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Inhibition of aldose reductase by tannoid principles ofEmblica officinalis: Implications for the prevention of sugarcataract
[摘要] Purpose: Aldose reductase (AR) has been a drug target because of itsinvolvement in the development of secondary complications of diabetesincluding cataract. Although numerous synthetic AR inhibitors (ARI) havebeen tested and shown to inhibit the enzyme, clinically synthetic ARIshave not been very successful. Therefore, evaluating natural sources forARI potential may lead to the development of safer and more effectiveagents against diabetic complications. In the present study we haveassessed the inhibition of AR by constituents of Emblica officinalisboth in vitro and in lens organ culture.Methods: E. officinalis is widely used against many chronicailments including diabetes. Aqeous extract of E. officinalis andits major constituent tannoids were tested for inhibition against bothrat lens and purified recombinant human AR. ARI potential of isolatedtannoids of E. officinalis were also investigated against osmoticstress in rat lens organ culture.Results: E. officinalis extract inhibited rat lens andrecombinant human AR with IC50 values 0.72 and 0.88 mg/mlrespectively. Since E. officinalis is a rich source of ascorbicacid, we investigated whether ascorbic acid was responsible for ARinhibition by E. officinalis extract. However, ascorbic acid did notinhibit AR even at 5 mM concentration. Further, we demonstrate that thehydrolysable tannoids of E. officinalis were responsible for ARinhibition, as enriched tannoids of E. officinalis exhibitedremarkable inhibition against both rat lens and human AR with IC50of 6 and 10 μg/ml respectively. The inhibition of AR by E.officinalis tannoids is 100 times higher than its aqueous extract andcomparable to or better than quercetin. Furthermore, the isolatedtannoids not only prevented the AR activation in rat lens organ culturebut also sugar-induced osmotic changes.Conclusions: These results indicate that tannoids of E.officinalis are potent inhibitors of AR and suggest that exploring thetherapeutic value of natural ingredients that people can incorporateinto everyday life may be an effective approach in the management ofdiabetic complications.
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[效力级别]  [学科分类] 生物化学/生物物理
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