title: Ruscogenin exerts beneficial effects on monocrotaline-induced pulmonary hypertension by inhibiting NF-κB expression.
abstract: This study aims to examine the effect of ruscogenin on pulmonary arterial hypertension (PAH) and to determine the mechanism underlying this effect. We isolated pulmonary vascular smooth muscle cells (PVSMCs) from the pulmonary artery of the rats; the PVSMCs were cultured in vitro and then were treated with platelet-derived growth factor (PDGF), PDGF + ruscogenin, or PDGF + ruscogenin + parthenolide. We randomized Sprague-Dawley rats into five groups as follows: control group, PAH group, low-dose group, medium-dose group, and high-dose group; the rats in the low-, medium-, and high-dose groups received the vehicle and ruscogenin 0.1, 0.4, and 0.7 mg/kg, respectively, from day 1 to day 21 after injection of monocrotaline (MCT). We measured the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP), and medial wall thickness of the pulmonary artery (PAWT). We examined the levels of the nuclear factor kappa B (NF-κB) protein by using immunohistochemistry and western blot analysis, and the mRNA levels of NF-κB in PVSMCs were evaluated using real-time polymerase chain reaction (PCR). The mPAP, RVSP, and PAWT and the protein and mRNA levels of NF-κB were significantly higher in the PAH model group than in the control group (P < 0.05). Ruscogenin induced a significant dose-dependent decrease in the mPAP, RVSP, and PAWT and in the NF-κB expression in the PAH group (P < 0.05), which suggests that ruscogenin will also exert dose-dependent effects on MCT-induced PAH through the inhibition of NF-κB.
authors.affiliation: Department of Respiratory Medicine, Huai'an First People's Hospital, Nanjing Medical University Huai'an, Jiangsu, 223300, P. R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Geriatric Intensive Care Unit, The First Affiliated Hospital, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, Huai'an First People's Hospital, Nanjing Medical University Huai'an, Jiangsu, 223300, P. R. China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University Nanjing 210029, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology; D013150:Spirostans / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D012717:Sesquiterpenes; D013150:Spirostans; C002669:parthenolide; D016686:Monocrotaline; C012541:ruscogenin
keywords: Ruscogenin; expression; monocrotaline; nuclear factor-kappa B; pulmonary hypertension