School of Medicine, University of Electronic Science and Technology of China & Department of Pharmacy, Sichuan Provincial People's Hospital, Chengdu, China.
Personalized Drug Therapy Key Laboratory of Sichuan Province & Sichuan Academy of Medical Sciences, Chengdu, China.
J Biol Regul Homeost Agents. 2019;33(5):1425-1436. doi: 10.23812/19-257A.
Aconitine (ACO), the main active component in Aconitum carmichaelii Debeaux (family: Ranunculaceae), has high cardiotoxicity, however the mechanisms of this effect remain unclear. Paeoniflorin (PF), the main chemical ingredient in herbaceous peony, can protect the heart from damage through antioxidant, vasodilatory and other effects. In this study, we focused on the mechanism by which PF reduces ACO cardiotoxicity. We selected H9c2 cells as the experimental model. MTT assay, Western blot analysis and real-time PCR were used to measure cell proliferation, apoptosis, ion channels and oxidative stress. Cell proliferation was significantly increased, the Bcl-2/Bax ratio and p53 level were upregulated, and Caspase-3 was slightly reduced in the ACO+PF group compared with the ACO group. SCN5A mRNA expression was significantly increased in the ACO+PF group compared with the ACO group, while RyR2 and Cx43 mRNA expression was decreased. Compared with the ACO group, the ACO+PF group showed marked decreases in extracellular lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA), while there was no difference in intracellular superoxide dismutase (SOD). The above data demonstrate that the cardiotoxicity of ACO in H9c2 cells was significantly decreased by PF.
乌头碱（ACO）是毛茛科（Ranunculaceae）植物乌头（Aconitum carmichaelii Debeaux）中的主要活性成分，具有很高的心脏毒性，但这种作用的机制尚不清楚。芍药苷（PF）是草本牡丹中的主要化学成分，具有抗氧化、血管扩张等作用，可保护心脏免受损伤。本研究主要关注 PF 降低 ACO 心脏毒性的机制。我们选择 H9c2 细胞作为实验模型。MTT 检测、Western blot 分析和实时 PCR 用于测量细胞增殖、凋亡、离子通道和氧化应激。与 ACO 组相比，ACO+PF 组细胞增殖显著增加，Bcl-2/Bax 比值和 p53 水平上调，Caspase-3 略有减少。与 ACO 组相比，ACO+PF 组 SCN5A mRNA 表达显著增加，而 RyR2 和 Cx43 mRNA 表达降低。与 ACO 组相比，ACO+PF 组细胞外乳酸脱氢酶（LDH）和细胞内丙二醛（MDA）显著降低，而细胞内超氧化物歧化酶（SOD）无差异。上述数据表明，PF 可显著降低 H9c2 细胞中 ACO 的心脏毒性。
