Osthole attenuates pulmonary arterial hypertension in monocrotaline-treated rats

Pulmonary arterial hypertension (PAH) is an insidious and progressive disease that is triggered by various cardiopulmonary diseases. Inflammation has an important role in the progression of PAH. Osthole (Ost) is a coumarin that has clear anti-inflammatory properties. The present study aimed to investigate the effects of Ost on PAH, and to explore the mechanism underlying this effect. Using the monocrotaline (MCT)-induced PAH rat model, the effects of Ost on PAH were investigated. Rats were subcutaneously administered a single dose of MCT (50 mg/kg) to establish the PAH model, followed by daily treatment with Ost (10 or 20 mg/kg) by gavage for 28 days. The mean pulmonary arterial pressure (mPAP) was measured and histological analysis was performed. The results demonstrated that Ost significantly decreased mPAP, and reduced thickening of the pulmonary artery, compared with in rats in the MCT group. To further determine whether the effects of Ost on MCT-induced PAH were associated with inflammatory responses, the nuclear factor-kappa B (NF-kappa B) p65 signaling pathway was investigated by western blot analysis. The results demonstrated that Ost increased inhibition of the NF-kappa B p65 signaling pathway. In conclusion, the results of the present study demonstrate that Ost may suppress the progression of MCT-induced PAH in rats, which may be, at least partially, mediated through modulation of the NF-kappa B p65 signaling pathway.