Genistein inhibits aldose reductase activity and high glucose-induced TGF-beta2 expression in human lens epithelial cells.
Aldose reductase (AR) and TGF-beta have been implicated in the development of diabetic complications, such as cataracts. In an attempt to obtain potential agents for the prevention of diabetic cataracts from natural products, we purified genistein from the roots of Pueraria lobata and investigated its inhibitory effects upon AR activity and its antioxidant effects on rat lenses. The inhibition of AR activity by genistein increased in a dose-dependent manner and the opacities of lenses were significantly improved when treated with genistein. In addition, we determined the effects of genistein on mechanisms induced by exposure to high glucose in human lens epithelial (HLE-B3) cells. We found that genistein was able to reduce the expression of TGF-beta2, alphaB-crystallin, and fibronectin mRNAs in HLE-B3 cells that were cultured in high glucose conditions. In addition, a reduction in glutathione (GSH) levels and thiobarbituratic acid-reactive substances was observed. These results show that genistein is protective against lens opacity and also inhibits high glucose-mediated toxic effects in HLE-B3 cells. These effects are likely achieved by preventing AR and cellular oxidation; therefore, genistein may be a potential therapeutic agent for preventing and treating complications associated with diabetes mellitus, such as diabetic cataracts.
Kim
Young Sook
YS
Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine, 461-24 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Korea.
Kim
Nan Hee
NH
Jung
Dong Ho
DH
Jang
Dae Sik
DS
Lee
Yun Mi
YM
Kim
Jong Min
JM
Kim
Jin Sook
JS
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003318:Corneal Opacity / Q000139:chemically induced / Q000473:pathology; D003459:Crystallins / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis; D019833:Genistein / Q000494:pharmacology*; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020011:Protective Agents; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis*; D014994:Xylose / Q000494:pharmacology
D003459:Crystallins; D004791:Enzyme Inhibitors; D005353:Fibronectins; D020011:Protective Agents; D053781:Transforming Growth Factor beta2; D014994:Xylose; D019833:Genistein; D000449:Aldehyde Reductase; D005947:Glucose