Aucubin protects against pressure overload‐induced cardiac remodelling via the β3‐adrenoceptor–neuronal NOS cascades

Article date: May 2018

By: Qing‐Qing Wu, Yang Xiao, Ming‐Xia Duan, Yuan Yuan, Xiao‐Han Jiang, Zheng Yang, Hai‐Han Liao, Wei Deng, Qi‐Zhu Tang in Volume 175, Issue 9, pages 1548-1566

Background and Purpose

Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart failure.

Experimental Approach

Initially, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pretreated with aucubin (1, 3, 10, 25 and 50 μM) were challenged with phenylephrine. Secondly, the transverse aorta was constricted in C57/B6 and neuronal NOS (nNOS)‐knockout mice, then aucubin (1 or 5 mg·kg−1 body weight day−1) was injected i.p. for 25 days. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers. Oxidative stress was evaluated by examining ROS generation, oxidase activity and NO generation. NOS expression was determined by Western blotting.

Key Results

Aucubin effectively suppressed cardiac remodelling; in mice, aucubin substantially inhibited pressure overload‐induced cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS abolished these cardioprotective effects of aucubin. Blocking or knocking down the β3‐adrenoceptor abolished the protective effects of aucubin in vitro. Furthermore, aucubin enhanced the protective effects of a β3‐adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of aucubin.

Conclusions and Implications

Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β3‐adrenoceptor/AC/cAMP pathway. These findings suggest that aucubin could have potential as a treatment for cardiac remodelling and heart failure.

DOI: 10.1111/bph.14164

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