title: Beta-glucogallin reduces the expression of lipopolysaccharide-induced inflammatory markers by inhibition of aldose reductase in murine macrophages and ocular tissues.
abstract: 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.
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Kun-Che
authors.initials: KC
authors.lastname: Chang
authors.forename: Brian
authors.initials: B
authors.lastname: Laffin
authors.forename: Jessica
authors.initials: J
authors.lastname: Ponder
authors.forename: Anna
authors.initials: A
authors.lastname: Enzsöly
authors.forename: János
authors.initials: J
authors.lastname: Németh
authors.forename: Daniel V
authors.initials: DV
authors.lastname: LaBarbera
authors.forename: J Mark
authors.initials: JM
authors.lastname: Petrash
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D005123:Eye / Q000187:drug effects* / Q000378:metabolism; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D014605:Uveitis / Q000188:drug therapy / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D047348:Hydrolyzable Tannins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D013012:Sorbitol; C060474:glucogallin; D000449:Aldehyde Reductase; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4