Study On Material Basis Of Xiaoshi Daozhi Of Aurantii Fructus Immaturus In Zhishi Daozhi Wan

Objective: Since not all of the ingredients in the medicinal materials could be transferred to pills in the pharmaceutical process,not all of the ingredients in pills could be dissolved in the gastric/intestinal fluid,all of the ingredients would not play the same role in the treatment of during the treatment,and the efficacy is the synergy of all medicinal materials in pills,the hypothesis of material Basis of Xiaoshi Daozhi of Aurantii Fructus Immaturus(AFI)in Zhishi Daozhi Wan(ZDW)was put forward to study the transfer of chemical constituents of AFI in pharmaceutical process of ZDW,the releases of chemical constituents of AFI in the gastric/intestinal fluid,the relationships between constituents and defects,and the transfer of components of AFI in decoction.By this way,the effective constituents of AFI in ZDW during the treatment of food accumulation syndrome were studied to provide reference for the development and utilization of ZDW.Methods: 1.The transfer of chemical constituents in pharmaceutical process: HPLC was used to determine the main constituents(synephrine Ⅰ,narirutin Ⅱ,naringin Ⅲ,hesperidin Ⅳ,neohesperidin Ⅴ,meranzin hydrate Ⅵ,marmin Ⅶ,limonin Ⅷ,tangeretin Ⅸ)in AFI.AFI fried with bran and ZDW.The contents of limonene and linalool were determined by GC-MS.Transfer rates were studied.Cluster analysis(CA),principal component analysis(PCA),and orthogonal partial least squares discriminant analysis(OPLS-DA)were performed.2.Release in the gastric/intestinal fluid: The contents of the above-mentioned Ⅰ～IX components in the artificial gastric /intestinal fluid of AFI and ZDW were determined,the transfer rates were calculated.3.The relationships between constituents and defects: The mouse model of food accumulation syndrome was established,the gastric residual rate,intestinal propulsion rate and the contents of gastrointestinal hormone(MTL,GAS,VIP)were used as the drug effect indicators,and the effect of AFIs and corresponding ZDWs were studied.Cluster analysis was used for results analysis.Pearson method was used to analyze the relationships of AFI and ZDW between ingredients and defects.4.The transfer effects caused by other medicinal in the decoction: HPLC was used to determine the contents of Ⅰ～IX in the single AFI decoction,compatibility decoction,and the transfer rates were studied.Results: 1.The defer of contents in pharmaceutical process: 1)After stir-frying with bran,In Aurantii Fructus Immaturus from Citrus aurantium(AFICa),the content of naringin increased,but the content of synephrine didn’t change significantly,while the contents of narirutin,hesperidin,neohesperidin,Marmin,limonin and tangeretin decreased in a certain extent.In Aurantii Fructus Immaturus from Citrus sinensis(AFICs),the contents of hesperidin increased,the content of synephrine didn’t changed obviously,the contents of limonin and other lipophilicity contents decreased.2)The contents neohesperidin,naringin and synephrine were high in the ZDW of AFICa,while the contents of hesperidin,narirutin and synephrine were high in the ZDW of AFICs.The synephrine could be transferred from AFI to ZDW with less loss.The transfer rates of flavonoid glycosides further increased after preparation.Limonin and tangeretin were completely lost.3)The results of multivariate statistical analysis showed that AFI,fried AFI and ZDW could be divided into two categories.The main contents of AFI causing difference classifications were neohesperidin,naringin,hesperidin in descending order,and the main contents of fried AFI causing difference classifications were hesperidin,naringin,neohesperidin in descending order,and and the main contents of ZDW causing difference classifications were hesperidin,neohesperidin,naringin in descending order.4)it is difficult that limonene and linalool were transferred from AFI to ADW.2.1)The transfer rates of synephrine of AFICa and AFICs were similar in artificial stomach/ intestinal fluid(both > 92.21%).The transfer rates of flavonoids and Marmin in artificial gastric fluid were lower than those in artificial intestinal fluid,while limonin and meranzin hydrate were on the contrary.The concentrations and transfer rates