Chinese Journal of Pharmacovigilance ›› 2024, Vol. 21 ›› Issue (6): 606-610.
DOI: 10.19803/j.1672-8629.20230682

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Effect of hypaconitine of radix aconiti carmichaeli on hERG channels in cardiac myocytes via miR-134 regulation

GE Yunxuan1,2, WANG Yuguang2, ZHANG Zhuo2, MA Zengchun2#, GAO Yue1,2,*   

  1. 1Faculty of Environment and Life Sciences, Beijing University of Technology, Beijing 100124, China;
    2Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China
  • Received:2023-11-02 Online:2024-06-15 Published:2024-06-18

Abstract: Objective To explore the mechanism by which hypaconitine regulates myocardial cell toxicity through miRNA-hERG pathway. Methods The gene expression level was measured by real-time fluorescence quantitative PCR, the protein expression was determined by Western blot, and hERG currents were recorded by the whole cell patch-clamp technique. Results Three major diester alkaloids could inhibit hERG protein and gene expressions, among which hypaconitine had the strongest inhibitory effect in a dose-dependent manner. Hypaconitine promoted the expression of miR-134 most significantly and the weakened inhibitory effect of hypaconitine on hERG protein gene was exhibited after the expression of miR-134 was decreased. Conclusion Hypoaconitine can decrease the rate of hERG channel inactivation and the expression of hERG by upregulating the expressions of related miRNAs. The inhibitory effect of hypaconitine on hERG may be an important cause of radix aconiti carmichaeli cardiotoxicity.

Key words: radix aconiti carmichaeli, hypaconitine, cardiomyocyte, myocardial toxicity, hERG pathway, miRNA, miR-134, protein, gene, expression

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