Study On The Metabolism Of Multi - Component Of Chuanxiong Based On

Most researchers are focus on the interaction between the chemical compositions that is the cutting-edge in the area. The single component metabolism and the metabolic interaction between the two components are clearly, while the method of the overall metabolic profile of more than two components is relatively rare. Generally, traditional Chinese medicine need to be orally administrated, multi-component combined effects of Chinese medicine plays a basic role in this case. To research the multi-component of traditional Chinese medicine in the overall vision is responsible for the characteristics of the role of the multi-component Chinese medicine. The liver is the major pharmaceutical and important metabolic organ, and the main site of drug biotransformation, but the function of the intestinal mucosa that contain the drugs phase I and phase II metabolism and its effect on the oral bioavailability of the drug researches has become the focus of pharmaceutical research in recent years, despite the main function of the small intestine that is absorption. This paper conducts the drug metabolic enzymes chemical composition interaction theory and technology to study the interaction between the liver and intestine of the multi-component of Chuanxiong.1. Establishment and verification of the HPLC method of simultaneous determination of five probe substrates of CYP450 enzymes. Preparing the rat liver microsomes as the production technology of liver microsomes. Selecting phenacetin, chlorzoxazone, omeprazole, tolbutamide, testosterone respectively as CYP1A2, CYP2E1, CYP2C19, CYP2C9, CYP3A4 probe substrates according to FDA guidelines, and incubating these five probe substrates with rat liver microsomes, and analyzed by HPLC to analyze the amount of reduction of the probe substrates, and established the vitro evaluation method of simultaneous determination of rat liver microsomes CYP450 enzymes cocktail probe substrates of five subtypes.2. The effects of the six single ingredients of Chuanxiong on the CYP450 enzyme was analyzed by cocktail probe substrate method. After establishing the suitable liver microsomal incubation, validating the model by the known positive inhibitor, and studying the effects of the six single ingredients of Chuanxiong on the CYP450 enzyme. The results showed that the model is satisfactory, and the IC50 value of senkyunolide A for CYP1A2 is 7.39 umol/L, for CYP2C9 is 2.87 μmol/L, for CYP2E1 IC50 is less than 0.01 μmol/L, for CYP3A4 is 102.20 μmol/L, for CYP2C19 is greater than 100μmol/L. The effect of senkyunolide A on CYP1A2, CYP2C9 is moderate degree of inhibition, and senkyunolide is a potent inhibitor of CYP2E1, the remaining five components are not affected or less impact on the CYP450 isozymes.3. The metabolism of water extract, the resin components and the six single component of Chuanxiong in the intestinal S9, intestinal microsome, liver microsomal. Preparation of samples that incubating with the intestinal S9, intestinal microsomal and liver microsome combined with HPLC, high-resolution mass spectrometer and other analytical chemistry methods. The results showed that one new metabolite was found after the water extract incubating with the intestinal S9, and two metabolites were found after 3-n-Butylphthalide and senkyunolide I incubating with the liver microsome.In conclusion, the present study provides systematic investigations on the in vitro inhibitory effects of six single component of Chuanxiong on P450 enzyme activities. Meanwhile, the metabolism of rat S9 fraction, rat intestine microsome and rat liver microsome on Chuanxiong water extract, the segmented multicomponent and six single component of Chuanxiong were investigated. The present study provide reference method and technology for research the metabolic interaction of multicomponent, and also provide new information for safe and appropriate use of Chuanxiong.