of naringin and hesperidin in artificial stomach / intestinal fluid of AFICs were significantly lower than those of AFICa in artificial stomach / intestinal fluid.2)The transfer rates of synephrine of ZDW were similar in artificial stomach / intestinal fluid,but slightly lower than those of in artificial stomach / intestinal fluid.The transfer rates of narirutin,naringin,hesperidin and neohesperidin of ZDW in artificial intestinal fluid were higher than the transfer rates of those in artificial gastric fluid.Both in artificial gastric / intestinal fluid,the transfer rates of naringin,hesperidin and neohesperidin in ZDW were lower than corresponding AFICa,the transfer rates of hesperidin in ZDW were higher than corresponding AFICs.3.1)AFI and ZDW had effects on mice with food accumulation syndrome,the Both medicinal materials and pills,the effects of AFICa were better than AFISs.The differences of effect beween ZDW by AFICs and ZDW by FAICa were less than the differences of effect beween AFICs and FAICa.2)when AFI was used alone,the effective constituents of it include synephrine,narirutin,naringin,hesperidin,neohesperidin,meranzin hydrate and marmin.In ZDW,the effective constituents of AFI were narirutin,naringin,hesperidin and neohesperidin.4.1)The best decocting condition of AFI decoction is as follows: 10 times of water,soaking30 min,and decocting for 2 times,2 hours for each time.2)Rhei Radix et Rhizoma,Atractylodis Maacrocephalae Rhizoma,Coptidis Rhizoma,Foria,Scutellariae Radix,Massa Medicata Fermentata and Alismatis Rhizoma had different effects on the transfer rate of AFI in decoction:After compatibility,Coptidis Rhizoma and Scutellariae Radix increased the transfer rate of synephrine,while Rhei Radix et Rhizoma,Atractylodis Maacrocephalae Rhizoma and Alismatis Rhizoma decreased the transfer rate of synephrine;Atractylodis Maacrocephalae Rhizoma,and Rhei Radix et Rhizoma increased the transfer rates of the four flavonoid glycosides,while Coptidis Rhizoma and Scutellariae Radix decreased the transfer rates of the four flavonoid glycosides;Alismatis Rhizoma and Coptidis Rhizoma increased the transfer rate of marmin,while Alismatis Rhizoma and Rhei Radix et Rhizoma decreased the transfer rate of Marmin;Atractylodis Maacrocephalae Rhizoma and Coptidis Rhizoma increased the transfer rate of meranzin hydrate,while other medicinal materials decreased the transfer rate of it.Alismatis Rhizoma increased the transfer rate of tangeretin,but other medicinal materials decreased the transfer rate of it;Massa Medicata Fermentata decreased the transfer rates of all components.Foria had little effect on the transfer rates of various constituents of AFI.When Coptidis Rhizoma and Massa Medicata Fermentata were combined with AFI the total content decreased,while the rest increased in varying degrees.Conclusions: Reasons 1)Synephrine,narirutin,naringin,hesperidin and neohesperidin are the main transfer constituents in the pharmaceutical process of ZDW and are the main release constituents of AFI in ZDW in artificial gastric / artificial intestinal fluid.2)Synephrine,narirutin,naringin,hesperidin,neohesperidin are closely related to the efficacy of AFI in the treatment of food accumulation.Narirutin,naringin,hesperidin and neohesperidin are closely related to the efficacy of ZDW in the treatment of food accumulation.3)The contents of synephrine,naringin,naringenin,hesperidin and neohesperidin could be used for separateing out different sources AFIs and corresponding fried AFIs/ ZDWs.Therefore,it is preliminarily considered that narirutin,naringin,hesperidin,and neohesperidin can be regard as the material basis of AFI in ZDW.Synephrine,narirutin,naringin,hesperidin,and neohesperidin can be regard as the material basis of AFI.In addition,we should pay attention to the interaction between AFI and other medicinal material in the decoction.This study can provide references for using drug,evaluating the quality of AFI and ZDW,further studying the compatibility mechanism,researching efficacy mechanism and improving the preparation method.But the transmission mechanism of AFI in the preparation of pills,the release mechanism in the gastrointestinal tract and the synergistic mechanism of effect need to be further studied.