Beta-glucogallin reduces the expression of lipopolysaccharide-induced inflammatory markers by inhibition of aldose reductase in murine macrophages and ocular tissues

被引:39
作者
Chang, Kun-Che [1 ,2 ]
Laffin, Brian [1 ]
Ponder, Jessica [2 ]
Enzsoely, Anna [3 ]
Nemeth, Janos [3 ]
LaBarbera, Daniel V. [2 ]
Petrash, J. Mark [1 ,2 ]
机构
[1] Univ Colorado, Dept Ophthalmol, Sch Med, Aurora, CO 80045 USA
[2] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO 80045 USA
[3] Semmelweis Univ, Dept Ophthalmol, Budapest, Hungary
关键词
Aldose reductase; BGG; Macrophage; LPS; ROS; Uveitis; ENDOTOXIN-INDUCED UVEITIS; EMBLICA-OFFICINALIS; DIABETIC-PATIENTS; SUGAR CATARACT; NITRIC-OXIDE; KAPPA-B; RATS;
D O I
10.1016/j.cbi.2012.12.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aldose reductase (AR) catalyzes the reduction of toxic lipid aldehydes to their alcohol products and mediates inflammatory signals triggered by lipopolysaccharide (LPS). Beta-glucogallin (BGG), a recently described AR inhibitor, was purified from extracts of the Indian gooseberry (Emblica officinalis). In this study, we found that BGG showed low cytotoxicity in Raw264.7 murine macrophages and effectively inhibited AR activity as measured by a decrease in sorbitol accumulation. In addition, BGG-mediated inhibition of AR prevented LPS-induced activation of JNK and p38 and lowered ROS levels, which could inhibit LPS-induced apoptosis. Uveitis is a disease of the eye associated with chronic inflammation. In this study, we also demonstrated that treatment with BGG decreased the number of inflammatory cells that infiltrate the ocular media of mice with experimental uveitis. Accordingly, these results suggest BGG is a potential therapy for inflammatory diseases. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:283 / 287
页数:5
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