Study On Chemical Component Changes And Parmacodynamic Effects Of Dachengqi Decoction

ObjectiveThe study on Dachengqi decoction compatibility of chemical composition changes, efficacy, pharmacokinetics, physical foundation and dose. Compatibility topics in all the party different combinations, medicine for frying method of different Fried method combined, rhubarb single herb frying method and so on many different levels, simultaneous determination of multiple indexes of large concentrations of Dachengqi decoction (DCQ)foundation of chemical compatibility, and tracking clarified pharmacological effects, the indexes of the pharmacokinetic properties ingredients, lay advance, mutual support and using mathematical model and statistical analysis method, the foundation Dachengqi decoction and pharmacological effects, expounds its compatibility the correlation of the scientific meaning and the dynamic process in the body for clinical application and preparation, and provide scientific basis for the development.Methods1 Compatibility of Dachengqi decoction component changes researchAccording to the complexity of traditional Chinese medicine, chemical composition of chromatographic mobile phase, proportion, detected wavelength, chromatographic column temperature, such as the quantity of incoming sample optimized, establish chromatographic conditions and applied to the whole party HPLC, UPLC-MS unified analysis method to analysis method, and made instrument precision, stability and method repeatability investigation samples.2 The effect of Dachengqi decoction to "hot" pharmacodynamics2.1 Influence of lapactic action about Dachengqi decoction to ABP miceIrrigation stomach to ABP mice with Dachengqi decoction, using intestine ink motional rate, observation defecate time,24h within 24h potablewater quantity, amount, the large bowel ABP mice bearing of the gas soup lapactic action.2.2 Effect of Dachengqi decoction to ET in plasmaIrrigation stomach to ABP mice with Dachengqi decoction, application of ABP mice with Limulus agent, detecting ET in blood and in ileum, then observing the influence of Dachengqi decoction to endotoxin of ABP mice.2.3 Effect of Dachengqi decoction to NO and TNF-αin plasmaIrrigation stomach to ABP mice with Dachengqi decoction, application of ABP mice with Limulus agent, detecting NO and TNF-αin plasma, then observing the influence of Dachengqi decoction to NO and TNF-αin plasma of ABP mice.3 Irrigation stomach with Dachengqi decoction pharmacokinetic in rats3.1 Study pharmacokinetic of anthraquinone of Dachengqi decoction in ratsEstablish and application anthraquinone ingredients like rats plasma samples processing method and HPLC conditions, detection big pile of gas fluids Fried liquid of anthraquinones into blood, through the analysis of rat medicated knowable, application of detection plasma pharmacokinetic software components DAS2.1.1 calculation pharmacokinetic parameters of [T1/2 (Ka) (h), T1/2 (Ke) (h), Cmax (mg/L), Tmax (h), AUCO-t (mg/L·h)].3.2 Study pharmacokinetic of the kind of honokiol of Dachengqi decoction in ratsEstablish and application ingredients in blood of rats. Honokiol plasma samples treatment process and UPLC-MS conditions, detection big pile of gas fluids Fried liquid ingredients like honokiol into blood, application DAS2.1.1 calculation pharmacokinetic software components of pharmacokinetic cpar-ameters.3.3 Study pharmacokinetic of flavonoids of Dachengqi decoction in ratsEstablish and application flavonoids ingredients in rat plasma samples processing method and HPLC conditions, detection big pile of gas fluids Fried liquid ingredients into the blood, application of pharmacokinetic software 3P97separately calculated flavonoids ingredients pharmacokinetic parame-ters.3.4 Metabolism research of Dachengqi decoction in ratsApplied the whole square HPLC, UPLC-MS unified analysis method, detection in rats metabolites free anthraquinones, Magnolol, honokiol, Naringin Hesperetin, Naringenin, Hesperidin, Neohesperidin.4 Concentration-response relationsApplication Pearson correlation analysis and grey relational analysis on bearing Dachengqi decoction’s ingredients and effections.Results1 Compatibility of Dachengqi decoction component changes researchThe results indicated that the peaks areas of Naringin, Neohesperidin, Honokiol and Magnolol didn’t increase, but yields of Hesperidin, Aloe-emodin, Rhein, Emodin were increased when four herbs decoct together. Dachengqi decoction, Dahuang, Houpo and Zhishi were extracted by Petroleum, Chloroform, Ethy acetate and n-Btannol, then compared these extracted liquids, the results indicated that most of chemical ingredients in single herbs of Dahuang, Houpo, Zhishi, Mangxiao were not found in the