Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Cardiovascular Research Institute, Wuhan University, Wuhan, China.
Br J Pharmacol. 2018 May;175(9):1548-1566. doi: 10.1111/bph.14164. Epub 2018 Mar 25.
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.
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 body weight day ) 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.
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 β -adrenoceptor abolished the protective effects of aucubin in vitro. Furthermore, aucubin enhanced the protective effects of a β -adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of aucubin.
Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β -adrenoceptor/AC/cAMP pathway. These findings suggest that aucubin could have potential as a treatment for cardiac remodelling and heart failure.
桃叶珊瑚苷是杜仲的主要成分，已被证明对氧化应激有深远的影响。由于氧化应激先前被证明会导致急性和慢性心肌损伤，我们测试了桃叶珊瑚苷对心脏重构和心力衰竭的影响。
最初，用桃叶珊瑚苷（1、3、10、25 和 50μM）预处理 H9c2 心肌细胞和新生大鼠心肌细胞，然后用苯肾上腺素进行挑战。其次，在 C57/B6 和神经元型一氧化氮合酶（nNOS）敲除小鼠中缩窄横主动脉，然后腹腔注射桃叶珊瑚苷（1 或 5mg·kg 体重·天）25 天。通过评估形态变化、超声心动图参数、组织学分析和肥大标志物来评估肥大。通过检查 ROS 生成、氧化酶活性和 NO 生成来评估氧化应激。通过 Western blot 测定 NOS 表达。
桃叶珊瑚苷有效抑制心脏重构；在小鼠中，桃叶珊瑚苷显著抑制压力超负荷诱导的心脏肥大、纤维化和炎症，而敲除 nNOS 则消除了桃叶珊瑚苷的这些心脏保护作用。阻断或敲低β-肾上腺素受体消除了桃叶珊瑚苷在体外的保护作用。此外，桃叶珊瑚苷通过增加细胞内 cAMP 水平增强了β-肾上腺素受体激动剂在体外的保护作用，而用腺苷酸环化酶（AC）抑制剂处理则消除了桃叶珊瑚苷的心脏保护作用。
桃叶珊瑚苷通过增加 nNOS 的表达来抑制心脏重构过程中的氧化应激，这一过程需要激活β-肾上腺素受体/AC/cAMP 途径。这些发现表明，桃叶珊瑚苷可能具有治疗心脏重构和心力衰竭的潜力。
