Preprint / Version 1

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

Authors

  • Kun-Che Chang aDepartment of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
  • Brian Laffin aDepartment of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
  • Jessica Ponder bDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Science, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
  • Anna Énzsöly cDepartment of Ophthalmology, Semmelweis University, Budapest, Hungary
  • János Németh cDepartment of Ophthalmology, Semmelweis University, Budapest, Hungary
  • Daniel LaBarbera bDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Science, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
  • J Petrash aDepartment of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA

Keywords:

Aldose reductase, BGG, Macrophage, LPS, ROS, Uveitis

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. Keywords: Aldose reductase, BGG, Macrophage, LPS, ROS, Uveitis

Author Biographies

Kun-Che Chang, aDepartment of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA

bDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Science, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA

J Petrash, aDepartment of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA

bDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Science, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA

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