PURPOSE: Aldose reductase (AR) has been a drug target because of its involvement in the development of secondary complications of diabetes including cataract. Although numerous synthetic AR inhibitors (ARI) have been tested and shown to inhibit the enzyme, clinically synthetic ARIs have not been very successful. Therefore, evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. In the present study we have assessed the inhibition of AR by constituents of Emblica officinalis both in vitro and in lens organ culture. METHODS: E. officinalis is widely used against many chronic ailments including diabetes. Aqeous extract of E. officinalis and its major constituent tannoids were tested for inhibition against both rat lens and purified recombinant human AR. ARI potential of isolated tannoids of E. officinalis were also investigated against osmotic stress in rat lens organ culture. RESULTS: E. officinalis extract inhibited rat lens and recombinant human AR with IC50 values 0.72 and 0.88 mg/ml respectively. Since E. officinalis is a rich source of ascorbic acid, we investigated whether ascorbic acid was responsible for AR inhibition by E. officinalis extract. However, ascorbic acid did not inhibit AR even at 5 mM concentration. Further, we demonstrate that the hydrolysable tannoids of E. officinalis were responsible for AR inhibition, as enriched tannoids of E. officinalis exhibited remarkable inhibition against both rat lens and human AR with IC50 of 6 and 10 microg/ml respectively. The inhibition of AR by E. officinalis tannoids is 100 times higher than its aqueous extract and comparable to or better than quercetin. Furthermore, the isolated tannoids not only prevented the AR activation in rat lens organ culture but also sugar-induced osmotic changes. CONCLUSIONS: These results indicate that tannoids of E. officinalis are potent inhibitors of AR and suggest that exploring the therapeutic value of natural ingredients that people can incorporate into everyday life may be an effective approach in the management of diabetic complications.
PURPOSE: Aldose reductase (AR) has been a drug target because of its involvement in the development of secondary complications of diabetes including cataract. Although numerous synthetic AR inhibitors (ARI) have been tested and shown to inhibit the enzyme, clinically synthetic ARIs have not been very successful. Therefore, evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. In the present study we have assessed the inhibition of AR by constituents of Emblica officinalis both in vitro and in lens organ culture. METHODS:E. officinalis is widely used against many chronic ailments including diabetes. Aqeous extract of E. officinalis and its major constituent tannoids were tested for inhibition against both rat lens and purified recombinant human AR. ARI potential of isolated tannoids of E. officinalis were also investigated against osmotic stress in rat lens organ culture. RESULTS:E. officinalis extract inhibited rat lens and recombinant human AR with IC50 values 0.72 and 0.88 mg/ml respectively. Since E. officinalis is a rich source of ascorbic acid, we investigated whether ascorbic acid was responsible for AR inhibition by E. officinalis extract. However, ascorbic acid did not inhibit AR even at 5 mM concentration. Further, we demonstrate that the hydrolysable tannoids of E. officinalis were responsible for AR inhibition, as enriched tannoids of E. officinalis exhibited remarkable inhibition against both rat lens and human AR with IC50 of 6 and 10 microg/ml respectively. The inhibition of AR by E. officinalistannoids is 100 times higher than its aqueous extract and comparable to or better than quercetin. Furthermore, the isolated tannoids not only prevented the AR activation in rat lens organ culture but also sugar-induced osmotic changes. CONCLUSIONS: These results indicate that tannoids of E. officinalis are potent inhibitors of AR and suggest that exploring the therapeutic value of natural ingredients that people can incorporate into everyday life may be an effective approach in the management of diabetic complications.
Authors: Kun-Che Chang; Brian Laffin; Jessica Ponder; Anna Enzsöly; János Németh; Daniel V LaBarbera; J Mark Petrash Journal: Chem Biol Interact Date: 2012-12-15 Impact factor: 5.192
Authors: Miguel A Lanaspa; Takuji Ishimoto; Christina Cicerchi; Yoshifuru Tamura; Carlos A Roncal-Jimenez; Wei Chen; Katsuyuki Tanabe; Ana Andres-Hernando; David J Orlicky; Esteban Finol; Shinichiro Inaba; Nanxing Li; Christopher J Rivard; Tomoki Kosugi; Laura G Sanchez-Lozada; J Mark Petrash; Yuri Y Sautin; A Ahsan Ejaz; Wataru Kitagawa; Gabriela E Garcia; David T Bonthron; Aruna Asipu; Christine P Diggle; Bernardo Rodriguez-Iturbe; Takahiko Nakagawa; Richard J Johnson Journal: J Am Soc Nephrol Date: 2014-05-29 Impact factor: 10.121