Studies On New Antitumor Target Of Coix Seed Extract, And Its Effects On Blood Lipids And Antioxidant Capacity

The present study focus is Coix seed extract obtained by supercritical CO₂ extraction. Firstly, the method of fatty acid synthase （FAS） activity determination was established using purified duck liver FAS in vitro, and the inhibition of Coix seed extract on FAS was studied to explore the inhibition mechanism. Secondly, effects of Coix seed extract on lipometablic enzymes and glycometablic enzymes in rats were studied. Thirdly, on the basis of previous studies, effects of Coix seed extract on blood lipids and antioxidant capacity in hyperlipemia rats were studied to develop new drugs, and pharmacodynamic action mechanisms were also explored. Finally, pharmacokinetic study of Coix seed extract in rats was conducted in order to obtain the pharmacokinetic marker related to pharmacodynamic action and target tissues. Experiments in vitro showed that the inhibition of Coix seed extract on FAS activity was significant and dose-dependent. Coix seed extract inhibited two active sites:β-ketoacyl reductases （KR） and enoyl reductase （ER）. Experiments in vivo showed that Coix seed extract inhibited FAS activity in the liver, elevated lipoprotein lipase （LPL） and hepatic lipase （HL） activity in the plasma, decreased malate dehydrogenase （MDH） and glucose-6-phosphate dehydrogenase （G-6-PD） activity, thereby inhibiting fatty acid synthesis and cutting off the resource of components and energy for tumor cell growth. The present study supports that FAS is a novel target of Coix seed extract for tumor therapy.Considering the regulation of Coix seed extract on lipometablic and glycometablic enzymes, we conducted experiments to investigate effects of Coix seed extract on blood lipids and antioxidant capacity in hyperlipemia rats. As a result, we found that Coix seed extract could obviously reduce serum total cholesterol （TC）, low density lipoprotein （LDL-C） concentrations, and significantly increased the total antioxidant capacity （T-AOC） in hyperlipemia rats. Moreover the antioxidant mechanism was speculated to be related to scavenging effects of the free radical and reactive oxidative species （ROS）, especially superoxide anion free radical （O₂-·）. Taken together, prevention and treatment actions of Coix seed extract on artherosclerosis （As） and coronary artery disease （CAD） were relevant to both the decrease of LDL-C concentration and the increase of T-AOC. It was implied that FAS was dual targets of Coix seed extract for both tumor therapy and hyperlipemia treatment. Moreover, the antitumor mechanism also might be related to the improvement of T-AOC in organism.Finally, in pharmacokinetic study it was found that triglyceride （TG） might be a pharmacokinetic marker, and pharmacokinetic model of Coix seed extract after intravenous injection is two-compartment model. Coix seed extract was distributed rapidly to play its pharmacodynamic action. TG the main ingredient in Coix seed extract was mainly distributed in liver, spleen, and lung in rats. TG content in stomach was lower, but certain concentration of TG in stomach could be kept for a longer time. All above results supported that Coix seed extract had good therapeutic effects on liver cancer, lung cancer, and stomach cancer.