LPS-enhanced IGF-IIR pathway to induce H9c2 cardiomyoblast cell hypertrophy was attenuated by Carthamus tinctorius extract via IGF-IR activation

Environ Toxicol. 2020 Feb;35(2):145-151. doi: 10.1002/tox.22850. Epub 2019 Nov 12.

Abstract

The use of herbs as alternative cardiovascular disease treatment has attracted a great deal of attention owing to their lower toxicity. Whether Carthamus tinctorius extract prevent cardiomyoblast cell hypertrophy remains unclear. The present study was performed to investigate the effect of C tinctorius extract (CTF) on rat cardiomyoblast cell H9c2 and the possible molecular mechanisms. H9c2 cells were treated with lipopolysaccharide (LPS; 2 μg/mL) for 12 hours, subsequently treated with CTF (1-25 μg/mL) The incubation continued for another 24 hours, and the cells were analyzed with actin staining assay, western blot analysis, and siRNA transfection assays. In the present study, the increased cell size induced by LPS was significantly decreased by pretreating at a concentration of 1-25 μg/mL CTF. It was found that CTF could inhibit cardiac hypertrophy induced by LPS and decrease hypertrophic proteins calcineurin, p-GATA-4, GATA-4, atrial natriuretic peptide, and B-type natriuretic peptide levels in H9c2 cells. Additionally, LPS-induced insulin-like growth factor-II receptor (IGF-IIR) hypertrophy pathway was downregulated by CTF. Moreover, IGF-IR siRNA or inhibitors both reversed the CTF effects, confirming that CTF activates IGF-1R to prevent LPS-induced H9c2 cardiomyoblast cell hypertrophy. The current findings indicate that CTF activates IGF-IR to inhibit IGF-IIR signaling pathway which resulted in reducing H9c2 cardiomyoblast cell hypertrophy induced by LPS.

Keywords: Carthamus tinctorius L. (Hong Hua); H9c2 cardiomyoblast cell; cardiac hypertrophy; insulin-like growth factor-I receptor.

MeSH terms

  • Animals
  • Cardiomegaly / prevention & control
  • Carthamus tinctorius / chemistry*
  • Cell Size
  • Dose-Response Relationship, Drug
  • Gene Knockdown Techniques
  • Lipopolysaccharides / pharmacology*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Receptor, IGF Type 2 / genetics
  • Receptor, IGF Type 2 / metabolism*
  • Signal Transduction

Substances

  • Lipopolysaccharides
  • Plant Extracts
  • Receptor, IGF Type 2
  • Receptor, IGF Type 1