Inhibition of aldose reductase by Aegle marmelos and its protective role in diabetic cataract

Ethnopharmacological relevance

Aegle marmelos (L.) Corr. Serr. (Aegle marmelos) leaves were extensively used in the Ayurvedic, Unani and Siddha systems of Indian medicine as an anti-diabetic agent, which serves as hypoglycemic agent. However, the significance of this plant on secondary complications of diabetes such as cataract remained unknown. The aim of the study was to investigate the possible anti-cataractous activity of Aegle marmelos against streptozotocin (STZ) induced diabetic cataract in rats.

Materials and methods

Aegle marmelos leaf extract was prepared using three different solvents (petroleum ether, ethyl acetate and methanol) and tested for inhibition against rat lens aldose reductase (AR), a key enzyme of polyol pathway. Furthermore, the pharmacological potential of Aegle marmelos extract was investigated against osmotic stress induced opacification of lens in ex vivo organ culture and streptozotocin (STZ) induced diabetic cataract in rats.

Results

Ethyl acetate extract of Aegle marmelos inhibited rat lens AR in vitro with an IC₅₀ value of ∼15 µg/ml. This extract also prevented the hyperglycemia induced increase in AR activity, sorbitol accumulation and opacification of rat lens in ex vivo lens organ culture. Supplementation of ethyl acetate extract of Aegle marmelos to STZ-induced diabetic rats decreased the blood glucose levels due to hyperglycemia and inhibited the AR activity and delayed cataract progression in dose dependent manner. α-crystallin isolated from diabetic rats fed with Aegle marmelos showed improved chaperone activity than that of isolated from rats naïve to Aegle marmelos.

Conclusion

This study indicates that ethyl acetate extract of Aegle marmelos has pharmacologically active components with a potential to inhibit rat lens AR and consequential decrease in osmotic stress. Besides this, the present study also demonstrates that the extract prevented loss of antioxidants contributing to the integrity of α-crystallin's chaperone activity and thereby delaying cataract.