Arctigenin ameliorates neointima formation induced by vascular injury by inhibiting inflammatory response and proliferation through the IL-6/JAK2/STAT3 pathway.

Abstract

In-stent restenosis (ISR) is the main risk for the failure of vascular stent implantation. Arctigenin (ARCG) as the active principle of Arctium lappa, possesses the ability to regulate proliferation and inflammation. This study was conducted to illuminate the role and mechanism of ARCG in ISR. The effects of ARCG on the inflammation and proliferation of vascular smooth muscle cells (VSMC) were detected. Then we profiled RNA transcript expression in the femoral arteries of restenosis patients and healthy donors along with the SwissTargetPrediction to identify the target of ARCG. VSMCs were stimulated with IL-6 to assess the effect and mechanism of ARCG in vitro, and the restenosis mouse models generated by the wire injury of the femoral arteries were used to explore the effect of ARCG on restenosis in vivo. We reported significantly increased levels of inflammation and IL-6/JAK/STAT3 pathway in tissue samples from patients with restenosis and restenosis mouse models. And ARCG inactivated the IL-6/JAK2/STAT3 pathway, inhibiting proliferation and inflammation in a dose-dependent manner. Moreover, ARCG treatment was found to inhibit intimal hyperplasia in restenosis mouse models. ARCG inhibits ISR by inhibiting proinflammatory response and proliferation of VSMCs via IL-6/JAK2/STAT3 pathway, providing a promising drug candidate for ISR.