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

Abstract

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