title: Bioactive compounds isolated from apple, tea, and ginger protect against dicarbonyl induced stress in cultured human retinal epithelial cells.
abstract: BACKGROUND
  Methylglyoxal (MGO) is known to be a major precursor of advanced glycation end products (AGEs) which are linked to diabetes and its related complications. Naturally occurring bioactive compounds could play an important role in countering AGEs thereby minimizing the risk associated with their formation.
  
  
  METHODS
  In this study, eight specific bioactive compounds isolated from apple, tea and ginger were evaluated for their AGEs scavenging activity using Human Retinal Pigment Epithelial (H-RPE) cells treated with MGO.
  
  
  RESULTS
  Among the eight specific compounds evaluated, (-)-epigallocatechin 3-gallate (EGCG) from tea, phloretin in apple, and [6]-shogaol and [6]-gingerol from ginger were found to be most effective in preventing MGO-induced cytotoxicity in the epithelial cells. Investigation of possible underlying mechanisms suggests that that these compounds could act by modulating key regulative detoxifying enzymes via modifying nuclear factor-erythroid 2-related factor 2 (Nrf2) function. MGO-induced cytotoxicity led to increased levels of AGEs causing increase in Nε-(Carboxymethyl) lysine (CML) and glutathione (GSH) levels and over expression of receptor for advanced glycation end products (RAGE). Data also showed that translocation of Nrf2 from cytosol to nucleus was inhibited, which decreased the expression of detoxifying enzyme like heme oxygenase-1 (HO-1). The most potent bioactive compounds scavenged dicarbonyl compounds, inhibited AGEs formation and significantly reduced carbonyl stress by Nrf2 related pathway and restoration of HO-1 expression.
  
  
  CONCLUSIONS
  These findings demonstrated the protective effect of bioactive compounds derived from food sources against MGO-induced carbonyl stress through activation of the Nrf2 related defense pathway, which is of significant importance for therapeutic interventions in complementary treatment/management of diabetes-related complications.
authors.affiliation: Department of Health Sciences, College of Arts & Sciences, Qatar University, Doha 2713, Qatar. Electronic address: chethan@qu.edu.qa.
authors.forename: Chethan
authors.initials: C
authors.lastname: Sampath
authors.affiliation: Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, NC 28081, United States.
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, NC 28081, United States.
authors.forename: Shengmin
authors.initials: S
authors.lastname: Sang
authors.affiliation: Department of Health Sciences, College of Arts & Sciences, Qatar University, Doha 2713, Qatar. Electronic address: ahmedna@qu.edu.qa.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ahmedna
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005233:Fatty Alcohols / Q000494:pharmacology; D020939:Zingiber officinale / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000009:adverse effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D027845:Malus / Q000737:chemistry*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology; D064209:Phytochemicals / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000009:adverse effects*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology; D013662:Tea / Q000737:chemistry*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D017127:Glycation End Products, Advanced; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D064209:Phytochemicals; D020011:Protective Agents; D000067759:Receptor for Advanced Glycation End Products; D013662:Tea; C048496:N(6)-carboxymethyllysine; D011765:Pyruvaldehyde; C040115:shogaol; D002392:Catechin; C007845:gingerol; C045651:epigallocatechin gallate; D051547:Heme Oxygenase-1; D005978:Glutathione; D008239:Lysine; D010693:Phloretin
keywords: Advanced glycation end products; Bioactive food compounds; Diabetes; HRPE cells; Methylyglyoxal; Oxidative stress