| Cardiovascular and cerebrovascular diseases have been major causes threatening human health.Exploring innovative drugs based on Traditional Chinese Medicine to prevent and treat cardiovascular and cerebrovascular diseases is an urgent task for pharmaceutical researchers nowadays.Blood stasis,as the pathological basis of cardiovascular and cerebrovascular diseases,exists in the whole stage of pathogenesis.Traditional Chinese Medicine holds that "blood-activating and stasis-relieving" plays important roles in these diseases.Salvia miltiorrhiza and safflower are the main herbs for the treatment of cardio-cerebral vascular diseases.The combination of Salvia miltiorrhiza – safflower is a classic blood-activating and stasis-relieving drug-pair for the treatment of cardio-cerebral vascular diseases used in clinical practice.The researches of Salvia miltiorrhiza – safflower are mainly focus on the pharmacodynamics or pharmacological mechanisms nowadays.The studies on its effective substances focus mostly on the main components of Salvia miltiorrhiza and safflower,include salvianolic acid,tanshinone and hydroxysafflor yellow A.However,the material basis related to the therapeutic effects of Salvia miltiorrhiza – safflower herb-pair in vivo has not been clarified and needs further investigation.Based on this,this paper carries out research work from the following aspects:1.Based on literatures-tracking and the related researches of our team,we summarized the chemical compositions,metabolism in vivo and main pharmacological effects of Salvia miltiorrhiza – safflower herb-pair in this chapter.2.Based on our previous discovery of "Liang Guanxi" characteristic metabolites related to herb pairs of miltiorrhiza – safflower,the current study collected plasma samples of normal and model rats at different time points after intravenous administration of Danhong injection.These plasma samples were analyzed to dectect the dynamic changes of drug ingredients,endogenous substances and metabolites by HPLC-Q-TOF/MS.Futhermore,we gave greater emphasis on the dynamic changes and tissue distribution of "Liang Guanxi" characteristic metabolites.Then the relativity of all above compounds was analyzed by SPSS software.This research found that the elimination time of the "Liang Guanxi" characteristic metabolites such as NM1 and NM2 in the model Danhong group prolonged compared to the normal Danhong group,and the metabolite NM1 was found distributed in tissues of heart,liver,spleen,lung,kidney.The metabolite NM4 was distributed in the brain,liver and kidney.NM1 and NM2 were strongly correlated with many drug ingredients,such as Salvianolic acid A,B,C,D and Caffeic acid.We speculated that NM1 and NM2 may be the metabolites of active pharmaceutical ingredients,while the metabolite NM3 is simultaneously correlated with NM1 and NM2,which was supposed as a secondary metabolite of NM1 or NM2.3.Based on the correlation analysis in the second part conent,combined with literature-tracking of Danhong Injection.In this chapter,the analysis method of HPLC-DAD was established to detect the main active components of Danhong injection including Danshensu,Protocatechuic aldehyde,Caffeic acid and Hydroxysafflor yellow A,P-Coumaric acid,Lithospermic acid,Salvianolic acid B,Salvianolic acid A and Salvianolic acid C.Besides,we finished the content determination of the above components in three different batches of Danhong injection.The rusult may provide a comprehensive basis for the quality evaluation of Danhong injection and its metabolism in vivo.4.Using the rat model of ischemic stroke as an example,we utilized MD-HPLC-ECD to measure the the neurotransmitter,pharmaceutical ingredient and metabolites in the brain of normal and model treatment groups.It showed that the levels of dopa,dopamine,serotonin and tyrosine in the model group were significantly changed compared to that in the control group.A callback was made and Danshensu was found in the cerebrospinal fluid after intravenous adminstration of Danhong injection within 0-90 minutes.It indicates that Danhong injection has a regulatory effect on monoamine neurotransmitter abnormalities caused by cerebral ischemia and the active component of Danshensu could penetrate the Blood-Brain-Barrier. |
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