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

Abstract

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.

Healthberry 865® and Its Related, Specific, Single Anthocyanins Exert a Direct Vascular Action, Modulating Both Endothelial Function and Oxidative Stress

“…In this regard, anthocyanins, natural pigments belonging to the flavonoid family, are widely distributed in the human diet, such as in beans, fruits, vegetables, and red wine [ 8 ]. It is well-accepted that these natural compounds present in fruits and plant-derived-foods are relevant because of their potential health-promoting effects, as suggested by the available experimental and epidemiological evidence [ 9 , 10 , 11 ]. For this reason, interest in the biochemistry and biological effects of anthocyanins has increased substantially during the last decade.…”

Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models

“…The SCFA butyrate can promote B10 cell generation by activating the p38 MAPK pathway [ 39 ]. The p38 MAPK pathway is activated in pulmonary hypertension [ 40 , 41 , 42 ]. We found an increased abundance of Ruminococcaceae in the HySu-induced group at week 4.…”

Blackberry consumption protects against e-cigarette-induced vascular oxidative stress in mice

“…While blackberry consumption itself was unable to decrease p-SAPK/JNK, other studies utilizing individual polyphenols, such as C3G, have demonstrated their ability to reduce other MAPKs, p38 specifically, in a model of pulmonary HTN. 50 Unexpectedly, blackberry consumption had no effect on antioxidant enzymes in the lung. However, given the minimal appearance of oxidative stress and blackberries ability to mitigate ROS production through decreased NOX4, antioxidant responses may have been unneeded.…”