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Effect of tanshinone IIA in an in vitro model of Graves’ orbitopathy

Authors
 Soolienah Rhiu  ;  Min Kyung Chae  ;  Eun Jig Lee  ;  Jong Bok Lee  ;  Jin Sook Yoon 
Citation
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.55(9) : 5900-5910, 2014 
Journal Title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN
 0146-0404 
Issue Date
2014
MeSH
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Antioxidants/pharmacology* ; Blotting, Western ; CCAAT-Enhancer-Binding Proteins/metabolism ; Case-Control Studies ; Cells, Cultured ; Chemokine CCL2/metabolism ; Diterpenes, Abietane/pharmacology* ; Dose-Response Relationship, Drug ; Female ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Graves Ophthalmopathy/drug therapy* ; Graves Ophthalmopathy/metabolism ; Humans ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Male ; Middle Aged ; Oxidative Stress/drug effects ; PPAR gamma/metabolism ; RNA, Messenger/metabolism ; Reactive Oxygen Species/metabolism
Keywords
Graves' orbitopathy ; adipogenesis ; heme oxygenase-1 ; inflammation ; orbital fibroblasts ; oxidative stress ; tanshinone IIA
Abstract
PURPOSE:
We investigated the therapeutic effect of nontoxic concentrations of tanshinone IIA (TanIIA) from Salvia miltiorrhiza in primary cultures of orbital fibroblasts from Graves' orbitopathy (GO).
METHODS:
The effect of TanIIA on IL-1β-induced proinflammatory cytokine (IL-6, IL-8, MCP-1) expression was determined by real-time PCR. Antioxidant activity was investigated by measuring intracellular reactive oxygen species (ROS) generation stimulated by cigarette smoke extract (CSE) and heme oxygenase-1 (HO-1) expression. To evaluate antiadipogenic activity, fibroblasts were subjected to a differentiation protocol, including peroxisome proliferator activator gamma (PPARγ) agonist, for 10 days, and exposed to TanIIA during adipocyte differentiation. Differentiated cells were stained with Oil Red O, and the expression of adipogenesis-related factors, PPARγ, and CCAAT-enhancer-binding proteins (C/EBP) α and β were determined by Western blot.
RESULTS:
Expression of IL-6, IL-8, and MCP-1 mRNA was inhibited by TanIIA pretreatment in a dose-dependent manner in GO orbital fibroblasts (P < 0.05). Tanshinone IIA decreased CSE- or H2O2-induced ROS levels in a dose-dependent manner and upregulated HO-1 protein expression in a time- and dose-dependent manner (P < 0.001). Treatment of orbital fibroblasts with TanIIA increased phosphorylated extracellular signal-regulated kinase (pERK), and an ERK inhibitor significantly blocked TanIIA-induced HO-1 upregulation. Adipogenesis was inhibited by TanIIA in a dose-dependent manner (P < 0.001), as evidenced by Oil Red O stain and decreased PPARγ and C/EBPα expression in Western blot analysis.
CONCLUSIONS:
Our study results suggest that TanIIA possesses significant anti-inflammatory, antioxidant, and antiadipogenic effects in primary orbital fibroblasts. These results provide the basis for further study of the potential use of TanIIA to treat GO. Tanshinone IIA showed significant anti-inflammatory, antioxidant, and antiadipogenic effects in primary orbital fibroblasts from Graves' orbitopathy patients. These results provide the basis for further study of the potential use of tanshinone IIA to treat Graves' orbitopathy.
Files in This Item:
T201403956.pdf Download
DOI
10.1167/iovs.14-14008
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Rhiu, Soolienah(유수리나)
Yoon, Jin Sook(윤진숙) ORCID logo https://orcid.org/0000-0002-8751-9467
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Lee, Jong Bok(이종복)
Chae, Min Kyung(채민경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100258
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