Effects Of Da Cheng Qi Tang Animal Plasma On IP₃R MRNA Expression In Interstitial Cells Of Cajal

Background: The pharmacokinetics of traditional Chinese medicine is a marginal subject to study the absorption, distribution, metabolism and excretion course of active ingredients. Through this research the understanding and acceptance of traditional Chinese medicine theory can be clarified and promoted. Grasping the characteristics of a bsorption, distribution, metabolism and excretion can develop the reasonable therapy programmes to promote clinical rational drug use, to enhance the effectiveness of clinical treatment. As representatives of Tongligongxia treatment, Da Cheng Qi Tang (DCQT) has significant effects in the treatment of gastrointestinal motility disorders. Emodin, Magnolol are the main effective components of DCQT, involved in the regulation of the calcium mobilization, promotion of signal transduction and accelerating gastrointestinal motility.The normal digestive function of the body. Any factors impacting on the normal gastrointestinal contraction and relaxation can lead to gastrointestinal motility disorder. Interstitial cells of cajal(ICC) which produce pacing , regulate basic electric rhythm, and link to the autonomic nervous and gastrointestinal smooth muscl,are as the key of gastrointestinal movement and control, relating to the incidence of many gastrointestinal motility disorders and gastrointestinal cancer. Therefore,it is very important to study pacing and potential regulatory mechanism of ICC. Ryanodine receptor (RyR) and Inositol 1,4,5-trisphosphate receptor (IP3R)play an important role in pacing the process of selecting the potential of ICC. The study of release mechanism of Endoplasmic reticulum calcium ion channels become a hotspot. As representatives of Tongligongxia therapy of Chinese traditional medicine, Da Cheng Qi Tang (DCQT) has significant effects in the treatment of gastrointestinal motility disorders. Emodin, Magnolol is the main effect components of DCQT,which involve in the regulation of the calcium mobilization.Objective: To study the pharmacokinetics of emodin and magnolol in rat after taking DCQT decoction. To establish a method of Preparative of Lyophilized Powder of animal drug plasma after taking DCQT. To study the effect of DCQT animal plasma on the expression of IP3R in jejunum ICC.Methods: Wistar rats were given a single ig dose of DCQT.The content of emodin and magnolol in rat tissue and plasma were measured by RP-HPLC. Pharmacokinetic parameters were determined from the plasma concentration-time data with the 3P97 software package. Wistar rats were fed with DCQT liquid,Dynamic monitoring plasma concentration curve was optimizedly made on the basis of sampling time. The plasma was collected and separated,the freeze-dried powder of the plasma was preparated,and the rate of preserving efficiency active ingredients was detect with RP-HPLC. The animal plasma after taking DCQT was prepared and the ICC of Wistar rat jejunum was isolated. The subtypes of IP3R expression in ICC in DCQT animal plasma group and in the control group were determened by RT-PCR.Results: There were good linear relationship between concentration of drug and chromatogram peak area in the two containts.They apeared two-compartment models with Tmax 1.38h and 0.27h,T1/2β30.68h and 6.68h,T1/2ka 0.65h and 0.093h respectively. Plasma protein binding rate were 74.56%in magnolol and 65.63% in emodin. There was significant difference in effective content between the long-term preservation of freeze-dried powder and the lower temperature cryopreservation active ingredient content. All mRNA subtypes of IP3R were expressed in ICC in jejunum of rats.The expression of IP3R mRNA increased obviously in DCQT animal plasma group than in the control(P<0.05), there was difference between high concentration DCQT animal plasma and low concentration DCQT animal plasma(P<0.05).Conclusions: magnolol and emodin were absorbted by rat gastrointestinal tract with good absorption rates after a single ig dose of DCQT.Magnolol and emodin were metabolized by the liver and excreted by the kindey. Lyophilized power of animal plasma after taking DCQT was more pharmacological benefits than that traditional method of poceparation of animal plasma taking DCQT. The plasma of taking DCQT in rat can significantly increase rat ICC IP3R expression.There were difference of expression of IP3R mRNA in different concentration of DCQT aminal plasma. And there was DCQT dose-dependent relationship.