Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 594, Issue 1-3, Pages 18-25Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2008.07.033
Keywords
aldose reductase; transforming growth factor-beta 2; diabetic complications; genistein; human lens epithelial (HLE-B3) cells
Categories
Funding
- Korea Institute of Oriental Medicine [L07010]
- Ministry of Education, Science & Technology (MoST), Republic of Korea [L07010] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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-beta 2, alpha B-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. (C) 2008 Elsevier B.V. All rights reserved.
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