The potential of asiaticoside for TGF-β1/Smad signaling inhibition in prevention and progression of hypoxia-induced pulmonary hypertension

Life Sci. 2015 Sep 15:137:56-64. doi: 10.1016/j.lfs.2015.07.016. Epub 2015 Jul 22.

Abstract

Aims: Asiaticoside (AS) is a saponin monomer extracted from the medicinal plant Centella asiatica, which has a variety of biological effects. We intended to investigate the effects of asiaticoside on a hypoxia-induced pulmonary hypertension (HPH) rat model and examine the possible effects of asiaticoside on TGF-β1/Smad signaling in vivo and in vitro.

Main methods: The rat HPH model was established by hypoxic exposure and asiaticoside was administered for four weeks. Parameters including the mean pulmonary artery pressure (mPAP), the right ventricular hypertrophy (RVH) and the percentage of medial wall thickness were used to evaluate the development of HPH. TGF-β1, TGF-β receptor, Smad2/3 and phospho-Smad2/3 expressions were detected and the proliferation, migration and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) adjusted by asiaticoside under the hypoxic condition were evaluated.

Key findings: Our data indicate that asiaticoside attenuated pulmonary hypertension, pulmonary vascular remodeling and RV hypertrophy in HPH rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-β1/Smad2/3 signaling and inhibiting the proliferation by inducing apoptosis of the PASMCs.

Significance: Given the preventative potential in animal models and in vitro, we propose asiaticoside as a promising protective treatment in HPH.

Keywords: Asiaticoside; Pulmonary arterial hypertension; Smad; TGF-β1; Vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Caspase 3 / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disease Progression
  • Heart Ventricles / drug effects
  • Heart Ventricles / pathology
  • Hypertension, Pulmonary / complications
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / prevention & control*
  • Hypertrophy / drug therapy
  • Hypoxia / complications
  • Hypoxia / drug therapy*
  • Hypoxia / pathology
  • Hypoxia / physiopathology
  • Male
  • Phosphorylation / drug effects
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism
  • Rats
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Signal Transduction / drug effects*
  • Smad2 Protein / biosynthesis
  • Smad3 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use*
  • Vascular Remodeling / drug effects
  • Vascular Remodeling / physiology

Substances

  • Receptors, Transforming Growth Factor beta
  • Smad2 Protein
  • Smad2 protein, rat
  • Smad3 Protein
  • Smad3 protein, rat
  • Transforming Growth Factor beta1
  • Triterpenes
  • Caspase 3
  • asiaticoside