Comparative Study On The Chemical Basis Pharmacology And Pharmacokinetics Of Analogous Formulas About Xiao-Cheng-Qi Tang

1 Background and objectiveXiao-Cheng-Qi Tang (XCQT) was early documented in Treatise on Febrile Diseases (Shang-Han-Lun). Hou-Po-San-Wu Tang (HPSWT) and Hou-Po-Da-Huang Tang (HPDHT) were recorded in Synopsis of Golden Chamber (Jin-Kui-Yao-Lve). They were all invented by Zhang Zhongjing, and were composed of three herbal medicines, Dahuang (rheum officinale), Houpo (Mangnolia officinalis), Zhishi (Citrus aurantium). These prescriptions have been traditionally used as a purgative to relieve constipation and to clear internal heat in the stomach and intestine. But due to the difference of dosage and decocting method, the indications of three formulas are also different to some extent. According to the guiding principles of traditional Chinese medicine, we can define the three formulas as analogous formulas about Xiao-Cheng-Qi Tang. To confirm the substance basis and full reveal the mechanism of their pharmacological actions in vivo, and then provide valuable data for its clinical use, the study investigated the pharmacokinetic properties of analogous formulas about Xiao-Cheng-Qi Tang.2 Methods and result2.1 Substantial basis research on analogous formulas about Xiao-Cheng-Qi Tang.Firstly, a simple and selective HPLC-UV method for simultaneous determination and quantification of anthraquinones, lignans and flavonoids in analogous formulas about Xiao-Cheng-Qi Tang was developed and validated, and the characteristic profiles of analogous formulas about Xiao-Cheng-Qi Tang aqueous extract were established for qualitative analysis.40 common peaks were detected in the characteristic profiles and were attributed to three single herbs respectively.18 major compounds were identified and confirmed by comparison with the standard samples on the full wave scanning.Besides, the HPLC-UV method was used to determination and quantification of 18 compounds in Xiao-Cheng-Qi Tang (XCQT), Hou-Po-San-Wu Tang (HPSWT) and Hou-Po-Da-Huang Tang (HPDHT). It was found that the contents of anthraquinones, lignans and flavonoids in different formulas were quite different, the extraction efficiencies of them were different as well. XCQT contained the greatest abundance of anthraquinones and flavonoid, HPSWT contained the greatest abundance of lignans.2.2 Pharmacological study on analogous formulas about Xiao-Cheng-Qi Tang.Phenol red excretion test, ammonia induced cough test, charcoal powder driving test were adopted to examine the effects of analogous formulas about Xiao-Cheng-Qi Tang on expectorant, cough and purgation separately. Statistical analysis of the results showed, HPSWT has more advantages on the treatment for expectorant and cough. XCQT and HPDHT are more effective to promote the motion of gastro-intestines. It’s consistent with the theory of traditional Chinese medicine.2.3 Pharmacokinetic study on analogous formulas about Xiao-Cheng-Qi Tang.The rat plasma samples were collected from the catheter links to rats which subjected to jugular vein surgery. The method of liquid-liquid extraction (LLE) was adopted for the pretreatment of plasma sample. Then an UPLC-MS/MS method for simultaneous determination of the representative constituent of XCQT analogous formulas included rhein, emodin, aloe-emodin, chrysophanol, physcion, magnolol, honokiol, narirutin, naringin, hesperidin, neohesperidin, hesperetin, naringenin, nobiletin in rat plasma was developed and validated. The results of specificity, linearity, intra-day and inter-day precisions, accuracy, and stablility for LC-MS assay are suitable for quantification of 14 compounds in rat plasma. This method was successfully applied for the PK property study of HQT at different dose.After the blood concentration of fourteen representative constituents were estimated by LC/MS analysis, the curve of drug concentration vs time was plot and the PK parameters (T1/2, Tmax, Cmax, AUCo-t, Vd/F, CL/F and MRT) of representative constituents were calculated by the software of WinNonlin 6.4. Finally, the PK differences of the fourteen representative constituents after oral administration XCQT, HPSWT and HPDHT were compared. It is found that the AUC0-t and Cmax of 14 compounds was dose-dependent. Compatibility of herbs affected the PK parameters of 14 compounds.3 ConclusionAs a conclusion, the present study revealed compatibility of herbs have an effect on the material basis, pharmacologic action and ADME of chemical components in Chinese medicine. Scientific compatibility base on syndrome is the key to guide clinical medication.