Effect of protocatechualdehyde on receptor for advanced glycation end products and TGF-beta1 expression in human lens epithelial cells cultured under diabetic conditions and on lens opacity in streptozotocin-diabetic rats.
Advanced glycation end products and transforming growth factor-beta (TGF-beta) have been implicated in the development of diabetic complications such as cataract. The diverse metabolic effects of protocatechualdehyde (PCA, 3, 4-dihydroxybenzaldehyde) include the inhibition of aldose reductase and oxidation, two processes that are involved in the development of complications in diabetic patients. Here, the potential therapeutic effects of PCA in the treatment of diabetic complications were studied by determining this compound's ability to inhibit the formation of advanced glycation end products-bovine serum albumin (BSA) and the expression of receptor for advanced glycation end products and TGF-beta1 in human lens epithelial cells cultured under diabetic conditions. In addition, the ability of PCA to suppress lens opacification in streptozotocin-diabetic rats was analyzed. PCA significantly reduced advanced glycation end products-BSA formation in vitro and was more effective than aminoguanidine. In human lens epithelial cells, PCA significantly inhibited the induction of receptor for advanced glycation end products protein and mRNA expression by the receptor for advanced glycation end products-specific ligand S100b. Moreover, PCA inhibited high glucose- or S100b-induced TGF-beta1 protein and mRNA expression as well as nuclear accumulation of phosphorylated Smad2/3. In streptozotocin-induced diabetic cataract in rats, oral administration of PCA (25 mg/kg body weight) for 8 weeks significantly ameliorated the development of lens opacity (cataract) with effect on glycemic control. These results suggest that PCA is of therapeutic interest with respect to the prevention of diabetic complications such as diabetic cataract.
Kim
Young Sook
YS
Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine, 461-24 Jeonmin-dong, Daejeon 305-811, Republic of Korea.
Kim
Nan Hee
NH
Lee
Sang Won
SW
Lee
Yun Mi
YM
Jang
Dae Sik
DS
Kim
Jin Sook
JS
D000284:Administration, Oral; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D015153:Blotting, Western; D002386:Cataract / Q000517:prevention & control*; D002396:Catechols / Q000494:pharmacology*; D002461:Cell Line, Transformed; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027561:Salvia miltiorrhiza / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000187:drug effects* / Q000378:metabolism
D001547:Benzaldehydes; D002396:Catechols; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D053773:Transforming Growth Factor beta1; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; C005581:protocatechualdehyde; D013311:Streptozocin