Ginsenoside Rg1 attenuates right ventricular remodeling in hypoxic pulmonary hypertension and is associated with suppression of HIF-1α–related glycolytic signaling

Abstract Objectives To determine whether ginsenoside Rg1 attenuates right ventricular remodeling in hypoxic pulmonary hypertension and whether this effect is associated with suppression of HIF-1α–related glycolytic signaling. Methods Male C57BL/6 mice were exposed to normobaric hypoxia (10 % O 2 ) for 4 weeks and assigned to control, model, sildenafil, Rg1, or HIF-1α knockdown groups (n=10 per group). Pulmonary function, hemodynamic parameters, right ventricular hypertrophy, histopathology, oxidative stress, apoptosis, immunofluorescence, and protein expression in right ventricular tissue were evaluated. Results Hypoxia reduced forced expiratory volume in 0.3 s/forced vital capacity and increased mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular hypertrophy index. It also induced myocardial disorganization, collagen deposition, oxidative stress, apoptosis, and increased expression of HIF-1α, glucose transporter 1, hexokinase 2, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3, lactate dehydrogenase A, transforming growth factor beta 1, Smad2, and collagen I. Rg1 significantly attenuated these abnormalities, with a pattern broadly comparable to HIF-1α knockdown. Conclusions Rg1 attenuated hypoxia-induced right ventricular remodeling and fibrosis and was associated with reduced oxidative injury, apoptosis, and HIF-1α–related glycolytic and profibrotic signaling.