Astragaloside IV Suppresses Hepatic Proliferation in Regenerating Rat Liver after 70% Partial Hepatectomy via Down-Regulation of Cell Cycle Pathway and DNA Replication

Molecules. 2021 May 13;26(10):2895. doi: 10.3390/molecules26102895.

Abstract

Astragaloside IV (AS-IV) is one of the major bio-active ingredients of huang qi which is the dried root of Astragalus membranaceus (a traditional Chinese medicinal plant). The pharmacological effects of AS-IV, including anti-oxidative, anti-cancer, and anti-diabetic effects have been actively studied, however, the effects of AS-IV on liver regeneration have not yet been fully described. Thus, the aim of this study was to explore the effects of AS-IV on regenerating liver after 70% partial hepatectomy (PHx) in rats. Differentially expressed mRNAs, proliferative marker and growth factors were analyzed. AS-IV (10 mg/kg) was administrated orally 2 h before surgery. We found 20 core genes showed effects of AS-IV, many of which were involved with functions related to DNA replication during cell division. AS-IV down-regulates MAPK signaling, PI3/Akt signaling, and cell cycle pathway. Hepatocyte growth factor (HGF) and cyclin D1 expression were also decreased by AS-IV administration. Transforming growth factor β1 (TGFβ1, growth regulation signal) was slightly increased. In short, AS-IV down-regulated proliferative signals and genes related to DNA replication. In conclusion, AS-IV showed anti-proliferative activity in regenerating liver tissue after 70% PHx.

Keywords: 70% partial hepatectomy; Astragali Radix; Astragalus membranaceus; astragaloside IV; huang qi; liver; liver regeneration; proliferation; rat.

MeSH terms

  • Animals
  • Cell Cycle* / drug effects
  • Cell Proliferation / drug effects
  • Cyclin D1 / metabolism
  • DNA Replication* / drug effects
  • Down-Regulation* / drug effects
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks / drug effects
  • Hepatectomy*
  • Hepatocyte Growth Factor / metabolism
  • Liver / cytology*
  • Liver / drug effects
  • Liver / surgery
  • Liver Regeneration / drug effects*
  • Male
  • Molecular Sequence Annotation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Sequence Analysis, RNA
  • Transforming Growth Factor beta1 / metabolism
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • RNA, Messenger
  • Saponins
  • Transforming Growth Factor beta1
  • Triterpenes
  • Cyclin D1
  • astragaloside A
  • Hepatocyte Growth Factor