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

Yang Xiao; Wei Chang; Qing-Qing Wu; Xiao-Han Jiang; Ming-Xia Duan; Ya-Ge Jin; Qi-Zhu Tang

doi:10.1055/s-0043-118663

Planta Medica, Table of Contents

Planta Med 2018; 84(02): 91-99
DOI: 10.1055/s-0043-118663

Biological and Pharmacological Activity

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 Xiao^*

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

,

Wei Chang^*

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

,

Qing-Qing Wu

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

,

Xiao-Han Jiang

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

,

Ming-Xia Duan

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

,

Ya-Ge Jin

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

,

Qi-Zhu Tang

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

› Author Affiliations

Abstract

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.

Key words

Cardiac fibroblast - TGFβ1 - iridoid - Aucubin - AMPKα - mTOR

Full Text

References

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