Ginsenoside Rg1 ameliorates hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and inflammation by regulating CCN1

Pulmonary arterial hypertension (PAH) is a chronic obstructive disease characterized by vascular remodeling. Studies have confirmed that ginsenoside Rg1 can improve pulmonary hypertension to a certain extent, but the potential mechanism by which it improves hypoxia-induced PAH remains unclear. The aim of this study was to investigate the therapeutic effect of ginsenoside Rg1 on hypoxia-induced PAH. The results showed that hypoxia promoted inflammation, EndMT, and vascular remodeling, which were accompanied by decreased CCN1 levels and increased p-NF kappa B p65, TGF-beta 1, and p-Smad 2/3 levels. Treatment with ginsenoside Rg1, recombinant CCN1, BAY-11-7082, and SB-431542 could prevent hypoxia-induced vascular remodeling, reduce the expression of the hypoxia-induced inflammatory cytokines TNF-alpha and IL-1 beta, inhibit the expression of the mesenchymal markers alpha-SMA and Vimentin and restore the expression of the endothelial markers CD31 and VE-cadherin to improve hypoxia-induced EndMT, which may be associated with the upregulation of CCN1 protein expression and downregulation of p-NF kappa B p65, TGF-beta 1, and p-Smad 2/3 in rats and cells. siRNA CCN1 transfection increased the expression of p-NF kappa B p65, TGF-beta 1, and p-Smad 2/3 and accelerated the occurrence and development of inflammation and EndMT after hypoxia. In summary, our study indicated that hypoxia-induced EndMT and inflammation play a role in hypoxic pulmonary hypertension (HPH). Ginsenoside Rg1 treatment could reverse hypoxia-induced EndMT and inflammation by regulating CCN1 and has potential value in the prevention and treatment of HPH.

Automated summary

The aim of this study was to investigate the therapeutic effect of ginsenoside Rg1 on hypoxia-induced pulmonary arterial hypertension (HPH). The results showed that ginsenoside Rg1 could reverse hypoxia-induced endothelial-mesenchymal transition (EndMT) and inflammation by regulating CCN1, which has potential value in the prevention and treatment of HPH. This study revealed the role of EndMT and inflammation in HPH and identified a potential treatment option.