Effects of ellagic acid and 2-(2,3,6-trihydroxy-4-carboxyphenyl)ellagic acid on sorbitol accumulation in vitro and in vivo.
Caesalpinia ferrea MART. (Leguminosae) called as Juca is one of the medicinal plants in Brazil used for diabetes. From the fruits of this plant, ellagic acid (EA) and 2-(2,3,6-trihydroxy-4-carboxyphenyl)ellagic acid (TEA) have been recently isolated as aldose reductase (AR) inhibitors. In this study, we examined to prove the inhibitory activity against AR of EA and TEA in vitro, and EA in vivo by measurement of the accumulation of sorbitol, which is the product of glucose reduction catalyzed by AR. TEA was not examined in vivo because of its shortage of yield from the fruits. EA and TEA significantly and dose-dependently inhibited sorbitol accumulation in erythrocytes, lens and sciatic nerve under incubating with glucose in vitro. EA at a dose of 75 mg/kg/d showed the most potent inhibition of sorbitol accumulation in erythrocytes, lens and sciatic nerve at 50, 75 and 100 mg/kg/d in vivo. These results suggest that the inhibitory activity of EA against AR causes to inhibit sorbitol accumulation by in vitro and in vivo experiments. EA is distributed in fruits and vegetables, so that taking them might be able to relieve diabetic complications.
Department of Natural Medicinal Chemistry, Kobe Pharmaceutical University, Motoyamakitamachi, Higashinada-ku, Japan.
Hidenori
H
Ueda
Kazuko
K
Kawanishi
Masataka
M
Moriyasu
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D029911:Caesalpinia; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism*
C451101:2-(2,3,6-trihydroxy-4-carboxyphenyl) ellagic acid; D007004:Hypoglycemic Agents; D004610:Ellagic Acid; D013012:Sorbitol; D000449:Aldehyde Reductase; D005947:Glucose