Antrodia cinnamomea ameliorates neointimal formation by inhibiting inflammatory cell infiltration through downregulation of adhesion molecule expression in vitro and in vivo

The increased vascular inflammation is a key event in the development of atherosclerotic lesions. Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing inflammation. However, the potential role of A. cinnamomea in cardiovascular diseases remains unexplored. Herein, using carotid arterial ligation models, we found that ethanol extract from A. cinnamomea (EEAC) significantly inhibited neointimal hyperplasia in a dose-dependent manner, accompanied with the reduced expression of activated p65 and inflammatory cytokines. We also show that EEAC ameliorated TNF-α-induced phosphorylation of p65 and pro-inflammatory cytokine expression in both vascular smooth muscle cells (VSMCs) and macrophages in vitro. Mechanistically, EEAC suppressed expression levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in VSMCs, which attenuates the ability of monocytes/macrophages adhesion to VSMCs. Furthermore, the expression level of these adhesion molecules and infiltration of monocytes/macrophages were also decreased in neointimal VSMCs of arteries pretreated with EEAC. Altogether, our results reveal a novel function of A. cinnamomea in suppressing vascular inflammation upon ligation injury during neointimal formation, likely through inhibition of inflammatory cell infiltration via downregulating the adhesion molecules in VSMCs. Thus, A. cinnamomea may offer a pharmacological therapy to slow down disease progression in patients with vascular injury.