Journal
EBIOMEDICINE
Volume 18, Issue -, Pages 179-187Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.03.021
Keywords
Piperine; Fibrosis; Cardiac fibroblast; PPAR-gamma; AKT
Funding
- National Natural Science Foundation of China [81270303, 81470516, 81470402, 81500184]
- Key Project of the National Natural Science Foundation of China [81530012]
- Department of Science and Technology of Hunan Province [2015SK20455]
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Mitogen-activated protein kinases (MAPKs) and AMP-activated protein kinase a (AMPK alpha) play critical roles in the process of cardiac hypertrophy. Previous studies have demonstrated that piperine activates AMPKa and reduces the phosphorylation of extracellular signal-regulated kinase (ERK). However, the effect of piperine on cardiac hypertrophy remains completely unknown. Here, we show that piperine-treated mice had similar hypertrophic responses as mice treated with vehicle but exhibited significantly attenuated cardiac fibrosis after pressure overload or isoprenaline (ISO) injection. Piperine inhibited the transformation of cardiac fibroblasts to myofibroblasts induced by transforming growth factor-beta (TGF-beta) or angiotensin II (Ang II) in vitro. This anti-fibrotic effect was independent of the AMPKa and MAPK pathway. Piperine blocked activation of protein kinase B (AKT) and, downstream, glycogen synthase kinase 3 beta (GSK3 beta). The overexpression of constitutively active AKT or the knockdown of GSK3 beta completely abolished the piperine-mediated protection of cardiac fibroblasts. The cardioprotective effects of piperine were blocked in mice with constitutively active AKT. Pretreatment with GW9662, a specific inhibitor of peroxisome proliferator activated receptor-gamma (PPAR-gamma), reversed the effect elicited by piperine in vitro. In conclusion, piperine attenuated cardiac fibrosis via the activation of PPAR. and the resultant inhibition of AKT/GSK3 beta. (C) 2017 The Authors. Published by Elsevier B.V.
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