Cyanidin‑3‑O‑β‑glucoside protects against pulmonary artery hypertension induced by monocrotaline via the TGF‑β1/p38 MAPK/CREB signaling pathway.

Pulmonary artery hypertension (PAH) is a disease with high morbidity and mortality. Cyanidin‑3‑O‑β‑glucoside (Cy‑3‑g), a classical anthocyanin, has a variety of biological effects. The present study evaluated whether Cy‑3‑g attenuated PAH, and explored the potential mechanism of action. Rats were injected with monocrotaline (MCT; 60 mg per kg of body weight) and then treated with Cy‑3‑g (200 or 400 mg per kg of body weight) for 4 weeks. Protein expression was determined in vitro in transforming growth factor‑β1 (TGF‑β1)‑mediated human pulmonary arterial smooth muscle cells (SMCs). The results indicated that Cy‑3‑g significantly inhibited the mean pulmonary artery pressure, right ventricular systolic pressure and right ventricular hypertrophy index, as well as vascular remodeling induced by MCT in PAH rats. Further experiments showed that Cy‑3‑g suppressed the expression of pro‑-inflammatory factors and enhanced the levels of anti‑inflammatory factors. Cy‑3‑g blocked oxidative stress and improved vascular endothelial injury. Cy‑3‑g also reduced the proliferation of SMCs. Furthermore, the MCT‑ and TGF‑β1‑induced increase in TGF‑β1, phosphorylated (p)‑p38 mitogen‑activated protein kinase (MAPK) and p‑cAMP‑response element binding protein (CREB) expression was blocked by Cy‑3‑g treatment in vivo and in vitro. These results indicated that Cy‑3‑g could prevent vascular remodeling in PAH via inhibition of the TGF‑β1/p38 MAPK/CREB axis.