title: Inhibition of TNF-α-mediated NF-κB Activation by Ginsenoside Rg1 Contributes the Attenuation of Cardiac Hypertrophy Induced by Abdominal Aorta Coarctation.
abstract: Ginsenoside Rg1 (Rg1), a protopanaxadiol saponin extracted from Chinese medicine Panax ginseng C.A. Meyer, has been demonstrated to inhibit the cardiac hypertrophy. However, the molecular mechanisms underlying the inhibition remain poorly understood. Activation of nuclear factor-kappa B (NF-κB) mediated by tumor necrosis factor α (TNF-α) gets involved in the cardiac hypertrophy. This study is designed to investigate the effects and the potential mechanism of Rg1 on the abdominal aorta coarctation (AAC)-induced cardiac hypertrophy with focus on TNF-α/NF-κB signaling pathway. The results showed that oral administration of Rg1 dose-dependently improved the pathological changes, decreased the ratios of left ventricular weight/body weight (LVW/BW) and heart weight/BW (HW/BW), corrected the dysfunction of the cardiac hemodynamics by decreasing the left ventricular systolic pressure and left ventricular end-diastolic pressure and increasing the maximal rate of left ventricular systolic and diastolic pressure (±dp/dtmax) compared with the AAC alone. Rg1 also downregulated the atrial natriuretic peptide mRNA expression and decreased the mRNA and protein expression of TNF-α in the heart tissue of rats compared with the AAC alone. In addition, Rg1 and BAY, the specific inhibitor of NF-κB, decreased the protein content and downregulated the mRNA expression of atrial natriuretic peptide in neonatal rat ventricular myocytes treated with TNF-α. Furthermore, Rg1 increased the protein expression of p65, the subunit of NF-κB, in cytoplasm and decreased the expression p65 in nucleus of the heart tissue of rats undergoing the AAC and of neonatal rat ventricular myocytes treated with TNF-α. The results suggested that Rg1 attenuates the AAC-induced cardiac hypertrophy through inhibition of TNF-α/NF-κB signaling pathway.
authors.affiliation: *Pharmacology Department, Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, China; †Obstetrics and Gynecology Department, Central Hospital of Yingkou Development Area, Yingkou, China; and ‡Internal Medicine-Cardiovascular Department, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Futian
authors.initials: F
authors.lastname: Tang
authors.forename: Meili
authors.initials: M
authors.lastname: Lu
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Qiuning
authors.initials: Q
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Mei
authors.forename: Chonghua
authors.initials: C
authors.lastname: Xu
authors.forename: Ronghui
authors.initials: R
authors.lastname: Han
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism; D001017:Aortic Coarctation / Q000188:drug therapy* / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C035054:ginsenoside Rg1