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

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 1 (TGF1, 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 -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 TGF1-induced proliferation in fibroblasts and inhibited the TGF1-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 AMPK inhibitor compound C. Collectively, our findings suggest that aucubin protects against TGF1-induced fibroblast proliferation, activation and function by regulating the AMPK/mTOR signal axis.

Aucubin exerts anti-osteoporotic effects by promoting osteoblast differentiation

“…Aucubin (AU) is an iridoid glycoside compound primarily derived from Eucommia ulmoides that has anti-osteoporotic effects [13]. It was previously found to promote angiogenesis, and displayed hepatoprotective, antiinflammatory, and anti-oxidative effects [14]. It was also shown to promote embryonic hippocampal neural stem cell differentiation in rats [15].…”

High-mobility group AT-hook 1 promotes cardiac dysfunction in diabetic cardiomyopathy via autophagy inhibition

“…Statistical significance was defined as a P value less than 0.05. In accordance with our previously published article, the method of power analysis for body weight with an α error of 5% and a power of 80% was used to determine the in vivo group sizes 27 . No samples were excluded from the analyses.…”

LncRNA SOX2OT/Smad3 feedback loop promotes myocardial fibrosis in heart failure

“…Therefore, the cells were identified as the required CFs with a purity of 98%. CFs were incubated with 10 μM ISO or 10 ng/ml TGF‐β1 for 24 hr to induce fibrosis 17–20 . CFs were treated with 1 μM SIS3 HCl to inhibit Smad3.…”

“…CFs were incubated with 10 μM ISO or 10 ng/ml TGF-β1 for 24 hr to induce fibrosis. [17][18][19][20] CFs were treated with 1 μM SIS3 HCl to inhibit Smad3.…”