Isorhamnetin alleviates symptoms and inhibits oxidative stress levels in rats with pulmonary arterial hypertension

Objectives: Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease with high mortality. Isorhamnetin (ISO), one of the main natural flavonoids extracted from sea buckthorn, has pharmacological effects such as anti-inflammatory, anti-proliferative and antioxidant. This study aimed to investigate the protective effect of ISO on PAH and its relationship with the phosphorylation of the c-Src tyrosine kinase (p-c-src)/NOX1 signaling pathway.

Materials and methods: Ninety-five rats were randomly divided into five groups. The normal group received only a subcutaneous injection of saline, while the other groups received a subcutaneous injection of monocrotaline(MCT) (60 mg/kg) to establish a PAH model. The treatment group received ISO (50, 100, 150 mg/kg/d) treatment for 21 days, and after 21 days, all rat lung tissues were separated.

Results: The results showed that ISO could significantly improve the hemodynamics of MCT-induced PAH rats, such as mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), and had inhibitory effects on right ventricular hypertrophy in PAH rats, and on pulmonary vascular remodeling in PAH rats. In addition, ISO can reduce the content of 5-hydroxytryptamine (5-HT) in PAH rats, increase the expression of Nrf2 protein in the lung tissue of PAH rats, activate the antioxidant system, enhance the activity of SOD in lung tissue of PAH rats, and inhibit NOX1, 5-HTT, p-c-src and Proliferating Cell Nuclear Antigen(PCNA) protein expression, and decrease MDA content.

Conclusion: Our research confirmed the therapeutic effect of ISO on MCT-induced PAH rats, which may be related to regulating the p-c-src/NOX1 signaling pathway.