Byun Jung Woo, Hwang Sena, Kang Chan Woo, Kim Jin Hee, Chae Min Kyung, Yoon Jin Sook, Lee Eun Jig
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.
Department of Internal Medicine Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4055-62. doi: 10.1167/iovs.15-19037.
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.
原儿茶醛（3,4 - 二羟基苯甲醛；PCA）是从丹参中提取的，在各种体内和体外实验中已报道其具有抗增殖、抗氧化和抗脂肪生成特性。本研究旨在概述PCA对眼眶成纤维细胞脂肪生成和透明质酸产生的抗氧化及抑制作用，以辅助设计Graves眼病（GO）的治疗方法。
我们评估了PCA对眼眶成纤维细胞的体外作用，这些细胞是从因严重GO接受眼眶减压手术患者的眼眶脂肪组织培养而来。对照组织取自无GO或Graves甲亢病史的接受眼眶手术的患者。
2,2 - 二苯基 - 1 - 苦基肼和2,2'- 偶氮二（3 - 乙基苯并噻唑啉 - 6 - 磺酸）二铵盐检测结果证实了处理后PCA的自由基清除作用。在蛋白质印迹分析中，原儿茶醛对细胞内活性氧生成表现出抑制作用，并上调了血红素加氧酶 - 1的表达。原儿茶醛减弱了TNF - α和IL - 1β诱导的透明质酸产生。油红O染色结果显示脂滴减少，并且在脂肪分化过程中用PCA处理后，脂肪生成相关蛋白过氧化物酶体增殖物激活受体（PPAR）-γ、CCAAT/增强子结合蛋白（c/EBP）-α和c/EBP - β的表达受到抑制。
在本研究中，PCA发挥了显著的抗氧化和抗脂肪生成作用，并抑制了GO眼眶成纤维细胞中透明质酸的产生。因此，PCA有可能用作GO的一种新的治疗选择。
