title: The potential of asiaticoside for TGF-β1/Smad signaling inhibition in prevention and progression of hypoxia-induced pulmonary hypertension.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Given the preventative potential in animal models and in vitro, we propose asiaticoside as a promising protective treatment in HPH.
authors.affiliation: Department of Rheumalogy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Rheumalogy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Rheumalogy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Ye
authors.affiliation: Key Laboratory of Heart and Lung, Respiratory Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Key Laboratory of Heart and Lung, Respiratory Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Pei-Liang
authors.initials: PL
authors.lastname: Wu
authors.affiliation: Key Laboratory of Heart and Lung, Respiratory Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Key Laboratory of Heart and Lung, Respiratory Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: wzyxywlx@163.com.
authors.forename: Liang-Xing
authors.initials: LX
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D006984:Hypertrophy / Q000188:drug therapy; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D051899:Smad2 Protein / Q000096:biosynthesis; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D066253:Vascular Remodeling / Q000187:drug effects / Q000502:physiology
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D053148:Caspase 3; C004446:asiaticoside
keywords: Asiaticoside; Pulmonary arterial hypertension; Smad; TGF-β1; Vascular remodeling