Triacetyl-3-hydroxyphenyladenosine, a derivative of cordycepin, attenuates atherosclerosis in apolipoprotein E-knockout mice

The cholesterol-modulating, immune-regulating and anti-inflammatory properties of cordycepin are well documented. Here we examined the effects of triacetyl-3-hydroxyphenyladenosine (THPA), a derivative of cordycepin, on the development of atherosclerosis (AS) in apolipoprotein E-knockout (apoE(-/-)) mice. The atherosclerotic lesion formation displayed by the oil red O staining-positive area was reduced significantly in either the aortic root section or the whole aorta en face in THPA-administrated apoE(-/-) mice. Plasma analysis by enzymatic method or enzyme-linked immunosorbent assay (ELISA) showed that high-density lipoprotein-cholesterol (HDL-C) was decreased, whereas apolipoprotein A-I (apoA-I) levels were markedly increased by THPA. In addition, ELISA and spectrophotometric measurement showed that plasma levels of tumor necrosis factor-alpha, interleukin-1 and malondialdehyde were decreased in mice treated with THPA. Realtime polymerase chain reaction detection disclosed that the expression of several transporters involved in reverse cholesterol transport was induced by THPA, and the expression of hepatic ABCA1 and apoA-I, which play roles in the maturation of HDL-C, was also elevated in the THPA-treated groups. Moreover, THPA enhanced the expression of endothelial nitric oxide synthase (NOS), and reduced the expression of inducible NOS and lectin-like oxidized LDL receptor-1 in the aorta, suggesting that THPA can exert endothelial protection effects. In addition, the expression or activation of several proinflammatory factors in the aorta was suppressed by THPA. In conclusion, our results reveal the inhibitory effects of THPA on AS in apoE(-/-) mice.