Gypenosides alleviates MCT-induced pulmonary arterial hypertension in rats by targeting oxidative stress, inflammation, and apoptosis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a severe heart-lung condition characterized by complex changes in the pulmonary vasculature, known as pulmonary vascular remodeling (PVR). Gypenosides (Gyp) possesses a range of pharmacological properties, including anti-inflammatory and anti-oxidant effects. This study aims to explore the impact of Gyp on pulmonary vascular remodeling, particularly in relation to its potential to counteract inflammation, oxidative stress, and apoptosis. MATERIALS AND METHODS: Twenty-four rats were randomly divided into four groups. MCT was administered via intraperitoneal injection at a 55 mg/kg dose to establish a PAH model. Gyp (150 mg/kg/day, Ig) was administered for 28 days, after which all lung tissues from the rats were isolated. RESULTS: The findings indicated that Gyp had a substantial positive impact on the hemodynamics of rats with PAH induced by MCT, including reductions in mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP). Additionally, it exhibited inhibitory effects on right ventricular hypertrophy and pulmonary vascular remodeling in these PAH-afflicted rats. MCT elevated the concentration of MDA (P<0.01 in the lung) while reducing the levels of SOD and GSH-PX (P<0.0001). Furthermore, MCT enhanced the expression of IL-6, TNF-α, and IL-1β (P<0.0001), as well as the mRNA expression of NF-κB (P<0.001) and the Bcl2 level (P<0.0001), while it lowered the expression of Bax (P<0.0001). Conversely, Gyp treatment effectively mitigated all of these alterations. CONCLUSION: This study represents the initial investigation showing that Gyp treatment attenuates PVR by inhibiting oxidative stress, inflammation, and apoptosis, providing a foundation for further research.