compound recipe of Dachengqi decoction, however, the content of chemical ingredients of Aloe-emodin, Rhein from Dahuang, Hesperidin from Zhishi were increased greatly in the plarity extraction, to constrast of Houpo. Total ionchromato-gram of Dachengqi decoction, rhubarb water extract, Magnolia officinalis water extract and Citrus aurantium water extract showed the following results, firstly, there was no Physcion or the chemical constituent of tR=18.97min existed in rhubarb water extract; secondly, the peaks areas of Magnolol decreased in the compound recipe of Dachengqi decoction;thirdly, compared with the single herb of Zhishi, the peak area of Hesperidin was increasd greatly in the compound recipe of Dachengqi decoction; but the chemical constituent of t1/2=28.83min and t1/2=34.04min were not existed in Zhishi water extract; lastly, the chemical constituent of t1/2=24.74min and t1/2=40.45min may be the new contents through the he compatibility of dosage change of Dachengqi decoction. Those talked above which also indicated that traditional decoction method of c was increase the Anthraquinone components of the medicine so as to enhance the effect to treat constipation.2 The effect of Dachengqi decoction to "hot" pharmacodynamicsTo establish ABP rat model, and to evaluat and verify the effect of Dachengqi decoction obout its subduce calorie and body temperature. Though observing the of intestinal propulsive movements, drinking, defecating time, ET of blood plasma, ET of ileum content, NO of blood plasma, tumor nerosis factor-a lever. The results shows that every experimental group could enhance ABP rats defecating, hastening intestinal propulsive movements, diminuting ET of plasma, lessening ET of ileum content, reducing tumor nerosis factor-a lever of blood plasma, increasing NO ever of blood plasma. The effect of the compatibility of Doehlert design Dachengqi decoction was inferior to classics compatibility of Dachengqi decoction.3 Irrigation stomach with Dachengqi decoction pharmacokinetic in ratsA stable, reliable, uniform HPLC and UPLC-MS analytical methods with good reproducibility was developed to study the changes of chemical ingredients between single herbs of Dahuang, Houpo, Zhishi, Mangxiao and the compound recipe of Dachengqi decoction in blood plasma of mice. The results indicated that Aloe-emodin, Rhein, Emodin, Chrysophanol, Physcion, Naringin, and Hesperetin were detected in mice blood plasma. The method for determining aloe-emodin、rhein、emdin、chysophanol and physcion in plasma has been established, and the pharmacokinetic parameters can be instructive for clinic application. After ig of dachengqi dection 9g·kg-1, T1/2(Ka) (h) were 0.362、1.034、1.918、1.89、0.656; T1/2(Ke) (h) were 0.311、1.173、2.330、2.188、0.810; Cmax(mg/L) were 48.47、21.69、10.49、5.76、38.76; Tmax (h) were 4、4、6、4、2; AUC0-t (mg/L·h) were 85.733、66.726、65.911、41.840、96.401; The method for determining Naringin and Hesperetin in plasma has been established, and the pharmacokinetic parameters can be instructive for clinic application. After ig of dachengqi dection 9g·kg-1, T1/2 (Ka) (h) were2.106、2.142; T1/2 (Ke) (h) were 5.842、5.491; Cmax(mg/L) were 3.492、2.574; Tmax (h) were 4h、4h; AUC0-t (mg/L·h) were 39.407、34.886. Honokiol and Magnolol were not found in blood plasma of mice. The chemical components from compatibility of Dachengqi decoction were defecated through stools of mice.4 Concentration-response relations4.1 PEARSON concentration-response relationsStudy related analysis shows that in this experiment process, application PEARSON correlation coefficient reflects big analysis with "bearing Dachengqi decoction with body heat" except the detailed between the pharmacodynamic close degree, experimental results show that with the big pile increased, gas soup dose Y1, its efficacy index Y4, Y5, Y2, Y6, Y7 Y8 (ABP mice intestine, ink propulsion data recorded as Y1 ABP mice, bowel time notes for Y2 ABP mice within 24h, will Y4 bowel quantity recorded as ABP mice, will remember in peripheral blood for Y5, content of ET ABP mice ileum content will be written in Y6, content of ET ABP mice for plasma will remember Y7, nitric oxide (NO) content for plasma ABP mice will be written for content of alpha TNF Y8) were measured drug also increases with increasing, and with the model group with significant difference meaning (P< 0.05). Y3 (ABP mice with 24h potablewater quantity) the difference was not significant meaning (P> 0.05).4.2 GRA spectrum efficiency relationsGRA analysis showed that, its connection order than the main 0.85 for 3, 4,6,8,10,14,17,18,38,50, peak, including flavonoids ingredients; Correlation between in 0.85-0.8, contains anthraquinones and honokiol composition.Conclusion1 Compatibility