Cordycepin inhibits vascular adhesion molecule expression in TNF-α-stimulated vascular muscle cells

Abstract

Abstract. Atherosclerosis is a chronic inflammatory disease, which is associated with the increased expression of adhesion molecules in vascular smooth muscle cells (VSMCs). Cordycepin is one of the major bioactive components of Ophiocordyceps sinensis that has been demonstrated to exert anti-atherogenic activity; however, its molecular mechanisms are poorly understood. The aim of the present study was to examine the in vitro effects of cordycepin on the tumor necrosis factor (TNF)-α-induced suppression of adhesion molecule expression. The results of the present study demonstrated that cordycepin markedly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in TNF-α-stimulated human aortic vascular smooth muscle cells (HA-VSMCs). Cordycepin significantly inhibited the TNF-α-induced mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) activation (P<0.05), markedly inhibited the TNF-α-induced expression level of nuclear factor (NF)-κB p65 and markedly prevented the TNF-α-associated degradation of IκBα in HA-VSMCs. The results of the present study suggest that cordycepin inhibits the expression of VCAM-1 and ICAM-1 in TNF-α-stimulated HA-VSMCs via downregulating the MAPK/Akt/NF-κB signaling pathway. Therefore, cordycepin may have a potential therapeutic application for preventing the advancement of atherosclerotic lesions.

A Systematic Review of the Biological Effects of Cordycepin

“…Activation of inflammatory signalling cascades leads to translocation of NFĸB from the cytoplasm to the nucleus and binding to DNA. We found 11 papers reporting a cordycepin-mediated reduction in the nuclear levels of NFĸB [ 28 , 43 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ]. In contrast, two papers reported no changes in the nuclear localisation of NFĸB [ 72 , 106 ].…”

“…In reviewing the impact of cordycepin on the phosphorylated level of Akt, the Ser 473 site was extensively studied (11 papers). Most studies (nine articles) demonstrated an inhibitory effect of cordycepin on Akt phosphorylation at Ser 473 [ 11 , 101 , 103 , 142 , 144 , 149 , 150 , 151 , 152 , 153 ]. Only one study found no effect [ 145 ].…”

“…Nine studies investigating the effect of cordycepin on P38 met the eligibility criteria. Four studies showed a repressive effect [ 101 , 103 , 112 , 174 ], whereas four papers described that cordycepin activates P38 by increasing the phosphorylation at Thr 180 /Tyr 182 [ 11 , 175 , 176 , 177 ]. A single study reported that cordycepin has no effect on P38 activation [ 178 ] ( Figure 8 d).…”

Cordycepin Accelerates Osteoblast Mineralization and Attenuates Osteoclast Differentiation In Vitro

“…We further examined the effect of cordycepin on OSCAR, cathepsin K and MMP9 mRNA expression levels, where 1 μ M cordycepin significantly downregulated RANKL-induced OSCAR, cathepsin K and MMP activation (Figures 5(c) , 5(d) and 5(e) ). Plus, NFATc1 and cFOS activation were caused by MAPK (mitogen-activated protein kinases) signaling, which is required for early osteoclast differentiation [ 28 , 29 ]. To confirm the molecular mechanism of cordycepin effects on MAPKs following the activation of RANKL in RAW264.7 cells, we investigated the phosphorylation of p38, ERK and JNK using a western blot.…”

Anti‐inflammatory effects of cordycepin: A review

“…In a PDGF‐stimulated RAoSMCs model, cordycepin is shown to cause significant downregulation of MMP‐2, −9, and − 13 expressions (S. W. Yang, Lim, et al, 2015). In a separate study, cordycepin is shown to decrease the expression of VCAM‐1 and ICAM‐1 in TNF‐α‐stimulated human aortic vascular smooth muscle cells via downregulating the MAPK/Akt/NF‐κB signaling pathways (Yan et al, 2017).…”