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

In Vivo. 2023 Mar-Apr;37(2):661-666. doi: 10.21873/invivo.13126.

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.

Keywords: T2D mice; Type 2 diabetes; diabetic retinopathy; diosgenin.

MeSH terms

  • Animals
  • Body Weight
  • Caspase 3
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Retinopathy* / etiology
  • Diabetic Retinopathy* / genetics
  • Diosgenin* / pharmacology
  • Mice
  • Sapogenins* / pharmacology

Substances

  • Caspase 3
  • Sapogenins
  • Diosgenin