This study explored the effect of pterostilbene (PTS) complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on right heart function, glutathione and glutaredoxin systems, and the expression of redox-sensitive proteins involved with regulation calcium levels in the experimental model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). After 7 days of PAH induction, rats received daily doses of the PTS:HPβCD complex (corresponding to 25, 50, or 100 mg·kg⁻¹ of PTS) or vehicle (control group, CTR0) (an aqueous solution containing HPβCD; CTR0 and MCT0 (MCT group that did not receive PTS treatment)) via oral administration for 2 weeks. The results showed that the PTS:HPβCD complex increased the content of reduced glutathione and the activity of glutathione-S-transferase and glutaredoxin in the right ventricle (RV) of MCT-treated rats in a dose-dependent manner. Additionally, at higher doses, it also prevented the reduction of stroke volume and cardiac output, prevented myocardial performance index (MPI) increase, reduced lipoperoxidation, reduced total phospholamban, and increased the expression of sarcoplasmic reticulum calcium ATPase in the RV of MCT-treated rats. These results demonstrate that the PTS:HPβCD complex has a dose-dependent antioxidant mechanism that results in improved cardiac function in experimental right heart failure. Our results open a field of possibilities to PTS administration as new therapeutic approach to conventional therapy for right ventricular dysfunction. Novelty Pterostilbene complexed with hydroxypropyl-β-cyclodextrin could be a new therapeutic approach. Pterostilbene complexed with hydroxypropyl-β-cyclodextrin reestablishes redox homeostasis through glutathione metabolism modulation, leading to an improved MPI in pulmonary arterial hypertension-provoked right heart failure.

Myocardial infarction (MI) and pulmonary arterial hypertension (PAH) are 2 prevalent cardiovascular diseases. In both conditions, oxidative stress is associated with a worse prognosis. Pterostilbene (PTE), an antioxidant compound, has been studied as a possible therapy for cardiovascular diseases. This study aims to evaluate the effect of PTE on oxidative stress in the hearts of animals with MI and in the lungs of animals with PAH. Male Wistar rats were used in both models. In the MI model, the experimental groups were sham, MI, and MI + PTE. In the PAH model, the experimental groups were control, PAH, and PAH + PTE. Animals were exposed to MI through surgical ligation of the left coronary artery, or to PAH, by the administration of monocrotaline (60 mg/kg). Seven days after undergoing cardiac injury, the MI + PTE animals were treated with PTE (100 mg/kg day) for 8 days. After this, the heart was collected for molecular analysis. The PAH + PTE animals were treated with PTE (100 mg/kg day) for 14 days, beginning 7 days after PAH induction. After this, the lungs were collected for biochemical evaluation. We found that PTE administration attenuated the decrease in ejection fraction and improved left ventricle end-systolic volume in infarcted animals. In the PAH model, PTE improved pulmonary artery flow and decreased reactive oxygen species levels in the lung. PTE administration promoted protective effects in terms of oxidative stress in 2 experimental models of cardiac diseases: MI and PAH. PTE also improved cardiac function in infarcted rats and pulmonary artery flow in animals with PAH.

Background: Pulmonary artery hypertension (PAH) is characterised by progressive pulmonary vascular remodelling and increased pulmonary vascular resistance, leading to right ventricular (RV) dysfunction and failure. Red araça (Psidium cattleianum) extract is derived from native Brazilian fruit rich in phenolic compounds with recognised antioxidant and anti-inflammatory properties. Objectives: The present study aimed to evaluate the preventive effects of red araça extract administration on RV remodelling and pulmonary arteriole alterations in rats with MCT-induced PAH. Methods: Male Wistar rats were divided into three groups: control, monocrotaline (MCT), and MCT + red araça extract. PAH was induced by a single intraperitoneal injection of MCT (60 mg/kg), and the treated group received red araça extract (5 mL/kg/day) by gavage for 21 days. Echocardiographic, hemodynamic, morphometric, molecular, and histological analyses were subsequently performed. Results: The MCT group exhibited increased pulmonary vascular resistance and RV hypertrophy, impaired RV function, elevated TLR4 and xanthine oxidative (XO) protein expression, elevated Akt activation, and marked increase in pulmonary arteriole wall thickness. Treatment with red araça extract prevented RV hypertrophy, reduced total pulmonary vascular resistance, preserved Akt activation similar to control, and decreased TLR4 and XO protein expression in the RV. In addition, administration of red araça extract prevented the increase in pulmonary arteriolar wall thickness. Conclusions: Collectively, these findings suggest that red araça extract attenuates cardiopulmonary alterations associated with experimental PAH, possibly involving modulation of the expression of proteins related to cardiac hypertrophy and inflammation.