title: Withania somnifera shows a protective effect in monocrotaline-induced pulmonary hypertension.
abstract: BACKGROUND
  Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored.
  
  
  OBJECTIVE
  The present study investigates the effect of W. somnifera root powder on monocrotaline (MCT)-induced PH in rats.
  
  
  METHODS
  In preventive studies, W. somnifera root powder (50 and 100 mg/kg/d, p.o.) was administered from day 1 following single administration of MCT (60 mg/kg, s.c.) in Sprague-Dawley (SD) rats. After 35 d, right ventricular pressure (RVP) was measured in anesthetized rats. Various physical markers of right ventricular hypertrophy (RVH) were measured in isolated hearts. Markers of endothelial function, inflammation, and oxidative stress were estimated in lung homogenate. Vasoreactivity of pulmonary arteries was also studied. In therapeutic treatment, W. somnifera (50 and 100 mg/kg/d, p.o.) was administered from day 21 to 35 post-MCT administration.
  
  
  RESULTS
  Preventive treatment with 50 and 100 mg/kg W. somnifera significantly reduced the RVP (32.18 ± 1.273 mm Hg and 29.98 ± 1.119 mm Hg, respectively, versus 42.96 ± 1.789 mm Hg of MCT) and all markers of RVH in MCT-challenged rats. There was an improvement in inflammation, oxidative stress and endothelial dysfunction, and attenuation of proliferative marker and apoptotic resistance in lungs. Therapeutic treatment with W. somnifera (100 mg/kg) also reduced RVP and RVH.
  
  
  CONCLUSIONS
  This study demonstrated that W. somnifera significantly protected against MCT-induced PH due to its antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective properties.
authors.affiliation: Division of Pharmacology .
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Kaur
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.forename: Sheeba S
authors.initials: SS
authors.lastname: Samuel
authors.forename: Himangshu K
authors.initials: HK
authors.lastname: Bora
authors.forename: Sharad
authors.initials: S
authors.lastname: Sharma
authors.forename: Shakti Deep
authors.initials: SD
authors.lastname: Pachauri
authors.forename: Anil K
authors.initials: AK
authors.lastname: Dwivedi
authors.forename: Hefazat H
authors.initials: HH
authors.lastname: Siddiqui
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006321:Heart / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008515:Medicine, Ayurvedic; D016686:Monocrotaline / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D028321:Plant Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D018517:Plant Roots / Q000737:chemistry; D011208:Powders; D017207:Rats, Sprague-Dawley; D032341:Withania / Q000737:chemistry*
chemical_list: D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D028321:Plant Preparations; D011208:Powders; D016686:Monocrotaline
keywords: Apoptosis; inflammation; proliferating cell nuclear antigen; pulmonary hypertension; right ventricle pressure; right ventricular hypertrophy