title: Therapeutic Effect of Protocatechuic Aldehyde in an In Vitro Model of Graves' Orbitopathy.
abstract: Protocatechuic aldehyde (3,4-dihydroxybenzaldehyde; PCA) is extracted from Salvia miltiorrhiza, and has been reported to possess antiproliferative, antioxidant, and antiadipogenesis properties in various in vivo and in vitro experiments. This study aimed to outline the antioxidant and suppressive effects of PCA on adipogenesis and hyaluronan production in orbital fibroblasts to help with designing therapeutic approaches for Graves' orbitopathy (GO).
  
  
  
  We assessed the in vitro effects of PCA on orbital fibroblasts, which were cultured from orbital fat tissue obtained from patients undergoing orbital decompression for severe GO. Control tissue was obtained from patients undergoing orbital surgery with no history of GO or Graves' hyperthyroidism.
  
  
  
  The 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt assay results confirmed the free radical scavenging effect of PCA after treatment. Protocatechuic aldehyde exhibited a suppressive effect on intracellular reactive oxygen species generation and upregulated heme oxygenase-1 expression in Western blot analysis. Protocatechuic aldehyde attenuated TNF-α and IL-1β-induced hyaluronan production. Oil Red-O staining results revealed a decrease in lipid droplets and suppressed expression of the adipogenesis-related proteins peroxisome proliferator-activated receptor (PPAR)-γ, CCAAT/enhancer binding protein (c/EBP)-α, and c/EBP-β upon treatment with PCA during adipose differentiation.
  
  
  
  In this study, PCA exerted significant antioxidant and antiadipogenic effects and inhibited the production of hyaluronan in GO orbital fibroblasts. Accordingly, PCA potentially could be used as a novel treatment option for GO.
authors: Department of Internal Medicine Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea 2Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Korea.
authors: Jung Woo
authors: JW
authors: Byun
authors: Department of Internal Medicine Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Sena
authors: S
authors: Hwang
authors: Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Korea.
authors: Chan Woo
authors: CW
authors: Kang
authors: Department of Internal Medicine Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Jin Hee
authors: JH
authors: Kim
authors: Departments of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.
authors: Min Kyung
authors: MK
authors: Chae
authors: Departments of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.
authors: Jin Sook
authors: JS
authors: Yoon
authors: Department of Internal Medicine Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Eun Jig
authors: EJ
authors: Lee
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000925:Anticoagulants / Q000494:pharmacology; D001547:Benzaldehydes / Q000494:pharmacology*; D015153:Blotting, Western; D002396:Catechols / Q000494:pharmacology*; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009915:Orbit / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D001547:Benzaldehydes; D002396:Catechols; D017382:Reactive Oxygen Species; C005581:protocatechualdehyde