Taken together,

inhibitors cordycepin may be a potential candidate antimetastatic agent through inhibiting the activity of MMPs and accelerating the release of TIMPs from cancer cells. In in vivo studies, Yoshikawa et al. investigated whether platelet aggregation accelerates hematogenous metastasis of B16-F1 mouse melanoma (B16-F1) GSK J4 solubility dmso cells in C57BL/6Cr mice and the effect of cordycepin on hematogenous metastasis accelerated by ADP. ADP significantly increased the number of metastatic lung nodules in mice injected intravenously with B16-F1 cells in a dose-dependent manner, and cordycepin significantly reduced the number of metastatic nodules of B16-F1 cells formed in the lung accelerated by ADP injected simultaneously with B16-F1 cells (17). Accordingly, ADP accelerated hematogenous metastasis and cordycepin had an inhibitory action on hematogenous metastasis of B16-F1 cells via the blocking of ADP-induced Galunisertib supplier platelet aggregation in vivo. In in vivo studies, Sprague-Dawley rats received a single i.v. injection of a colloidal carbon solution, and then the clearance rate from the blood was measured. The rats had been administered WECS p.o. daily at a dose of 200 mg/kg for twenty-five days

until the day before the injection of colloidal carbon. The half-life of the colloidal carbon in the blood of rats administered WECS at 200 mg/kg was significantly shorter than that of the control rats (18). These results indicate that orally administered WECS activates one of the immune systems in rats. In in vitro studies, Yamaguchi et al. indicated that WECS

exhibited potent antioxidant and antilipid peroxidation activities and inhibited the accumulation of cholesteryl ester in macrophages via the suppression of low-density lipoprotein (LDL) oxidation (19). Furthermore, Yamaguchi et al. showed that WECS administered orally prevented cholesterol deposition in the aorta of atherosclerotic ICR mice by the inhibition of LDL oxidation mediated Sodium butyrate by free radicals rather than by reduction of the serum lipid level (20). Guo et al. reported that cordycepin administered i.g. at 25 and 50 mg/kg for two weeks prevented hyperlipidemia in Syrian golden hamsters fed a high-fat diet via the activation of AMP-activated protein kinase (AMPK) (21). In addition, Won et al. demonstrated that cordycepin injected orally at 10 mg/kg for 14 days attenuated neointimal formation by inhibiting reactive oxygen species-mediated responses in vascular smooth muscle cells in Sprague-Dawley rats (22). Accordingly, cordycepin, as an active ingredient of WECS, may exert beneficial effects on the formation of atherosclerotic lesions induced by oxidative stress.