Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats

- We demonstrate the activation of NLRP3 inflammasome in MCT-induced PAH.
- We find that Ellagic acid can ameliorate MCT-induced PAH.
- Ellagic acid inhibits NLRP3 inflammasome signal pathway in MCT-induced PAH.

BackgroundPulmonary 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.MethodsMale Sprague-Dawley rats received EA (30 and 50 mg/kg/day) or vehicle one day after a single-dose of monocrotaline (MCT, 60 mg/kg). Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were assessed 4 weeks later. Activation of the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome pathway in the lungs was assessed using Western blot analysis.ResultsMCT 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.ConclusionsEllagic acid ameliorates monocrotaline-induced pulmonary artery hypertension via exerting its anti-oxidative property inhibiting NLRP3 inflammasome signal pathway in rats.