG-treated group; however, glucose levels were not markedly different between the DG- and PBS-treated groups. Total retinal thickness, thickness of the photoreceptor and outer nuclear layers, and loss of ganglion cells significantly improved in the retina of the DG-treated T2D mice compared with those in the PBS-treated T2D mice. Cleaved caspase-3 level significantly decreased in the retina of the DG-treated T2D mice. Conclusion: DG alleviates DR pathology and exerts a protective effect on the T2D mouse retina. The inhibitory effects of DG on DR may involve mechanisms of the anti-apoptotic pathway.