Planta Med
DOI: 10.1055/s-0043-118663
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Aucubin Protects against TGFβ1-Induced Cardiac Fibroblasts Activation by Mediating the AMPKα/mTOR Signaling Pathway

Yang Xiao1, 2, 3, Wei Chang1, 2, 3, Qing-Qing Wu1, 2, 3, Xiao-Han Jiang1, 2, 3, Ming-Xia Duan1, 2, 3, Ya-Ge Jin1, 2, 3, Qi-Zhu Tang1, 2, 3
  • 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
  • 2Cardiovascular Research Institute, Wuhan University, Wuhan, PR China
  • 3Hubei Key Laboratory of Cardiology, Wuhan, PR China
Further Information

Publication History

received 05 May 2017
revised 05 August 2017

accepted 16 August 2017

Publication Date:
25 August 2017 (eFirst)


Fibrosis is a key feature of various cardiovascular diseases and compromises cardiac systolic and diastolic performance. The lack of effective anti-fibrosis drugs is a major contributor to the increasing prevalence of heart failure. The present study was performed to investigate whether the iridoid aucubin alleviates cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac fibroblasts were incubated with aucubin (1, 10, 20, 50 µM) followed by transforming growth factor β1 (TGFβ1, 10 ng/mL) stimulation for 24 h. Fibrosis proliferation was measured by cell counting kit-8 assay. The differentiation of fibroblasts into myofibroblasts was determined by measuring the expression of α-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related proteins in myofibroblasts were analyzed by western blot and real-time PCR to confirm the anti-fibrosis effect of aucubin. As a result, aucubin suppressed TGFβ1-induced proliferation in fibroblasts and inhibited the TGFβ1-induced activation of fibroblasts to myofibroblasts. In addition, aucubin further attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, this protective effect was related to increased adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKα inhibitor compound C. Collectively, our findings suggest that aucubin protects against TGFβ1-induced fibroblast proliferation, activation and function by regulating the AMPKα/mTOR signal axis.