Effects of D-Limonene on aldose reductase and protein glycation in diabetic rats

Diabetes mellitus and hyperglycemia can lead to other health complications. The pathogenesis of diabetes mellitus can affect numerous tissues in the eye structure and cataracts are one of the major causes of visual impairment in diabetes mellitus patients. In this study, we aim to investigate the ability of D-limonene to inhibit aldose reductase hypoglycemic activity in lens organ culture and its anti-glycating properties in STZ-induced cataracts of rats with diabetes. D-limonene repressed aldose reductase in-vitro with IC50 ranges of ~13.9 ± 0.31 µg/mL in an uncompetitive manner. This compound also prevented hyperglycemic induced increases in aldose reductase activity, accumulation of sorbitol, altered crystalline proteins (α, β and γ), and opacification of the rat lens in ex-vivo lens organ culture. Supplementation of D-limonene in STZ-induced diabetic rats restored these changes and delayed the progression of cataracts. This study demonstrates that D-limonene is a pharmaceutically active component that inhibits rat-lens aldose reductase. Therefore, this study showed that D-limonene prevents advanced glycation end product formation contributing to the integrity of α-crystallin chaperone activity and delays cataract development. It has been concluded, D-limonene has a role in inhibiting aldose reductase activity and advanced glycation end products formation in vivo, and in delaying the development of diabetic cataracts. Further studies of D-limonene are needed to assess other complications in DM as they may provide additional evidence for establishing D-limonene as a potential pharmacological target therapy for diabetes mellitus complications. Keywords: D-limonene, Aldose reductase, α-Crystalline, Advanced glycation, End products, Cataracts