Effect of free and nanoemulsified β-caryophyllene on monocrotaline-induced pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), right ventricular (RV) failure and premature death. Compounds with vasodilatory characteristics, such as β-caryophyllene, could be promising therapeutics for PAH. This study aimed to determine the effects of free and nanoemulsified β-caryophyllene in lung oxidative stress and heart function in PAH rats. Male Wistar rats (170 g, n = 6/group) were divided into four groups: control (CO), monocrotaline (MCT), monocrotaline + β-caryophyllene (MCT-Bcar) and monocrotaline + nanoemulsion with β-caryophyllene (MCT-Nano). PAH was induced by MCT (60 mg/kg i.p.), and 7 days later, treatment with β-caryophyllene, either free or in a nanoemulsion (by gavage, 176 mg/kg/day) or vehicle was given for 14 days. Echocardiographic and hemodynamic measurements were performed, and after, the RV was collected for morphometry and the lungs for evaluation of oxidative stress, antioxidant enzymes, total sulfhydryl compounds, nitric oxide synthase (NOS) activity and endothelin-1 receptor expression. RV hypertrophy, increased PVR and RV systolic and diastolic pressures (RVSP and RVEDP, respectively) and increased mean pulmonary arterial pressure (mPAP) were observed in the MCT group. Treatment with both free and nanoemulsified β-caryophyllene reduced RV hypertrophy, mPAP, RVSP and lipid peroxidation. The reduction in RVSP was more pronounced in the MCT-Nano group. Moreover, RVEDP decreased only in the MCT-Nano group. These treatments also increased superoxide dismutase, catalase and NOS activities and decreased endothelin-1 receptors expression. Both β-caryophyllene formulations improved mPAP, PVR and oxidative stress parameters. However, β-caryophyllene in a nanoemulsion was more effective in attenuating the effects of PAH.

Keywords: Endothelial dysfunction; Monocrotaline; Nanoemulsion; Oxidative stress; Pulmonary arterial hypertension; β-Caryophyllene.