糖基化
糖基化终产物
链脲佐菌素
醛糖还原酶
内科学
内分泌学
化学
受体
糖尿病
转化生长因子
医学
作者
Young Sook Kim,Nan Hee Kim,Sang Won Lee,Yun Mi Lee,Dae Sik Jang,Jin Sook Kim
标识
DOI:10.1016/j.ejphar.2007.05.054
摘要
Advanced glycation end products and transforming growth factor-β (TGF-β) 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-β1 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-β1 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.
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