Article

Curcumin administration suppresses collagen synthesis in the hearts of rats with experimental diabetes

Authors: Shuang GUO1, Xiang-wen MENG1, Xiao-song YANG1, Xiu-fen LIU1, Chang-han OU-YANG1, Chao LIU1
1 Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China
Corresponding to: Chang-han OU-YANG: ouyangcch@163.com, Chao LIU: tnbsys_liuchao@126.com,
DOI: 10.1038/aps.2017.92
Received: 12 February 2017
Accepted: 5 June 2017
Advance online: 14 September 2017

Abstract

Abstract
Cardiac fibrosis is considered the initial change of diabetic cardiomyopathy (DCM). We have shown that curcumin alleviates collagen deposition in DCM, but the mechanism remains unknown. In this study we sought to investigate the effects of curcumin on cardiac fibrosis in vivo and in vitro and to elucidate the underlying mechanisms. Experimental diabetes was induced in rats by injection of lowdose streptozotocin (STZ) combined with high energy diet. The rats were orally treated with curcumin (300 mg·kg-1·d-1) for 16 weeks. Curcumin administration significantly suppressed the deposition of type I and type III collagens in the heart tissues of diabetic rats, accompanied by markedly reduced TGF-β1 production, suppressed TβR II levels and Smad2/3 phosphorylation, and increased Smad7 expression. Similar effects were observed in human cardiac fibroblasts exposed to high glucose (HG, 30 mmol/L) or exogenous TGF- β1 (5 ng/mL). Furthermore, TGF-β1 or HG treatment significantly increased the phosphorylation levels of AMPK and p38 MAPK in the fibroblasts. Application of curcumin (25 μmol/L) inhibited TGF-β1- or HG-induced AMPK/p38 MAPK activation and suppressed collagen synthesis in the fibroblasts. These effects were similar to those of the AMPK inhibitor compound C (10 μmol/L) but opposite to the effects of the AMPK activator metformin (2 mmol/L) in the fibroblasts. Our results demonstrate that curcumin suppresses diabetesassociated collagen synthesis in rat myocardium not only by inhibiting TGF-β1 production and canonical Smad signaling but also by blocking the non-canonical AMPK/p38 MAPK pathway.
Keywords: cardiac fibrosis; diabetes; curcumin; TGF-β; Smad signaling; AMPK/p38 MAPK; compound C; metformin

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