Inhibitory effects of formononetin on the monocrotaline‑induced pulmonary arterial hypertension in rats

Abstract

Pulmonary arterial hypertension (PaH) is a fatal syndrome resulting from enhanced pulmonary arterial pressure and pulmonary vessel resistance. Perivascular inflammation and extracellular matrix deposition are considered to be the crucial pathophysiologic bases of PaH. Formononetin (FMn), a natural phytoestrogen isolated from red clover (Trifolium pratense), has a variety of proapoptotic, anti-inflammatory and anti-tumor activities. However, the therapeutic effectiveness of FMn for PaH remains unclear. in the present study, 60 mg/kg monocrotaline (McT) was first used to induce PaH in rats, and then all rats were treated with different concentrations of FMn (10, 30 and 60 mg/kg/day). at the end of this study, the hemodynamics and pulmonary vascular morphology of rats were evaluated. Specifically, matrix metalloproteinase (MMP)2, transforming growth factor β1 (TGFβ1) and MMP9 were measured using western blot and immunohistochemical staining. collagen type I, collagen type III, fibronectin, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, erK and nF-κB were quantified using western blotting. The results demonstrated that FMN significantly alleviated the changes of hemodynamics and pulmonary vascular morphology, and decreased the McT-induced upregulations of TGFβ1, MMP2 and MMP9 expression levels. Meanwhile, the expression levels of collagen type I, collagen type III and fibronectin in rat lungs decreased after FMn treatment. Furthermore, the phosphorylated erK and nF-κB also decreased after FMn treatment. Taken together, the present study indicated that FMn serves a therapeutic role in the McT-induced PaH in rats via suppressing pulmonary vascular remodeling, which may be partially related to erK and nF-κB signals.

Sodium Selenite Attenuates Balloon Injury-Induced and Monocrotaline-Induced Vascular Remodeling in Rats

“…Pulmonary arterial hypertension is also a common but devastating cardiovascular disease based on VR ( Thompson and Lawrie, 2017 ). In the present study, we used the previously described method to establish a pulmonary arterial hypertension model ( Wu et al, 2020 ) and observed that the rats, which received daily SSE treatments two weeks subsequent to the MCT injection, had large decreases in right ventricular hypertrophy, pulmonary arterial remodeling, and pulmonary artery pressure compared with only MCT injected rats. Collectively, these results show the suppressive effect of SSE on VR-related diseases.…”

Naringin Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension Through Endothelial-To-Mesenchymal Transition Inhibition

“…Collectively, both in vivo and in vitro studies demonstrate that naringin is able to delay the development of PAH through the inhibition of EndMT. ERK and NF-κB signalling pathways have been reported as important factors in the maintenance of pulmonary vascular homeostasis (Cai et al, 2019;Wu et al, 2020). Increasing evidences have demonstrated the associations of ERK and NF-κB signalling pathways in the EndMT in PAH.…”

“…Right ventricle systolic pressure (RVSP) measurement was conducted as in a previous study (Wu et al, 2020). Briefly, pentobarbital sodium (60 mg/kg, Sigma-Aldrich, MO, United States) through intraperitoneal (i.p.)…”

Potential mechanisms of formononetin against inflammation and oxidative stress: a review

“…For example, studies showed that FMNT decreased the level of p-NF-κB p65 and increased the level of IκBα, the inhibitor of NF-κB, in the liver from concanavalin-A-induced autoimmune hepatitis mice, showing a powerful immunomodulatory property . FMNT also possess activity of restraining monocrotalinetreated pulmonary arterial hypertension, whose pharmacological mechanism was related to the downregulation of phosphorylated ERK and NF-κB (Wu et al, 2020). In addition to the inflammation model mentioned above, NF-κB pathway plays a critical role in mastitis.…”