title: Osteomeles schwerinae extracts inhibits the binding to receptors of advanced glycation end products and TGF-β1 expression in mesangial cells under diabetic conditions.
abstract: BACKGROUND
  Osteomeles schwerinae C. K. Schneid. (Rosaceae, OSSC) is a medicinal plant traditionally used to treat various diseases in Asia. The chemical constituents of OSSC have an inhibitory effect on aldose reductase activity, which has been implicated in the pathogenesis of diabetic complications. However, the protective effects of the pharmacological activity and potential mechanisms in diabetic nephropathy are still not known.
  
  
  OBJECTIVE
  In the present study, OSSC extracts and major compounds were examined for their effects on binding to the receptors of advanced glycation end products (RAGE) and on transforming growth factor-beta1 (TGF-β1) expression-related signal mechanisms in mouse glomerular mesangial cells (GMCs).
  
  
  METHODS
  A simple, rapid and efficient method was developed for the simultaneous determination of the marker compounds in the ethanol extract of the leaves and twigs of OSSC using HPLC-diode array detector (DAD). In this study, we determined the effects of OSSC extract and hyperoside on AGE and RAGE binding, and studied the mechanism of OSSC extract effects on AGE-bovine serum albumin (BSA)-treated GMCs. GMCs overexpressing human RAGE were cultured in AGE-BSA labeled with Alexa 488, and OSSC extract. AGE/RAGE binding were measured using fluorescence (excitation 485 nm/emission 528 nm). TGF-β1 protein expression levels were determined by western blot analyses.
  
  
  RESULTS
  OSSC extracts of leaves and twigs inhibited on AGE/RAGE binding and TGF-β1 protein expression in a dose-dependent manner in GMCs. Furthermore, OSSC extracts reduced the effects on AGE-BSA-induced reactive oxidative species (ROS) formation and nuclear translocalization of transcription factor NF-κB. OSSC extracts inhibited phosphorylation of extracellular signal-regulated protein kinases1/2 (ERK1/2), p38 mitogen-activated protein kinases (p38MAPK), and IκB. Hyperoside also inhibited AGE/RAGE binding and ROS formation, and reduced TGF-β1 expression and IkB phosphorylation.
  
  
  CONCLUSIONS
  OSSC extracts and hyperoside may attenuate AGE/RAGE binding and expression of TGF-β1 by downregulating of pERK1/2, p38MAPK and IκB phosphorylations in GMCs under diabetic condition and retard the development of diabetic complications such as diabetic nephropathy.
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, South Korea.
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, South Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Jung
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, South Korea.
authors.forename: Ik-Soo
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, South Korea.
authors.forename: Bo-Jeong
authors.initials: BJ
authors.lastname: Pyun
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, South Korea. Electronic address: kiomjskim@gmail.com.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000517:prevention & control; D015536:Down-Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves; D018547:Plant Stems; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D027824:Rosaceae / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D053773:Transforming Growth Factor beta1; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; C021304:hyperoside; D011794:Quercetin; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Advanced glycation end products; Diabetic nephropathy; Glomerular mesangial cell; Hyperoside; Osteomeles schwerinae; Transforming growth factor-beta1