title: Punicalagin Prevents Hypoxic Pulmonary Hypertension via Anti-Oxidant Effects in Rats.
abstract: Punicalagin (PG), a major bioactive ingredient in pomegranate juice, has been proven to have anti-oxidative stress properties and to exert protective effects on acute lung injuries induced by lipopolysaccharides. This study aimed to investigate the effects of PG treatment on hypoxic pulmonary hypertension (HPH) and the underlying mechanisms responsible for the effects. Rats were exposed to 10% oxygen for 2 wk (8 h/day) to induce the HPH model. PG (5, 15, 45[Formula: see text]mg/kg) was orally administered 10[Formula: see text]min before hypoxia each day. PG treatments at the doses of 15 and 45[Formula: see text]mg/kg/d decreased the mean pulmonary arterial pressure (mPAP) and alleviated right ventricular hypertrophy and vascular remodeling in HPH rats. Meanwhile, PG treatment attenuated the hypoxia-induced endothelial dysfunction of pulmonary artery rings. The beneficial effects of PG treatment were associated with improved nitric oxide (NO)-cGMP signaling and reduced oxidative stress, as evidenced by decreased superoxide generation, gp91[Formula: see text] expression and nitrotyrosine content in the pulmonary arteries. Furthermore, tempol's scavenging of oxidative stress also increased NO production and attenuated endothelial dysfunction and pulmonary hypertension in HPH rats. Combining tempol and PG did not exert additional beneficial effects compared to tempol alone. Our study indicated for the first time that PG treatment can protect against hypoxia-induced endothelial dysfunction and pulmonary hypertension in rats, which may be induced via its anti-oxidant actions.
authors.affiliation: * Department of Respiratory Medicine, Xi'an Central Hospital Xi'an 710003, China.|† Department of Respiratory Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Shao
authors.affiliation: * Department of Respiratory Medicine, Xi'an Central Hospital Xi'an 710003, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: * Department of Respiratory Medicine, Xi'an Central Hospital Xi'an 710003, China.
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.affiliation: * Department of Respiratory Medicine, Xi'an Central Hospital Xi'an 710003, China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Du
authors.affiliation: * Department of Respiratory Medicine, Xi'an Central Hospital Xi'an 710003, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.affiliation: † Department of Respiratory Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D009569:Nitric Oxide; C115642:punicalagin; D010100:Oxygen
keywords: Endothelial Function; Hypoxic Pulmonary Hypertension; Nitric Oxide; Oxidative Stress; Punicalagin