Isolation And Identification Of The Chemical Constituents Of Xanthoceras Sorbifolias Wood And Pharmacokinetic Investigation Of Its Seven Major Chemical Constituents

Xanthoceras sorbifolia Bunge(Sapindaceae)is a shrub widely distributed in northern china,such as Liaoning,Hebei,and Inner Mongolia.As an important Mongolian medicine,the dried wood of the plant is often prescribed with other traditional medicines to treat rheumatism,gout and other diseases.Up to now,studies on the chemical constituents and pharmacological actions of X.sorbifolia wood have not been thoroughly carried out.In this study,the chemical constituents of X.sorbifolias wood were isolated and identified,the pharmacokinetic properties of seven major chemical constituents were investigated,and their constituents in different parts of X.sorbifolias were compared.Two phenolic acids(1 protocatechuic acid,2 isochlorogenic acid B)and ten flavonoids(3 rutin,4 myricetin,5 3,3',4',5,7-pentahydroxyflavanone,6 procyanidin A-2,7 catechin,8 dihydromyricetin,9 cinnamtannin B-1,10 gallocatechin,11 epigallocatechin,12 epicatechin)were isolated and purified from X.sorbifolias wood by chromatography on Sephadex LH20,ODS column and preparative HPLC.The structures of these 12 compounds were determined by HPLC-MS and NMR spectroscopic methods.Compound 2 and 9 were reported from this plant genus for the first time.These constituents were used as reference compounds for further pharmacokinetic and quantification studies.Comparative study of the pharmacokinetic behaviors gavaged with a single constituent,epicatechin or dihydromyricetin,with those gavaged with the methanol extract of X.sorbifolias wood was carried out.It was found that the blood drug level in single constituent gavaged group was lower than that of the methanol extract gavaged groups.The metabolism and excretion rate of certain constituent might be decreased by other constituents in the extract.As X.sorbifolias wood is often used in the form of the wood powder directly in Mongolian traditional medicine,we compared the pharmacokinetic properties of 7 blood absorbable chemical constituents after oral administration to rats of X.sorbifolias wood powder and of its extract.It was interesting to find for the first time that the plasma level of epicatechin in rats gavaged with X.sorbifolias wood powder was significantly higher than that gavaged with methanol extract.While the plasma concentration of xanthocerasic acid is just the opposite.The results indicated that the non-extractable epicatechin polymer in X.sorbifolias wood powder could degradated into epicatechin in vivo and consequently elevate the blood epicatechin level.This assumption is confirmed by incubating X.sorbifolias wood powder in artificial digestive juices in vitro,in which,the wood powder released more epicatechin than the extract did.The lipophilic xanthocerasic acid could be extracted more efficiently with methanol than with digestive juice,which might be the reason that the blood xanthocerasic acid level was higher in methanol extract gavaged groups.In order to fully explore the utilization value of X.sorbifolias,we quantified the chemical constituents in different parts(leaves,petiole,branches,stem wood and seeds)of this plant using HPLC-MS.Catechin,epicatechin and procyanidin A-2 were detected in each parts.3,3',4',5,7-Pentahydroxyflavanone,myricetin and dihydromyricetin were mainly found in branches and stems.However,xanthocerasic acid was only detected in the stems.In this study,12 chemical constituents of X.sorbifolias wood were isolated and identified for pharmacokinetic and quantification studies.For the first time,the differences of blood drug level after oral administration of X.sorbifolias wood powder,the methanol extract and pure constituents were investigated.Distribution of the major bioactive compounds in different parts of X.sorbifolias was also investigated.The obtained data provided theoretical basis for further development and utilization of this plant.