of Dachengqi decoction component changes research1.1 The establishment of the test method of HPLC and UPLC-MSThe stable, reliable and reproducible methods have established the entire party HPLC, UPLC-MS.1.2 Different polarities component changes between single herb and DCQGenerally, its polarity composition in all the square of dissolution rate increased. But on rhubarb (aloe emodin, rhubarb acid) and frutus aurantii composition increasing compatibility, mainly produces comprehensive efficacy and rhubarb and frutus aurantii polarity composition dissolution, magnolia bark lower polarity composition dissolution has great concern.1.3 UPLC-MS research on single herb and DCQThe comprehensive contrast DCQ, rhubarb water frying fluid, magnolia officinalis water frying fluid and frutus aurantii water frying fluid LC ESI-MS and theDCQ retention time for 24.74min and composition of 40.15 min for four single herb but appear, because compatibility of separate and detect limitations of large cap, the current did not keep time for Dachengqi decoction of 24.74 min and 40.15 min, and identification of the ingredients to make structure. These content changes corresponding ingredients, peak may be compatibility based effects of chemicals.2 The effect of Dachengqi decoction to "hot" pharmacodynamics2.1 Influence of lapactic action about Dachengqi decoction to ABP miceDachengqi decoction promoted ABP mice rapid defecated, also can made the ABP mice defecate bate ABP mice, and dry excrement satisfied quickly eduction body outside, avoid the dung of substances in the body produces more heat, playing the role of "FuDiChouXin"2.2 Effect of Dachengqi decoction to ET in plasmaDachengqi decoction reduce endotoxin level in plasma and intestinal; Reduce endotoxin the same as reduces the levels of endotoxin on heat release and endotoxin heat production chance, improve the clinical effect.2.3 Effect of Dachengqi decoction to NO and TNF -αin plasmaDachengqi decoction significantly reduced TNF -αlevel in blood of ABP mice. Based on literatures can turn reduce inflammation for possible mechanisms of induction:(1) movement function, strengthen the gastrointestinal tract, reduce blood flow increased bowel intestinal mucosa permeability; (2) cut macrophages activity, reducing TNF-αetc inflammatory cytokine produced and released, (3) to prevent against oxygen free radicals, peroxidation damage, Etc.3 Irrigation stomach with Dachengqi decoction pharmacokinetic in rats3.1 Study pharmacokinetic of anthraquinone of Dachengqi decoction in ratsThe stable controllable, reproducible and accurately methods established. Through analysising plasma of rats, emodin, aloe emodin, rhein, phenol and emodin armour ether are detected in plasma. Application pharmacokinetic software- DAS2.1.1 separately calculated the five components plasma pharmacokinetic parameters, the obtained free anthraquinones five are embodied in one room model.3.2 Study pharmacokinetic of the kind of honokiol of Dachengqi decoction in ratsThe stable controllable, reproducible and accurately methods established. Through analysising plasma of rats, emodin, aloe emodin, rhein, phenol and emodin armour ether are detected in plasma. There is no Magnolol or Honokiol in plasma.3.3 Study pharmacokinetic of flavonoids of Dachengqi decoction in ratsThe stable controllable, reproducible and accurately methods established. Through analysising plasma of rats, emodin, aloe emodin, rhein, phenol and emodin armour ether are detected in plasma. Application pharmacokinetic software-3P97 separately calculated the Hesperitin, Naringenin in plasma pharmacokinetic parameters, the obtained free anthraquinones five are embodied in one room model.3.4 Metabolism research of Dachengqi decoction in rats Free anthraquinones, and honokiol, honokiol mainly eliminated from feces way. To ig to DCQ, then detecting 24h urine, feces rats in the analysis, which can display are Hesperidin, Naringin, Neohesperetin, and Hesperitin, Naringenin in plasma. Overall, quercetin yuan form the amount of eliminated from more than nucleoside proportion.4 Concentration-response relationsSelect emodin, rhubarb acid of aloe, phenol of rhubarb as part of a quality control, process optimization index and efficacy material foundation has certain scientific. This study in traditional Chinese medicine theory and practice will be under the guidance of analytical chemistry, TCM, pharmacological, statistics and computer technologies combining bearing, further clarify big material base of the gas soup discussed the compatibility of the mechanism, the compound material foundation for the big drug, bearing Dachengqi decoction. It compatibility and diagnose the methodology of the study provides theory basis.