Study On Multi - Component Absorption And Sequential Metabolism Of Chuanxiong

The efficacy of multicomponent drugs is the comprehesive function of a variety of components in the face of multiple targets. Currently, single component’s metabolic res earch is relatively mature and metabolic interaction between two components has already been explained clearly. However, the method of the overall metabolic profile of more t han two muilticomponent is relatively rare. We use the multicomponent sequential metab olism method to carry out researches. Chuanxiong is chosen as the carrier and the expe riment is carried out that the whole journey of absorption and metabolism of oral multi component in the body from dissolution before the oral absorption to through the blood-brain barrier on the base of chuanxiong clinically used for cerebrovascular disease Pow der is the main kind of traditional chinense medicine so we choose it carriy out the dis solve before the oral absorption experiment. The medicinal broth (water decoction extrac t), which used most commonly in traditional chinese medicine, is choosen to do the mu lticomponent sequential metabolism.Chuanxiong multicomponent segments which have dif ferent invironment are preparation using macroporous adsorption resin separation enrichm ent technology to elaborate metabolic profile of the natural multicomponent drugs.1 In vitro dissolution study of components in Chuanxiong powder.before absorption. According to Chinese pharmacopoeia method, the paddle method was adopted and the UV spectrophotometric method was developed to determine the in vitro dissolution quan tity of total phenolic acid in chuanxiong oral powder in five medium (water, O.lmol/L hydrochloric acid, acetate buffer of 4.5, phosphate buffer of pH6.8, phosphate buffer of pH7.4) with ferulic acid as index. Drawing the dissolution curve and using the similar f actor method and the weibull model to evaluate it. The result showed that dissolution q uantity of total phenolic acid in chuanxiong oral powder in five medium was different. The dissolution quantity in water, O.lmol/L hydrochloric acid, acetate buffer of 4.5 and phosphate buffer of pH6.8 was similar and fit the weibull model, but it mutated in pho sphate buffer of pH7.4 and had reached the maximum amount when it was 30 min. Th e conclusion is that dissolution quantity in the media from the acidic to neutral then al kaline is gradually increasing and the dissolution time is shorted. Dissolution curve is si milar in the acidic and neutral media. Total phenolic acid of chuanxiong oral powder di ssolves out fast and completely in the alkaline medium.2 The sequential metabolism of multicomponent detected at the same time by HPL C-UV in Chuanxiong in rat To establish the fingerprint of Chuanxiong aqueous extract using HPLC and detect the changing profiling of multicomponent at the same time. In vitro incubation, in situ closed-loop methods and in vivo blood sampling were used to study the sequential metabolism The process contained:① metabolism of the physical e nvironment in the digestive.② intestinal flora metabolism.③gut wall metabolism.④ hepatic metabolism. The four steps keep continuity in space and time, so named multic omponent sequential metabolism (MSM).The result showed that there are 17 components were detected in the fingerprint of Chuanxiong aqueous extract and they were basically stable in the digestive juice. In vivo metabolism,5 components were metabolized by i ntestinal flora,7 components were metabolized by liver,2 new components were the m etabolites of intestinal flora and 1 component was the metabolites of liver. Using MSM method to clarify multicomponent metabolic profiling was feasible and provide theoreti cal and experimental basis for the metabolism of Chinese medicine.3 The absorption and sequential metabolism in rat of multicomponent in Chuanxion g using LC/MS. Firstly, in situ closed-loop method was used to study the the changing process of multicomponent following stomach-intestine-liver after the oral at the same t ime LC/MS was used too. The result showed that ferulic acid, senkyunolide J/N, senky unolide I,3-hydroxybutylphthalide and senkyunolide G were absorbed in protype form a nd senkyunolide A, M, H and Q were metabolized in liver. Secondly, through lavaging chuanxiong water extraction, cerebrospinal fluid is detected. Senkyunolide Ⅰ is detected i n the brain. Combined the results of MSM, Senkyunolide Ⅰ is absorbed in protype form in vivo and finally reach the target. So senkyunolide Ⅰ may be the target component. Thirdly, intestinal lymphatic absorption model is established. No component is detected i n the lymph, the reason may be related to the dosage form or components in chuanxio ng don’t have lymphatic absorption. But this can provides technical guidance for other experiments.4 The preparation of the segmented multicomponent of Chuanxiong and the differe nee of the sequential metabolism of the segments. The plant chemical means is used to cut multiple components into several pieces which have fewer components and further t he metabolic experiments are carried out, which will be more efficient. Components in chuanxiong water extract are cut into 4 segments by the microporous resin using EtOH of various concentrations. They are water elution,10% alcohol elution,30% alcohol el ution and 50% alcohol elution. HPD 100 is chosen to prepare the segments. Then 10% alcohol elution,30% alcohol elution and 50% alcohol elution are chosen to carry out t he sequential metabolism.30% alcohol elution contains ferulic acid, senkyunolide J/N, s enkyunolide I, senkyunolide H and 3-hydroxybutylphthalide. Ferulic acid may be metabo lized in liver and a new component is generated, which are different from that in chua nxiong water extrat. Senkyunolide H is metabolized in liver and the remaining three co mponents are absorbed in protype form, which are the same with that in water extrat. 50% alcohol elution contains senkyunolide Ⅰ, senkyunolide H, senkyunolide G and 3-hyd roxybutylphthalide. Senkyunolide H is metabolized in liver and the remaining three com ponents are absorbed in protype form, which are the same with that in water extrat.5 Summaries and discussions. Innovations of this paper are as follows:(1) Taking experience by the determination and the evaluation methods of dissolution o f the chemical drug, dissolution feature of total phenolic acid in Chuangxiong powder is carried out, which will provide reference basis for the Chinese medicine dissolution stu dies.(2) Sequential metabolic methods is uesd to evaluate the dynamic process of absorptio n and metabolism of multicomponent after the oral Chinese medicine. Considering the multicomponent environment changed, the metabolism of the components may change to o. The macroporous resin is chosen to cut the multicomponts into several segments. Th en the sequential metabolism of the segments is carried out. This will provide the refer ence method for traditional Chinese medicine metabolism research.