The PK-PD Study Of The Therapeutic Effect From Imperatorin On Big Mices With Nitroglyyerin-induced Migraine

This paper used imperatorin which is the main active ingredient of edible resource-Angelica as the object of study,carried out the PD research on blood and cerebral cortex of big mices with nitroglyyerin-induced migraine,systematically explained the relationship between imperatorin and NO,5-HT,CGRP,PGE2,?-EP,determined the significant indicators and carried out the PK-PD study of the therapeutic effect.And it combined the PK research with the PK-PD model,laid the foundation of the mechanism of action that imperatorin can relieve migraine systematically.At the same time,provided a theoretical basis for the development of Angelica health food.In the PD research on blood and cerebral cortex of big mices with nitroglyyerin-induced migraine,it measured the relationship between trial medicines and NO,5-HT,CGRP,PGE2,?-EP on blood and cerebral cortex of big mices with nitroglyyerin-induced migraine.The result showed that three hours after modeling,the tested drugs can increased the NO and5-HT in the plasma of the big mices with nitroglyyerin-induced migraine.The effect was clear but weak.Meanwhile,after modeling,the tested drugs can increased the PGE2,5-HT and CGRP in the cerebral cortex of the big mices with nitroglyyerin-induced migraine.The effect was clear and obvious,and it can be used as the significant indicators index.In the research of the PK-PD model,it used the no lag time two compartment-PK model,Hill-PD model,and then used the effect compartment indirectly to link the PK room and PD room.PK-PD fitting results showed that imperatorin significantly reduced the final amount of NO of the peripheral circulation after modeling,and weakly reduced the final amount of CGRP of the brain tissue after modeling.The results showed: the major pathway of the imperatorin against the nitroglycerin migraine was control the concentration of NO.Imperatorin can weakly reduced the central-related factors.Thus,imperatorin alleviate the main mechanism of migraine may be associated with reduced peripheral vasodilator substance concentration.The main mechanism of relieving migraine using imperatorin may associated with reducing the concentration of peripheral blood vessels.