Abstract
Pulmonary arterial hypertension (PAH) is a destructive and rare disorder characterized by a progressive increase in pulmonary artery pressure and vasoconstriction, ultimately leading to right ventricular failure and death. 18β-Glycyrrhetinic acid (18β-GA) is an active ingredient in the commonly used Chinese herbal medicine radix glycyrrhizae, and it possesses antioxidant, anti-inflammatory, anti-tumor, and other pharmacological properties. This study aimed to determine whether 18β-GA has protective effects against monocrotaline (MCT)-induced PAH and whether it is associated with oxidative stress. The PAH of rats was induced by MCT (60 mg/kg) and oral administration of 18β-GA (100, 50, or 25 mg/kg/day), sildenafil (30 mg/kg), or saline for 21 consecutive days. The development of PAH was evaluated by hemodynamic parameters and right ventricular hypertrophy index. Hematoxylin and eosin staining, Masson trichrome staining, and electron microscopy were used to determine the degree of vascular remodeling and proliferation in lung tissue. Moreover, the antioxidant capacity and malondialdehyde levels in the lungs were measured according to the instructions provided by the test kits, and the expression levels of nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) and Nox4 were detected through Western blot analysis. Results of our study indicated that 18β-GA treatment significantly improved the hemodynamic and pathomorphological data of the rats, reduced the changes in oxidative stress biomarkers, and inhibited Nox2 and Nox4 expression. Our research indicated that 18β-GA has a protective effect against MCT-induced PAH by inhibiting oxidative stress in rats.
Highlights
Pulmonary arterial hypertension (PAH) is a severe and multifactorial cardiovascular syndrome that restricts flow through pulmonary arterial circulation, and it is characterized by pulmonary arterial pressure of ≥25 mmHg at rest and ≥30 mmHg when moving
At 6 weeks after MCT was administered, mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) levels significantly increased in the MCT group compared with that in the control group (p < 0.01; Figure 4), and this result demonstrated the successful establishment of the MCT-induced rat model
The rats treated with 18β-Glycyrrhetinic acid (18β-GA) (100 and 50 mg/kg) and sildenafil (30 mg/kg) demonstrated significantly lower mPAP and RVSP levels than the MCT group (p < 0.01 and p < 0.05, respectively; Figure 4). All these results demonstrated that oral administration of 18β-GA could alleviate MCT-induced PAH in rats
Summary
Pulmonary arterial hypertension (PAH) is a severe and multifactorial cardiovascular syndrome that restricts flow through pulmonary arterial circulation, and it is characterized by pulmonary arterial pressure of ≥25 mmHg at rest and ≥30 mmHg when moving. It is distinguished by resistance of pulmonary arteries and an increase in pulmonary arterial pressure, which trigger subsequent right. The conventional pharmaceutical therapies for PAH, including prostacyclin analogs, phosphodiesterase type-5 enzyme (PED-5) inhibitors, and endothelin receptor antagonists (Aiello et al, 2016), are unsatisfactory because of their toxic side effects and limited effects on the inhibition of disease progression (Humbert et al, 2010). The discovery and development of safe and effective agents to prevent or delay the progression of PAH in the field of traditional medicine are of critical clinical significance (Galiè and Manes, 2013)
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