Potential Role of Hesperidin in Improving Experimental Pulmonary Arterial Hypertension in Rats via Modulation of the <scp>NF</scp>‐<scp>κB</scp> Pathway

This study was designed to evaluate the therapeutic effects of hesperidin, an anti-inflammatory compound, on pulmonary arterial hypertension (PAH). A PAH rat model was established using monocrotaline (MCT, 60 mg/kg). Next, the experimental animals were assigned into the following four groups (n = 6 per group): Control group, MCT group, MCT + H20 group (20 mg/kg hesperidin), and MCT + H40 group (40 mg/kg hesperidin). According to the experimental outcomes, the PAH rat model was built successfully. In PAH animals, hesperidin significantly reduced right ventricular systolic pressure, Fulton index, and mean pulmonary arterial pressure. Concurrently, it improved pulmonary artery velocity-time integral and acceleration time, as well as alleviated pulmonary artery and right ventricular remodeling. On a molecular level, hesperidin inhibited the expression of vascular endothelial-cadherin, alpha-smooth muscle actin, matrix metalloproteinase-9, and transforming growth factor beta. Also, hesperidin downregulated pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, IL-18, chemokine C-C motif ligand 2, and C-X-C motif chemokine ligand 1 levels, and reduced the number of CD68+ cells in tissue samples. Further analysis revealed that hesperidin could inhibit the activation of p-IκB-α and p-p65 in samples induced by MCT. Collectively, these findings suggest that hesperidin may inhibit inflammation through the NF-κB pathway, thereby improving experimental PAH in rats induced by MCT.