Glycyrrhiza uralensis promote the metabolism of toxic components of Aconitum carmichaeli by CYP3A and alleviate the development of chronic heart failure

PLoS One. 2022 Jun 27;17(6):e0270069. doi: 10.1371/journal.pone.0270069. eCollection 2022.

Abstract

Aconitum, as "the first drug of choice for invigorating Yang and saving lives", has been widely used for the treatment of heart failure. However, toxic components of Aconitum can easily lead to serious arrhythmia, even death (Y. CT., 2009; Zhang XM., 2018). In this study, a High Performance Liquid Chromatography (HPLC) method for the determination of aconitine (AC), mesaconitine (MA) and hypaconitine (HA) was established; The effect of Glycyrrhiza on CYP3A1 / 2 mRNA expression was detected by RT-PCR; SD rats were given Aconitum and compatibility of Glycyrrhizae and Aconitum by gavage respectively, the blood concentration of toxic components were determined by LC-MS / MS; The CHF rat model was established by intraperitoneal injection of adriamycin (2.5 mg / kg), and were randomly divided into model, Aconitum, the compatibility of Glycyrrhizae and Aconitum and Captopril group, 5 mice/group. After 4 weeks of gavage, the corresponding indexes were detected by ELISA and HPLC. The results showed that Ketoconazole significantly inhibited the metabolites of AC, MA and HA; Glycyrrhiza induced CYP3A gene expression; The level of ALD in the compatibility of Glycyrrhizae and Aconitum group was significantly lower than that in Aconitum group. After intervention with the compatibility of Glycyrrhizae and Aconitum, ATP increased, ADP decreased significantly. In conclusion, we found Glycyrrhiza promoted the metabolism of toxic components of Aconitum by up regulating the expression of CYP3A, and reduced the content of BNP, Ang II and ALD, improved the energy metabolism disorder of myocardium, alleviated the development of CHF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitine / pharmacology
  • Aconitum* / metabolism
  • Aconitum* / toxicity
  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Cytochrome P-450 CYP3A / genetics
  • Drugs, Chinese Herbal* / pharmacology
  • Glycyrrhiza uralensis* / metabolism
  • Heart Failure* / prevention & control
  • Mice
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Drugs, Chinese Herbal
  • Plant Extracts
  • Cytochrome P-450 CYP3A
  • Aconitine

Grants and funding

This study was supported by National Natural Science Foundation of China (81904171), Jiangsu Postdoctoral Research Foundation (2020Z388), Top Talent Support Program for young and middle-aged people of Wuxi Health Committee, General fund of Wuxi health committee (M202033).