title: Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats.
abstract: BACKGROUND
  Pulmonary artery hypertension (PAH) is characterized by vascular remodeling, high pulmonary blood pressure, and right ventricular hypertrophy. Oxidative stress, inflammation and pulmonary artery remodeling are important components in PAH. Ellagic acid (EA) is a phenolic compound with anti-oxidative, anti-inflammatory, and anti-proliferative properties. This study aimed to investigate whether EA could prevent the development of monocrotaline (MCT)-induced PAH in rats.
  
  
  METHODS
  Male Sprague-Dawley rats received EA (30 and 50mg/kg/day) or vehicle one day after a single-dose of monocrotaline (MCT, 60mg/kg). Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were assessed 4weeks later. Activation of the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome pathway in the lungs was assessed using Western blot analysis.
  
  
  RESULTS
  MCT induced PAH, oxidative stress, and NLRP3 inflammasome activation in vehicle-treated rats. EA reduced the right ventricle systolic pressure, the right ventricular hypertrophy and the wall thickness/external diameter ratio of the pulmonary arteries compared with vehicle. EA also inhibited the MCT-induced elevation of oxidative stress, NLRP3, and caspase-1, IL-β in the lungs and the elevated levels of brain natriuretic peptide (BNP) and inflammatory cytokines in serum.
  
  
  CONCLUSIONS
  Ellagic acid ameliorates monocrotaline-induced pulmonary artery hypertension via exerting its anti-oxidative property inhibiting NLRP3 inflammasome signal pathway in rats.
authors.affiliation: Department of Pediatric Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Pediatric Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. Electronic address: gx.chan@163.com.
authors.forename: Guang-xian
authors.initials: GX
authors.lastname: Chen
authors.affiliation: Department of Pediatric Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Meng-ya
authors.initials: MY
authors.lastname: Liang
authors.affiliation: Department of Pediatric Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Yao
authors.affiliation: Department of Pediatric Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. Electronic address: wuzhk@mail.sysu.edu.cn.
authors.forename: Zhong-kai
authors.initials: ZK
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins; D004195:Disease Models, Animal; D004610:Ellagic Acid / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D058847:Inflammasomes / Q000037:antagonists & inhibitors*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D004610:Ellagic Acid; D016686:Monocrotaline
keywords: Ellagic acid; Inflammation; NLRP3 inflammasome; Oxidative stress; Pulmonary artery hypertension