| Aim and significance:Based on our previous foundation,the Polygala tenui-folia,Magnolia officinalis and component compatibility absorption characteristics and pharmacokine-tic parameters had been discussed in different rat intestinal bowel from the aspect of pharmacokinetics and intestinal absorption.Explain the reason why Magnolia officinalis officinalis ease Poly gala tenuifolia gastrointestinal side effects and to reveal the real scientific connotation of "mutual detoxification".This paper had explored the mechanism of "mutual detoxification" between Magnolia officinalis officinalis and Polygala tenuifolia,providing some methods and ideas for relationship compatibility and attenuation mechanism of Traditional Chinese Medicine.This rese-arch has important academic value and scientific significance in Chinese medicine theory system.Methods:? This study Corrects perforate volume by the gravimetric method in rat unidirectional intestine perfusion model,the mass concentration of intestinal perfu-sion glycosides and phenolic components had been measured by HPLC-DAD meth-od,and the absorption site,co-solvent,an inhibitor of the test drug absorption,Calcul-ating the absorption rate constant(Ka)and apparent absorption coefficient(Papp)examine also been examined.? Concentration of Glycosides and the phenolic in blood were measured at various time points by HPLC-DAD method,which included Polygala tenuifolia,Magnolia officinalis and compatible decoction,extracts and hydrolyzate.To use non-compartmental model,the plasma concentration of rats-time data were analyzed and processed and obtained pharmacokinetic parameters respectively.Statistically analyz-ed the main pharmacokinetic parameters and difference of compatibility components before and after by Winnonlin 6.3 pharmacokinetic analysis software.Results:(1)Studies of single pass perfusion intestinal absorption character-istics and inhibiting intestinal effects:? The establishment of a single Poly gala tenuifolia,Magnolia officinalis Determination of intestinal perfusion method.The results show that single tenuifolin index components of Ka,Papp values indicate the trend of colon>jejunum>ileum>duodenum;Ka and Papp's values,there was no signify cant difference between honokiol and magnolol of single Magnolia officinalis(P>0.05),which's Ka value similar with tenuifolin.Ka and Papp values of Polygala tenuifolia and Magnolia officinalis Combination 1:1 in the group of tenuifolin in the colon and 1:2 groups in the jejunum,ileum and colon that were significantly lower than those of single Polygala tenuifolia group(P<0.05);Ka,Papp values of 1:2 compatibility group were significantly higher than the same amount of the single Magnolia officinalis group(P<0.05,P<0.01).? Results on intestinal absorption inhibitor showed:Concentration of 0.1 mmol·L-1 verapamil hydrochloride of(VH)P-gp inhibitor is added Polygala tenuifolia,it can significantly increase the value of the tenuifolin Ka saponins(P<0.05);added indomethacin(IT)which is MRP2 inhibitors,Ka was no significant difference in comparison with the control group(P>0.05).The different concentrations of P-gp inhibitors VH and after MRP2 inhibitor indomethacin IT in Magnolia officinalis,Ka,Papp was no significant difference in comparison with the control group(P>0.05).(2)Pharmacokinetic studies:?HPLC-DAD analysis of Magnolia officina-lis,Polygala tenuifolia decoction and extract of rat plasma and honokiol,magnolol and tenuifolin is established.The precipitated protein were selected optimum extraction solvents and solvent systems to determine each index component Polygala tenuifolia,Drawing of each component concentration-time curve.?Based on the above analysis,the pharmacokinetic parameters of each compo-nent be calculated.The results showed that the compatibility of the hydrolyzate group tenuifolin peak concentration(Cmax)was significant less than a single flavor Poly gala tenuifolia hydrolyzate group(P<0.01),time to peak(Tmax),clearance(CL/F)are very significantly larger than a single flavor Polygala tenuifolia group(P<0.01),whereas no significant differencebetween the half-life(t1/2)(P>0.05);Honokiol Tmax of com-patibility extract group was significantly greater than the single herb Magnolia officin-alis officinalis extract group(P<0.01),and the apparent volume of distribution(V/F),clearance(CL/F)were highly significant less than a single flavor Magnolia officinalis group(P<0.01);Magnolol t1/2,V/F,mean residence time(MRT(0?tn))was significant-ly greater than the single Magnolia officinalis officinalis group(P<0.05),while the elimination rate constant(Ke),drug area under the curve(AUC(0?tn))were significantly smaller than a single flavor of Magnolia officinalis officinalis group(P<0.01).?After the rats were fed extracts of different toxic chi-square test:The results showed that the toxicity of Magnolia officinalis bark decoction of Polygala tenuifolia compatibility significantly lower than that of a single flavor Polygala tenuifolia(P<0.01);Polygala tenuifolia compatibility Magnolia officinalis officinalis extract significant toxicity less than a single flavor Polygala tenuifolia(P<0.05).After Polygala tenuifolia extract hydrolyzate and Magnolia officinalis compatibility,toxicity is eliminated totally.Polygala tenuifolia compatibility with different methods around the Magnolia officinalis overall toxicity analysis:After Polygala tenuifolia compatibility Magnolia offcinalis,toxicity was significantly lower than that of a single flavor Polygala tenuifolia(P<0.01).Conclusions:? intestinal absorption:Polygala tenuifolia compatibility Magnolia officinalis officinalis,the absorption Polygala tenuifolia glycosides in the jejunum,ileum and colon was significantly reduced,Magnolia officinalis officinalis phenolic compounds absorb a significant increase in the ileum,Polygala tenuifolia with Magnolia officinalis officinalis 1:2 is slightly better than 1:1 and 1:3 ratio.?Inhibitors on:Polygala tenuifolia single flavor,which contains tenuifolin is affected by P-gp efflux,but not affected by MRP2,it may indicate if the tenuifolin formulation containing P-gp inhibitors associated with it may facilitate its absorption.The single flavor contains honokiol and magnolol not be affected by MRP2 and P-gp.?Pharmacokinetics:After Polygala tenuifolia and Magnolia officinalis phenolic glycosides compatibility,Honokiol clearance rate was significantly reduced.Half-life of magnolol was significant increaseed,peak time was delayed,peak concentration was reduced,its clearance rate in effect on the Polygala tenuifolia glycosides had been increasing.?Different extracts of Polygala tenuifolia toxicity:It was trend of extract>decoction>extract hydrolyzate;Magnolia officinalis compatibility with later can significantly decrease mortality Polygala tenuifolia.Studies suggest,Magnolia officinalis reduce toxicity and gastrointestinal side effects,and Magnolia officinalis may inhibit the absorption of phenolic constituents Polygala tenuifolia glycosides,and to accelerate its clearance,thus reducing its toxic side effects,showing "mutual detoxification"compatibility relationship.Phenols in Magnolia offcinalis played a role that relieving side effect of Polygala tenuifolia probably. |
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