Inhibition of cytochrome P4502E1 by lemongrass and the primary aldehyde constituent of lemongrass, citral.

摘要

Cytochrome P4502E1, the ethanol-inducible form, metabolizes and activates a significant number of substrates to more toxic products and the induction of CYP2E1 by ethanol is thought to result in increased oxidative stress in hepatocytes. One proposed mechanism for this increased oxidative stress is the increased production of hydrogen peroxide by CYP2E1 via a so called "uncoupling" of its NADPH oxidation activity. A main hypothesis of this research is that the main aldehyde constituent found in Lemongrass, citral, will be able to block the activity of CYP2E1, and consequently demonstrate physiological antioxidant properties.The induction of the phase II enzyme is an important process involved in cellular oxidative stress response, by which the oxidative toxicants can be eliminated or inactivated before they damage the critical cellular macromolecules. Phase II detoxifying genes provide protection to the cell against the toxicities of ROS and reactive intermediates produced during phase I metabolism.In this research, cell culture, RT-PCR and electrophoresis gel technology will be used for monitoring the induction of antioxidant genes by a variety of different natural products.